Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Bortezomib

The healthy control group mainly collected patients with other chronic diseases or blood tumors who did not meet the exclusion criteria and were not diagnosed with multiple myeloma. Also，we need some healthy volunteers. Healthy volunteers refer to people without serious physical disease, immune disease and family history of mental illness.There is no distinction between age, gender and nationality.

In the exposure group, all patients with multiple myeloma met the inclusion and did not meet exclusion criteria, including planning for autologous stem cell transplantation or not. There is no distinction between age, gender and nationality.

Objective To observe the safety and efficacy of bortezomib related biomarkers. Including genes, metabolites, etc

Lihong Liu, Doctor

With the emergence of new drugs, the short-term survival rate of multiple myeloma has been significantly increased. However, in clinical treatment, doctors found that different patients may present different clinical efficacy and adverse reactions when using standard treatment. Some studies have shown that gene and metabolic differences in patients with multiple myeloma may be an important factor affecting clinical efficacy.

In this project, peripheral blood samples and bone marrow from patients with multiple myeloma will be studied by using the methods of genomics, proteomics, metabonomics and transcriptomics. It is expected to find biomarkers and genes related to clinical efficacy, adverse reactions, and blood concentration of bortezomib in peripheral blood samples. If the sample size is large enough, the project team expects to establish a prediction model for the efficacy and safety of bortezomib containing regimen for multiple myeloma patients through the above studies. Investigators hope that the evaluation system can provide a reference for clinical formulation of appropriate drug delivery scheme.

Evaluation of Clinical Treatment of Multiple Myeloma Based on Multi-omics

Evaluating Study of Clinical Treatment of Multiple Myeloma Based on Analytical Omics

Beijing Chao Yang Hospital

professor

Skin and Connective Tissue Diseases

Digestive System Diseases

Wounds and Injuries

Symptoms and General Pathology

Breast Neoplasms

Intestinal Diseases

Inflammatory Bowel Diseases

Hernia

Gastrointestinal Diseases

Gastroenteritis

Patients entering into elective surgery. These will be divided into three subgroups:

A. Patients with cancer. This will include patients with malignancy of the gastrointestinal and colorectal tract (including those excised by microsurgery) cancer of the breast or solid tumours of the kidney.

B. Patients with benign diseases of the bowel requiring surgery e.g. inflammatory bowel disease C. Benign surgical conditions, usually operated on in a day surgery setting. These will specifically be of the biliary tree (gall stones) and the anterior abdominal wall (e.g. Hernia surgery)

Patients presenting to Accident and emergency under the care of the general surgery on call team will be recruited into this study group. This study group will have the following subgroups:

A. Acute abdominal pain, as per the previous ethical clearance B. Patients with acute sepsis thought to be of surgical origin. C. Patients suffering major trauma with an Injury severity score of \>15, multiple injuries, who require surgery or who have \>1 organ system that is failed or who are admitted to the intensive care department.

Ara W Darzi, PC, KBE

Jeremy K Nicholson, FMedSci

Elaine Holmes, PhD

This work will use a new approach to measure how surgery effects human biochemistry and metabolism. It will create a metabolic signature or 'phenotype' for surgical injury that will help clinicians choose the right surgical treatments for an individual. This is because metabolism is based on an individual's genes, disease burden and environmental influences such as gut microbiota. This study will use a scientific method based on computational analysis of spectra taken from techniques known as Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. This science is called 'metabonomics' and it has many advantages. Firstly, it provides a measure of thousands of metabolites at a single moment in time that are unique to the individual and it therefore gives a 'systems' overview of a persons metabolism. Secondly it is able to process many hundreds of samples quickly. The investigators are aiming to integrate the investigators metabolic data with genetic information about patients or bacteria wherever possible. This will be the first time that a 'systems biology' approach has been used in surgery, with potentially significant gains to me made in pre operative risk stratification and optimisation. By performing this analysis at all stages of the surgical journey (preoperatively, during the operation and after the surgery) it will ensure the right treatments are given to the right patient at the right time. By creating longitudinal models of the biochemical responses to surgery, predict at a much earlier stage those patients at risk of developing complications. This will improve outcome after surgery. This work will use a metabonomic approach to create new tools for surgeons to use during operations based on tissue biology. For example the investigators will be able to measure the metabolic content of tumours in real time by measuring the biological content of diathermy smoke. This has the potential to change intra-operative decision making and further improve outcome.

A systems perspective can improve surgical decision making both before and after surgery in real time. Specifically, we hypothesize that it may provide diagnostic and prognostic information of importance that is more accurate than current biochemical approaches. This is because it accounts for important environmental influences on surgical outcome such as pharmacotherapy and the gut microbiota.

The secondary hypothesis is that this approach can provide real time molecular feedback to the operator during surgery about tissue type and pathology.

This work will therefore need to study patients having surgery under a range of different conditions and states, and by varying types of surgical intervention. It is known that patients with cancer for example have quite different metabolic requirements to those without. This has significant implications for the development of personalized management strategies for patients with cancer undergoing surgery. It is essential that this study definitively proves that the technology is able to make a description between patients with significantly different disease states and also that it can differentiate this from the type and magnitude of the surgical procedure being performed and the timing of the surgery. Therefore, this work will involve a heterogeneous patient cohort.

Study design:

This study will be subject to research governance structures provided internally within the department of Biosurgery and Surgical technology in conjunction with the section of Biomolecular medicine for the safe use of samples and machinery. It will also possess a clinical steering committee to assess the progress, clinical outcomes, safety and timely completion of the work.

Two separate clinical groups will be recruited for this trial. The first will be those patients undergoing elective procedures, the second will be those undergoing emergency procedures. Each of these groups will contain subcategories of clinical conditions, upon which the study will focus.

Elective surgery (n=200):

A. Patients with cancer. This will include patients with malignancy of the gastrointestinal and colorectal tract (including those excised by microsurgery) cancer of the breast or solid tumors of the kidney.

B. Patients with benign diseases of the bowel requiring surgery e.g. inflammatory bowel disease C. Benign surgical conditions, usually operated on in a day surgery setting. These will specifically be of the biliary tree (gall stones) and the anterior abdominal wall (e.g. Hernia surgery)

Patients will be recruited if seen under the 'two week' wait rule with suspected cancer for the general surgery, upper GI surgery, Breast and Urology surgery teams at St. Mary's hospital in the outpatient setting.

Patients attending for elective inpatient surgery under the general, upper GI or breast surgery teams at St. Mary's hospital, London will be recruited at the pre admission clinic.

Acute surgery (n=200)

Patients presenting to Accident and emergency under the care of the general surgery on call team will be recruited into this study group. This study group will have the following subgroups:

A. Acute abdominal pain, as per the previous ethical clearance B. Patients with acute sepsis thought to be of surgical origin. C. Patients suffering major trauma with an Injury severity score of \>15, multiple injuries, who require surgery or who have \>1 organ system that is failed or who are admitted to the intensive care department.

Exclusion criteria:

All patients under the age of 18 years All patients who are pregnant Patients receiving Advanced Life Support by cardiopulmonary resuscitation on their arrival in hospital.

Patients with advanced cancer only suitable for palliative care at presentation to the clinical team.

Patients presenting for the first time with other known malignancies for which they are receiving treatment e.g. Prostate cancer Patients already recruited into other clinical studies.

This study will be broken down into two separate phases:

Preclinical work:

Preclinical work for biofluid analysis in elective and acute surgical admissions has already been performed in both animal and human studies in Magic Angle Spinning (MAS)-1H NMR (also known as solid state NMR as the tissue does not require preparation), MS, and Matrix Assisted Laser Desorption Ionization (MALDI)-MS. Samples from previous studies gained under ethical clearance will be analyzed using these techniques for methodological optimization. This will entail metabonomic and metagenomic profiling of colorectal cancer samples (Ethics Ref: 07/H0712/112 and 06/Q0403/16) and from samples taken from patients with acute pancreatitis and the acute abdomen (Ethics Ref: 05/Q0403/201).

Non essential (i.e. Benign or pathologically normal tissue) excised and due for incineration taken from consenting patients during routine surgery will be collected for analysis by: Mass spectrometry of smoke plumes collected from a range of electrocautery devices. This will allow optimization of MS protocols and it will define the chemical parameters for normal tissue and for various tissue types.

b. Malignant tissue excised from breast, colon and upper GI cancers will be tested for its capacity to detect normal and malignant disease by the use of the intelligent knife ex vivo. This will be performed under the guidance of histopathologists, and it will not interfere with pathological staging or treatment of cancers.

Development of translational software for analytical interpretation of complex biochemical metadata by non scientific staff will be developed using these data. This work will use current intensive care clinical databases.

Clinical work:

The aim is for the technology to be readily applicable to patients having surgery within the NHS. Therefore, patients will be recruited from two surgical pathways:

Acute Care: Patient recruitment

Patients will be recruited whilst in Accident and Emergency. Only patients admitted via this route will be eligible for study inclusion. Patients will be provided with an information sheet and the patient will be left for 30 minutes to consider the study. Consent will be taken in private, by an adequately qualified and trained individual. When consented, patients will be asked to complete a questionnaire to provide medical and surgical history, and metabolic information that could influence results.

It will not be possible to gain consent in some cases as patients may be unconscious or unable to consent due to injury. In these cases samples will be taken, and when the patient gains consciousness and capacity formal consent will be taken. If at this stage, the patient states they do not want to be included in the study their samples will be withdrawn. In the event of a patient's death, the samples will be included in the study. This is because the capacity of these tests to predict mortality is a primary end point.

Elective Care: Patient recruitment

Patients will be recruited in the outpatient setting where ever possible to ensure that they have adequate time to take on board the clinical information and to consent. We will sample patients on their admission to hospital for treatment after the decision for surgery has been made.

Sample Collection:

Samples will be collected at set time points during the patient journey in both cases. Samples will be obtained at the same time as standard clinical investigations to minimize discomfort for the patient, and they will not be taken in excess of standard sample times prevent unnecessary investigation for the patient. Sample collection will be coordinated with the clinical biochemistry team at St. Mary's hospital where ever possible to prevent unnecessary and time consuming sampling.

Pre operation:

Plasma and urine collection:

1. At their arrival in Accident and Emergency. Every 24 hours for the duration of their admission or until surgery, discharge or treatment defined as surgical, radiological or invasive therapeutic intervention.

If the patient remains in hospital for prolonged rehabilitation or non surgical therapy, samples will be taken weekly until discharge.

Stool sample

First bowel motion after arrival in A+E. Preoperative and pre bowel preparation sample before surgery. This will be given either in clinic or on the ward.

Tissue sample collection

Preoperative biopsy

In the event that patients are sent for routine endoscopic or biopsy, samples of tissue will be taken for metabonomic analysis.

b. Intra-operative.

Analysis of smoke plumes by MS will be performed for each case. This will not interfere with the standard operation and the operating surgeon will not be asked to make a decision based on the data from the experiment. In cases of cancer resections, tissue samples will be collected in keeping within the principals of oncological surgery. In the cases of breast surgery, sentinel lymph nodes will also be harvested and analyzed by NMR. During colorectal surgery, tissue from the mesorectum will be taken for analysis from standard collection points and in upper GI cancer resections, similar principals will apply for sampling. In acute or emergency situations, tissue will also be taken from areas of tissue thought to be at risk of ischemia (e.g. anastomotic sites were bowel is to be joined).

Stool and small bowel effluent will be harvested at the time of surgery so that the effect of surgery on the gut microbial ecosystem can also be accounted for.

c. Post operative.

Urine and plasma will be sampled daily post operatively in keeping with current clinical practice for the first week. Where ever possible, no extra samples will be collected beyond those sampled by the clinical staff.

Stool samples will also be collected. The first bowel motion will be collected after surgery, and then each motion until the first week is completed, and then weekly after this.

The first motion from stoma / ileostomy: If stoma sited, daily samples will be taken for the first week.

Weekly samples will then be collected until discharge.

In the event that a patient returns to theatre, the sample collection sequence will re commence.

All clinical data will be recorded for the duration of the patient stay. This will refer to pre operative information and assessment where possible, physiological data, radiological findings, clinical biochemistry, surgical and clinical outcome and length of stay. This will be anonymous and coded.

On discharge, patients will be bought back to clinic at 8 weeks for clinical assessment as per the routine analysis. Samples of urine, blood and stool will be taken at this time. Oncological patients will be followed up for five years as per the oncology protocol at St. Mary's Hospital Paddington.

1. Urine
2. Blood (plasma)
3. Stool / small bowel content
4. Tissue (Colon, small bowel,stomach,eosophagus, breast, lymph nodes)

SurgicAl Metabolic Phenotyping Longitudinal Evaluation Study

Metabolic Phenotyping and Systems Biology in Surgery

Daily sampling of patients during the post operative period to determine early biomarkers for the development of sepsis

All resected cancers will be done so using the intelligent knife. Samples will be analysed by histology as per standard clinical practice. It will be determined if the intelligent knife can reduce positive resection margins.

To determine if long term metabonomic phenotyping can predict both local and distant recurrence after oncological recurrence of cancers.

We will determine novel biomarkers for predicting organ failure after injury (trauma) and surgery

This study will determine whether a systems biology approach can predict mortality before other routinely used clinical biomarkers.

Imperial College London

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Dysbiosis

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Natriuretic Agents

Reproductive Control Agents

Other Dietary Supplements

Drospirenone

Ethinyl Estradiol

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Contraceptive Agents

Drospirenone and ethinyl estradiol combination

Contraceptives, Oral

Contraceptive Agents, Female

Mineralocorticoid Receptor Antagonists

Mineralocorticoids

Hormones

Hormone Antagonists

Diuretics

Diuretics, Potassium Sparing

Contraceptives, Oral, Hormonal

Contraceptive Agents, Hormonal

Estrogens

Acidophilus

Bifidobacterium

Participants are healthy women and there are no interventions.

Participants are PCOS patients and only will be given lifestyle interventions.

Participants are PCOS patients and will be given lifestyle interventions + Probiotic Agent interventions.

Participants are PCOS patients and will be given lifestyle intervention + Oral contraceptive interventions.

1. Balance the diet;
2. Limit high-calorie and high-fat food intake, reduce eating out, and establish regular eating habits;
3. Monitor body weight, avoid sedentary, get more sun and regular activities;
4. Mental health regulation.

Lifestyle intervention

Patients have to take a probiotic powder (product name: Tangwen Tai, lactobacillus plantarum LP45 + Lactobacillus acidophilus La28 + Bifidobacterium lactobacillus BAL531) twice a day for three months.

Probiotic Agent

The patient needs to take drospirenone ethinyl estradiol tablets (trade name: Yousi Yue) 1 tablet daily for 3 months.

Oral contraceptive

Rong Chen, Ph. D.

Xu Zhang, master

Rong Chen, Ph. D

Xu Zhang, Master

Polycystic ovary syndrome (PCOS) has a significant impact on women's health, but its pathogenesis is not yet clear. Dysbiosis of gut microbiota may play a role in the pathological change of PCOS. Most of the current researches are still limited to the use of amplicon sequencing to compare the basic taxonomic differences of gut microbiota between PCOS patients and normal controls. Overall analysis of microbiome species, genes, function, metabolism, and immunity in PCOS is still lacked. In this research, we would perform metagenomic sequencing to find the characteristics of gut microbiota of PCOS and to explore their correlations with metabolic, immune, and clinical symptoms. Finally, different interventions (lifestyle interventions, lifestyle interventions + oral probiotic, lifestyle interventions+ compound oral contraceptives) would be used to explore the change of gut microbiome in PCOS patients. This research will not only help the understanding of the pathophysiology of PCOS, but also provide a reference for the selection of clinical treatment options.

1. Data quality assurance: ① all inspections and measurements will be performed by either the hospital or the sequencing company personnel according to standard operating procedures (SOPs), except for saliva and stool samples, which will be self-collected by patients. For sample collection, we will provide text descriptions of the SOPs as well as video instruction. Designated staff will be assigned for support and can be contacted if participants have any queries concerning sample collection; ② a case report form (CRF) will be prepared according to the current SOPs, and detailed instructions will be provided to ensure consistency in data collection. At the same time, each CRF will be properly stored at least 5 years for verification and backtracking; ③ all experimental data will be logged into the database to ensure information accuracy based on the existing data; ④ we will keep the contact information of each participant, remind them of precautions during participation, and conduct regular follow-ups.
2. Sample size determination: The number of participants is based on comparable sample sizes in the literature. In this trial, there will be 50 healthy individuals (control group) and 150 PCOS (polycystic ovary syndrome) patients. The 150 PCOS patients will be randomly assigned to three intervention groups. This sample size accounts for a plausible insufficiency of data caused by patient dropouts and withdrawals before the study is completed. The participation cycle is of approximately four months, followed by a 2-year follow-up.
3. Metagenomic sequencing technology Metagenomic sequencing is the main technique used in this study. Metagenomics, also known as economics, was first proposed by Handelman and studies the molecular composition of microbial populations, their interactions, and gene functions.

   In medicine, metagenomics compares the structural and functional changes of human microbial communities under normal and disease states. It can analyze the diversity and the functional differences of microbial communities from healthy individuals and from patients with diseases, thus determine how diseases relate to changes in the microbial communities and in their respective metabolic networks. Therefore, metagenomics provides theoretical evidence for disease prevention, detection, and treatment. At present, the internationally renowned Human Microbiome Project (HMP, http://www.hmpdacc.org/) and the Metagenomics of the Human Intestinal Tract (MetaHIT) are typical applications of metagenomics in medicine.

   \[Metagenomic species, genes, and functional annotation\]

   ① Data quality control: the sequenced raw data will contain a certain amount of low-quality data, so quality control must be performed. Only high-quality data can correctly reflect the actual occurrence of microorganisms in the sample.

   ② Metagenome assembly: based on Clean Data, individual samples will be assembled separately at first, then reads that do not participate in the assembling above will be combined and mixed for assembly. This will increase the sequencing depth of low-abundance species in each sample and provide more sequencing information for each species.

   ③ Gene prediction: MetaGeneMark will be used for gene prediction based on single samples and mixed-assembled scaftigs. The redundancy of all predicted genes will be reduced to obtain a Uniq gene set. Then, the Clean Data of each sample will be compared to the gene set and the abundance of the gene set will be determined for each sample.

   ④ Species annotation: Clean Data will be used for quality control. It will be compared with an annotated according to reference genome databases of bacteria, archaea, viruses, and fungi from NCBI. A species abundance table will be obtained for each sample at different classification levels.

   ⑤ Functional annotation: functional annotation and abundance statistics will be based on the Uniq gene set and the KEGG database.

This study will collect 50 healthy participants and 150 PCOS participants. At the same time, 150 patients with PCOS will be randomly divided into the lifestyle intervention group, lifestyle interventions + Probiotic Agent group, lifestyle intervention + oral contraceptive group by random number table method.

Polycystic ovary syndrome (PCOS) is a syndrome of endocrine disorders characterized by sparse ovulation or anovulation, high androgen or insulin resistance, and polycystic ovary. PCOS is a woman-specific disease, so participants must be women.

The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.

The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of Polycystic Ovary Syndrome.

According to national laws and regulations, human genetic resources may not be provided abroad.

Based on the gene and species composition of each sample, the Chao1 and Shannon indexes, as well as the observed OTUs (operational taxonomic units), will be calculated in order to identify the differences in gene and species diversity for each group.

The Spearman correlation coefficient between genes will be calculated, and genes with strong correlation will be grouped into one cluster, as a CAG. The abundance of CAGs in each sample will be determined Furthermore, the significantly enriched species in the control and PCOS groups will be enumerated for network display.

The LEfSe discriminant analysis will be used to screen for significant differences between groups. The dimensionality reduction will be implemented by LDA, and the impact of function difference will be evaluated to obtain the LDA score and identify significantly different functions between groups.

For the obtained species, genes, or functions with significant difference, the correlation between them and clinical indicators will be calculated, and key biomarkers with significant and strong correlation will be identified.

Use glucose tolerance and insulin test (75gOGTT+insulin) to assess whether the patient has insulin resistance, as well as the level of insulin resistance.

Six-sex-hormone tests, one of the clinical examination items, will be performed to measure androgen levels in the subjects.

Peking Union Medical College

Peking Union Medical College Hospital

Stomach Neoplasms

Atrophy

Gastritis, Atrophic

Gastritis

Stomach Diseases

Chronic Graft Versus Host Disease

Stomach Cancer

Healthy Volunteers with Balanced Constitution(n=10).

Healthy Volunteers with Qi Deficiency Constitution(n=10).

Healthy Volunteers with Damp-heat Constitution(n=10).

Superficial Gastritis with Spleen-qi Deficiency Syndrome(n=10).

Superficial Gastritis with Damp-heat Syndrome(n=10).

Atrophic Gastritis with Spleen-qi Deficiency Syndrome(n=10).

Atrophic Gastritis with Damp-heat Syndrome(n=10).

Gastric Cancer with Spleen-qi Deficiency Syndrome(n=10).

Gastric Cancer with Damp-heat Syndrome(n=10).

Xiaopu Sang

Leiming You

Anlong Xu

Spleen Deficiency Syndrome(SDS)is a widely researched issue, but due to the limitations of the research methods, the scientific mechanism of SDS is biased and not comprehensive. SDS would be researched in this project deeply and systematically with modern life-scientific methods. Based on the previous work, the participants, with SDS, suffering from Qi deficiency syndrome--chronic superficial gastritis--chronic atrophic gastritis--gastric cancer would be included, and the corresponding research would be conducted at the molecular-cell-gastric tissue level, and at the same time, systematical biological database of SDS would be built by systematical biological methods, such as pioneered SPARS sequencing technology created in our research group, proteomics and metabonomics. Under the above work, the investigators would conduct data mining and molecular network analysis, and then verify the key functions. By analyzing the systematical biological features of syndrome and its relationships with constitution and disease, this study would provide a new basis for objective reality of syndrome, and also offer a crucial premise of revealing biological basis for syndrome correctly, which is of important theoretical and practical significance.

System Biology of Spleen Deficiency Syndrome

System Biology Research of Spleen Qi Deficiency Associated "Qi Deficiency Constitution-Disease"

Endoscopic diagnosis standard of chronic gastritis according to Chinese Society of Digestive Endoscopy.

Pathological diagnosis standard of chronic gastritis according to Chinese Society of Gastroenterology.Pathological diagnosis standard of gastric cancer according to Ministry of Health P.R.China

Beijing University of Chinese Medicine

President

Study participation will be offered to women, newly diagnosed with a gynecological malignancy who are due to be treated with pelvic radiotherapy.

Cohort Observation

Jervoise Dr Andreyev, MA, Phd

Scientists have developed an instrument which works like an "electronic nose". It is able to "sniff" smells and separate different smells by their electronic "signature". Studies using an electronic nose strongly suggest that smelling samples taken from humans (e.g. urine/ stool/ sweat/ tears) can identify different electronic smell signature from people with different diseases and in the future might be a new and easier way to diagnose serious conditions at an earlier stage.

In a very small study, it has been successfully shown that using an electronic nose to sniff a stool sample does seem to identify people before they have had any radiotherapy - who will go on to get serious bowel side effects of radiotherapy. If this finding is correct, this is very important as it would allow the cancer doctors the option to change the way they give radiotherapy if they knew that a person was at very high risk of serious side effects from the treatment and to start treatment for the side effects at a much earlier stage.

In this study the investigators want to confirm in a larger study whether the previous findings are correct, and to see whether similar results can be obtained by sniffing urine rather than stool (that would be much easier for everyone) and identify exactly which part of the complicated "smell" signature is different in the people who will get side effects. This may lead for the investigators to able to identify why people are making this specific smell and then do something about changing the smell before treatment starts. The likeliest cause for the production of a smell which predisposes to side effects is a specific group of germs living in the bowel. If these germs can be identified, then there are many possible ways of changing these germ populations in advance of radiotherapy.

Enormous improvements have been made in treating cancer in recent years leading to hugely improved survival, however, treatment not infrequently can lead to side effects. Of all the possible long term physical side effects of cancer treatment, gastrointestinal (GI) symptoms are the most common and can have a great impact on daily activity. It is becoming increasingly clear that development of side effects in the bowel is not just related to the dose and way the radiotherapy is delivered.

There have been enormous improvements in outcomes for patients diagnosed with cancer in recent years. Patients survive longer and the number of survivors after cancer therapy increases 3% annually in the UK and 11% in the USA.It is estimated that there will be 4 million cancer survivors in the UK by 2030.Patients after cancer treatments have many unmet needs which are often caused by the very therapies given to cure or control the cancer. Of all the possible chronic physical side effects of cancer treatment, gastrointestinal (GI) symptoms are the most common and not only have the greatest impact on daily activity but also frequently carry serious financial, psychological and social implications.

During treatment for the cancer, GI symptoms are common and their causes are poorly researched despite their impact on patients' quality of life and the fact that when they occur they often require dose reduction or cessation of chemotherapy and/or radiotherapy with potential impact on outcome. In addition, the GI side effect may not settle once anti-cancer treatment is stopped. In patients receiving radiotherapy for a tumor in the pelvis, more severe acute reactions predispose to worse long term side effects.

At least 17,000 British patients are treated annually with radiotherapy for pelvic cancer. Up to 80% of these patients are left with chronic alteration in GI function, 50% state that this affects their daily activity and 30% that this change in function has a moderate or severe effect. While progress has been made in defining optimal management of chronic changes in bowel function after cancer treatment and UK multi-professional guidance to aid clinicians has been published it would be extremely valuable to be able to predict those in advance who might go on to develop serious problems as a result of radiotherapy so as to have the opportunity to provide them with pre-treatment counseling, potentially modify the cancer treatment and introduce toxicity modifying therapies at the earliest opportunity.

It is widely believed that technical advances in the delivery of radiotherapy will abolish GI problems however, recent compelling data demonstrate that 30% of patients treated with "perfect" radiotherapy - meeting every described constraint still develop significant un-predicted problems. While mechanisms by which gastrointestinal symptoms occur after cancer treatment are starting to be understood and personal parameters which change the risk profile for individuals are being identified (body mass index, concomitant chemotherapy, use of a statin or ACE inhibitor, the presence of diabetes mellitus, hypertension, connective tissue disorders or HIV infection) the reasons why some patients remain symptom free whilst others experience severe side effects remains under researched.

It has become clear that development of GI toxicity is not solely related to the dose and way the radiotherapy is delivered, and a phenomenon independent of the radiation called the 'the consequential effect' is a second reason why some people get chronic side effects after radiotherapy. An important driver of the 'consequential effect' is increasingly believed to be the microbiota, the vast numbers of bacteria that live in our guts. The gastrointestinal microbiota are a complex ecosystem of up to 1,000 bacterial species in any one individual. The species vary greatly between individuals but within each individual, the flora composition remains stable for the majority of the species over time. The diversity of the microbiota is high in healthy people and low in people with GI side effects after pelvic radiotherapy, a process which very closely parallels findings in people with other much more intensively researched inflammatory conditions of the bowel.

Normal gut flora produce gases from their metabolites (Volatile Organic Compounds or VOCs). The gold standard for analyzing volatile organic compounds is gas chromatography/mass spectrometry (GCMS).

GCMS analyses gasses to identify all chemical components of that gas. However, this is very expensive and requires a specialized laboratory to process the samples hence is not a viable option in day to day clinical practice.

Two alternative techniques can be applied to analyse those VOCs: electronic sensing (e-nose) or High Field Asymmetric Ion Mobility Spectrometry (FAIMS).

Electronic sensing techniques are applied via an instrument (electronic nose) that attempts to replicate the biological olfactory system, by investigating samples as a whole, instead of identifying specific chemicals within a complex sample. The air above the sample (head space) is drawn into the e-nose and passed across an array of chemical sensors. The size of the array varies, but most are between 6 and 32 sensors. As each sensor is dissimilar, the interaction between the sensor and the sample is unique and an olfactory signature for this complex odor can be created.

Fields Asymmetric Waveform Ion Mobility Spectometry (FAIMS) is a new technology capable of separating gas phase ions at atmospheric pressure and at room temperature. As with the electronic nose, FAIMS can be used for the real time analysis of complex chemical components, looking at the total chemical composition of a sample. Differences in the way the ionised molecules move in high electric fields are used to draw a mobility signature of a complex sample.

The e-nose and FAIMS techniques have been used successfully in small studies to diagnose lung disease, diabetes, bladder cancer, tuberculosis, cyanide poisoning, renal failure and schizophrenia. Focusing on gastrointestinal disorders, consistent changes in the VOCs produced by patients with inflammatory bowel disease, bile acid malabsorption, gastrointestinal cancer, coeliac disease, Clostridium difficile infection can be identified compared to healthy individuals.

In a paper published in 2012 of a retrospective blinded pilot study using the e-nose in 23 patients in whom the investigators analysed stool samples collected immediately before the start of radiotherapy. Of the 23 patients selected, 11 subsequently had minimal or no side effects from radiotherapy and 12 had severe toxicity. The e-nose analysed the samples and astonishingly identified with 100% accuracy two completely distinct groups of patients: those who would develop severe toxicity during radiotherapy and those who would not. The results of this study suggest that the substantial differences in the volatile gases produced by stool samples in the two populations, have a critical impact on toxicity and the reason that different fermentation products occur is either because the microbiological composition of stool differs between the two groups, or because bacterial function is somehow different. Whatever the reason, these findings suggests that the microbiota plays a critical role in the initiation of radiation induced inflammation are completely consistent with findings from other studies using very complex methodologies and with studies investigating the role of the microbiota in other GI conditions .

Patients will be asked to provide stool and urine samples and complete symptom assessment questionnaires at 6 time points: baseline (before treatment), 2 and 6 weeks after starting radiotherapy, 6 months after completion of radiotherapy and 12 and 24 months after completion of treatment. In addition, patients will be asked to provide a rectal swab and a saliva sample, which will be stored and potentially used at a later stage to characterize any differences in the microbial populations present. (Funding will be sought elsewhere to analyse these samples).

Using an Electronic Nose to Predict Gastrointestinal Consequences of Pelvic Radiotherapy

A 6 point difference in the olfactory signatures in different samples (rectal swab, stool sample,urine, sample saliva sample) between patients who develop severe toxicity\* and those with no or minimal toxicity.

The Bristol stool chart categorizes the types of stool a person passes into 7 categories. It is a helpful tool to assess stool consistency in combination with other tools assessing GI symptoms, however it does not describe the severity of toxicity so no cut off values.

For IBDQ a higher score will indicate a better Quality of Life (QoL). A change in IBDQ will indicate the level of patients QoL over the study period.

University of Warwick

Royal Marsden NHS Foundation Trust

Nutritional and Metabolic Diseases

Insulin Resistance

Hypoglycemic Agents

Insulin

Insulin, Globin Zinc

BMI、WHR、FSH、LH、PRL、T、E2、TG、CHOL、LDL-C、HDL-C、FBG、OGTT、FINS、insulin release test、HOMA index、identification of metabolites

all the indicators

Jinbang Xu

Jingjing Dun

The type-2 diabetes mellitus（T2DM）, metabolic syndrome, cardiovascular disease complications induced by polycystic ovary syndrome(PCOS) with insulin resistance(IR）, which become serious threat to public health. In this observational study, obese patients with PCOS,nonobese patients with PCOS, PCOS patients with impaired glucose tolerance（IGT）, PCOS patients with type-2 diabetes mellitus（T2DM）, and healthy volunteers would enrolled into this study, through the Liquid Chromatography-Mass Spectrometry coupled to Mass Spectrometry（ LC-MS/MS）and Rapid Resolution Liquid Chromatography（RRLC） and Quadrupole Linear Trap（QTRAP）Mass Spectrometry coupled to Mass Spectrometry （MS/MS）analysis of serum samples collected from PCOS patients and healthy volunteers to screen the biomarker of diagnosis for PCOS with insulin resistance, to explore the correlation between traditional chinese medicine （TCM） syndrome（phlegm, kidney yin deficiency, kidney yang deficiency, qi stagnation and blood stasis，dampness-heat of liver channel）and metabolites of PCOS.

1. The selection of research subjects: All the subjects collect from Fujian Maternity and Child Health Hospital.
2. The participants will be divided into five groups：obese with PCOS，nonobese with PCOS，PCOS with IGT，PCOS with T2DM，healthy volunteers.the syndrome type of PCOS will be divided into five types: phlegm, kidney yin deficiency, kidney yang deficiency, liver qi stagnation and blood stasis syndrome, dampness-heat of liver channel.
3. Ethical requirements and subjects' informed consent Before clinical trials begin, the program needs to be approved by the ethics committee to approve and sign the approval.The subjects need fully aware of the clinical trial and are given sufficient time to consider whether they are willing to participate in the trial, and to sign the informed consent form.
4. Indicator test (the cost of all health volunteers are paid by the research) (1)Physical examination: blood pressure, height, body weight,waist circumference,hip circumference，body mass index(BMI),waist-hip ratio（WHR）.

(2)Endocrine hormones: collect serum from all the subjects，use the enzyme linked immunosorbent assay (ELISA) method to detect the level of serum follicle-stimulating hormone（FSH）,luteinizing hormone（LH）,prolactin（PRL）,estradiol（E2）,testosterone（T）. Blood lipid: glycerin three vinegar (TG), cholesterol (CHOL) detect by enzymatic method, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) detect by the turbidity method. Glucose tolerance and insulin release test after glucose loading: all subjects were fasting for 8 to 10 h, check the fasting blood glucose(FBG)and fasting insulin （FINS）.The oral glucose tolerance test（OGTT）and insulin release test were performed in the next morning.

5.Study on the characteristics of metabolism

（1）Through the sample pretreatment method, analyzes the optimization of the condition of mass spectrometry, according to the requirements of the metabolism to establish the blood sample LC-MS/MS metabolism analysis method.（2）Carry out the analysis of metabolism and data collection.（3）Model building and data analysis（4）Use RRLC and QTRAP type MS/MS with positive and negative ion detection mode with the combination of hyphenated techniques, combined with the method of data statistics,to establish multiple reaction monitoring（MRM） detection, to verify the precision and sensitivity of the method.

6.Statistical methods: All data use statistical product and service solutions18.0（SPSS18.0）software package for statistical analysis. According to the character of clinical trial data (measurement, classification and grade data), select the appropriate statistical analysis method.receiver operating characteristic curve（ROC） analysis of the potential metabolites selected from the targeting metabolic biomarker.

A Metabolomic Study of Polycystic Ovary Syndrome With Insulin Resistance and Its Relationship With TCM Syndrome Types

Fujian Maternity and Child Health Hospital

Collect serum from all the subjects , through the sample pretreatment method,the metabolic features are first scanned by using Liquid Chromatography-Mass Spectrometry coupled w ith Mass Spectrometry,extracted ion-pairs were fetched to type RRLC and QTRAP(MS/MS) for multiple reaction monitoring（MRM） detection,Peak detection and alignment from the raw date use Analyst Quantitation software ,use SIMCA-P11.0 to conduct principle component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) model,use SPSS18.0 software package for statistical analysis

use the ELISA method to detect the levels of serum FSH

use the ELISA method to detect the levels of serum LH

use the ELISA method to detect the levels of serum PRL

use the ELISA method to detect the levels of serum T

use the ELISA method to detect the levels of serum E2

use the enzymatic method to detect the levels of serum TG

use the enzymatic method to detect the levels of serum CHOL

use turbidity method to detect the levels of serum LDL-C

use turbidity method to detect the levels of serum HDL-C

use glucose oxidase method to detect the levels of serum FBG

The levels of blood glucose about 1, 2, 3 hours after glucose loading

use radioimmunoassay to detect the levels of serum FINS

The levels of Insulin about 1, 2, 3 hours after glucose loading

The goal of this observational study is to draw the characteristic maps of genomics, transcriptome, proteomics, metabolomics, etc. in 600 patients with gynecological rare pathological types of malignant tumors. Then it is planned to explore the molecular mechanism and find some new targets for diagnosis and treatment, and design and establish the database system of the above rare tumors.

Prospective Multi-omics Observational Study of Gynecological Rare Pathological Tumors

Draw the characteristic maps of imaging omics, genomics, transcriptome, proteomics, pathological omics, metabolomics, etc. of patients with gynecological rare pathological types of malignant tumors, and explore the molecular mechanism thus finding some new targets for diagnosis and treatment.

Design and establish the database system of the above gynecological rare pathological types of tumors.

Integrate the characteristic maps of imaging omics, genomics, transcriptome, proteomics, pathological omics, metabonomics, etc. to study their possible relevance.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Clinical Treatment of Multiple Myeloma Based on Multi-omics	NCT04678089	Multiple Myelom... Bortezomib	Bortezomib	18 Years - 100 Years	Beijing Chao Yang Hospital
SurgicAl Metabolic Phenotyping Longitudinal Evaluation Study	NCT01378013	Colon Cancer Breast Cancer Trauma Inflammatory Bo... Hernia		18 Years -	Imperial College London
The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.	NCT03843736	Polycystic Ovar...	Lifestyle inter... Probiotic Agent Oral contracept...	18 Years - 45 Years	Peking Union Medical College Hospital
System Biology of Spleen Deficiency Syndrome	NCT02915393	Gastritis, Atro... Gastric Cancer		18 Years - 65 Years	Beijing University of Chinese Medicine
Using an Electronic Nose to Predict Gastrointestinal Consequences of Pelvic Radiotherapy	NCT02649491	Cancer Toxicity Malignancy	Cohort Observat...	18 Years - 90 Years	Royal Marsden NHS Foundation Trust
Evaluation of Clinical Treatment of Multiple Myeloma Based on Multi-omics	NCT04678089	Multiple Myelom... Bortezomib	Bortezomib	18 Years - 100 Years	Beijing Chao Yang Hospital
A Metabolomic Study of Polycystic Ovary Syndrome With Insulin Resistance and Its Relationship With TCM Syndrome Types	NCT02992093	PCOS	all the indicat...	18 Years - 40 Years	Fujian Maternity and Child Health Hospital
Prospective Multi-omics Observational Study of Gynecological Rare Pathological Tumors	NCT05985941	Rare Gynecologi... Multi-omics Ana...		18 Years -	RenJi Hospital
Tumor Response Prediction in Neoadjuvant Chemoradiation of Locally Advanced Rectal Cancer Using Metabonomics Analysis	NCT03149978	Locally Advance...		18 Years - 75 Years	Fudan University
The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.	NCT03843736	Polycystic Ovar...	Lifestyle inter... Probiotic Agent Oral contracept...	18 Years - 45 Years	Peking Union Medical College Hospital
A Multi-omics Study of Metastatic Prostate Cancer (MOSMPCA)	NCT04660617	Prostate Cancer...		40 Years -	West China Hospital
A Metabolomic Study of Polycystic Ovary Syndrome With Insulin Resistance and Its Relationship With TCM Syndrome Types	NCT02992093	PCOS	all the indicat...	18 Years - 40 Years	Fujian Maternity and Child Health Hospital

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