Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS: The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

The effect of COVID-19 infection on patients with rheumatic diseases in China.

OBJECTIVES: At the end of 2022, the COVID-19 outbreak erupted in China, and BA.5.2 or BF.7 subtypes of Omicron novel variations were implicated in more than 90% of the cases. We created a real-world questionnaire survey to better understand how this new variant pandemic was affecting rheumatic patients in China. METHODS: During the COVID-19 outbreak in China, the subjects of this study were rheumatic patients and non-rheumatic individuals (control group), who were matched for sex and age. Professional physicians carefully questioned the participants before administering a questionnaire as part of the study. This study focused on the general baseline characteristics, clinical symptoms and treatment after COVID-19 infection, and the target populations' awareness of COVID-19. RESULTS: The study included 1130 participants, of whom 572 were assigned to the rheumatic group and 558 to the control group. The percentage of vaccinated controls was significantly higher than that of rheumatic patients (90.1% vs. 62.8%, p < 0.001), while the rate of COVID-19 infection was not significantly different between the two groups (82.3% vs. 86.6%, p = 0.051). Patients with rheumatic disease experienced substantially more days of fever following infection (2.87 ± 3.42 vs. 2.18 ± 1.65, p = 0.002) compared to individuals in the control group. The rheumatic patients had a greater prevalence of cough (67.1% vs. 54.0%, p < 0.001), somnipathy (13.8% vs. 6.0%, p < 0.001), and conjunctivitis/ophthalmodynia (5.3% vs. 2.1%, p = 0.008), while dry throat/throat pain/weakness (49.9% vs. 59.4%, p = 0.003), myalgia/osteodynia (33.3% vs. 41.8%, p = 0.003), and dyspnea (14.0% vs. 25.3%, p < 0.001) were more likely to occur in non-rheumatic group after infection. Human immunoglobulin (2.1% vs. 0.2%, p = 0.006), glucocorticoids (19.5% vs. 1.6%, p < 0.001), oxygen support (6.8% vs. 2.1%, p < 0.001), and traditional Chinese medicine (21.9% vs. 16.6%, p = 0.037) were all more frequently used by rheumatic patients with COVID-19 infection. People in the control group were more confused about whether to use masks in following social activities after contracting COVID-19 (14.7% vs. 7.6%, p = 0.001). In the control group, more individuals than patients with rheumatic disease (25.1% vs. 13.4%, p < 0.001) expressed an interest to receive the vaccine again. After being exposed to COVID-19, the majority of rheumatic patients (66.9%) reported no discernible change, only 29.1% reported a worsening of their symptoms, and the remaining 4% indicated an improvement. CONCLUSIONS: After the COVID-19 outbreak in China, the proportion of patients with rheumatic diseases infected with the virus was similar to that of normal individuals. But the clinical symptoms, follow-up treatment requirements, and awareness of the COVID-19 among rheumatic patients were distinct from those among non-rheumatic patients, necessitating the use of individualized diagnosis and treatment plans as well as health advice by medical professionals in clinical work. Key Points • Despite there were different comorbidities and vaccination rates, the rate of COVID-19 infection in patients with rheumatic disease was similar to that of normal individuals. • After COVID-19 infection, rheumatic patients and normal controls had different clinical symptoms and drug usage. • After being exposed to COVID-19, the majority of rheumatic patients felt no significant change in the primary disease, while the normal controls was more likely to accept a new vaccine injection and confused about whether to use masks in following social activities.

Effect of traditional Chinese medicine combined group psychotherapy on psychological distress management and gut micro-biome regulation for colorectal cancer survivors: a single-arm phase I clinical trial.

OBJECTIVE: To evaluate the efficacy and feasibility of utilizing Traditional Chinese Medicine (TCM) combined group psychotherapy intervention on psychological distress management and gut micro-biome regulation for colorectal (CRC) survivors. METHODS: A single-arm phase I clinical trial was conducted between December 2020 and December 2021 in Xiyuan Hospital and Beijing Cancer Hospital in China. Inclusion criteria included stage I-III CRC survivors after radical surgery with age between 18 and 75. The intervention was a 6-week online TCM combined group psychotherapy intervention including 90-min communication, TCM lifestyle coaching, self-acupressure guidance, and mindfulness practice led by TCM oncologist and psychiatrist each week. Outcomes were measured by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Fear of Cancer Recurrence Inventor (FCRI), and Quality of Life Questionnaire (QLQ-C30). Fecal samples before and after intervention were collected for 16Sr RNA analysis. RESULTS: We recruited 40 CRC survivors and 38 of them finally completed all interventions with average age of 58±13 years' old. Paired t-test showed that SAS at week 2(35.4±5.8), week 4 (37.9±10.5) and week 6 (31.3±6.4) during the intervention was significantly lower than baseline (42.1±8.3, p<0.05 respectively). SDS score also declined substantially from baseline (38.8±10.7) to week 2 (28.3±8.8, p<0.001) and week 6 (25.4±7.7, p<0.001). FCRI decreased from 19.4±7.2 at baseline to 17.5±7.1 at week 4 (p=0.038) and 16.3±5.8 at week 6 (p=0.008). Although changes of QLQ-C30 were not statistically prominent, symptom burden of insomnia and fatigue significantly alleviated. The abundances of gut microbiota Intestinibacter, Terrisporobacter, Coprobacter, and Gordonibacter were all significantly elevated after intervention. CONCLUSIONS: TCM combined group psychotherapy intervention is feasible and effective to reduce CRC survivors' psychological distress and modulate certain gut bacteria which might be associated with brain-gut axis effect. It is necessary to carry out with phase II randomized controlled clinical trial.

Factors associated with 25-hydroxyvitamin D level in Chinese hospitalized patients with systemic lupus erythematosus: a retrospective cohort study.

We aimed to investigate the factors associated with vitamin D deficiency and changes in 25 (OH)D levels, as well as the impact of those changes on disease activity and renal function among SLE patients. This retrospective cohort study was based on the medical records of SLE patients hospitalized between 2010 and 2021. We collected relevant information from this patient population. Logistic regression analysis was employed to determine the factors associated with vitamin D deficiency and increased 25 (OH)D levels, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) accordingly. At baseline, among the 1257 SLE patients, the median and interquartile range of 25 (OH)D levels were 14 (9, 20) ng/ml, with 953 (75.8%) patients exhibiting 25 (OH)D deficiency (< 20 ng/ml). The presence of 25 (OH)D deficiency was found to be associated with renal involvement and a high glucocorticoid (GC) maintenance dose. Among the 383 patients who were followed up for an average of 18 months, an increase of at least 100% in 25 (OH)D levels was positively associated with a decreased GC maintenance dose and vitamin D3 supplementation, with adjusted odds ratios(OR) (95% confidence interval [CI]) of 2.16 (1.02, 4.59) and 1300 (70, 22300), respectively. Furthermore, an increased level of 25 (OH)D was significantly associated with a decrease in the Disease Activity Index 2000 score and the urinary protein/creatinine ratio. Patients with SLE have low vitamin D levels, especially those with impaired kidney function. Increased 25 (OH)D levels can be achieved through supplementation with high doses of vitamin D3 and are associated with improvements in disease activity and the urinary protein/creatinine ratio.

Acupuncture improves certain aspects of sleep in hematopoietic stem cell transplantation patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: High-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) is associated with a high symptom burden including sleep disturbance. Here we present the results of a secondary analysis of a randomized, sham-controlled trial assessing the effect of acupuncture on sleep quality during HSCT. METHODS: Adult multiple myeloma patients undergoing inpatient and outpatient autologous HSCT were randomized and blinded to receive either true or sham acupuncture (by licensed acupuncturists) once daily for 5 days starting the day after chemotherapy. Sleep onset, total sleep time, sleep efficiency percentage and sleep-onset latency time were assessed using an actigraphy-based sleep monitor. A multivariate regression analysis was conducted to compare the average area-under-the-curve of five acupuncture intervention days for each sleep outcome between groups, adjusted by baseline score and inpatient or outpatient chemotherapy stratum. RESULTS: Over 32 months, 63 patients were enrolled. Participants undergoing true acupuncture experienced a significant improvement in sleep efficiency when compared to sham (-6.70, 95% CI -13.15, -0.25, p = 0.042). Subgroup analysis showed that the improvement was more prominent in the inpatient setting (-9.62, 95% CI -18.76, -0.47; p = 0.040). True acupuncture tended to improve wake time after sleep onset (WASO; -10.95, p = 0.054). Between-group differences in other sleep related variables were not statistically significant. CONCLUSION: Our data suggest that true acupuncture may improve certain aspects of sleep, including sleep efficiency and possibly WASO, in multiple myeloma patients undergoing HSCT. By studying patient reported outcomes in future larger scale studies, acupuncture's role in improving sleep quality during HSCT treatment could be further elucidated. TRIAL REGISTRATION NUMBER: NCT01811862 (ClinicalTrials.gov).

Role of Traditional Chinese Medicine Syndrome Type, Gut Microbiome, and Host Immunity in Predicting Early and Advanced Stage Colorectal Cancer.

OBJECTIVE: To investigate the role of Traditional Chinese Medicine (TCM) syndrome type, gut microbiome distribution, and host immunity function in predicting the early and advanced clinical stages of colorectal cancer (CRC). METHODS: A cross-sectional case-control study was performed which included 48 early stage and 48 advanced patients with CRC enrolled from March 2018 to December 2020. 16S rRNA gene sequencing was performed to analyze the gut microbiomes of the patients, while T and B lymphocyte subsets in peripheral blood were assessed using flow cytometry. TCM syndrome type was measured using the spleen deficiency syndrome (SDS) scale. RESULTS: The abundance levels of Prevotella, Escherichia-Shigella, and Faecalibacterium in the gut microbiota were significantly increased in the advanced group, while Bacteroides was significantly decreased. Phascolarctobacterium was detectable only in the early metaphase group, whereas Alistipes was detectable only in the advanced group. The lymphocyte (P = .006), T helper cell (TH) (P = .002), cytotoxic T cell (TC) (P = .003), double positive T cell (DPT) (P = .02), and total T counts (P = .001) were significantly higher in the early metaphase group than in the advanced metaphase group. Compared with patients with early stage CRC, the advanced group had a higher SDS score. After adjusting for clinical stage, Spearman's correlation analysis showed interactions among gut microbiome abundance, T cell level, and SDS score. Multivariate logistic analysis showed that after controlling for the SDS score, abundance of Alistipes and Faecalibacterium, and double negative T cell (DNT) level, DPT was significantly associated with a lower risk of advanced-stage disease (hazard ratio, 0.918; P = .022). CONCLUSION: Our study suggested associations between clinical stage, SDS, gut microbiota, and T lymphocytes, which provided insights for a potential prediction model for the disease progression of CRC.

Does physical activity associate with gut microbiome and survival outcomes of Chinese metastatic colorectal cancer patients? A secondary analysis of a randomized controlled trial.

Background: This study aimed to evaluate associations between physical activities, gut microbiome and survival outcomes among Chinese metastatic colorectal cancer (mCRC) patients. Methods: We conducted a secondary analysis nested in a randomized controlled clinical trial (RCT) of a traditional Chinese herbal medicine for mCRC patients (ChiCTR2000029599). After one-month intervention, we followed up patients every six months for survival outcomes and the last follow-up was in August 2022 (median follow-up time 28.6 months). We assessed patients' physical activity (PA) through short form of the International Physical Activity Questionnaire (IPAQ-SF) and collected patients' stool samples at baseline. Kaplan-Meier survival analyses and Cox regression models were used to evaluate the association between PA level and overall survival outcomes. 16S rRNA sequencing approaches were utilized for the gut microbiome analysis. Results: Among 40 mCRC patients enrolled in the original RCT, 15 patients were still alive at the time of the last follow-up. The mean IPAQ score was 2569.5 MET-min/week for all patients, indicating a moderate PA level. Specifically, there were 7 patients in high PA level group, 2 patients in low PA level group and the rest were in middle PA group. Gut microbiome community difference analysis showed that patients with high PA levels had a significantly higher alpha diversity than that of the middle PA group (131.53 vs. 98.12, p = 0.04), an increased abundance of Phascolarctobacterium and Ruminococcaceae and a decreased abundance of Megasphaera at the genus level. Cox regression model showed that after controlling for the original tumor site and TCM treatment, high PA level was independently associated with a lower risk of death (relative risk 0.13, p = 0.014). Conclusions: High PA level could be associated with survival benefits among Chinese mCRC patient through its potential role on modulating gut microbiome. Our results could be referred to patients' education and future clinical study design.

Celastrol ameliorates osteoarthritis via regulating TLR2/NF-κB signaling pathway.

Objectives: Osteoarthritis (OA) is a joint disease characterized by degeneration of joint cartilage and is a significant cause of severe joint pain, physical disability, and impaired quality of life in the aging population. Celastrol, a Chinese herbal medicine, has attracted wide interests because of its anti-inflammatory effects on a variety of diseases. This study aimed to investigate the effect of celastrol on OA as well as the mechanisms in vivo and in vitro. Methods: A rat knee OA model was established using "medial collateral ligament transection (MCLT) + partial meniscectomy (pMMT)". Eight weeks after surgery, the OA rats started to receive intra-articular injection of celastrol (1 mg/kg) once a week. Safranin O-fast green (S&F) and hematoxylin and eosin (H&E) staining were used to estimate histopathological changes. Micro-CT was used to evaluate bone volume of the subchondral bone of the knee joint. Chondrocytes were isolated from the knee cartilage of rats and OA patients. Enzyme linked immunosorbent assay (ELISA), Western Blot (WB), Polymerase Chain Reaction (PCR), and Immunohistochemistry (IHC) were used to detect the expression of inflammatory factors and stromal proteins, respectively. Results: We found that celastrol treatment significantly delayed the progression of cartilage damage with a significant reduction in osteophyte formation and bone resorption in OA rat model. In IL-1ß-stimulated rat chondrocytes, celastrol significantly suppressed the production of inflammatory factors such as cyclooxygenase-2 (COX2), interleukin-6 (IL-6), and prostaglandin E2 (PEG2), and reduced IL-1ß-induced matrix degradation by down-regulating the expression of matrix metalloproteinase 13 (MMP13). In addition, we found that toll-like receptor 2 (TLR2) was up-regulated in OA patients and rat knee OA models, while celastrol inhibited TLR2 signal and its downstream nuclear factor-kappa B (NF-κB) phosphorylation. Conclusion: In summary, celastrol may improve OA by inhibiting the TLR2/NF-κB signaling pathway, which provides innovative strategies for the treatment of OA.

Efficacy of Quxie Capsule in Metastatic Colorectal Cancer: Long-Term Survival Update of A Double-Blind, Randomized, Placebo Controlled Trial.

OBJECTIVE: To verify the efficacy of Quxie Capsule in patients with metastatic colorectal cancer (mCRC). METHODS: It was a block randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into 2 groups at a 1:1 ratio. The patients in the treatment group received conventional therapy including chemotherapy, radiotherapy, targeted therapy and supportive care, and Chinese herbal medicine combined with Quxie Capsule (each capsule of 0.4 g was orally administered at 50 mg/kg, twice daily, day 1-20, in a 30-day course) for 3 months. The patients in the control group received conventional therapy and Chinese herbal medicine combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to therapy lines, right or left-sided colon, targeted therapy and RAS gene status to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until December 31st, 2018. RESULTS: Median follow-up time was 19.4 months. The median OS was 23.9 months in the treatment group [95% confidence interval (CI) 15.9-28.5] vs. 14.3 months in the control group (95% CI 11.3-21.4, P<;0.05). Hazard ratio (95% CI) was 0.55 (0.31-0.95, P=0.040). There were no significant differences between the two groups in PFS (P>0.05). In the subgroups of ⩾second-line therapy, non-targeted therapy, RAS gene wild type and left-sided colon, the treatment group showed a significant survival benefit compared with the control group (P<;0.05 or P<;0.01), respectively. CONCLUSION: Quxie Capsule can reduce the risk of death and prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733).

Effect of Jianpi Bushen Sequential Formula on Adjuvant Chemotherapy of Colon Cancer: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients' adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer. METHODS: A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy. DISCUSSION: This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518).

Effectiveness of Herbal Medicine for Leukopenia/Neutropenia Induced by Chemotherapy in Adults with Colorectal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of Chinese Herbal Medicine (CHM) on leukopenia/neutropenia induced by chemotherapy in adults with colorectal cancer (CRC). METHODS: Eight electronic databases were searched from their inception to June 2020. Randomized controlled trials with clarified sequence generation were qualified. Two reviewers independently conducted the screening and data extraction. Methodological quality was assessed using the Risk of Bias tool. RevMan 5.4 was applied to the meta-analysis. RESULTS: Twenty-seven studies involving 1867 participants were qualified, of which 26 were included in the quantitative synthesis. Meta-analysis showed that CHM significantly reduced the incidence of leukopenia induced by chemotherapy (RR = 0.69; 95% CI 0.59-0.82), as well as the grade 3/4 leukopenia (RR = 0.71; 95% CI 0.55-0.90). Meanwhile,CHM decreased the occurrence of neutropenia (RR = 0.52, 95% CI 0.35-0.77), especially for the grades 3/4 neutropenia (RR = 0.42, 95% CI 0.27-0.64). Twenty-six of the included studies focused on the adverse events related to CHM. CONCLUSION: CHM may relieve neutropenia/leukopenia induced by chemotherapy in adults with colorectal cancer.

Patient Reported Traditional Chinese Medicine Spleen Deficiency Syndrome (TCM-SDS) Scale for Colorectal Cancer: Development and Validation in China.

INTRODUCTION: Spleen Deficiency Syndrome (SDS) is recognized as one of the most common Traditional Chinse Medicine (TCM) syndromes in patients with colorectal cancer (CRC). However so far there is no existing patient-reported outcome (PRO) to evaluate SDS. Our study aimed to develop and validate a PRO TCM-SDS scale for CRC in China. METHODS: We developed an initial 8-item TCM-SDS scale for CRC based on literature review and consultation with experts. We then pilot tested the scale (n = 40) and performed item revision. We conducted a survey study among CRC patients from oncology clinics at a TCM Hospital to further determine the reliability and validity of the scale. RESULTS: Among 100 patients finally enrolled and analyzed in the survey study, 46% were female with median age of 60 years old, 77% had left side tumors and 23% had stage IV disease. Factor loading indicated that there were three domains within TCM-SDS scale. The final TCM-SDS scale involves 5 items including "I feel loss of appetite," "I feel abdomen fullness," "I feel my arms and legs lack strength," "I feel short of breath when talking," and "My stool is formless" (Cronbach's alpha coefficient 0.76). We calculated the total score of the scale by summing the 5 individual items and normalizing them to a value maximum of 10, with higher scores indicating greater burden of spleen deficiency syndrome. The average spleen deficiency score for all patients was 3.55 ± 1.54. Among them, those who had stage IV disease had higher scores than stage I-III patients (4.30 vs 3.38, P = .015). Test-retest reliability after 2 weeks showed Pearson coefficient of 0.67 and all items were highly related (P < .001). Compared with healthy controls, CRC patients had significantly higher spleen deficiency scores (3.55 vs 3.23, P = .045). CONCLUSION: The patient-reported TCM-SDS scale for CRC showed adequate initial reliability and validity. The development of the scale provided an outcome measurement tool, which could facilitate future studies to better evaluate the role of TCM in treating CRC.

Exploring the Safety, Effectiveness, and Cost-Effectiveness of a Chinese Patent Medicine (Fufang E'jiao Syrup) for Alleviating Cancer-Related Fatigue: A Protocol for a Randomized, Double-Blinded, Placebo-Controlled, Multicenter Trial.

OBJECTIVE: To provide higher level evidence on the benefits of a Chinese patent medicine (CPM) (Fufang E'jiao Syrup, FFEJS) for alleviating cancer-related fatigue (CRF), this article describes a protocol for a randomized controlled trial. METHODS/DESIGN: We designed a double-blind, placebo-controlled stratified permuted block randomization clinical trial on CRF among 3 types of cancer in China. Participants will be equally allocated to FFEJS group or placebo group according to the randomization sequence and the hospitals they were enrolled at. Each patient will receive 20 ml of either the study formula FFEJS or a placebo formula, 3 times a day for 6 weeks. The follow-up period will be another 4 weeks for safety evaluation. The primary outcome is the difference in improvement of fatigue as measured with the Revised Piper Fatigue Scale-Chinese Version (RPFS-CV). Secondary outcomes include change in fatigue (measured by routine blood panel and hormones in peripheral blood) and QoL (measured by Edmonton symptom assessment scale and Functional Assessment of Cancer Therapy). Patient safety will be measured by liver, renal or cardiac damage, and the risk of FFEJS having a tumor promotion and progression effect will be monitored throughout this study. Cost-effectiveness will also be evaluated mainly by incremental cost per each quality-adjusted life year gained. DISCUSSION: This article describes the study design of a CPM for CRF in patients with advanced cancer through exploring the effectiveness, safety, and cost-effectiveness of FFEJS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04147312. Registered on 1 Sep 2019.

Quxie Capsule Modulating Gut Microbiome and Its Association With T cell Regulation in Patients With Metastatic Colorectal Cancer: Result From a Randomized Controlled Clinical Trial.

AIM: Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. METHOD: We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients' stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. RESULTS: We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter, Eubacterium, and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. -0.76, P = .002), Collinsella (coef.-0.61, P = .02), Ruminiclostridium_9 (coef. -0.64, P = .01). CONCLUSION: QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.

Effects of auricular acupuncture on appetite in patients with advanced cancer: a pilot randomized controlled trial.

BACKGROUND: Over half of patients with advanced cancer report appetite loss or anorexia. Previous studies have shown the benefit of acupuncture for cancer-related nausea and vomiting, but limited evidence exists for its role in appetite improvement. Our study aimed to evaluate the feasibility and safety of auricular acupuncture to improve appetite for cancer patients with advanced disease. METHODS: We performed a two-arm parallel, pilot randomized controlled trial (RCT) of auricular acupuncture versus usual care control in patients with stage III or IV cancer who experienced appetite loss. The primary outcome was changed in the Simplified Nutritional Appetite Questionnaire (SNAQ; score range, 4-20) between two groups from baseline to weeks 2 and 4, with secondary outcomes including change in weight, as well as an additional evaluation at week 8 for durability of treatment effects. We used independent two-sample t-test for the change in mean score for each outcome during or after treatment. We assessed the interaction between time and treatment from baseline to weeks 2, 4, and 8 using mixed-effects models by ANOVA test. RESULTS: We randomized 55 patients to auricular acupuncture (N=27) or control group (N=28). By week 4, the auricular acupuncture group had a significantly higher escalation in the SNAQ score than the control group compared with baseline [mean difference 3.69; 95% confidential interval (95% CI): 2.5, 4.8; P<0.001] and experienced a 51.4% improvement in appetite. From baseline to weeks 2 and 4, patients lost a little weight in the control group but gained weight in the auricular acupuncture group. Between baseline and week 4, change in the SNAQ score was significantly associated with change in weight (P=0.001). No adverse events (AEs) were reported during the study. CONCLUSIONS: Compared to usual care, auricular acupuncture is feasible and safe to improve appetite and help patients with advanced cancer gain weight.

Black Phosphorus-Loaded Separable Microneedles as Responsive Oxygen Delivery Carriers for Wound Healing.

Oxygen carriers are attracting extensive interest in biomedical research and clinical applications such as wound healing, alternative blood transfusion, and acute trauma treatment. Great efforts have been devoted to the generation of oxygen carriers with special functions and properties to meet specific demands. Here, we present black phosphorus (BP)-loaded separable responsive microneedles (MNs) with oxygen carrying and controllable oxygen delivering ability for wound healing. Such MNs are composed of a polyvinyl acetate (PVA) backing layer and gelatin methacryloyl (GelMA) tips that are loaded with BP quantum dots (BP QDs) and hemoglobin (Hb). Taking advantage of the fast dissolvability of PVA, the backing layer soon disappears after the MNs are applied to skin and the noncytotoxic, biocompatible GelMA tips are left inside the skin. Due to the excellent photothermal effect of BP QDs and the reversible oxygen binding property of Hb, the local temperature of the skin will increase after near-infrared ray irradiation, resulting in the responsive oxygen release. Notably, the practical performance of such MNs has been demonstrated by treating the full-thickness cutaneous wounds of a type I diabetes rat model, indicating their potential value in wound healing and other related biomedical fields.

Evaluating Cancer Patients' Expectations and Barriers Toward Traditional Chinese Medicine Utilization in China: A Patient-Support Group-Based Cross-Sectional Survey.

BACKGROUND: Traditional Chinese medicine (TCM) is widely used among Chinese cancer patients. However, little is known about Chinese patients' expectations and barriers toward using TCM for cancer. METHODS: We conducted a cross-sectional survey within a patient-support group, the Beijing Anti-Cancer Association. We measured the outcome, Chinese cancer survivors' expectations and barriers toward TCM utilization, using a modified version of ABCAM (Attitudes and Beliefs towards Complementary and Alternative Medicine), the ABTCM (Attitudes and Beliefs towards Traditional Chinese Medicine). We used multivariate models to evaluate the impact of socioeconomic status and clinical factors on their expectations and barriers (including treatment concerns and logistical challenges domain) toward TCM. RESULTS: Among 590 participants, most patients expected TCM to boost their immune system (96%), improve their physical health (96%), and reduce symptoms (94%). Many had logistical challenges (difficulty decocting herbs (58%) and finding a good TCM physician (55%)). A few were concerned that TCM might interfere with conventional treatments (7.6%), and that many TCM treatments are not based on scientific research (9.1%). In the multivariable regression model, age ≤60 years was independently associated with higher expectation score ( P = .031). Age ≤60 years (coefficient 5.0, P = .003) and localized disease (coefficient 9.5, P = .001) were both associated with higher treatment concerns. Active employment status (coefficient 9.0, P = .008) and localized disease (coefficient 7.5, P = .030) were related to more logistical challenges. CONCLUSION: Age and cancer stage were related to Chinese cancer patients' perceived expectations and barriers toward TCM use. Understanding these attitudes is important for reshaping the role that TCM plays in China's patient-centered comprehensive cancer care model.

Influence of family on expected benefits of complementary and alternative medicine (CAM) in cancer patients.

BACKGROUND: Cancer patients often use complementary and alternative medicine (CAM) based on recommendations from family. However, the relationship between family endorsement of CAM and the patient's expectation of its benefits has never been quantified. METHODS: Between 2010 and 2011, we conducted a cross-sectional survey study among patients with a diagnosis of cancer recruited from thoracic, breast, and gastrointestinal medical oncology clinics at a single academic cancer center. We performed multivariate linear regression analyses to evaluate the relationship between perceived family endorsement of and expected benefits from CAM, adjusting for covariates. RESULTS: Among the 962 participants, 303 (31.3%) reported family endorsement of CAM use. Younger patients and those who had college or higher education were more likely to report family endorsement (both p < 0.05). Patients with family support had expectation scores that were 15.9 higher than patients without family support (coefficient 15.9, 95% CI 13.5, 18.2, p < 0.001). Participants with family encouragement of CAM use were also more likely to expect CAM to cure their cancer (12 vs. 37%) and prolong their life (24 vs. 61%). These relationships remained highly significant after adjusting for covariates). CONCLUSIONS: Family endorsement of CAM use is strongly associated with patient expectation of its clinical efficacy, including expectations for cure and improved survival. These findings underscore the importance of including family in counseling and education on CAM use in order to achieve realistic patient expectations, maximize benefits, and avoid potential medical adverse effects through herb-drug interactions or rejections of conventional care.

Do Perceived Needs Affect Willingness to Use Traditional Chinese Medicine for Survivorship Care Among Chinese Cancer Survivors? A Cross-Sectional Survey.

Purpose We aimed to quantify Chinese cancer survivors' perceived needs for survivorship care and to evaluate whether these needs could impact their willingness to use traditional Chinese medicine (TCM). Methods We conducted a cross-sectional survey with members of the Beijing Anti-Cancer Association in China. We measured perceived needs with the seven-item Brief Chinese Cancer Survivorship Needs Scale that assesses psychological, functional, nutritional, social, body image, pain, and symptom needs. The outcome variable was willingness to use TCM for survivorship care. We performed multivariable logistic regression analyses to evaluate whether perceived needs are associated with willingness. Results A total of 600 patients were invited, with a response rate of 81%. The mean (standard deviation) score of the perceived needs scale (0 to 10) was 4.4 (2.2), with the majority of participants endorsing nutritional (72%), symptom (65%), and psychological (54%) needs. Among survivors, 387 (80%; 95% CI, 76% to 83%) were willing to use TCM for survivorship care. In multivariable analysis, a higher perceived needs score (adjusted odds ratio [OR], 1.33; 95% CI, 1.14 to 1.56; P < .001) was associated with greater willingness to use TCM. Specifically, nutritional (OR, 3.17; 95% CI, 1.79 to 5.62; P < .001) and symptom needs (OR, 3.15; 95% CI, 1.79 to 5.55; P < .001) had the strongest relationship. Conclusion A higher level of perceived needs, especially in the areas of nutrition and symptoms, was associated with greater willingness to use TCM for survivorship care.

Growth of Integrative Medicine at Leading Cancer Centers Between 2009 and 2016: A Systematic Analysis of NCI-Designated Comprehensive Cancer Center Websites.

Background: Cancer centers have increasingly offered integrative medicine therapies in response to their patients' unmet needs. We evaluated the growth of integrative medicine in leading academic cancer centers in the United States as reflected by their public-facing websites. Methods: We performed a systematic review of 45 National Cancer Institute (NCI)-designated comprehensive cancer center websites. Two researchers independently evaluated whether the websites provided information regarding integrative medicine modalities and, if so, whether the services were provided in the same health system. They compared the proportion of cancer centers providing the information on each modality in 2016 with the data from the prior study in 2009. Results: The most common integrative medicine therapies mentioned on the 45 NCI-designated comprehensive cancer center websites were exercise (97.8%) and acupuncture and meditation (88.9% each), followed by yoga (86.7%), massage (84.4%), and music therapy (82.2%). The majority of the websites also provided information on nutrition (95.6%), dietary supplements (93.3%), and herbs (88.9%). The most common therapies offered in the health systems were acupuncture/massage (73.3% each), meditation/yoga (68.9% each), and consultations about nutrition (91.1%), dietary supplements (84.4%), and herbs (66.7%). Compared with 2009, there was a statistically significant increase in the number of websites mentioning acupuncture, dance therapy, healing touch, hypnosis, massage, meditation, Qigong, and yoga (all P < .05). Conclusions: Leading US cancer centers increasingly present integrative medicine content on their websites, and the majority of them provide these services to patients in the same health systems.