Predictive value of TCM tongue characteristics for chemotherapy-induced myelosuppression in patients with lung cancer.

This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (n = 52) or the test group (n = 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (OR = 3.67), Karnofsky performance status score (OR = 0.11), and the number of high-toxic drugs in chemotherapy regimens (OR = 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.

Electroacupuncture for the treatment of cancer pain: a systematic review and meta-analysis of randomized clinical trials.

Objective: This paper aims to review the current evidence on electroacupuncture as an effective and safe therapy for cancer pain management. Methods: Five databases were searched from their inception through November 11, 2022. Only the randomized controlled trials that meet the eligibility criteria were finally included in the study. Literature screening and data extraction were performed independently by two reviewers, and RevMan 5.3 used for meta-analysis. Results: A total of 17 RCTs met our inclusion criteria. We used 8 indicators to estimate the meta-analysis results, most of which proved statistically significant, including VAS scores, NRS scores, and KPS scores. To be specific, VAS scores (MD = -1.41, 95% CI: -2.42 to -0.41, P = 0.006) and NRS scores (MD = -1.19, 95% CI: -1.72 to -0.66, P < 0.0001) were significantly lower in the treatment group compared to the control group. The treatment group's KPS scores (MD = 5.48, 95% CI: 3.27 to 7.69, P < 0.00001) were higher than those of the control group. Also, in the treatment group, the number of burst pain (MD = -2.66, 95% CI: -3.32 to -1.99, P < 0.00001) and side effect rates (RR = 0.51, 95% CI: 0.39 to 0.67, P < 0.00001) greatly reduced, while the response rate (RR = 1.17, 95% CI: 1.09 to 1.26, P < 0.0001) significantly increased compared to the control group. Conclusion: This study demonstrates the advantages of electroacupuncture in the treatment of cancer pain. Meanwhile, rigorous RCTs should be designed and conducted in the future to further demonstrate the exact efficacy of electroacupuncture. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022376148.

Diagnostic efficacy of high-frequency ultrasound and X-ray contrast enema in colonic strictures after necrotizing enterocolitis: a retrospective study.

OBJECTIVE: To compare the efficacy of high-frequency ultrasound and X-ray contrast enema in the diagnosis of colonic strictures after necrotizing enterocolitis. METHODS: This study included pediatric patients who developed progressive abdominal distension or constipation after conservative treatment for necrotizing enterocolitis at our hospital between June 2012 and April 2020. All patients had high-frequency ultrasounds and X-ray contrast enema, and we used surgery, pathology, and telephone return visits as the reference standard. Patients with colonic strictures were confirmed by surgery and pathology. A patient was considered without colonic stricture if no stricture was reported or did not have related symptoms during telephone return visits. The areas under the Receiver operating characteristic (ROC) curves were used as evaluation indexes to compare the differential efficacy of high-frequency ultrasound and X-ray contrast enema. RESULTS: A total of 81 patients have been included in this study. Among them, 49 patients were diagnosed with colonic strictures after necrotizing enterocolitis. The AUCs for high-frequency ultrasound and X-ray contrast enema were 0.990 vs 0.938, respectively (p > 0.05). CONCLUSION: The diagnostic efficacy of high-frequency ultrasound was similar to that of X-ray contrast enema, furthermore this study also demonstrates the benefits of using high-frequency ultrasound to identify colonic strictures after necrotizing enterocolitis.

The interactions between traditional Chinese medicine and gut microbiota: Global research status and trends.

Background: There is a crosstalk between traditional Chinese medicine (TCM) and gut microbiota (GM), many articles have studied and discussed the relationship between the two. The purpose of this study is to use bibliometric analysis to explore the research status and development trends of the TCM/GM research, identify and analyze the highly cited papers relating to the TCM/GM. Methods: A literature search regarding TCM/GM publications from 2004 to 2021 was undertaken on August 13, 2022. The main information (full record and cited references) of publications was extracted from the Science Citation Index Expanded (SCI-E) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package, CiteSpace and VOSviewer were used for bibliometric analysis. Results: A total of 830 papers were included. The publication years of papers were from 2004 to 2021. The number of papers had increased rapidly since 2018. China had the most publications and made most contributions to this field. Nanjing University of Chinese Medicine and Beijing University of Chinese Medicine were in the leading productive position in TCM/GM research, Chinese Academy of Chinese Medical Sciences had the highest total citations (TC). Duan Jin-ao from Nanjing University of Chinese Medicine had the largest number of publications, and Tong Xiao-lin from China Academy of Chinese Medical Sciences had the most TC. The Journal of Ethnopharmacology had the most published papers and the most TC. The main themes in TCM/GM included the role of GM in TCM treatment of glucolipid metabolism diseases and lower gastrointestinal diseases; the mechanism of interactions between GM and TCM to treat diseases; the links between TCM/GM and metabolism; and the relationship between GM and oral bioavailability of TCM. Conclusion: This study gained insight into the research status, hotspots and trends of global TCM/GM research, identified the most cited articles in TCM/GM and analyzed their characteristics, which may inform clinical researchers and practitioners' future directions.

Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

Efficacy of Wen-Luo-Tong on Peripheral Neuropathy Induced by Chemotherapy or Target Therapy: A Randomized, Double-Blinded, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy. METHODS: This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30). RESULTS: After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05). CONCLUSION: WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).

A Single-Arm Phase II Study to Evaluate Efficacy and Safety of First-Line Treatment With DCVAC/LuCa, Standard of Care Chemotherapy and Shenqi Fuzheng Injection in Advanced (Stage IIIB/IV) Non-Small Cell Lung Cancer Patients.

OBJECTIVES: To evaluate the efficacy and safety of first-line treatment with a dendritic cell vaccination for lung cancer (DCVAC/LuCa), standard of care chemotherapy and Shenqi Fuzheng injection in patients with advanced (stage IIIB/IV) non-small cell lung cancer. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed recurrent metastatic or advanced NSCLC (stage IIIB/IV) with wild-type epidermal growth factor receptor (EGFR) or EGFR mutation which does not confer increased tumor susceptibility to EGFR-interacting drugs were recruited. For the treatment period, the first cycle of standard of care therapy (SoC) started 2 to 14 days after the leukapheresis procedure. SoC continued 4 to 6 cycles. DCVAC/LuCa was administered from the second cycle of SoC. DCVAC/LuCa was administered in a 3-week cycle schedule (5 doses) and then in a 6-week cycle schedule. Shenqi Fuzheng injection was administered 3 days before each DCVAC/LuCa administration for a total of 14 daily doses. Patients would undergo disease evaluation by computed tomography (CT) scan every 3 months. The primary and secondary endpoint was efficacy with regard to objective response rate (ORR) and progression free survival (PFS). The safety profile was measured by: incidence, type, and severity of all adverse events (AEs), laboratory abnormalities (blood routine test, urine test, and chemical test), physical status, and vital signs. Qi insufficiency was evaluated by tongue diagnosis and questionnaire survey with "Classification and Determination of constitution in TCM." RESULTS: Twenty-three patients from 3 hospitals who received combination therapy were included. ORR was 34.8% (95% CI:16.4%-57.3%). Median duration of response was 5.51 m (95% CI:2.70-8.32). Median PFS was 10.72 m (95% CI:4.52-16.93), 1-year survival was 77.8%. mOS was 21.97 m (95% CI:13.68-30.25). There was 1 severe AE related to a history of heart disease and there were no adverse events related to DCVAC/LuCa treatment. Qi insufficiency was improved significantly (P < .0001) from 41.19 ± 14.58 before treatment to 10.52 ± 16.58 after treatment. CONCLUSION: DCVAC/LuCa, combined with standard of care chemotherapy and Shenqi Fuzheng injection exhibited good benefit in Chinese patients with recurrent metastatic or advanced (stage IIIB/IV) NSCLC, and also significantly improved Qi insufficiency constitution. There were no related adverse events with DCVAC/LuCa treatment.

Constructing tongue coating recognition model using deep transfer learning to assist syndrome diagnosis and its potential in noninvasive ethnopharmacological evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongue coating has been used as an effective signature of health in traditional Chinese medicine (TCM). The level of greasy coating closely relates to the strength of dampness or pathogenic qi in TCM theory. Previous empirical studies and our systematic review have shown the relation between greasy coating and various diseases, including gastroenteropathy, coronary heart disease, and coronavirus disease 2019 (COVID-19). However, the objective and intelligent greasy coating and related diseases recognition methods are still lacking. The construction of the artificial intelligent tongue recognition models may provide important syndrome diagnosis and efficacy evaluation methods, and contribute to the understanding of ethnopharmacological mechanisms based on TCM theory. AIM OF THE STUDY: The present study aimed to develop an artificial intelligent model for greasy tongue coating recognition and explore its application in COVID-19. MATERIALS AND METHODS: Herein, we developed greasy tongue coating recognition networks (GreasyCoatNet) using convolutional neural network technique and a relatively large (N = 1486) set of tongue images from standard devices. Tests were performed using both cross-validation procedures and a new dataset (N = 50) captured by common cameras. Besides, the accuracy and time efficiency comparisons between the GreasyCoatNet and doctors were also conducted. Finally, the model was transferred to recognize the greasy coating level of COVID-19. RESULTS: The overall accuracy in 3-level greasy coating classification with cross-validation was 88.8% and accuracy on new dataset was 82.0%, indicating that GreasyCoatNet can obtain robust greasy coating estimates from diverse datasets. In addition, we conducted user study to confirm that our GreasyCoatNet outperforms TCM practitioners, yet only consuming roughly 1% of doctors' examination time. Critically, we demonstrated that GreasyCoatNet, along with transfer learning, can construct more proper classifier of COVID-19, compared to directly training classifier on patient versus control datasets. We, therefore, derived a disease-specific deep learning network by finetuning the generic GreasyCoatNet. CONCLUSIONS: Our framework may provide an important research paradigm for differentiating tongue characteristics, diagnosing TCM syndrome, tracking disease progression, and evaluating intervention efficacy, exhibiting its unique potential in clinical applications.

Application Potential of Plant-Derived Medicines in Prevention and Treatment of Platinum-Induced Peripheral Neurotoxicity.

As observed with other chemotherapeutic agents, the clinical application of platinum agents is a double-edged sword. Platinum-induced peripheral neuropathy (PIPN) is a common adverse event that negatively affects clinical outcomes and patients' quality of life. Considering the unavailability of effective established agents for preventing or treating PIPN and the increasing population of cancer survivors, the identification and development of novel, effective interventions are the need of the hour. Plant-derived medicines, recognized as ideal agents, can not only help improve PIPN without affecting chemotherapy efficacy, but may also produce synergy. In this review, we present a brief summary of the mechanisms of platinum agents and PIPN and then focus on exploring the preventive or curative effects and underlying mechanisms of plant-derived medicines, which have been evaluated under platinum-induced neurotoxicity conditions. We identified 11 plant extracts as well as 17 plant secondary metabolites, and four polyherbal preparations. Their effects against PIPN are focused on oxidative stress and mitochondrial dysfunction, glial activation and inflammation response, and ion channel dysfunction. Also, ten clinical trials have assessed the effect of herbal products in patients with PIPN. The understanding of the molecular mechanism is still limited, the quality of clinical trials need to be further improved, and in terms of their efficacy, safety, and cost effectiveness studies have not provided sufficient evidence to establish a standard practice. But plant-derived medicines have been found to be invaluable sources for the development of natural agents with beneficial effects in the prevention and treatment of PIPN.

Effect of Chinese Herbal Compound LC09 on Patients With Capecitabine-Associated Hand-Foot Syndrome: A Randomized, Double-Blind, and Parallel-Controlled Trial.

Background: LC09 is composed with 5 kinds of traditional Chinese herbal medicines (Astragalus membranaceus, flowers carthami, lithospermum, geranium wilfordii, and radix angelicae) which are used in China and developed over several thousand years. Aim: To assess the effectiveness and safety of herbal compound LC09 on patients with capecitabine-associated hand-foot syndrome (HFS). Materials and Methods: In this randomized, double-blind, and parallel-controlled study, 156 patients that diagnosed with HFS were randomly assigned to a treatment group (n = 78) or control group (n = 78). Patients were evaluated every week by the National Cancer Institute (NCI) grade and Numerical Rating Scale (NRS) pain scores. The Dermatology Life Quality Index (DLQI) scale and Instrumental Activity of Daily Living (IADL) scale were used to assess the quality of life before the treatment, and at 1 week and after the treatment of 2 cycles. Results: At the baseline, no significant differences were observed between the 2 groups. After treatment, significant differences in NCI grade and NRS pain scores were observed between the 2 groups (P < .01). In addition, HFS effectiveness rate and pain alleviation rate were significantly higher in the treatment group compared with the control group (P < .01). Furthermore, the chemotherapy completion rate between 2 groups was significantly different (P = .002). In addition, no adverse reactions were observed in either LC09 or control group. Conclusion: LC09 can decrease NCI grade and significantly alleviate pain in HFS patients. Besides, it can also increase chemotherapy completion rate.

Efficacy and safety of Shengjiang Xiexin decoction in prophylaxis of chemotherapy-related diarrhea in small cell lung cancer patients: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Diarrhea is a common adverse reaction in patients with cancer receiving chemotherapy, for which there is currently no effective method of treatment. Shengjiang Xiexin decoction (SXD), a classic traditional Chinese medicine (TCM) formula, has shown efficacy in alleviating irinotecan-induced diarrhea in preliminary clinical studies. The current study is designed to assess the efficacy and safety of SXD for prophylaxis against irinotecan-induced diarrhea. Additionally, we employ a new approach to analyze and evaluate the data based on the patients' uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype, which predicts the risk of diarrhea. METHODS AND DESIGN: A prospective, double-blind, randomized, placebo-controlled trial will be conducted in patients with small cell lung cancer (SCLC) from five hospitals in China. For this study, 100 irinotecan-naïve patients will be randomly allocated to either the SXD or placebo arms in a 1:1 ratio. Stratified randomization will be used to divide subjects by UGT1A1 genotype into groups with differing risk of diarrhea. The trial will consist of two cycles of chemotherapy with 14 days of oral administration of SXD or placebo administered beginning between 3 days before and up to 11 days after initiation of each chemotherapy cycle. The primary study outcome is the incidence of diarrhea. Secondary outcomes include the degree of diarrhea, the degree of neutropenia, the rate of alterations in chemotherapy regimens, the amount of antidiarrheal drug taken, the rate of hospitalization, and evaluation of chemotherapy efficacy. DISCUSSION: This study is the first to use the UGT1A1 genotype to stratify patients into groups based on their risk of diarrhea, and to provide a complete assessment of chemotherapy-related diarrhea (CRD), including records of diarrhea duration, grading the severity of diarrhea, and evaluating concomitant symptoms. Study results will provide high-level clinical evidence on the use of SXD as prophylaxis for CRD. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. Retrospectively registered. http://www.chictr.org.cn/edit.aspx?pid=25250&htm=4c.

The theoretical method and clinical application of testicular torsion.

INTRODUCTION: This study aims to explore the theoretical method and clinical application of manipulation reduction for testicular torsion. METHODS: A total of 28 patients with testicular torsion were recruited from the Emergency Surgery Department of Beijing Children's Hospital affiliated to Capital Medical University from July 2016 to July 2018. Among these patients, 22 patients (age: 10.80 ± 3.50 years old) were treated with manual reduction using the elastic retraction method and push-and-turn method. Observation indexes included dramatically alleviated or completely disappeared pain without general anesthesia; the spermatic cord being smooth and unknotted; the restoration of the suffered testis to normal anatomical position under ultrasonography monitoring; blood flow signals increased in the affected testis and epididymis, which was regarded as the main sign of a successful reduction. RESULTS: Among the 22 cases who received manual reduction, 19 patients were successfully treated (left side: n = 11, right side: n = 8) with a total success rate of 86.36%. The other three cases showed either incomplete (n = 2) or failed (n = 1) reposition. Among the 19 patients who were successfully treated by manual reduction, 2 of them did not undergo prophylactic orchiopexy, and no abnormalities were found during the follow-up. CONCLUSION: The reduction of testicular torsion using the elastic retraction method and push-and-turn method may improve the success rate of the manual reduction of testicular torsion, especially for incomplete testicular torsion. Furthermore, manual reduction may help increase the rate of testicular salvage in a timely manner before emergency surgery. Hence, this skill should be extended to primary hospitals to reduce the possibility of testectomy caused by testicular torsion.

Clinical study for external Chinese herbal medicine LC09 treating hand-foot skin reaction associated with the antitumor targeted drugs: Protocol for a prospective, randomized, controlled, double-blind, and monocentric clinical trial.

BACKGROUND: Molecular targeted anticancer drugs such as multikinase inhibitors have shown obvious therapeutic advantages in a variety of tumors. The occurrence of hand-foot skin reaction (HFSR) is positively correlated with therapeutic effect, but it is also the most common cause of dose limiting toxicity for this treatment. This can lead to interruption or decrement of the treatment, a reduction in quality of life for patients, as well as potentially leading to secondary infections. As a result, the curative effect of targeted anticancer drugs will be negatively impacted. Currently, there is no certain and effective therapy. External use of Chinese herb medicine LC09 in the early treatment of HFSR has shown positive outcomes, but it is necessary to carry out further clinical research to confirm. OBJECTIVES: The purpose of this study was to investigate the efficacy and safety of topical soaks of Chinese herbal medicine LC09 for HFSR induced by molecular targeted anticancer drugs. METHODS: The trial is a prospective, randomized, controlled, double-blind, monocentric, and interventional study. A total of 66 patients with HFSR will be recruited and randomly assigned to receive either LC09 Granules or placebo. The primary outcomes are the assessment of HFSR grade and pain score. The secondary outcomes are the evaluation of the quality of life, incidence of targeted drug dosage reduction, and incidence of targeted drug withdrawal. DISCUSSION: This prospective, randomized clinical trial will provide valuable data regarding the efficacy and safety of topical soak treatments with LC09 granules for HFSR. Positive results would provide evidence-based complementary therapeutic approach future treatments of HFSR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, http://www.chictr.org.cn, ChiCTR1900023679. Registered on 7 June 2019.

Herb medicine for relieving radiation induced oral mucositis: A systematic review and meta-analysis protocol.

BACKGROUND: Oral mucositis (OM) is a common and unavoidable side effect in patients suffering from head and neck cancer who are undergoing radiotherapy. It is characterized by unbearable pain, as well as eating and speech disorders. This has serious negative effects on the patients' quality of life and can even reduce radiotherapy tolerance, ultimately resulting in a poor prognosis. At present, many prevention and treatment methods are still in the experimental stage, and the efficacies are controversial. METHODS: Four English databases: Medline via pubmed, EMBASE, the Cochrane Library, Web of Science and another 4 Chinese databases: China National Knowledge Infrastructure (CNKI), China Science and Technology Journal database (VIP), Wanfang Database and CBM, will be searched from inception to August 2019. All randomized controlled trials in Chinese and English language will be included. Literature selection, data extraction and quality assessment will be completed by 2 independent authors. The primary outcomes will include the incidence of OM (1-4 grade) and the pain degree. The onset time of OM, the improvement rate for quality of life, and any adverse effects will be evaluated as the secondary outcomes. The data will be synthesized by Review Manager and Stata software. RESULTS: This study provides a high-quality synthesis from existing evidence for Chinese herbal medicine in radiotherapy induced OM treatment, according to the criteria: incidence of OM, onset time of OM, status changes in quality of life and adverse events. CONCLUSION: This study will provide evidence to help determine whether Chinese herbal medicine is effective and safe for use in the prevention and/or treatment of radiotherapy induced OM. ETHICS AND DISSEMINATION: No additional formal ethical recognition or informed consent is required since no primary data collection is involved. The study result will be published in peer-reviewed journals or at related conferences.PROSPERO registration number: PROSPERO CRD42019141900.

Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting toxicity of many anti-neoplastic agents, especially paclitaxel, and oxaliplatin. Up to 62% of patients receiving paclitaxel regimens turn out to develop CIPN. Unfortunately, there are so few agents proved effective for prevention or management of CIPN. The reason for the current situation is that the mechanisms of CIPN are still not explicit. Traditional Chinese Medicine (TCM) has unique advantages for dealing with complex diseases. Wen-Luo-Tong (WLT) is a TCM ointment for topical application. It has been applied for prevention and management of CIPN clinically for more than 10 years. Previous animal experiments and clinical studies had manifested the availability of WLT. However, due to the unclear mechanisms of WLT, further transformation has been restricted. To investigate the therapeutic mechanisms of WLT, a metabolomic method on the basis of UPLC- MS was developed in this study. Multivariate analysis techniques, such as principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA), were applied to observe the disturbance in the metabolic state of the paclitaxel-induced peripheral neuropathy (PIPN) rat model, as well as the recovering tendency of WLT treatment. A total of 19 significant variations associated with PIPN were identified as biomarkers. Results of pathway analysis indicated that the metabolic disturbance of pathways of linoleic acid (LA) metabolism and glycerophospholipid metabolism. WLT attenuated mechanical allodynia and rebalanced the metabolic disturbances of PIPN by primarily regulating LA and glycerophospholipid metabolism pathway. Further molecular docking analysis showed some ingredients of WLT, such as hydroxysafflor yellow A (HSYA), icariin, epimedin B and 4-dihydroxybenzoic acid (DHBA), had high affinity to plenty of proteins within these two pathways.

Application of Computer-Aided Tongue Inspection for Preliminary Screening of Esophageal Cancer.

OBJECTIVE: To differentiate patients with esophageal cancer or premalignant lesions from the high-risk population for preliminary screening of esophageal cancer using a feature index determined by a computer-aided tongue information acquisition and processing system (DS01-B). METHODS: Totally, 213 patients diagnosed with esophageal cancer or premalignant lesions and 2,840 normal subjects were collected including primarily screened and reexamined, all of them were confirmed with histological examinations. Their tongue color space values and manifestation features were extracted by DS01-B and analyzed. Firstly, the analysis of variance was performed to differentiate normal subjects from patients with esophageal cancer and premalignant lesions. Secondly, the logistic regression was conducted using 10 features and gender, age to get a predictive equation of the possibility of esophageal cancer or premalignant lesions. Lastly, the equation was tested by subjects undergoing primary screening. RESULTS: Saturation (S) values in the HSV color space showed significant differences between patients with esophageal cancer and normal subjects or those with mild atypical hyperplasia (P<0.05); blue-to-yellow (b) values in the Lab color space showed significant differences between patients with esophageal cancer or premalignant lesions and normal subjects (P<0.05). Logistic regression analysis showed that the computer-aided tongue inspection approach had an accuracy of 72.3% (2008/2776) in identifying patients with esophageal cancer or premalignant lesions for preliminary screening in high-risk population. CONCLUSION: Computer-aided tongue inspection, with descriptive and quantitative profile as described in this study, could be applied as a cost- and timeefficient, non-invasive approach for preliminary screening of esophageal cancer in high-risk population.

A model for anticancer surveillance was pharmacologically developed to evaluate vitality principle in breast cancer rats.

OBJECTIVE: To evaluate vitality principle in breast cancer rats by pharmacologically developing a model for anticancer surveillance. METHODS: The breast cancer in rats was replicated with 7,12-Dimethylbenz[a]anthracene (DMBA, i.g., 100 mg/kg) at d001. The anticancer surveillance was defined as the intervals between the primary sensitization and the first challenge stirred with complete Freund's adjuvant (CFA), the various intervals (k = 0.80) were dominated from d025 (600.00 h) to d095 (2288.82 h). The optimal surveillant status was confirmed with the median effective interval (EI50) from tumor volume regressive curve, for developing the pharmacodynamic model. The tumor and tumor infiltrating lymphocyte histopathology was used to confirm the immune surveillance being affected with CFA in breast cancer tumorigenesis. The availability of this model was confirmed with Shugan Liangxue prescription (SLP), from the vitality principle, and assured further from interleukin-12 levels. RESULTS: The regressive curve was set up between the intervals and tumor volumes, the EI50 in SLP-treated rats (1475.00 h, YSLP = 0.1026 + 0.8780/[1 + 10(27.1425-8.565x)]) was postponed, which was 1.87 multiple of the EI50 in CFA rats (791.40 h, y = -0.0525 + 0.9452/[1 + 10(30.4870-10.52x)], so did prepone the curve between the intervals and the immunological biomarker, serum interleukin-12 levels, the EI50 in SLP-treated rats (744.90 h, YSLP = -0.0145 + 0.7455/[1 + 10(52.09636-18.13x)]) be 0.78 multiple of the EI50 in CFA rats (960.10 h, YCFA = 0.2460 + 0.7270/[1 + 10 (-67.1546 + 22.52x)]), this immunological action being mediated the anticancer prognosis. Tumor histology was confirmed the more tumor infiltrating lymphocytes activated in SLP rats with CFA stirred immunity than rats only received CFA. CONCLUSION: The model for anticancer surveillance was pharmacologically established as the optimal interval (791.40 h) between the primary sensitization and the first challenge stirred with complete Freund's adjuvant. This available model was confirmed with SLP, from the vitality principle, for evaluating immunological effects against breast cancer.

Validation and Application of the MD Anderson Symptom Inventory for Traditional Chinese Medicine (MDASI-TCM).

Background: The MD Anderson Symptom Inventory (MDASI) is a brief, yet thorough, patient-reported outcomes measure for assessing the severity of common cancer-related symptoms and their interference with daily functioning. We report the development of an MDASI version tailored for use with Traditional Chinese Medicine in China (the MDASI-TCM). Methods: Chinese-speaking patients with mixed cancer types (n = 317) participated in the study. The development and validation process included four steps: 1) identify candidate TCM-specific items, with input from patients, oncologists, and TCM specialists; 2) eliminate candidate TCM items lacking relevance, based on patient report; 3) psychometrically examine the MDASI-TCM's validity and reliability in cancer patients receiving TCM-based care; and 4) cognitively debrief patients to assess the MDASI-TCM's relevance, understandability, and acceptability. Results: Seven TCM-specific symptom items (sweating, feeling cold, constipation, bitter taste, coughing, palpitations, and heat in palms/soles) were clinically and psychometrically meaningful to add to the core MDASI. Approximately 61% of patients had moderate to severe symptoms (rated ≥5 on the MDASI-TCM's 0-10 scale). Cronbach α coefficients were .90 for symptom-severity items and .93 for interference items, indicating internal consistency reliability. Known-group validity was substantiated by the MDASI-TCM's detection of differences in symptom severity according to performance status (P < .001) and interference levels by cancer stage (P < .05). Cognitive debriefing indicated that patients found the MDASI-TCM to be an understandable, easy-to-use tool. Conclusions: The Chinese MDASI-TCM is a valid, reliable, and concise measure of symptom severity and interference that can be used to assess Chinese cancer patients and survivors receiving TCM-based care.

Preventive Effects of a Chinese Herbal Formula, Shengjiang Xiexin Decoction, on Irinotecan-Induced Delayed-Onset Diarrhea in Rats.

Irinotecan is a well-known chemotherapy drug for the treatment of various cancers. However, delayed-onset diarrhea is a common adverse reaction, limiting the application of the drug. The study presented was designed to evaluate the preventive effects of Shengjiang Xiexin decoction (SXD) on irinotecan-induced diarrhea and to explore the possible mechanisms of this action. We established a diarrhea rat model. The condition of the rats was observed. The proliferation and apoptosis of intestinal cells were measured using immunohistochemical assays and a caspase-3 activity assay, respectively. The expression of Lgr5 and CD44 staining were used to observe intestinal stem cells (ISCs). In addition, the activity of ß-glucuronidase in the rats' feces was measured. Our results showed that the number of proliferating intestinal cells in the SXD groups was obviously higher, while the activity of caspase-3 was lower. The expression of Lgr5 and the integrated option density (IOD) of CD44 stain were increased significantly by SXD. Additionally, SXD decreased the activity of ß-glucuronidase after irinotecan administration. In conclusion, SXD exhibited preventive effects on irinotecan-induced diarrhea, and this action was associated with an inhibitory effect on intestinal apoptosis and ß-glucuronidase and a promotive effect on intestinal cell proliferation due to increased maintenance of ISCs.

Effects of Shengjiangxiexin decoction on irinotecan-induced toxicity in patients with UGT1A1*28 and UGT1A1*6 polymorphisms.

OBJECTIVE: To evaluate the efficacy of Shengjiangxiexin decoction (SXD), prepared with a formula from Traditional Chinese Medicine (TCM), in reducing irinotecan-induced hematological and gastrointestinal toxicities in patients with UDP-glucuronosyltransferase (UGT)1A1*28 and UGT1A1*6 polymorphisms. METHODS: This clinical trial included 115 patients receiving irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) treatment. All patients consented to UGT1A1*28 and *6 gene polymorphism detection prior to chemotherapy. SXD were administered from 1 day prior to chemotherapy to 6 day post chemotherapy. Chemotherapy induced adverse reactions (neutropenia, diarrhea, nausea, vomiting, anorexia and infection) were recorded, and short-term effect of chemotherapy was evaluated regularly. RESULTS: A total of 50 patients had *1/*1 wild genotype, 58 patients had single allele variants with genotype *1/*6 or *1/*28 , and 7 patients had two alleles variants with genotype *6/*6, *28/*28 or *6/* 28. In *1/*6 or *1/*28 patients (high risk group), 9 patients (15.5% ) developed Ⅰ-Ⅱ grade diarrhea and no patient developed severe diarrhea; neutropenia occurred in 19 patients (32.8%) and only 3 patients (8.6% ) developed sever neutropenia. There were no significant differences in any toxic effects (neutropenia, diarrhea, nausea, vomiting, anorexia or infection) between *6 or *28 variant patients (high risk group) and wild type patients. No sever toxicity was found in high risk two alleles variants patients (*6/*6, *6/*28 or *28/*28). No significant differences were observed between UGT1A1*6/*28 polymorphisms and clinical response of chemotherapy. CONCLUSION: SXD could significantly reduce irinotecan-induced hematological and gastrointestinal toxicities in UGT1A1*28 or *6 variant patients (high risk group), while this treatment didn't affect clinical response of chemotherapy.