Polycystic ovarian syndrome （PCOS） is a common endocrine and metabolic disease mainly occurring among women of childbearing age. Its main symptoms include menstrual disorders， acne， hirsutism， infertility， oily skin， acanthosis nigricans， and obesity. Currently， the etiology and pathogenesis of PCOS remain unclear. Classical formulas， which have rigorous compatibility， concise composition， precise alignment with syndromes， and definitive therapeutic effects， demonstrate unique practical and scientific value in the treatment of PCOS. These formulas exhibit significant clinical efficacy， mild adverse effects， and sustained therapeutic outcomes. To explore the current status and mechanisms of classical formulas in treating PCOS， on the basis of Zhang Zhongjing's academic thoughts on gynecological diseases， this paper reviewed the relevant literature on the treatment of PCOS with classical formulas in recent years. The findings reveal that the pathogenesis of PCOS predominantly involves a combination of internal deficiency and superficial excess， closely related to dysfunction of the liver， spleen， and kidney. The root cause lies in deficiency， and on this basis， there are also symptoms of qi stagnation， blood stasis， phlegm obstruction， and dampness encumbrance. Commonly used classical formulas for treating this disease include Guizhi Fuling pills， Danggui Shaoyao powder， Wenjing decoction， and Jingui Shenqi pills. These classical formulas have good clinical efficacy in treating PCOS. Their mechanisms of action may be related to improving serum levels of sex hormones， increasing the dominant follicle diameter and endometrial thickness， alleviating insulin resistance， lowering glucose and lipid metabolism， inhibiting oxidative and inflammatory reactions in the ovarian tissue， regulating the intestinal flora， correcting the flora disorder， protecting the intestinal barrier function， and regulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. The above research results can help doctors use classical formulas flexibly， broaden diagnostic and therapeutic approaches for PCOS and provide ideas for improving the traditional Chinese medicine diagnosis and treatment plan for PCOS.

Polycystic ovarian syndrome （PCOS） is a common endocrine and metabolic disease mainly occurring among women of childbearing age. Its main symptoms include menstrual disorders， acne， hirsutism， infertility， oily skin， acanthosis nigricans， and obesity. Currently， the etiology and pathogenesis of PCOS remain unclear. Classical formulas， which have rigorous compatibility， concise composition， precise alignment with syndromes， and definitive therapeutic effects， demonstrate unique practical and scientific value in the treatment of PCOS. These formulas exhibit significant clinical efficacy， mild adverse effects， and sustained therapeutic outcomes. To explore the current status and mechanisms of classical formulas in treating PCOS， on the basis of Zhang Zhongjing's academic thoughts on gynecological diseases， this paper reviewed the relevant literature on the treatment of PCOS with classical formulas in recent years. The findings reveal that the pathogenesis of PCOS predominantly involves a combination of internal deficiency and superficial excess， closely related to dysfunction of the liver， spleen， and kidney. The root cause lies in deficiency， and on this basis， there are also symptoms of qi stagnation， blood stasis， phlegm obstruction， and dampness encumbrance. Commonly used classical formulas for treating this disease include Guizhi Fuling pills， Danggui Shaoyao powder， Wenjing decoction， and Jingui Shenqi pills. These classical formulas have good clinical efficacy in treating PCOS. Their mechanisms of action may be related to improving serum levels of sex hormones， increasing the dominant follicle diameter and endometrial thickness， alleviating insulin resistance， lowering glucose and lipid metabolism， inhibiting oxidative and inflammatory reactions in the ovarian tissue， regulating the intestinal flora， correcting the flora disorder， protecting the intestinal barrier function， and regulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. The above research results can help doctors use classical formulas flexibly， broaden diagnostic and therapeutic approaches for PCOS and provide ideas for improving the traditional Chinese medicine diagnosis and treatment plan for PCOS.

OBJECTIVE To comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis. METHODS The six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action. RESULTS In terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation. CONCLUSIONS Three oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.

Objective:To compare the efficacy of radial forearm flap and anterolateral thigh flap in repairing soft tissue defects after oral cancer surgery and to explore their indications.Methods:A retrospective analysis was conducted on clinical data of patients with oral cancer treated at the Department of Stomatology, Affiliated Hospital of Nantong University, from May 2019 to February 2023. Patients were divided into two groups based on the repair method: the radial forearm flap group and the anterolateral thigh flap group. The groups were compared in the following aspects. (1) Surgical parameters including defect area after oral cancer resection, flap area, flap preparation time, operation time, and length of hospital stay. (2) Inflammatory markers (interleukin-6 and C-reactive protein levels) measured 1 day before surgery and 1 day after surgery. (3) Flap survival rate was calculated. (4) Complication rates was calculated in the flap donor area and infection rates in the oral recipient area within 6 months postoperatively. (5) Six months postoperatively, the patient’s oral function was assessed by a physician using the University of Washington quality of life scale (UW-QOL). The evaluation included assessments of oral opening, speech, and eating functions. Each parameter was scored on a scale of 0 to 10 (higher scores indicated better recovery). (6) Quality of life was assessed using the 36-item short form health survey scale(SF-36) at 2, 4 and 6 months postoperatively, with scores ranging from 0 to 100 (higher scores indicated better quality of life). (7) Patient satisfaction was assessed at 6 months postoperatively, with satisfaction levels categorized as satisfied, basically satisfied, and dissatisfied. The satisfaction rate was calculated as (satisfied + basically satisfied ) cases / total cases in each group × 100%. Statistical analysis was performed using SPSS 22.0. Measurement data were expressed as Mean±SD, and comparisons between groups were conducted using t-tests. Count data were expressed as cases and (or) percentages, and comparisons were made using chi-square test. P<0.05 was considered statistically significant. Results:The radial forearm flap group included 48 cases (32 males, 16 females), aged (49.3±5.0) years, with a body mass index (BMI) of (23.0±1.1) kg/m 2 and a disease course of (6.5±2.1) months. The group had 21 cases of tongue cancer, 12 of floor of mouth cancer, and 15 of buccal cancer, including 40 squamous cell carcinomas and 8 basal cell carcinomas. The anterolateral thigh flap group included 32 cases (20 males, 12 females), aged (50.1±5.0) years, with a BMI of (23.0±1.0) kg/m 2 and a disease course of (7.0±2.2) months. The group had 16 cases of tongue cancer, 7 cases of floor of mouth cancer, and 9 cases of buccal cancer, including 27 squamous cell carcinomas and 5 basal cell carcinomas. There were no significant differences in gender, age, BMI, disease course, tumor location, or pathological type between the two groups ( P>0.05). The defect area after oral cancer resection was smaller in the radial forearm flap group[ (39.0±1.3) cm 2 ] compared to the anterolateral thigh flap group[ (40.3±2.2) cm 2] ( t=3.32, P=0.001). There were no significant differences in flap area, flap preparation time, or length of hospital stay between the two groups ( P>0.05). The operation time was shorter in the radial forearm flap group [(5.1±1.1) h] compared to the anterolateral thigh flap group [(6.8±2.8) h] ( t=0.26, P<0.001). There were no significant differences in interleukin-6 and C-reactive protein levels between the two groups 1 day before surgery and 1 day after surgery ( P>0.05). The flap survival rates were 97.9% (47/48) in the radial forearm flap group and 93.8% (30/32) in the anterolateral thigh flap group, with no significant difference( P>0.05). Postoperative donor site complications mainly included infection, pigmentation, itching, etc. The overall incidence of complications in the donor site of the radial forearm flap [33.3% (16/48)] was higher than that in the anterolateral thigh flap group [12.5% (4/32)], and the difference was statistically significant ( χ2=4.44, P=0.035). There was no significant difference in infection rates in the oral recipient area between the two groups ( P>0.05). Six months postoperatively, the average scores for oral opening, speech, and eating functions were above 7 in both groups, with no significant differences ( P>0.05). Quality of life scores improved over time in both groups, with average scores above 90 at 6 months postoperatively, and no significant differences at any time point ( P>0.05). The patient satisfaction rate was 91.7% (44/48) in the radial forearm flap group and 90.6% (29/32) in the anterolateral thigh flap group, with no significant difference ( P>0.05). Conclusion:Both radial forearm flap and anterolateral thigh flap can effectively repair soft tissue defects after oral cancer resection, significantly improving patients’oral function. The anterolateral thigh flap provides sufficient tissue volume and is suitable for patients with larger defect areas. The radial forearm flap is suitable for patients with a smaller defect area after oral cancer resection. Its surgical procedure is relatively less complex and offers an advantage in reducing surgery time. However, the donor site complications are higher with the radial forearm flap compared to the anterolateral thigh flap.

Objective To retrieve,evaluate and summarize the relevant evidence on malnutrition management among maintenance hemodialysis(MHD)patients to provide clinical medical staff with evidence-based guidelines for managing malnutrition in MHD patients.Methods Using the"6S"pyramid model of evidence,We searched UpToDate,BMJ best clinical practice,the Australian JBI evidence-based health care centre database(JBI),Medive,the International Guidelines Collaborative Network(GIN),Agency for Healthcare Research and Quality Network,the UK National Institute of Clinical Medicine Guidance Library(NICE),Scottish Inter-College Guide Collaboration network,the Ontario Registered Nurses Association(RNAO),Guidelines Network of International Society of Nephrology,American Nephrology Foundation Guidenet,British Nephrology Society,Society of Nephrology,Chinese Medical Association,Improving Kidney Disease Outcomes Worldwide,International Society of Renal Nutrition and Metabolism,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Nutrition Society,PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang,VIP and CBM,to collect relevant guidelines,expert consensus,clinical decision,evidence summary,recommended practice,best practice,systematic evaluation and clinical practice,from the establishment to the date of April 10th,2023,for literature on malnutrition management of MHD patients.The literature included guidelines,expert consensuses,clinical decision-making studies,evidence summaries,recommended practices,best practices,and systematic reviews.Two researchers independently evaluated,extracted,and integrated the evidence.The evidence was graded by the evidence pre-grading system of the Evidence-based Healthcare Center of Joanna Briggs Institute(JBI).Results A total of 16 articles were included and summarized,comprising 5 guidelines,3 expert consensuses,1 clinical decision-making study,1 evidence summary,and 6 systematic reviews.Thirty-nine pieces of the best evidence were integrated,covering 5 key aspects(39 evidences):screening and assessment,nutritional requirements,nutritional supplement,other interventions,and monitoring and education.Conclusions The best evidence summary of malnutrition management among MHD patients in this study is scientifically rigorous and systematic.Clinical medical staff can use the best evidence to develop personalized malnutrition management programs for MHD patients.

Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

Objective To explore the relevant protective/risk factors during the development of coronary heart disease blood stasis evidence in the process of pre-existing evidence based on the macro-,meso-,and micro-health state characterization parameter system of Chinese medicine state science.Methods 253 cases of coronary heart disease to be investigated were collected from the outpatient and inpatient departments of the Department of Cardiology in the hospitals affiliated to Hunan University of Traditional Chinese Medicine,and questionnaires were formulated according to the three dimensions of macro,meso,and micro,and the collected parameters were categorized with Python software,and the patients were diagnosed as pre-coronary heart disease blood stasis evidence(150 cases)and coronary heart disease blood stasis evidence(100 cases),and statistical analyses were performed with frequency analysis,χ2 test,and Logistic regression and other methods for statistical analysis.Results ①The results of univariate analysis showed that:age,BMI,history of smoking,history of alcohol consumption,history of hypertension,history of diabetes mellitus,average monthly high temperature,air quality,season,type of occupation,social environment,coronary artery angiographic stenosis,diastolic blood pressure,systolic blood pressure,creatinine,uric acid and total cholesterol differed between patients diagnosed as pre-Coronary artery disease blood stasis evidence and those diagnosed as Coronary artery disease blood stasis evidence,and all the differences were statistically significant(P<0.05).② Binary logistic regression analysis showed that age,BMI,history of alcohol consumption,type of occupation,coronary angiographic stenosis,diastolic blood pressure,creatinine,and dark red tongue were independent risk factors.A prediction model was established:P=1/[1+exp(16.522-1.427×age-0.975×BMI-3.55×drinking history+1.982×monthly average high temperature+0.709×season-1.827×occupational type-1.1×coronary angiographic stenosis-0.072×diastolic blood pressure-0.076×creatinine+2.398×dizziness-4.108×dark red tongue+4.169×pulse asthenia)],the model prediction rate was 90.5%.Conclusion The logistic regression model of coronary heart disease with blood stasis evidence is good with clinical diagnosis,which lays the foundation for the exploration of the state between the already diseased and undiseased of coronary heart disease,and provides important basic data for the theory of subhealth.

Objective:To compare the efficacy of radial forearm flap and anterolateral thigh flap in repairing soft tissue defects after oral cancer surgery and to explore their indications.Methods:A retrospective analysis was conducted on clinical data of patients with oral cancer treated at the Department of Stomatology, Affiliated Hospital of Nantong University, from May 2019 to February 2023. Patients were divided into two groups based on the repair method: the radial forearm flap group and the anterolateral thigh flap group. The groups were compared in the following aspects. (1) Surgical parameters including defect area after oral cancer resection, flap area, flap preparation time, operation time, and length of hospital stay. (2) Inflammatory markers (interleukin-6 and C-reactive protein levels) measured 1 day before surgery and 1 day after surgery. (3) Flap survival rate was calculated. (4) Complication rates was calculated in the flap donor area and infection rates in the oral recipient area within 6 months postoperatively. (5) Six months postoperatively, the patient’s oral function was assessed by a physician using the University of Washington quality of life scale (UW-QOL). The evaluation included assessments of oral opening, speech, and eating functions. Each parameter was scored on a scale of 0 to 10 (higher scores indicated better recovery). (6) Quality of life was assessed using the 36-item short form health survey scale(SF-36) at 2, 4 and 6 months postoperatively, with scores ranging from 0 to 100 (higher scores indicated better quality of life). (7) Patient satisfaction was assessed at 6 months postoperatively, with satisfaction levels categorized as satisfied, basically satisfied, and dissatisfied. The satisfaction rate was calculated as (satisfied + basically satisfied ) cases / total cases in each group × 100%. Statistical analysis was performed using SPSS 22.0. Measurement data were expressed as Mean±SD, and comparisons between groups were conducted using t-tests. Count data were expressed as cases and (or) percentages, and comparisons were made using chi-square test. P<0.05 was considered statistically significant. Results:The radial forearm flap group included 48 cases (32 males, 16 females), aged (49.3±5.0) years, with a body mass index (BMI) of (23.0±1.1) kg/m 2 and a disease course of (6.5±2.1) months. The group had 21 cases of tongue cancer, 12 of floor of mouth cancer, and 15 of buccal cancer, including 40 squamous cell carcinomas and 8 basal cell carcinomas. The anterolateral thigh flap group included 32 cases (20 males, 12 females), aged (50.1±5.0) years, with a BMI of (23.0±1.0) kg/m 2 and a disease course of (7.0±2.2) months. The group had 16 cases of tongue cancer, 7 cases of floor of mouth cancer, and 9 cases of buccal cancer, including 27 squamous cell carcinomas and 5 basal cell carcinomas. There were no significant differences in gender, age, BMI, disease course, tumor location, or pathological type between the two groups ( P>0.05). The defect area after oral cancer resection was smaller in the radial forearm flap group[ (39.0±1.3) cm 2 ] compared to the anterolateral thigh flap group[ (40.3±2.2) cm 2] ( t=3.32, P=0.001). There were no significant differences in flap area, flap preparation time, or length of hospital stay between the two groups ( P>0.05). The operation time was shorter in the radial forearm flap group [(5.1±1.1) h] compared to the anterolateral thigh flap group [(6.8±2.8) h] ( t=0.26, P<0.001). There were no significant differences in interleukin-6 and C-reactive protein levels between the two groups 1 day before surgery and 1 day after surgery ( P>0.05). The flap survival rates were 97.9% (47/48) in the radial forearm flap group and 93.8% (30/32) in the anterolateral thigh flap group, with no significant difference( P>0.05). Postoperative donor site complications mainly included infection, pigmentation, itching, etc. The overall incidence of complications in the donor site of the radial forearm flap [33.3% (16/48)] was higher than that in the anterolateral thigh flap group [12.5% (4/32)], and the difference was statistically significant ( χ2=4.44, P=0.035). There was no significant difference in infection rates in the oral recipient area between the two groups ( P>0.05). Six months postoperatively, the average scores for oral opening, speech, and eating functions were above 7 in both groups, with no significant differences ( P>0.05). Quality of life scores improved over time in both groups, with average scores above 90 at 6 months postoperatively, and no significant differences at any time point ( P>0.05). The patient satisfaction rate was 91.7% (44/48) in the radial forearm flap group and 90.6% (29/32) in the anterolateral thigh flap group, with no significant difference ( P>0.05). Conclusion:Both radial forearm flap and anterolateral thigh flap can effectively repair soft tissue defects after oral cancer resection, significantly improving patients’oral function. The anterolateral thigh flap provides sufficient tissue volume and is suitable for patients with larger defect areas. The radial forearm flap is suitable for patients with a smaller defect area after oral cancer resection. Its surgical procedure is relatively less complex and offers an advantage in reducing surgery time. However, the donor site complications are higher with the radial forearm flap compared to the anterolateral thigh flap.

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.