ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis （UC） through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor （AhR） axis. METHODS Mice were randomly divided into normal group （normal saline）， model group （normal saline）， microbiota depletion-model group （normal saline）， microbiota depletion-Huangqin decoction group （9.1 g/kg， by crude drug， similarly hereinafter）， Huangqin decoction group and mesalazine group （positive control group， 0.4 g/kg）， with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling， each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration， body weight change ratio， disease activity index （DAI） score， and colon length were evaluated； colon pathological changes were observed； serum levels of interleukin-6 （IL-6）， IL-10， IL-22， and tumor necrosis factor-α （TNF-α） were measured； the expressions of Occludin， zonula occluden-1 （ZO-1）， and AhR in colon tissue were detected； fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group， Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio， colon length， serum content of IL-10， the expressions of Occludin， ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid （IPA）， N -acetylserotonin （NAS） and indole-3-acetic acid （IAA） were all significantly increased （ P ＜0.05）； DAI score， serum levels of IL-6， TNF-α， and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased （ P ＜0.05）； gut microbiota structure was improved， with increased relative abundances of beneficial bacteria such as Lactobacillus ， and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However， after antibiotic-induced microbiota depletion， although Huangqin decoction significantly increased the content of NAS in the feces of mice， the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA， thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects.

ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine （5-HT） signaling pathway in rats with functional dyspepsia （FD） and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， model group， mosapride group （1.575 mg·kg^-1）， and Yueju Wan low-， medium-， and high-dose groups （0.735， 1.47， and 2.94 g·kg^-1， respectively）. The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling， rats were administered the corresponding drugs by gavage for 28 days. After treatment， gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT， tryptophan hydroxylase （TPH）， and substance P （SP） were detected by enzyme-linked immunosorbent assay （ELISA）， and acetylcholine （ACh） levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor （5-HT4R）， SP， and acetylcholinesterase （AChE） in colon tissue， as well as 5-hydroxytryptamine 3 receptor （5-HT3R）， SP， and AChE in hypothalamic tissue. Immunohistochemistry （IHC） was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group， the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased （P<0.01）. Serum levels of 5-HT， SP， ACh， and TPH were significantly reduced （P<0.01）. Histopathological examination revealed irregular arrangement of glands in the gastric antrum， slight mucosal atrophy， and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue， as well as 5-HT3R， SP， and AChE in hypothalamic tissue， were significantly decreased （P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced （P<0.01）. Compared with the model group， all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate （P<0.01）. The glands in the gastric antrum were more regularly arranged， with no inflammatory cell infiltration observed. Serum levels of 5-HT， SP， ACh， and TPH were significantly increased （P<0.01）. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue and 5-HT3R， SP， and AChE in hypothalamic tissue were significantly upregulated （P<0.05， P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was significantly increased （P<0.01）. ConclusionYueju Wan has preventive and therapeutic effects on FD， and its mechanism may be related to regulation of the 5-HT signaling pathway， promotion of brain-gut peptide secretion， and enhancement of gastric motility.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Chaihu Guizhi Ganjiangtang was first recorded in the Treatise on Cold Damage （Shang Han Lun）. This prescription is composed of Bupleuri Radix， Scutellariae Radix， Cinnamomi Ramulus， Zingiberis Rhizoma， Trichosanthis Radix， Ostreae Concha， and Glycyrrhizae Radix et Rhizoma. It has the effects of soothing Lesser Yang， warming the spleen， and stimulating the generation of body fluid. It is mainly used to treat digestive tract diseases such as chronic cholecystitis （CC）， irritable bowel syndrome， and non-alcoholic fatty liver disease. Dyspepsia caused by CC presents a variety of gastrointestinal symptoms such as abdominal pain， poor appetite， postprandial fullness， aversion to greasy food， soft stool， and bitter mouth， being a type of biliary dyspepsia. In modern medicine， dyspepsia caused by CC is mainly managed by medical treatment and surgical treatment. Internal medicine mainly focuses on reducing inflammation， promoting the function of gallbladder， resolving stones， alleviating spasms， and relieving the pain for CC， demonstrating definite short-term efficacy but suffering from single effects， high recurrence rate， and poor compliance. Although surgical treatment can cure cholecystitis， it is accompanied by the increased incidence of adverse events such as abdominal pain， diarrhea， and dyspepsia. Modern clinical studies have confirmed that Chaihu Guizhi Ganjiangtang can significantly alleviate the symptoms such as abdominal pain and dyspepsia of CC patients. Pharmacological studies have found that Chaihu Guizhi Ganjiangtang mainly contains active ingredients such as Bupleuri Radix saponins， baicalin， cinnamaldehyde， gingerol， Trichosanthis Radix polysaccharide， Ostreae Concha polysaccharide， and Glycyrrhizae Radix et Rhizoma total flavonoids. Chaihu Guizhi Ganjiangtang can ameliorate the symptoms of dyspepsia caused by CC by inhibiting inflammatory responses， improving gallbladder contraction and gastrointestinal motility， regulating the bile acid-intestinal flora axis and the brain-gut axis， and modulating blood lipids through multiple targets. By reviewing the previous literature， this article summarizes the research progress in the treatment of dyspepsia caused by CC with Chaihu Guizhi Ganjiangtang and its main active ingredients as well as the pathogenesis of this disease and puts forward the shortcomings and improvement strategies for the current research. The review aims to provide a reference for the further research on Chaihu Guizhi Ganjiangtang in the treatment of dyspepsia caused by CC.

OBJECTIVE To investigate the mechanism by which Qiaobai cold compress solution （QBCS） improves acne vulgaris （AV） based on transcriptomics and animal experiments. METHODS Rats were randomly divided into a blank control group （ n ＝6） and a modeling group （ n ＝30）. AV models were established in the modeling group by topical application of oleic acid to the inner surface of both ears， combined with subcutaneous injection of Cutibacterium acnes suspension into the auricle. Successfully modeled rats were further divided into the model group， positive control group （Tretinoin cream， 0.045 g/kg）， and QBCS low-， medium-， high-dose groups [3.55， 7.11， 14.22 g/kg （calculated by the amount of crude drug） ] ， with 6 rats in each group. Rats in each d rug group were treated with the corresponding drugs once daily for 14 consecutive days. After the final administration， changes in the appearance of the ears and histopathological changes in the ear tissues were observed， and serum levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β， were measured. Auricular tissues from the blank control group， model group and QBCS medium-dose group were collected for transcriptome sequencing. Differential expressed genes （DEGs） were screened and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis， followed by validation using real-time quantitative polymerase chain reaction and Western blot assay. RESULTS Compared with the model group， rats in all QBCS groups showed alleviated auricular acne symptoms， with reduced epidermal thickening， sebaceous gland hyperplasia， and inflammatory cell infiltration. Serum levels of TNF-α （except for the QBCS low-dose group）， IL-6 （except for the QBCS low-dose group） and IL-1β were significantly decreased （ P ＜0.05）. A total of 590 DEGs were identified （blank control group vs. model group）， and 596 DEGs were identified （model group vs. QBCS medium-dose group）. Above DEGs （blank control group vs. model group） were mainly enriched in Toll-like receptor （TLR） and nuclear factor-kappa B （NF-κB） signaling pathways， etc. Validation experiments showed that， compared with model group， low-， medium- and high-dose of QBCS reduced， to varying degrees， the mRNA expression of TNF-α， TLR2， interferon-γ and CXC chemokine ligand 8 in the auricular tissues of AV rats， increased the mRNA expression of peroxisome-proliferator-activated receptor gamma and tumor protein 53， and inhibited the phosphorylation of NF-κB p65 protein as well as the expressions of TLR2 and myeloid differentiation primary response protein 88（MyD88） （ P ＜0.05）. CONCLUSIONS QBCS can alleviate auricular inflammation and skin lesions in AV rats. This effect may be related to inhibition of the TLR/MyD88/NF-κB signaling pathway， thereby suppressing the expression of downstream inflammatory factors such as TNF-α.

Ethical review represents the core of the scientific and technological ethical governance， and its quality depends on the participation of ethics. The absence of ethics and ethical experts will compromise the quality of the review. According to the spirit of the Guidelines on Strengthening the Governance over Ethics in Science and Technology， this paper analyzed the process of separating scientific and technological ethics from the field of scientific research morality， clarified the ethical attributes of ethical review， and argued that scientific research and technological innovation activities originated from ethics. On this basis， the fundamental principle of “ethics first” was proposed， aiming to proactively embed ethical considerations throughout the entire process of scientific and technological activities. This principle was the primary requirement for ensuring governance effectiveness and can also eliminate the risk of ethics being obscured in ethical governance. In practice， “ethics first” manifested specifically in dimensions such as prioritizing academic systems， prioritizing publicity， education， and training， as well as further advancing ethical considerations.

Objective: To explore the correlation between Candida albicans and the development of oral leukoplakia (OLK), and to provide a basis for improving the pathogenic mechanism of the malignant transformation of OLK. Methods: Oral microbiome data were obtained from public databases (NCBI BioProject, PRJNA788378; GEO, GSE227919), and bioinformatic methods were employed to evaluate the correlation between Candida albicans infection and OLK. Approval was obtained from the institutional Medical Ethics Committee. A tissue microarray was constructed using samples collected from an OLK clinical cohort. Hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining were performed to analyze the relationship between the Candida albicans detection rate and clinicopathological features. Approval was obtained from the institutional Animal Ethics Committee. A mouse model was established by combining 4-nitroquinoline-1-oxide (4NQO) in drinking water with oral inoculation of Candida albicans (4NQO + Candida albicans group), while mice treated with 4NQO in drinking water and PBS served as the control group (4NQO + PBS group). The degree of epithelial dysplasia was compared between the two groups to assess the impact of Candida albicans infection on lesion progression (defined in this study as the progression from mild/moderate epithelial dysplasia to severe dysplasia/carcinoma in situ or invasive squamous cell carcinoma). Results: Bioinformatic analysis revealed that the detection rate of Candida albicans in OPMDs and OLK tissues was significantly higher than that in the healthy control group. Staining results of clinical samples demonstrated that Candida albicans colonized OLK lesions; compared with Candida albicans-negative patients, positive patients exhibited a state of high-grade progression. Animal experiments indicated that, compared with the 4NQO + PBS group, the degree of oral epithelial dysplasia in the 4NQO + Candida albicans group was significantly exacerbated, and the malignant transformation rate was higher, suggesting that Candida albicans promotes the high-grade progression of OLK. Conclusion Candida albicans exhibits a increasing trend during the malignant progression of the OLK. It aggravates the degree of epithelial dysplasia in OLK and promotes its transformation into high-grade lesions, suggesting that Candida albicans plays a crucial promoting role in the high-grade progression of OLK.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.