Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Objective:To investigate the clinical characteristics of infantile cholestasis caused by IFT122 gene variants and the molecular mechanism underlying its impact on primary cilia.Methods:The clinical data of an infant with cholestasis from the Children′s Hospital of Fudan University in September 2022 were retrospectively analyzed. The whole-exome sequencing was performed to identify candidate variants, which were validated by Sanger sequencing in the family. Immortalized cell lines were generated using lentiviral infection, followed by immunofluorescence staining to assess the impact of the variants on primary cilia. Intergroup comparisons were performed using the independent sample t-test and Mann-Whitney U test .Results:The proband was a 4-month-old male infant presenting with jaundice, distinctive facial features, and sagittal craniosynostosis. Blood biochemistry indicated elevated direct bilirubin, total bile acids, and transaminases, with markedly increased γ-glutamyltransferase (GGT). Liver pathology demonstrated giant cell hepatitis with cholestasis and bile duct dysplasia. Genetic analysis identified compound heterozygous variants in IFT122 (NM_052989.3) gene c.88G>C (p.Ala30Pro) and c.240G>C (p.Trp80Cys), which co-segregated with the disease in the family. Immunofluorescence analysis demonstrated that the IFT122 gene compound heterozygous missense variants not only significantly reduced the proportion of cilia-positive cells but also led to aberrant ciliary localization of ADP-ribosylation factor-like protein 13B (ARL13B).In addition, ciliary deposition with phosphatidylinositol polyphosphate 5-phosphatase type Ⅳ (INPP5E) was reduced. All differences were statistically significant (all P<0.05). Conclusion:The compound heterozygous missense variants in IFT122 gene not only impair ciliogenesis but also disrupt the ciliary localization of ARL13B and INPP5E, ultimately resulting in high-GGT infantile cholestasis.

Tourette syndrome （TS） is a highly prevalent neurodevelopmental disorder in children， clinically characterized primarily by motor and/or vocal tics. Its pathogenesis is associated with hyperactivity of the dopaminergic system in the basal ganglia， and current medical treatments are limited by adverse reactions and unsatisfactory efficacy. In traditional Chinese medicine （TCM）， TS is classified under categories such as "liver wind" and "convulsions"， and is considered to be closely related to liver dysregulation. Uncariae Ramulus Cum Uncis （URCU） is a commonly used wind-dispelling herb. URCU has a clearly defined origin and a rich chemical composition， with alkaloids as its major active constituents， including rhynchophylline and isorhynchophylline. Its plasma components include multiple prototype alkaloids， which exhibit metabolic differences and phenomena such as enterohepatic circulation. Its brain-entering components possess blood-brain barrier permeability， and their distribution is associated with pharmacological effects. In recent years， increasing numbers of studies have focused on the pharmacological effects and mechanisms of the active components of URCU in the treatment of TS. This article systematically reviews the mechanisms by which URCU and its main active constituents exert therapeutic effects on TS from the following aspects： regulation of monoamine and amino acid neurotransmitters to improve neurotransmitter system imbalance， neuroprotection and intervention in neuroinflammation-related pathways； antioxidant effects through activation of antioxidant signaling pathways， and immunomodulatory functions influencing immune cells and the gut microbiota. In addition， the clinical application of compound formulas containing URCU in the treatment of TS is summarized， with the aim of providing new perspectives for further research on the pharmacological mechanisms of URCU and the treatment of TS.

Tourette syndrome （TS） is a highly prevalent neurodevelopmental disorder in children， clinically characterized primarily by motor and/or vocal tics. Its pathogenesis is associated with hyperactivity of the dopaminergic system in the basal ganglia， and current medical treatments are limited by adverse reactions and unsatisfactory efficacy. In traditional Chinese medicine （TCM）， TS is classified under categories such as "liver wind" and "convulsions"， and is considered to be closely related to liver dysregulation. Uncariae Ramulus Cum Uncis （URCU） is a commonly used wind-dispelling herb. URCU has a clearly defined origin and a rich chemical composition， with alkaloids as its major active constituents， including rhynchophylline and isorhynchophylline. Its plasma components include multiple prototype alkaloids， which exhibit metabolic differences and phenomena such as enterohepatic circulation. Its brain-entering components possess blood-brain barrier permeability， and their distribution is associated with pharmacological effects. In recent years， increasing numbers of studies have focused on the pharmacological effects and mechanisms of the active components of URCU in the treatment of TS. This article systematically reviews the mechanisms by which URCU and its main active constituents exert therapeutic effects on TS from the following aspects： regulation of monoamine and amino acid neurotransmitters to improve neurotransmitter system imbalance， neuroprotection and intervention in neuroinflammation-related pathways； antioxidant effects through activation of antioxidant signaling pathways， and immunomodulatory functions influencing immune cells and the gut microbiota. In addition， the clinical application of compound formulas containing URCU in the treatment of TS is summarized， with the aim of providing new perspectives for further research on the pharmacological mechanisms of URCU and the treatment of TS.

Objective: The cross sectional study aimed to identify predominant co-occurrence patterns among six common mental health issues in college students, so as to provide empirical basis for designing targeted interventions. Methods: From October 2024, a total of 9 837 students from 4 universities in Xiangtan City, Hunan Province, participated in the current study by multistage random cluster sampling method. Participants completed self report measures, including the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 item Scale (GAD-7), Young s Internet Addiction Diagnostic Questionnaire, the Adolescent Insomnia Symptom Self rating Scale, the Ottawa Self injury Inventory, and the Brief Community Assessment of Psychic Experiences Questionnaire. Demographic and co-occurrence characteristics were first compared using Chi square or trend Chi-square tests, followed by application of the Apriori algorithm to mine association rules for primary co-occurrence patterns. Results: The detection rate of co-occuring the common mental health issues was 46.44%. The detection rate was significantly higher in female than in male students (50.42%, 43.61%; χ 2=44.46) and in students from rural versus urban areas (47.22%, 44.60%; χ 2=5.67) (both P <0.05). Significant differences were observed among freshmen, sophomores, juniors, and seniors (46.63%, 48.35%, 45.05% , 43.66%, respectively; χ 2=9.22, P <0.05), although no statistically significant trend was detected ( χ 2 trend =3.75, P = 0.05 ). Association rule mining identified “anxiety + depression” “anxiety + psychotic experiences + depression” and “anxiety + sleep disorder + depression” as the combinations with the highest support. In addition, “anxiety+depression+Internet addiction+psychotic experiences =>sleep disorder (>= refered to the occurrence of the latter item under the condition that the former item occurs)” and “anxiety + depression+Internet addiction=>sleep disorder” were combinations with relatively high confidence. Conclusions Co-occurrence of these mental health issues among college students is high and exhibits diverse patterns. Strategies to address this burden should prioritize integrated interventions that target these specific combinations of factors.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

ObjectiveTo investigate the effect of quercetin on acute gouty arthritis （GA） in rats by inhibiting the reactive oxygen species （ROS）/NOD-like receptor protein 3 （NLRP3）/interleukin-1β （IL-1β） signaling pathway. MethodsSixty SPF-grade male SD rats were randomized into normal， model， colchicine （0.3 mg·kg^-1）， and low-， medium-， and high-dose （25， 50， 100 mg·kg^-1， respectively） quercetin groups （n=10）. The rats in the dosing groups were administrated with the corresponding drugs （10 mL·kg^-1） by gavage once a day for one week. An equal volume of normal saline was given by gavage to rats in normal and model groups. One hour after drug administration on day 5， an acute GA model was established in other groups except the control group via intra-articular injection of monosodium urate （MSU） suspension into the right posterior ankle joint cavity. The joint swelling and gait were scored at the time points of 6， 12， 24， 48 h after modeling. Histopathological alterations in the ankle joint tissue from each group were assessed by hematoxylin-eosin （HE） staining. Malondialdehyde （MDA）， xanthine oxidase （XOD）， and total superoxide dismutase （T-SOD） assay kits were used to assess the levels of MDA， XOD， and T-SOD in the serum. The levels of tumor interleukin-6 （IL-6）， necrosis factor-α （TNF-α）， and IL-1β in the rat serum， as well as ROS in the ankle joint tissue， were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was performed to determine the protein levels of NLRP3， thioredoxin-interacting protein （TXNIP）， apoptosis-associated speck-like protein containing a CARD domain （ASC）， precursor cysteinyl aspartate-specific proteinase-1 （pro-Caspase-1）， cleaved Caspase-1 （Caspase-1 p20）， and IL-1β in the ankle joint tissue. Real-time PCR was employed to assess the mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue. ResultsCompared with the normal group， the model group exhibited decreased spontaneous activity， mental fatigue， increased ankle joint swelling and gait scores （P<0.01）， aggravated synovial tissue edema and inflammatory cell infiltration （P<0.01）， elevated levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， a declined level of T-SOD （P<0.01）， up-regulated protein levels of NLRP3， TXNIP， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.01）， and up-regulated mRNA levels of NLRP3， TXNIP， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Compared with the model group， the medium- and high-dose quercetin groups showed improved general conditions， decreased gait scores （P<0.05， P<0.01）， reduced joint swelling （P<0.01）， alleviated synovial tissue edema and inflammatory cell infiltration （P<0.05， P<0.01）， lowered levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， increased levels of T-SOD （P<0.01）， down-regulated protein levels of TXNIP， NLRP3， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.05， P<0.01）， and down-regulated mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Low-dose quercetin also ameliorated some of the above parameters （P<0.05， P<0.01）. ConclusionQuercetin exerts anti-GA effects by blocking the ROS/NLRP3/IL-1β signaling pathway， downregulating NLRP3 inflammasome activation， and inhibiting the production of pro-inflammatory cytokines including TNF-α， IL-1β， and IL-6.

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.