OBJECTIVE To explore the risk factors for acute kidney injury （AKI） in children with steroid-resistant nephrotic syndrome （SRNS） during tacrolimus treatment and construct a predictive model. METHODS A retrospective selection was made of 155 children diagnosed with SRNS and treated with tacrolimus at Xuzhou Children’s Hospital from January 1， 2022， to December 31， 2023， serving as the study subjects. Various clinical data of the children were collected by reviewing the medical record system. Children who developed AKI during medication were assigned to the AKI group （n＝26）， and those who did not develop AKI were assigned to the control group （n＝129）. Univariate and multivariate Logistic regression analyses were used to screen independent risk factors. A clinical predictive model was constructed based on significant variables， and nomogram， calibration curve， receiver operator characteristic curve， and decision curve were drawn to evaluate the model’s performance. RESULTS Univariate analysis showed that blood urea nitrogen （BUN）， serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， the maximum trough concentration （cmin） of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， concurrent hypertension， and the use of non-steroidal anti-inflammatory drugs were influencing factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. Multivariate Logistic regression analysis revealed that BUN≥9.58 mmol/L， Scr≥125 μmol/L， eGFR＜37 mL/（min·1.73 m2）， tacrolimus maximum cmin≥11.26 ng/mL，CYP3A5*3/*3 genotype， concurrent infection， and concurrent hypertension were independent risk factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. The constructed clinical predictive model had an area under the curve of 0.747， showing good agreement between predicted and actual AKI occurrence and demonstrating favorable clinical net benefit in predicting AKI in children. CONCLUSIONS Impaired baseline renal function （elevated BUN， elevated Scr， and decreased eGFR）， elevated maximum cmin of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， and hypertension during treatment are independent risk factors for AKI in children with SRNS during tacrolimus treatment. The established clinical predictive model provides a scientific basis for implementing risk stratification management.

To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.

BACKGROUND:Total flavonoids from Sophora flavescens have a variety of pharmacological effects,including anti-inflammatory,immunomodulatory,antioxidant,and anti-hepatic injury,but the therapeutic effects and mechanisms in non-alcoholic fatty liver disease are not clear.OBJECTIVE:To reveal the mechanism of total flavonoids from Sophora flavescens in the treatment of non-alcoholic fatty liver disease using bioinformatics,network pharmacology and zebrafish experimental validation.METHODS:A zebrafish model of non-alcoholic fatty liver disease was constructed to observe lipid accumulation,pathomorphologic changes,and expression of inflammatory genes in the liver of zebrafish after treatment with total flavonoids from Sophora flavescens.The active ingredients of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease-related targets were obtained from TCMSP,Swiss Target Prediction,and Bat-man databases.STRING was used to perform protein-protein interaction network analysis,GO functional enrichment and KEGG pathway enrichment analysis.Based on the GSE33814 dataset,the differentially expressed genes of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease intersection targets were screened out.Correlation analysis and receiver operating characteristic curve were performed using R4.3.2 software.Core genes were verified by the validation set GSE89632.RT-qPCR and western blot assays were performed to verify the expression of core pathway-related genes and proteins.RESULTS AND CONCLUSION:(1)Total flavonoids from Sophora flavescens could improve lipid accumulation in the liver of zebrafish with non-alcoholic fatty liver disease,significantly inhibited the elevation of lipid and aminotransferase levels in zebrafish(P<0.05),and regulated the expression of genes related to inflammation and lipid metabolism.(2)A total of 168 common targets were obtained using the network pharmacology,and top 10 core genes,identified by Cytoscape topology analysis,were HSP90AA1,STAT3,PIK3R1,MAPK1,AKT1,RXRA,PIK3CA,EGFR,JAK2,and ESR1.GO and KEGG analysis pathways mainly included insulin resistance,lipids,and atherosclerosis.There were a total of 59 differentially expressed genes after intersection of total flavonoids from Sophora flavescens and non-alcoholic fatty liver disease targets.The receiver operating characteristic curve and validation set analyses yielded six core targets that were significantly different between healthy individuals and patients with non-alcoholic fatty liver disease(P<0.01).(3)RT-PCR and western blot results verified that total flavonoids from Sophora flavescens inhibited the activation of the JAK2/STAT3 signaling pathway in zebrafish.To conclude,total flavonoids from Sophora flavescens may alleviate the inflammatory response through the JAK2/STAT3 signaling pathway,thus inhibiting lipid accumulation and improving non-alcoholic fatty liver disease.

Objective To establish the phylogenic relationships among genus Botrychium,and to develop better molecular markers,along with to gain better understanding of cytonuclear coordination patterns of RuBisCO enzyme,the current article sampled two species(e.g.Botrychium ternatum(Thunb.)Sw.and Botrychium virginianum(L.)Sw.),and applied sequencing approaches for the data mining.Methods The assembly results of chloroplast(cp)genomes from B.ternatum and B.virginianum were determined via de novo hybrid assemble approach with the help of short reads(Illumina)and long reads(PacBio and Nanopore).Then the phylogenic relationships of 18 fern species were reconstructed based on the protein coding sequences from the cp genome and the rbcS gene,which were fished out of the RNA-seq data from SRA database,respectively.Then the adaptive selection and co-evolutionary analysis were employed to investigate the evolutionary trajectories of rbcL(cp genome)and rbcS(nuclear genome)genes.Results The full length of cp genome in the two genus Botrychium species were determined as 139 063 bp(NC_060644)and 139 372 bp(OR609363).Then 92 SSR sites and 78 SSR sites were identified in the current two cp genomes,respectively.The collinearity analysis showed high relevant relationship between the current two species,and significant relationship within both species among the inverted repeats regions.The adaptation and coevolution investigations illustrated the following results:①Coevolution network exists between RBCL and RBCS subunits from the fern RuBisCO enzyme.②Positively selected sites were significantly detected among both rbcL and rbcS genes.③Two coevolutionary pair sites from the two genes(e.g.site 11 in RBCL and site 106 in RBCS)were significantly positively selected,which may demonstrate a molecular pattern for the fern species fine-tuning the RuBisCO enzyme during the long earth history via the cytonuclear coordination.Conclusion Our current research shed a new light on the phylogenetic relationship of the genus Botrychium among the fern backbone-tree and provided amount of cpSSR sites with the potential as molecular markers for further population study on B.ternatum and B.virginianum.Moreover,our adaptation and coevolution investigations on rbcL and rbcS genes might indicate that the underlying cytonuclear coordination between the organelle and nuclear in cell of fern species for fine-tuning the key photosynthesis enzyme RuBisCO to gain better fitness according to the changing environment of earth during the geologic time-scale.

Neurodegenerative disorders(NDDs)are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations.Increasing evidence suggested that mitochondrial quality control(MQC)serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria.Herein,we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs,emphasizing mitochondrial dynamic stability,the clearance of damaged mitochondria,and the generation of new mitochondria.In addition,traditional Chinese medicines(TCMs)and their active monomers targeting MQC in NDD treatment have been demonstrated.Consequently,we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC,aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

To introduce the general thinking,guidelines,work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition,and to summarize and figure out the main characteristics on dosage forms,physico-chemical testing,microbial and biological testing,ref-erence standards and guidelines.The newly revised general chapters of pharmacopoeia give full play to the norma-tive and guiding role of the Chinese Pharmacopoeia standard,track the frontier dynamics of international drug regu-latory science and the elaboration of monographs,expand the application of state-of-the-art technologies,and stead-ily promote the harmonization and unification with the ICH guidelines;further enhance the overall capacity of TCM quality control,actively implement the 3 R principles on animal experiments,and practice the concept of environ-mental-friendly;replace and/orreduce the use of toxic and hazardousreagents,strengthen the requirementsofdrug safety control.This paper aims to provide a full-view perspective for the comprehensive,correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

AIM To compare the contents of caffeic acid,ferulic acid,narirutin,calycosin,glycyrrhizic acid and atractylenolide Ⅲ of modified Liujunzi Decoction(MLJZD)during small test,pilot test(500,1 500 L)and large production.METHODS The samples were taken after soaking for 60 min,boiling for 0,5,10,15,20,30 min in the first decoction,and boiling for 5,10,15,20 min in the second decoction,respectively,after which the HPLC fingerprints were established,the contents of active constituents were determined.RESULTS There were 6 common peaks in the HPLC fingerprints for small test and pilot test,while 5 common peaks were observable in the HPLC fingerprints for large production,along with the similarities of more than 0.980.During pilot tests at different time points,various active constituents demonstrated consistent content changing trends,whose total content was higher than those during small test and large production.CONCLUSION Process amplification exhibits a little influence on active constituent contents in MLJZD,which don't show increasing trends with the expansion of container and enhancement of dosage.