This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Quality Control

OBJECTIVE To explore the characteristics and influencing factors of immune-related adverse events （irAEs） induced by tislelizumab in patients with liver cancer. METHODS A retrospective cohort of 203 liver cancer patients treated with tislelizumab in Guangxi Medical University Cancer Hospital from May 2022 to March 2024 was included. These patients were divided into an irAEs group （58 cases） and a non-irAEs group （145 cases）. Clinical data were collected and compared between the two groups. A multivariate logistic regression model was employed to analyze factors influencing the occurrence of irAEs and establish a predictive model. The receiver operator characteristic （ROC） curve was plotted to evaluate the predictive value of the model for the occurrence of irAEs. The correlation between irAEs and overall survival （OS） as well as progression free survival （PFS） in patients was analyzed using the Kaplan-Meier method. RESULTS The irAEs induced by tislelizumab in liver cancer patients were predominantly grade 1-2 （89.71%）， mainly manifesting as hematological toxicity （42.65%） and hepatotoxicity （20.59%）， and mostly occurred within 1-12 cycles after tislelizumab treatment. Compared with liver cancer patients without underlying liver diseases， those with chronic hepatitis B had a higher incidence of irAEs. Statistically significant differences were observed between the irAEs and non-irAEs groups in terms of the number of patients with a China Liver Cancer Staging （CNLC） stage ≥Ⅱ， white blood cell count， neutrophil count， systemic immune-inflammation index （SII）， and neutrophil-to-lymphocyte ratio （NLR） （P＜0.05）. Multivariate Logistic regression analysis revealed that CNLC stage ≥Ⅱ was an independent risk factor for the occurrence of irAEs （P＝0.027）. The ROC curve indicated that neutrophil count， white blood cell count， NLR， and SII all demonstrated certain predictive potential for the occurrence of irAEs （with area under the curve values of 0.614， 0.592，0.591， and 0.589， respectively）. The Kaplan-Meier survival curve showed no statistically significant differences in PFS and OS between the irAEs and non-irAEs groups， among patients with different grades of irAEs， and among irAEs patients with different CNLC stages （P＞0.05）. CONCLUSION The irAEs induced by tislelizumab in liver cancer patients are relatively mild （grade 1-2），mainly manifesting as hematological toxicity and hepatotoxicity. Liver cancer patients with concurrent chronic hepatitis B are at a higher risk of developing irAEs. CNLC stage ≥Ⅱ is an independent risk factor for irAEs induced by tislelizumab. Neutrophil count， white blood cell count， NLR， and SII have certain predictive value for the occurrence of irAEs.

Objective: To investigate the expression of triple motif protein 21 (TRIM21) at different time points in Cisplatin induced acute kidney injury (Cis-AKI) mouse model and its correlation with pathological score . Methods: Acute kidney injury (AKI) model was induced by intraperitoneal injection of cisplatin (20 mg/kg) . Peripheral blood serum was collected at 12 , 24 , 48 and 72 h , respectively . Body weight and kidney mass were also recorded . The dynamic changes of serum creatinine ( SCr) and urea nitrogen ( BUN) were detected . The expressions of TRIM21 protein and endoplasmic reticulum stress (ERS) proteins GRP78 , GRP94 , P-elf2αand CHOP were de- tected by Western blot. HE staining was used to observe the pathology of renal tissue and analyze the correlation between the expression of TRIM21 protein at different time points . Results: Compared with the control group , the renal body ratio of Cis-AKI mice significantly increased at 48 h and 72 h (P < 0. 01) . SCr and BUN of Cis-AKI mice significantly increased at 48 h and 72 h compared with control group ( P < 0. 01) . HE staining showed that compared with the control group , the renal pathological scores of Cis-AKI mice increased at 12 and 24 h ( P < 0. 000 1) . At the same time , the expression of TRIM21 protein significantly increased at 24 h (P < 0. 01) . Com- pared with the control group , the renal pathological score of Cis-AKI mice significantly increased at 48 h ( P < 0. 000 1) , and the protein expression of TRIM21 , CHOP and GRP78 was significantly up-regulated at 48 h (P < 0. 05) . Compared with the control group , the renal pathological score of Cis-AKI mice significantly increased at 72 h (P < 0. 000 1) , and the expression of TRIM21 , GRP94 and P-elf2αproteins was significantly up-regulated at 72 h (P < 0. 05) . The results of correlation analysis showed that the expression of TRIM21 protein at different time points was positively correlated with the HE pathological scores at different time points (P < 0. 000 1) . Conclusion At different time points , TRIM21 may participate in the pathological progression of Cis-AKI by affecting ERS ,and it is positively correlated with renal pathological scores , which is expected to become a potential early diagnos- tic marker and intervention target.

Objective: To establish an in vitro cell model of Cobalt dichloride(CoCl2)-induced epithelial-mesenchymal transition(EMT) in rat renal tubular epithelial cells(NRK-52E). Methods: NRK-52E cells were cultured in vitro and randomly divided into a blank control group(NC group) and a CoCl2 treatment group. The CoCl2 treatment group underwent 1, 2, 3, and 4 cycles of treatment, with each cycle consisting of CoCl2 treatment for 9 h followed by recovery in CoCl_2-free medium for 3 h. The optimal concentration and time of CoCl_2-induced EMT were screened using the CCK-8 assay. Morphological changes in cells were observed using light microscopy and phalloidin staining. The expression levels of EMT marker proteins were detected by Western blot and immunofluorescence. Results: Compared with the NC group , stimulation by 100 μmol/L CoCl2 for 48 h significantly induced apoptosis (P < 0. 01) , meeting the requirements for subsequent experiments. Western blot results showed that the expression of hypoxia-inducible factor-1 α (HIF-1α ) and α-smooth muscle actin ( α-SMA) significantly increased in the 3-cycle group treated with 100 μmol/L CoCl2 for 9 h followed by recovery for 3 h ( P < 0. 001) , indicating the most pronounced fibrotic response. Observations under light microscopy and rhodamine-labeled phalloidin staining revealed that the morphological changes and cytoskeletal rearrangement of NRK-52E cells were most significant in the 3-cycle group treated with 100 μmol/L CoCl2 for 9 h followed by recovery for 3 h , demonstrating the best model stability. Immunofluorescence results showed that compared with the NC group , the fluorescence intensity of the fibrous matrix protein Collagen I significantly increased in the 3-cycle group treated with 100 μmol/L CoCl2 for 9 h followed by recovery for 3 h ( P < 0. 001) . Conclusion The protocol involves treating NRK-52E cells with 100 μmol/L CoCl2 for 9 h , following 3 h of recovery in CoCl2 -free medium. Repeating this cycle three times can establish an in vitro EMT model.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

Objective To investigate the one-year postpartum weight retention for patients with gestational diabetes mellitus(GDM)and analyze its related influencing factors,so as to improve the postpartum weight retention.Methods GDM women who were diagnosed and gave birth at the Obstetrics and Gynecology Hospital,Fudan University from Oct 2022 to May 2023 were selected as the research subjects.The GDM postpartum weight status survey questionnaire was used to conduct a survey of one-year postpartum weight retention status and analyze relevant influencing factors.Results A total of 150 GDM postpartum women were included,with a weight retention rate of 46.7%one year after delivery,including a high weight retention rate of 25.3%.The follow-up rate of postpartum glucose tolerance was 36.0%,and the influencing factors of postpartum weight retention were excessive gestational weight gain(OR=2.883,95%CI:1.226-6.779)and the presence of dietary risk(OR=4.604,95%CI:1.065-19.903).Conclusion The one-year postpartum weight retention after GDM is relatively high.The possible influencing factors are excessive weight gain during pregnancy and dietary risk after delivery.Attention should be paid to the weight and healthy diet management of GDM during pregnancy and postpartum from multiple dimensions.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.