Objective:To explore the independent risk factors for chemoresistance during gemcitabine plus cisplatin (GC) adjuvant chemotherapy in patients with locally advanced bladder cancer after radical cystectomy and to construct a related predictive model.Methods:The clinical data of 228 patients with locally advanced bladder cancer who received GC chemotherapy after radical cystectomy at Beijing Friendship Hospital, Capital Medical University, from January 2013 to June 2024 were retrospectively analyzed. Among them, 184 were males, and 44 were females, with an average age of (68.8±10.6)years and an average body mass index (BMI) of (24.2±3.6)kg/m 2. According to tumor progression during chemotherapy, patients were divided into a chemotherapy-resistant(CR) group ( n=59) and a non-chemotherapy-resistant(NCR) group ( n=169). Independent sample t-test, chi-square test, and non-parametric test were used to compare general clinical characteristics and relevant examination results during chemotherapy between the two groups. Multivariate linear regression analysis was used to identify independent risk factors for GC chemoresistance. Propensity score matching (PSM) was used to match the TNM stage data between the two groups, and Kaplan-Meier and log-rank tests were used to compare overall survival(OS)after matching. Results:The median number of chemotherapy cycles was 3 in the CR group and 4 in the NCR group. Compared with the NCR group, CR patients were younger [(66.3±9.4) years vs.(69.7±10.9)years], had a higher proportion of kidney transplantation history[6.8%(4/59) vs. 0.6%(1/169)], hypertension [50.8%(30/59) vs. 36.1%(61/169)], coronary heart disease[23.7%(14/59) vs.9.5% (16/169)], and hydronephrosis [13.6%(8/59) vs. 4.1%(7/169)](all P<0.05). CR patients had a higher proportion of T 4 stage [20.3% (12/59) vs. 5.9% (10/169)], N 2 stage [42.4% (25/59) vs. 8.3% (14/169)], multifocal tumors at initial diagnosis [59.3% (35/59) vs. 26.6% (45/169)], and larger maximum tumor diameter [2.5 (1.5, 3.4) cm vs. 1.6 (1.2, 2.5) cm] (all P < 0.05). The CR group showed higher proportions of long-term urinary tract infection (UTI) [90.1% (53/59) vs. 7.7% (15/169)], higher systemic immune-inflammation index (SII) [991.6 (451.0, 1577.9) vs. 462.8 (309.0, 766.7)], absolute neutrophil count [6.5(4.1, 7.8)× 10 9/L vs. 3.9 (2.9, 5.1)× 10 9/L], and platelet count [(220.0 ± 96.2)× 10 9/L vs. (191.0 ± 64.8)× 10 9/L], but lower albumin levels [(34.3 ± 4.2) g/L vs. (39.9 ± 3.8) g/L] and albumin-to-globulin ratio (A/G) [(1.2 ± 0.3) vs. (1.3 ± 0.2)] (all P < 0.05). Multivariate linear regression analysis identified only T stage and long-term UTI as independent risk factors for GC chemoresistance( P<0.05).The probability of GC chemoresistance in bladder cancer patients was calculated as: P(Chemoresistance)=[0.155×T stage+ 0.624×(long-term UTI)]×100%(long-term UTI = 1 if present during chemotherapy, otherwise=0). After PSM, survival analysis showed that the median OS was significantly higher in the NCR group (55 months) than that in the CR group (30 months) ( P=0.020). Conclusions:This study demonstrates that advanced T stage and persistent UTI are independent risk factors for GC chemotherapy resistance in locally advanced bladder cancer patients. Based on these findings, a predictive model for chemotherapy resistance probability was constructed using multivariate linear regression analysis.

Objective:To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS).Methods:A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children′s Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). Results:The infant was born prematurely at 35 + 3 weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c. 1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. Conclusion:This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c. 1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.

OBJECTIVE: To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS). METHODS: A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children's Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). RESULTS: The infant was born prematurely at 35⁺³ weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c.1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. CONCLUSION This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c.1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.
Humans ; Serine Peptidase Inhibitor Kazal-Type 5/genetics* ; Netherton Syndrome/genetics* ; Female ; Infant, Newborn ; Infant, Premature ; Mutation ; Exome Sequencing ; Male

OBJECTIVES: To establish a prognostic model for primary liver cancer (PLC) using bioinformatics methods. METHODS: Based on the data from 404 patients in the Cancer Genome Atlas (TCGA) database, we constructed a prognostic model integrating the differentially expressed genes, anoikis, and immune-related genes (DAIs) using univariate Cox regression and the LASSO-Cox approach. The predictive ability of the model was evaluated using Kaplan-Meier method and receiver-operating characteristic curves, and a nomogram was developed to facilitate its clinical applications. Gene set enrichment analysis (GSEA) was performed to explore the associated pathways and relationship between the DAIs and the tumor immune microenvironment, and the half-maximal inhibitory concentration (IC₅₀) of liver cancer drugs was calculated using the "pRRophetic" R package. We also detected the expression of SEMA7A in paired tumor and adjacent tissues from liver cancer patients. RESULTS: We constructed and validated a prognostic model based on 7 DAIs (NR4A3, SEMA7A, IL11, AR, BIRC5, EGF, and SPP1), and obtained consistent results in both the TCGA training cohort and GEO validation cohort (GSE14520), where the patients in the low-risk group were characterized by more favorable clinical outcomes and immune status. By integrating this prognostic signature with clinical information, a composite nomogram was generated. Somatic mutation analysis showed that TTN, TP53, and CTNNB1 mutations accounted for the largest proportion of total mutations, and the patients in the low-risk-low-TMB group had higher survival rate. Drug sensitivity analysis revealed differences in sensitivity to chemotherapeutic agents between high- and low-risk groups and between TP53 mutations and non-mutations. In clinical tissue specimens, SEMA7A expression was significantly higher in liver cancer tissues than in the adjacent tissues. CONCLUSIONS We established a new prognostic model based on DAIs for predicting clinical outcomes and therapeutic response of patients with primary liver cancer.
Humans ; Liver Neoplasms/diagnosis* ; Prognosis ; Anoikis ; Nomograms ; Computational Biology ; Tumor Microenvironment ; Semaphorins/metabolism*

Chimeric antigen receptor-modified T(CAR-T)cell therapy,as a new type of cellular immunotherapy,has shown good clinical efficacy in the treatment of malignant hematological tumors,especially B-cell acute lympho-blastic leukemia.However,there are problems such as antigen loss and immune evasion in single-target selection,so multi-target therapy strategies are gradually gaining attention.Multi-target CAR-T can effectively avoid antigen escape caused by a single target by targeting multiple tumor-associated antigens at the same time,reduce the risk of recurrence,and is expected to improve the therapeutic effect.This paper primarily discusses the structural types of multi-target CAR-T cell therapy and its clinical trial applications in the treatment of B-cell acute lymphoblastic leu-kemia(B-ALL),aiming to provide future references for the treatment of B-ALL.

Objective To explore the risk factors for obstetric septic shock.Methods The clinical data of 122 obstetric sepsis patients from Jan.2013 to Apr.2025 were retrospectively analyzed.The patients were assigned to shock group(n=26)or non-shock group(n=96)based on whether they progressed to septic shock.Variables including age,body mass index,multiple pregnancy,sequential organ failure assessment(SOFA)score,organ dysfunction status,white blood cell count(WBC),neutrophil count(NEU),neutrophil ratio,platelet count,procalcitonin,C-reactive protein,lactate(Lac),and D-dimer were recorded.Multivariate logistic regression analysis was used to identify the independent risk factors for obstetric septic shock.The predictive efficacy of these factors was evaluated using receiver operating characteristic(ROC)curve analysis.Results The proportions of patients aged≥35 years,and those with respiratory,cardiac,or central nervous system dysfunction,were significantly higher in the shock group than in the non-shock group,and the SOFA score,WBC,NEU,neutrophil ratio and Lac level were significantly higher in the shock group(all P＜0.05).Multivariate logistic regression analysis showed that increased NEU(odds ratio[OR]=1.093,95%confidence interval[CI]1.022-1.169,P=0.010)and age≥35 years(OR=3.433,95%CI 1.112-10.602,P=0.032)were independent risk factors for obstetric septic shock.ROC curve analysis showed that NEU had predictive value for obstetric septic shock(area under curve=0.741,95%CI 0.634-0.848),with an optimal cut-offvalue of 17.17×109/L.Conclusion Increased NEU and age≥35 years are independent risk factors for obstetric septic shock.NEU has predictive value for the development of obstetric septic shock and may serve as an important indicator for clinical assessment and timely treatment.

Objective:To investigate the relationship between serum insulin-like growth factor-1 (IGF-1) levels and intracranial or extracranial atherosclerosis in patients with cerebral small vessel disease (CSVD).Methods:A total of 407 patients with CSVD admitted to Xiangya Hospital of Central South University between July 2021 and September 2023 were enrolled in the study. Carotid duplex ultrasound was used to measure the internal diameter, intima-media thickness (IMT), vascular wall thickness, plaque property score, stenosis index, and stenosis ratio of the bilateral common carotid arteries, internal carotid arteries, external carotid arteries, and vertebral arteries. Magnetic resonance angiography was used to assess the degree of stenosis in intracranial arteries. Patients were divided into 4 groups based on the serum IGF-1 levels (low level group:≤5.21 ng/ml, medium level group:>5.21 ng/ml and ≤10.73 ng/ml, high level group:>10.73 ng/ml and ≤24.26 ng/ml, extremely high level group:>24.26 ng/ml). The IMT of the common carotid artery, carotid plaques, diameters of various cervical vascular lumens, carotid artery diameter stenosis, and intracranial artery stenosis in 4 groups of the patients were compared. The relationship between IGF-1 and intracranial and extracranial atherosclerosis was analyzed by univariate Logistic regression analysis and multivariate Logistic regression analysis.Results:There were inter group differences among the 4 groups in internal carotid artery diameter [low level group 5.45 (0.50) mm vs medium level group 5.32 (0.55) mm vs high level group 5.30 (0.55) mm vs extremely high level group 5.30 (0.50) mm; H=8.210, P=0.042]. The carotid IMT [low level group 0.80 (0.05) mm vs medium level group 0.80 (0.05) mm vs high level group 0.83 (0.03) mm vs extremely high level group 0.83 (0.09) mm; H=8.107, P=0.044], the proportion of carotid artery vascular wall thickening [low level group 52.9%(54/102) vs medium level group 48.0%(49/102) vs high level group 68.3%(69/101) vs extremely high level group 60.8%(62/102); χ2=9.889, P=0.020], the carotid artery plaque property score [low level group 1 (2) vs medium level group 2 (2) vs high level group 2 (2) vs extremely high level group 2 (2); H=8.913, P=0.030] and the proportion of anterior cerebral artery stenosis [low level group 2.9%(3/102) vs medium level group 2.0%(2/102) vs high level group 4.0%(4/101) vs extremely high level group 10.8%(11/102); χ2=10.473, P=0.014] had inter group differences among the 4 groups, and the differences were statistically significant. Univariate Logistic regression analysis indicated that carotid artery vascular wall thickening ( OR=1.197, 95% CI 1.003-1.429, P=0.046), anterior cerebral artery stenosis ( OR=1.814, 95% CI 1.148-2.867, P=0.011), and basilar artery stenosis ( OR=1.530, 95% CI 1.084-2.159, P=0.015) were correlated with IGF-1 levels. Multivariate Logistic regression analysis revealed that after adjusting for age, gender, low-density lipoprotein cholesterol (LDL-C), and C-reactive protein, IGF-1 was positively correlated with the carotid artery vascular wall thickening ( OR=1.311, 95% CI 1.014-1.696, P=0.039); after adjusting for age, IGF-1 was positively correlated with the anterior cerebral artery stenosis ( OR=2.130, 95% CI 1.201-3.776, P=0.010); after adjusting for gender, low-density lipoprotein cholesterol, and cholesterol levels, IGF-1 was positively correlated with basilar artery stenosis ( OR=1.688, 95% CI 1.063-2.681, P=0.027). Conclusions:There is an association between IGF-1 levels and intracranial and extracranial atherosclerosis in patients with CSVD. IGF-1 may play a role in the development and progression of atherosclerosis in CSVD.

Objective Five chloroplast(cp)genomes from members of genus Polygonatum were assembled by hybrid assembly technique,and their intraspecic and interspecific differences were analyzed by comparative genomic method.Codon usage patterns and influencing factors were determined,and the cp genome data were applied to understand the phylogenomic relationships in the entire genus Polygonatum along with the available data.Methods In this study,the chloroplast genomes of 5 species of genus Polygonatum were assembled using Unicycler software.Sequence alignment,collinearity analysis,boundary analysis and other methods were used to evaluate the interspecific differences of these five species.Nucleotide polymorphism analysis was used to discover the high-variation sites of the five species and their related species,predict the distribution of different long repeat sequences and SSRs,and then analyze the use bias of Polygonatum code.Finally,phylogenetic tree was constructed with the coding sequences of other 47 genus Polygonatum and their closely related species to explore their phylogenetic relationships in this study.Results ①Chloroplast genomes of 155 408-155 623 bp were assembled from five species of Polygonatum.A total of 132-133 genes were annotated,and 369 long repeats and 1553 simple repeats were detected.②The contraction and expansion of chloroplast genomes in 8 species were not obvious at the IRs boundary,and the size and distribution of individual genes at the LSC-IRs-SSC boundary,such as ndhF gene and ycf1 gene,were slightly different.No interspecific or intraspecific rearrangement was observed in 8 species.③ The high-variation regions of the 8 chloroplast genomes are mainly located in two single-copy regions,the duplicate copy region is relatively conserved,and the coding region is more conserved than the non-coding region.High nucleotide polymorphic loci rps16-trnQ,trnS-trnG,trnTUGU-trnL,ndhF-rpl32 and rpl32-trnL are located in the single copy region and most of them are gene spacer regions.④ The codon preference results showed that the codon preference of the five species was similar and mainly affected by selection pressure,and the third base of the codon played A dominant role and mainly ended in A/U.RSCU clustering heat map shows that PK and PZ,PCB and PS have close relationship.⑤ Phylogenetic trees divided 52 species into five branches:Ⅰ,Ⅱ,Ⅲ,ⅣandⅤ.PS,PK,PCB,PCZ and PZ were divided into ⅣandⅤbranches,among which PK and PZ were most closely related,while PCZ was more distant than the other four,was divided into the Ⅴbranch alone.Conclusion This study provided a reference for the phylogenetic research and molecular marker development of the medicinal plants of the Polygonum genus.

Objective To provide scientific basis for layout planning and standardized cultivation the species of Chrysanthemum indicum complex in future periods,the potential ecological suitable areas was analyzed,.Methods By collecting distribution data of 1379 valid C.indicum complex species nationwide and 104 ecological factors,combined with MaxEnt model and ArcGIS software,the potential ecological distribution areas of C.indicum complex under 17 different climate scenarios was analyzed.Results Precipitation and solar radiation are key environmental variables affecting the suitable habitats of C.indicum complex.The most suitable regions for the growth of C.indicum complex was concentrated in Hubei(C.indicum L.),Shanxi(C.lavandulifolium),Jiangsu(C.nankingense),and Hubei(C.indicum var.aromaticum)regions.Under different scenarios,the suitable habitat area for C.indicum L.and C.lavandulifolium showed an overall decreasing trend,while those for C.indicum var.aromaticum and C.nankingense showed an expanding trend.The centroid shift indicates sensitivity of C.indicum complex to climate change.Conclusion The potential distribution areas of C.indicum complex is classified into ecological suitability levels,providing important reference for the sustainable use,introduction cultivation,and scientific zoning of related resources.

Objective:To investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.