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: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 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 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.