OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

Objective: To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics. Methods: Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method. Results: A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported. Conclusions The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.

Objective:To compare the outcomes of multiple scales, primarily the speech, spatial, and other qualities of hearing scale for parents（SSQ-P）, in children with ipsilateral vs. Contralateral cochleareimplantat ion（CRI）. Methods: A total of 69 children who received cochlear implantation surgery from April 1999 to June 2024 were included. Patients were divided into two groups based on whether the implantation was on the same side. General information such as gender, age, age at initial implantation and reimplantation was collected. The primary caregivers of the children were followed up by telephone using the categories of auditory performance（CAP）, speech intelligibility rating（SIR）, and SSQ-P questionnaires. Statistical methods including stepwise regression, linear regression, and permutation tests were employed to investigate if there were any statistically significant differences in the scores of CAP, SIR, SSQ-P total, SSQ-P speech perception, SSQ-P spatial hearing, and SSQ-P auditory quality dimensions between the ipsilateral and contralateral reimplantation groups. Results:Of the 69 children included, 62 were in the ipsilateral reimplantation group with a mean age of 11.1 years, and 7 were in the contralateral reimplantation group with a mean age of 11.7 years. Statistical analysis showed that patients in the contralateral reimplantation group had significantly lower SSQ-P total scores （P<0.05） and spatial hearing dimension scores （P<0.05） than those in the ipsilateral reimplantation group after controlling for the corresponding confounders. Conclusion:The effect of ipsilateral reimplantation of cochlear implants is superior to that of contralateral reimplantation in terms of overall auditory function and spatial hearing in daily life for children, but the mechanisms require further investigation.
Humans ; Cochlear Implantation ; Child ; Parents ; Speech Perception ; Male ; Cochlear Implants ; Female ; Hearing ; Surveys and Questionnaires ; Speech ; Child, Preschool

Objective To explore the application value of serological markers in the screening of malignant tumor bone metastasis.Methods A total of 113 patients with malignant tumor bone metastasis first diag-nosed in a hospital from June 2023 to February 2024 were selected as case group.Another 80 patients with malignant tumor without bone metastasis diagnosed in the same period were selected as the control group.The levels of serological markers[serum calcium(Ca),parathyroid hormone(PTH),Ca/PTH,procollagen type 1 amino-terminal propeptide(P1NP),beta-C-terminal telopeptide of type 1 collagen(β-CTX)and N-terminal mid-fragment of osteocalcin]were compared between the two groups.Receiver operating characteristic(ROC)curves were plotted to analyze the value of serological markers in screening for bone metastases of lung canc-er,prostate cancer and breast cancer.Multivariate Logistic regression was used to analyze the related factors of malignant tumor bone metastasis.Results The levels of Ca,Ca/PTH,β-CTX and P1NP in case group were significantly higher than those in control group,while PTH in case group was lower than that in control group,with statistical significance(P<0.05).ROC curve results showed that Ca,PTH,Ca/PTH,P1NP and β-CTX had high efficacy in screening malignant tumor bone metastases,and the area under the curve(AUC)was 0.718,0.699,0.712,0.648 and 0.593,respectively.Multivariate Logistic regression analysis showed that Ca/PTH and P1NP were the influencing factors of bone metastasis in malignant tumor(OR=5.036,1.013,P<0.05).The AUC of Ca,PTH and Ca/PTH screening for bone metastasis of lung cancer were 0.781,0.652 and 0.669,respectively.The AUC of β-CTX and P1NP screening for bone metastasis of prostate cancer were 0.800 and 0.815 respectively.The AUC of Ca and P1NP screening for breast cancer with bone metastasis was 0.751 and 0.794,respectively.Conclusion Serological markers(Ca,PTH,Ca/PTH,P1NP and β-CTX)are valuable in screening for malignant tumor bone metastasis.

Objective To evaluate the results of anorectal dynamics in patients with severe rec-tocele.Methods A retrospective analysis was conducted on the clinical data of 38 patients defini-tively diagnosed with severe rectocele at the pelvic floor center of the anorectal department of Nanjing Hospital of Traditional Chinese Medicine from January 2020 to January 2023.All patients underwent anorectal manometry,and the results of anorectal dynamics were analyzed.Results A total of 15 pa-tients(39.47％)had elevated anal resting pressure(ARP),20(52.63％)had normal ARP,and 3(7.89％)had decreased ARP.Five patients(13.16％)had elevated maximum anal sphincter pressure(MASP),9(23.68％)had normal MASP,and 24(63.16％)had decreased MASP.Nor-mal defecation relaxation reflex was observed in 15 patients(39.47％),and abnormal defecation re-laxation reflex was observed in 23 patients(60.53％).Ten patients(26.32％)had normal rectal defecation pressure,and 28(73.68％)had decreased rectal defecation pressure.Eleven patients(28.95％)had elevated rectal initial sensory threshold(RIST),27(71.05％)had normal RIST.Fifteen patients(39.47％)had elevated rectal defecation sensory threshold,21(55.26％)had normal rectal defecation sensory threshold,and 2(5.26％)had decreased rectal defecation sensory threshold.Three patients(7.89％)had elevated rectal maximum tolerable volume,26(68.42％)had normal rectal maximum tolerable volume,and 9(23.68％)had decreased rectal maximum tolerable vol-ume.ARP was moderately positively correlated with the chronic constipation severity(CSS)score(P=0.007,r=0.429),and abnormal defecation relaxation reflex was moderately negatively correla-ted with the CSS score(P=0.019,r=-0.329).In 3 patients(7.89％),both ARP and MASP were decreased,and both ARP and MASP were elevated in 5 patients(13.16％).Conclusion Pre-operative anorectal dynamics analysis is necessary for patients with severe rectocele to formulate a reasonable individualized surgical plan and postoperative rehabilitation program.

Pulmonary vascular remodeling is the core pathological feature in the onset and pro-gression of pulmonary arterial hypertension(PAH).Currently,there is no well-defined therapeutic strategy that can effectively delay or reverse this process.Despite the widespread clinical application of targeted vasodilator drugs,patients still face a high risk of mortality and adverse cardiovascular e-vents,suggesting an urgent need to explore new pathological mechanisms and therapeutic targets.In recent years,the relationship between dyslipidemia and PAH has garnered increasing attention.This article aimed to review the role of lipid metabolism disorders in pulmonary vascular remodeling in pul-monary arterial hypertension and its underlying mechanism,with the hope of providing new interven-tion targets for the treatment of PAH,thereby improving patient survival rates and quality of life.

ObjectiveThis study aims to explore the molecular mechanism of endometrial cell senescence during the window of implantation （WOI） in unexplained recurrent spontaneous abortion （URSA） and the intervention effect of Bushen Huoxue method through the integrated research strategy of bioinformatics， machine learning， and animal experiments. MethodThe microarray gene sets of the endometrium of healthy women of childbearing age and patients with URSA during WOI were retrieved through the gene expression omnibus （GEO） database. The differentially expressed genes （DEGs） of URSA were screened by using the limma package of R language. Weighted gene co-expression network analysis （WGCNA） was used to obtain the most relevant module genes of URSA， and the gene ontology （GO） enrichment analysis and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis were performed. Gene sets related to cell senescence were obtained by the Human Gene Database （GeneCards） and Online Mendelian Inheritance in Man （OMIM）. The Venn online mapping software was used to screen the intersection genes of DEGs of URSA， the most relevant module genes， and the genes related to cell senescence. Then， the search tool for the retrieval of interacting genes/proteins （STRING） was used to analyze the protein-protein interaction （PPI） network of the interacting genes， and the hub genes were screened through Cytohubba. In addition， the least absolute selection and shrinkage operator （LASSO） and random forest algorithm were used to screen diagnostic genes related to cell senescence of URSA. Finally， mouse models with URSA were established and randomly divided into the model group， Bushen Huoxue group， and aspirin group， with six mice in each group， and six normal pregnant mice were selected as a blank group. The Bushen Huoxue group was given Shoutai pill combined with Danggui powder formula granular liquid （12.35 g·kg^-1） by gavage， and the aspirin group was gavaged with aspirin at a dose of 0.011 mL·g^-1. The blank group and model group were given the same volume of distilled water by gavage. Drug administration began on the first day after the discovery of vaginal thrombus （recorded as the first day of gestation， i.e. GD1）， and the mice were sacrificed 12 hours after administration at GD5. The endometrium samples were collected. Quantitative real-time polymerase chain reaction （Real-time PCR） and immunofluorescence were used to detect the expression of cell senescence-related diagnostic genes in the endometrium tissue of URSA mice during WOI and the intervention effect of the Bushen Huoxue method. ResultThe gene set of the GSE165004 microarray was included for bioinformatics analysis. According to the “limma” package of R language， 585 DEGs of URSA were selected （P<0.05）. WGCNA results suggested that the gene in the magenta module was the most closely related to URSA （r=0.32， P<0.05）. The results of the KEGG analysis of the magenta module suggested that the genes were mainly enriched in cell senescence， Hippo， and NF-κB signaling pathways （P<0.05）. In addition， 2 138 genes related to cell senescence were obtained from Genecards and OMIM websites. The Venn online mapping tool was used to obtain 27 intersecting genes of DEGs of URSA， the magenta module genes， and cell senescence-related genes， namely， cell senescence-related DEGs in endometrium tissue during WOI of URSA. PPI analysis showed that synuclein alpha （SNCA）， heme oxygenase 1 （HOMX1）， and matrix metallopeptidase 1 （MMP1） were hub genes. Besides， four diagnostic genes were identified by LASSO regression and random forest， including gelsolin （GSN）， cyclin2 （CCND2）， RB binding protein 8 （RBBP8）， and lysophosphatidic acid receptor 1 （LPAR1）. Animal experiments confirmed that the mRNA level and fluorescence intensity of GSN were significantly increased （P<0.05）， while the mRNA and fluorescence intensity of CCND2， LPAR1， and RBBP8 were significantly decreased （P<0.05） in the model group when compared with the blank group. The expression level of GSN was decreased （P<0.05）， while the expression levels of CCND2， LPAR1， and RBBP8 were remarkably increased （P<0.05） in the Bushen Huoxue group when compared with the model group. ConclusionThe senescence of endometrial cells during WOI of URSA is related to multiple genes. Bushen Huoxue method can act on multiple targets that are related to cell senescence， which may be the key mechanism of improving endometrial receptivity in URSA.

OBJECTIVE To explore the impact and mechanism of curcumin on endometriosis （EMS） model rats based on Notch1 signaling pathway. METHODS Female SD rats with synchronized estrous cycles were implanted with autologous endometrium on the abdominal wall to construct EMS model. EMS rats were randomly divided into model group， low-， medium- and high-dose groups of curcumin （60， 120， 240 mg/kg）， and Notch 1 inhibitor DAPT group （7 mg/kg）. The sham surgery group was also established， with 10 rats in each group. Rats in each group received intragastric administration or injection via caudal veins with the corresponding drugs for 4 weeks. Endometriotic lesions were observed and measured using ultrasound and visual inspection， and their volumes were calculated. Histopathological morphology of the lesion tissues was observed. The levels of interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the abdominal cavity fluid， as well as the mRNA and protein expression levels of Notch1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor （VEGF） in the endometriotic lesions were measured. RESULTS Compared with the model group， the volume of endometriotic lesions in the low- ， medium- and high-dose groups of curcumin and the DAPT group was significantly decreased （P＜0.05）； atrophy or disappearance of columnar epithelium， cyst disappearance； the levels of IL-1β， IL-6， and TNF- α （except for the low-dose curcumin group） in the abdominal cavity fluid， as well as the mRNA （except for MMP-9 and VEGF in the low-dose curcumin group） and protein （except for MMP-9 in the low-dose curcumin group） expression levels of Notch1， MMP-9， and VEGF in the endometriotic lesions were significantly decreased （P＜0.05）. The curcumin high-dose group and DAPT group showed superior results in most indicators compared to the curcumin low- and medium-dose groups. CONCLUSIONS Curcumin has an improving effect on EMS， and its mechanism may be related to inhibiting Notch1 signaling pathway， reducting local inflammatory responses， and inhibiting ectopic endometrial invasion and angiogenesis.

Objective:To investigate the expression and clinical significance of microRNA-124(miR-124)and microRNA-1976(miR-1976)in the serum of patients with Parkinson's disease(PD).Methods:A total of 58 patients with PD were selected from September 2020 to June 2022 and categorized as the PD group.The Unified Parkinson's Disease Rating Scale(UPDRS)score was used to divide the PD patients into two groups: those with a UPDRS score≤60(25 patients)and those with a UPDRS score >60(33 patients). The Hoehn-Yahr grading scale was used to grade the PD patients.Additionally, 30 healthy individuals who had undergone a physical examination during the same period were selected as the control group.After collecting the subjects' serum, we performed real-time fluorescent quantitative PCR(qRT-PCR)to detect the expressions of miR-124 and miR-1976 in the serum.Logistic regression analysis was employed to analyze the influencing factors, and the diagnostic significance of serum miR-124 and miR-1976 in PD patients was evaluated using the receiver operating characteristic(ROC)curve.To predict the target genes of miR-1976, we utilized several software including TargetScan and Mirtarbase.Results:Compared to the control group, the PD group showed a significant down-regulation of serum miR-124 expression[(1.49±0.36) vs.(1.02±0.32)]( t=8.85, P<0.001), while miR-1976 expression was sharply up-regulated[(0.98±0.30) vs.(1.33±0.37)]( t=6.92, P<0.001). The low expression of serum miR-124 and the overexpression of miR-1976 were identified as independent risk factors for PD( OR>1, P<0.05). The Hoehn-Yahr rating of PD patients with a UPDRS score above 60 was higher than that of patients with a UPDRS score below 60[(3.42 ± 0.73) vs.(2.16 ± 0.42)]( t=3.05, P<0.05). However, there was no significant difference in serum miR-124 and miR-1976 expression between groups with different UPDRS scores[miR-124: (1.09±0.26) vs.(0.98±0.38)( t=0.89, P>0.05); miR-1976: (1.42±0.43) vs.(1.23±0.68)( t=0.62, P>0.05)]. The ROC analysis results demonstrated that miR-124 and miR-1976 had area under the curve(AUC)values of 0.832 and 0.797, respectively, in diagnosing PD.The corresponding cutoff values were 1.205 and 1.196, respectively.The sensitivity for miR-124 was 74.1%, while for miR-1976 it was 51.8%.The specificity for miR-124 was 77.8%, and for miR-1976 it was 90.1%.When both miR-124 and miR-1976 were combined in the diagnosis of PD, the AUC was 0.912, with a sensitivity of 76.4% and a specificity of 93.2%.Furthermore, it was found that miR-1976 targeted the PINK1 gene, suggesting its potential as a target gene in PD. Conclusions:The expression of miR-124 was found to be decreased in PD patients, while the expression of miR-1976 was increased.Both miR-124 and miR-1976 showed some reference value in PD diagnosis, and their combined diagnostic value was higher.This suggests that further study on their significance is warranted.However, it should be noted that the expressions of miR-124 and miR-1976 were not found to be correlated with the UPDRS score of PD patients.

Objective: To investigate epidemiological characteristics of notifiable infectious diseases in Zhejiang Province in 2023, so as to provide the evidence for strengthening prevention and control of infectious diseases. Methods: Data pertaining to notifiable infectious diseases reported in Zhejiang Province in 2023 were retrieved from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The incidence and mortality were analyzed according to the classification of notifiable infectious diseases and transmission routes, and epidemiological characteristics of infectious diseases were descriptively analyzed. Results: Thirty types of notifiable infectious diseases with 2 955 699 cases and 427 deaths were reported in Zhejiang Province in 2023, with a reported incidence rate of 4 493.93/105 and a reported mortality rate of 0.649 2/105. A total of 679 notifiable infectious disease emergencies were reported, with 26 514 cases and 1 case death (rabies). The emergencies mainly occurred in schools and preschool institutions, with 621 cases accounting for 91.46%. There were 1 case of cholera reported in class A notifiable infectious diseases and no death, 22 types of class B notifiable infectious diseases, with a reported incidence rate of 552.46/105 and a reported mortality rate of 0.644 7/105, and 8 types of class C notifiable infectious diseases, with a reported incidence rate of 3 941.48/105 and a reported mortality rate of 0.004 6/105. The incidence rates of respiratory, intestinal, blood-borne and sexually transmitted, natural and insect-borne infectious diseases were 4 028.67/105, 381.59/105, 81.15/105 and 1.35/105, respectively, according to transmission routes. Influenza (3 561.78/105) and COVID-19 (423.77/105) reported the highest incidence, and AIDS (0.477 4/105) and tuberculosis (0.130 8/105) reported the highest mortality. Conclusion The incidence rates of respiratory and intestinal infectious diseases were high in Zhejiang Province in 2023, and schools and preschool institutions were the main places of diseases occurred.