Objective To analyze the epidemiological characteristics of leptospirosis in China from 2010 to 2022, so as to provide insights into formulation of the leptospirosis control strategy. Methods All data pertaining to clinically diagnosed cases and confirmed cases of leptospirosis reported in China from January 1, 2010 to December 31, 2022 was collected from Chinese Disease Prevention and Control Information Management System. The spatial, temporal and population distributions, and report and diagnosis institutions of leptospirosis cases were analyzed using a descriptive epidemiological method. Results A total of 4 559 leptospirosis cases were reported in China from 2010 to 2022, with an annual average number of 351 cases, and the number of reported leptospirosis cases reduced from 679 cases in 2010 to 158 cases in 2018. A total of 4 276 leptospirosis cases were reported in Sichuan Province, Yunnan Province, Guangdong Province, Hunan Province, Fujian Province, Zhejiang Province, Guangxi Zhuang Autonomous Region, Anhui Province, Jiangxi Province and Guizhou Province, accounting for 93.79% of the total number of leptospirosis cases in China. The number of leptospirosis cases had recently appeared a remarkable decline in Yunnan Province, while a significant rise was seen in the number of leptospirosis cases in two provinces of Zhejiang and Guangdong. No leptospirosis cases were reported in Henan Province from 2010 to 2020; however, there were 5 cases and 2 cases reported in 2021 and 2022, respectively. There was only one leptospirosis case reported in Shaanxi Province from 2010 to 2017; however, leptospirosis cases were reported in the province for 5 consecutive years since 2018. Leptospirosis cases were reported throughout the year in China from 2010 to 2022, with the peak of incidence found during the period between August and October, and the peak of leptospirosis incidence varied in provinces. A higher number of leptospirosis cases was seen among men than among women, with a male to female ratio of 2.3:1, and the median age of leptospirosis cases was 50 years (interquartile range, 23 years), with the highest proportion of leptospirosis cases reported at ages of 51 to 60 years (23.21%). Among all reported leptospirosis cases, 53.28% were confirmed cases, and the proportion of confirmed cases increased from 35.05% in 2010 to 61.66% in 2022. In addition, there were 67.22% of leptospirosis cases (2 937 cases) reported by comprehensive hospitals, 20.44% (893 cases) by disease control and prevention institutions, 7.23% (316 cases) by grassroots healthcare institutions and 5.10% (223 cases) by other healthcare and medical institutions, and the mortality of reported leptospirosis cases was 1.07% in China from 2010 to 2022, with a higher mortality seen among men than among women (1.39% vs. 0.36%; χ² = 9.52, P = 0.002). Conclusions The incidence of leptospirosis remained at a low level in China from 2010 to 2022, and southern China was still the main endemic area for leptospirosis. The epidemiological characteristics of leptospirosis cases varied in endemic provinces, and leptospirosis cases had been continued to be reported in Shaanxi and Henan provinces, which should be paid much attention to. Intensified surveillance of leptospirosis, improved diagnosis and treatment capability of leptospirosis cases and leptospirosis control with adaptations to local circumstance are recommended.

Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4⁺CXCR5⁺IFN-γ⁺Tfh1 cells, CD4⁺CXCR5⁺IL-17A⁺Tfh17 and CD4⁺CXCR5⁺IL-21⁺Tfh21 cells, and a significant decrease in the percentage of CD4⁺CXCR5⁺IL-10⁺Tfh10 cells and CD4⁺CXCR5⁺FOXP3⁺Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.
Animals ; Mice ; Dermatitis, Atopic/drug therapy* ; Interleukin-17 ; T Follicular Helper Cells ; Janus Kinase 2 ; Dinitrochlorobenzene ; Inflammation ; Cell Differentiation ; Signal Transduction

Objective To investigate the mechanism of C-C motif chemokine ligand 5(CCL5)modulation by extracellular matrix stiffness in non-small cell lung cancer(NSCLC)and to determine the effect of CCL5 on the immunotherapy response of NSCLC.Methods The correlation between extracellular matrix stiffness and CCL5 expression in NSCLC was analyzed with the TCGA database.Polyacrylamide hydrogels with different stiffness were designed according to the extracellular matrix stiffness of NSCLC,and H1299 cells responding to the mechanical loading of hydrogel matrix stiffness were subjected to transcriptome sequencing.High matrix stiffness was verified to promote the expression of CCL5 by using sequence.Results High extracellular matrix stiffness upregulated CCL5 expression,and interferon-γ mediated signaling pathway might be involved in the process.NSCLC patients with high CCL5 expression had a greater abundance of cytotoxic T-cells in tumor tissue and reacted favorably to anti-programmed cell death protein 1 treatment.Conclusion Increased extracellular matrix stiffness promotes CCL5 synthesis,and CCL5 enhances immunotherapy responsiveness in NSCLC by increasing cytotoxic T cell infiltration in tumor tissue.

The development of molecular imaging has been going on for more than 20 years. During this period, a large number of new imaging technologies for molecular imaging have been proposed, but only a small number of them have successfully achieved clinical transformation, entered the actual clinical application and achieved significant clinical results. Among them, intraoperative navigation based on fluorescence molecular imaging and quantitative analysis technology based on medical imaging big data are being carried out in more and more clinical trials and have gradually won wide recognition. Through the in-depth integration of these two technologies with artificial intelligence, a series of research results have been achieved in multiple clinical diagnosis and treat-ment processes such as preoperative diagnosis, intraoperative navigation and postoperative prediction of digestive system tumors, providing new technical support in the field of medical imaging for the individualized diagnosis and treatment of patients with digestive system diseases.

Objective:To explore the mechanism of Dabuyuanjian in Against alzheimer's disease(AD)through network phar-macology and molecular docking technology,and to verify the molecular mechanism discovered by animal experiments.Methods:Net-work pharmacology was used to analyze the active ingredients and targets of AD in the treatment of large supplementary yuan decoc-tion.The core components of the drug were verified by molecular docking with the core protein by using AutoDock and PyMOL soft-ware.AD model mice were treated with Dabuyuanjian,and the core pathways which discovered were verified.Results:A total of 80 active ingredients and 107 disease targets were screened out.Dabuyuanjian had 95 targets in the treatment of AD,of which 35 were core targets.GO enrichment found that it mainly involved in programmed cell death process,apoptosis process and signal transduction regulation,etc.KEGG signaling pathway enrichment found that it mainly involved PI3K/Akt signaling pathway,Wnt signaling pathway,AMPK signaling pathway,etc.Morris water maze experiment showed that Dabuyuanjian could reduce the escape latency of AD mice,and increase the number of crossing platform and time's target quadrant.Immunohistochemistry(IHC)showed that Dabuyuanjian could increase the number of positive labeled-NeuN cells in the hippocampal CA3 region of AD mice.Immunofluores-cence(IF)showed that Dabuyuanjian could inhibit the expression levels of(GFAP)and ionized calcium-binding protein 1(IBA1)in the hippocampal CA3 region of AD mice.Western blot experiments showed that Dabuyuanjian could increase the expression levels of phosphorylated adenylate-activated protein kinase α(AMPKα)and silent information regulator 1(SIRT1)in the hippocampus of AD mice.Conclusion:This study explores the mechanism of Dabuyuanjian against AD,and find that Dabuyuanjian can improve cognitive impairment,neuron loss and neuroinflammation via activating AMPK/SIRT1 signaling pathway of AD.

Objective:To study the effects of Jianpi Qinghua Decoction on hepatocyte apoptosis under non-alcoholic fatty liver disease (NAFLD), and to discuss its mechanism.Methods:Totally 29 C57 mice were randomly selected and fed a 60% high fat diet for 16 weeks, while the remaining 6 mice were given regular feed as the normal group. After successful modeling, 12 mice with larger body weight were divided into TCM group and model group using a random number table method, while continuing to receive high-fat feed. The TCM group was orally administered Jianpi Qinghua Decoction 20.961 g/kg. The normal group and model group were orally administered an equal volume of distilled water once a day, with continuous intervention for 4 weeks. The levels of GOT and GPT in blood were detected by ELISA, the deposition of triglyceride in liver was detected by oil red O, and the apoptosis of liver cells was detected by TUNEL fluorescence staining. Western blot was used to detect the expressions of cleaved Caspase-3, Caspase-3, Bax, Bcl-2, JNK and p-JNK.Results:Compared with the model group, the body weight and GPT in the TCM group significantly decreased ( P<0.05), TG deposition was significantly reduced, apoptosis range of liver cells was significantly reduced, and cleaved Caspase-3/Caspase-3, p-JNK/JNK and the expression of Bax significantly decreased ( P<0.05). The expression of Bcl-2 increased ( P<0.05). Conclusion:Jianpi Qinghua Decoction can inhibit JNK protein phosphorylation and effectively reduce liver cell apoptosis in NAFLD mice, which may delay the progression of NAFLD towards cirrhosis and liver cancer.

ObjectiveTo study the effects of Toddalia asiatica alcohol extract on autophagy and apoptosis of non-small cell lung cancer A549 cells， and to explore its possible mechanism. MethodA549 cells were cultured in vitro. Cell counting kit-8 （CCK-8） was used to detect the proliferation of A549 cells， and cell survival rate was calculated to screen the drug concentration. The apoptosis in each dose group and that after the use of 3-methyladenine （3-MA）， an autophagy inhibitor， were detected by flow cytometry combined with Annexin V-FITC/PI double staining. Western blot was used to detect the expression levels of apoptosis-related proteins such as B cell lymphocytoma-2（Bcl-2）， Bcl-2-associated X protein（Bax）， microtubule-associated protein 1 light chain 3 （LC3）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， activated poly （Adenosine diphosphate） ribonucleotide polymerase （cleaved PARP1）， PARP1， activated death activator （t-Bid）， Bid， and ubiquitin-binding protein p62 in each group and those after the use of 3-MA. ResultCompared with the conditions in the control group， the cell survival rate in 0.25 g·L^-1 group （P<0.05）， and 0.5， 1， 2， 4 g·L^-1 groups （P<0.01） was decreased after 24 h intervention. Additionally， the cell survival rate was reduced in a concentration-dependent manner at 48 h and it was less than 10% at 4 g·L^-1 （P<0.01）. Compared with the conditions in the control group， the total apoptosis rate in 0.5 g·L^-1 group was increased （P<0.05）， and the apoptosis rate in 1 and 2 g·L^-1 groups was also increased （P<0.01）. Compared with the 2 g·L^-1 group and 3-MA group， the 3-MA combined with T. asiatica alcohol extract had significantly decreased apoptosis rate （P<0.01）. Compared with the conditions in the control group， elevated expression of pro-apoptotic proteins cleaved PARP1， Bax and t-Bid in 1 and 2 g·L^-1 groups （P<0.05， P<0.01）， and reduced expression of Bid in the 2 g·L^-1 group （P<0.01） were found. Compared with the conditions in the control group， the expression of anti-apoptotic protein Bcl-2 （P<0.05， P<0.01） and the level of p62 （P<0.01） were down-regulated in 0.5， 1， 2 g·L^-1 groups， while the level of LC3 Ⅱ protein was up-regulated （P<0.01）， with certain concentration dependence. ConclusionT. asiatica alcohol extract could significantly inhibit the proliferation of A549 cells， which might be related to promoting autophagy and inducing apoptosis.

Objective:To summarize the experience of personalized treatment of pediatric prepuce trauma.Methods:The clinical data of children with prepuce trauma treated in the Department of Pediatric Surgery of the First Affiliated Hospital of Zhengzhou University from January 2019 to March 2021 were analyzed retrospectively. First, pediatric prepuce trauma was classified and graded before treatment, and then the treatment plans were developed with the informed consent of the children’s parents. Mild injuries were treated conservatively. In moderate injuries, in situ suture repair and frenuloplasty were performed. In severe injuries, modified circumcision and prepuce flap prepuceplasty were performed. In extremely severe injuries, composite flap (scrotal and mons pubis flap combined with prepuce flap) prepuceplasty was performed. The children were followed up for penile appearance and urinary and erectile function postoperatively.Results:A total of 36 male children, aged 6 months to 10 years, were enrolled in the study. Type of foreskin trauma: 7 cases of foreskin tie injury, 7 cases of inner plate injury, 12 cases of outer plate injury, and 10 cases of combined inner and outer plate injury; degree of foreskin trauma: 9 cases of mild injury, 6 cases of moderate injury, 19 cases of severe injury, and 2 cases of extremely severe injury. 9 of the 36 cases were treated conservatively; 4 cases were treated with in situ suture repair; 5 cases were treated with in situ suture repair + circumcision; 12 cases were treated with modified circumcision; 4 cases were treated with foreskin flap penile circumcision, and composite flaps (scrotal and mons pubis flaps as advancement flap + prepuce flap) were applied in 2 cases. All the children were followed up for 3~6 months. The appearance of the penis and scrotum was good, and the urination and erectile function were normal after treatment. The parents of the children were satisfied with the treatment results.Conclusions:For the treatment of pediatric prepuce trauma, it is necessary to comprehensively consider the location of the prepuce involved and the degree of prepuce injury and adopt an appropriate personalized treatment plan, which can achieve better results.

Objective:To summarize the experience of personalized treatment of pediatric prepuce trauma.Methods:The clinical data of children with prepuce trauma treated in the Department of Pediatric Surgery of the First Affiliated Hospital of Zhengzhou University from January 2019 to March 2021 were analyzed retrospectively. First, pediatric prepuce trauma was classified and graded before treatment, and then the treatment plans were developed with the informed consent of the children’s parents. Mild injuries were treated conservatively. In moderate injuries, in situ suture repair and frenuloplasty were performed. In severe injuries, modified circumcision and prepuce flap prepuceplasty were performed. In extremely severe injuries, composite flap (scrotal and mons pubis flap combined with prepuce flap) prepuceplasty was performed. The children were followed up for penile appearance and urinary and erectile function postoperatively.Results:A total of 36 male children, aged 6 months to 10 years, were enrolled in the study. Type of foreskin trauma: 7 cases of foreskin tie injury, 7 cases of inner plate injury, 12 cases of outer plate injury, and 10 cases of combined inner and outer plate injury; degree of foreskin trauma: 9 cases of mild injury, 6 cases of moderate injury, 19 cases of severe injury, and 2 cases of extremely severe injury. 9 of the 36 cases were treated conservatively; 4 cases were treated with in situ suture repair; 5 cases were treated with in situ suture repair + circumcision; 12 cases were treated with modified circumcision; 4 cases were treated with foreskin flap penile circumcision, and composite flaps (scrotal and mons pubis flaps as advancement flap + prepuce flap) were applied in 2 cases. All the children were followed up for 3~6 months. The appearance of the penis and scrotum was good, and the urination and erectile function were normal after treatment. The parents of the children were satisfied with the treatment results.Conclusions:For the treatment of pediatric prepuce trauma, it is necessary to comprehensively consider the location of the prepuce involved and the degree of prepuce injury and adopt an appropriate personalized treatment plan, which can achieve better results.

Objective: To explore the roles and mechanisms of long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) in promoting invasion and metastasis of esophageal squamous carcinoma (ESCC). Methods: Real time quantitative polymerase chain reaction (qPCR) was used to detect the expression of SNHG6 in ESCC and matched para-carcinoma tissues. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the expression of SNHG6 in ESCC cell lines (TE1, Yes-2, Eca9706 and Kyse150). Then, TE1 cell line which harbored highest expression of SNHG6 was used in following experiments. siRNAs were used to knock down the expression of SNHG6. Clone formation, wound-healing and transwell assay were used to detect the abilities of proliferation, migration andinvasionofTE1cells,respectively.Westernblottingwasusedtodetecttheexpressions of MMP-2, MMP-9andZEB1 protein before and after knockdownofSNHG6inTE1cells.Results:SNHG6washighlyexpressedinESCC tissues, compared to para-carcinoma tissues (P<0.01). The expression of SNHG6 was significantly decreased after transfection of SNHG6siRNA (all P<0.01). The abilities of proliferation, migration and invasion of TE1 cells in si-SNHG6-1 and si-SNHG6-2 group were significantly lower than those in the control group (all P<0.01). The expressions of ZEB1, MMP-2and MMP-9 in si-SNHG6-1 and si-SNHG6-2 group were significantly lower than those in the control group (all P<0.05). Conclusion: SNHG6 is highly expressed in ESCC tissues and promotes the malignant biological behavior of ESCC cells. Its mechanism of promoting the occurrence and development of ESCC may be related to the upregulation of ZEB1 expression.