Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Tea green leafhopper(TGL),Empoasca onukii,is of biological and economic interest.Despite numerous studies,the mechanisms underlying its adaptation and evolution remain enig-matic.Here,we use previously untapped genome and population genetics approaches to examine how the pest adapted to different environmental variables and thus has expanded geographically.We complete a chromosome-level assembly and annotation of the E.onukii genome,showing nota-ble expansions of gene families associated with adaptation to chemoreception and detoxification.Genomic signals indicating balancing selection highlight metabolic pathways involved in adaptation to a wide range of tea varieties grown across ecologically diverse regions.Patterns of genetic vari-ations among 54 E.onukii samples unveil the population structure and evolutionary history across different tea-growing regions in China.Our results demonstrate that the genomic changes in key pathways,including those linked to metabolism,circadian rhythms,and immune system functions,may underlie the successful spread and adaptation of E.onukii.This work highlights the genetic and molecular basis underlying the evolutionary success of a species with broad economic impacts,and provides insights into insect adaptation to host plants,which will ultimately facilitate more sustain-able pest management.

From August 2019 to December 2019, 74 patients with choledocholithiasis underwent laparoscopic lithotomy, including 68 cases with primary suture of common bile duct and 6 cases with T-tube drainage. The operation time, postoperative length of hospital stay, hospitalization cost and complications of the two groups were compared. The operation time and length of postoperative hospital stay in primary suture were shorter than those in T-tube drainage group[ (88.1±29.9) min vs. (144.2±30.7) min; (3.9±1.5) d vs. (7.2±3.8) d, both P<0.05]; the hospitalization cost was lower[ (29 578±1 072) Yuan vs. (37 468±2 844) Yuan, P<0.05]. There was no significant difference in the incidence of postoperative complications between two groups ( P>0.05). The primary suture seems to be superior to T-tube drainage in laparoscopic lithotomy, however, two methods have different indications and should be selected according to the individual conditions of patients.

Objective To investigate the strategies in dealing with intraoperative CO2 embolizm during Laparoscopic hepatectomy (LH).Methods We collected and analyzed data from patients who underwent laparoscopic hepatectomy (LH) in our hospital from Jan.2013 to Aug.2017.There were 321 patients.The criteria for the diagnosis of CO2 embolism were rapid intraoperative decrease in petCO2 and SPO2 accompanied with tachyarrhythmia.Results 12 patients were diagnosed to have CO2 embolism.The rate was 3.7％.For these 12 patients,10 patients were dealt with laparoscopically and 2 patients were converted to open surgery.Conclusion CO2 embolism did not rarely occur in LH patients.Sophisticated operations and careful manipulation in LH are the only ways to prevent CO2 embolism.

Objective To determine the in vitro effects of the traditional Chinese medicines, berberine, matrine and baicalin, on the proliferation and lipid synthesis of human immortalized sebocyte SZ95, and to investigate their possible mechanisms of action on sebaceous glands at the cellular level. Methods Inverted microscopy was used to observe cell morphology and determine toxic concentrations of the compounds. The MTT method was adopted to examine the effects of different concentrations of berberine, matrine and baicalin on SZ95 cell proliferation after 24 h, 48 h and 72 h of incubation. Lipid contents in the SZ95 cells were labeled with Nile red and analyzed by flow cytometry. Results The toxic concentrations were 1?10-3 mol/L, 1?10-4 mol/L, 1?10-3 mol/L for baicalin, berberine and matrine, respectively. Berberine reduced sebocyte proliferation in a dose- and time-dependent manner, with an inhibitory concentration 50 (IC50) of 2.9?10-5 mol/L and 1.4?10-5 mol/L after 48 h and 72 h of incubation, respectively. When the concentration of matrine was 0.05). Lipogenesis of SZ95 cells showed a 26.9% increase with 1?10-3 mol/L matrine. Conclusions Our results indicate that berberine and baicalin can inhibit proliferation and lipid synthesis of SZ95 sebocytes in vitro, which suggests a possible clinical role in treating acne.

Objective To investigate the changes of hair growth with the increase of age and to develop a new practical method to evaluate the extent of aging. Methods After the approval of the ethnic committee, 96 healthy volunteers (44 males, 52 females, aged 30 ~ 78 years) were recruited into the study and divided into 4 groups based on the age: 30-group, 40-group, 50-group and 60-group. Macrophotographs were taken from the vertex. Hair density and percentages of black hairs were counted using Photoshop7.0 software. Ten hairs were randomly plucked from the specified scalp area,and the diameters of hair shaft and hair bulb were examined by a micrometer. The percentages of the follicles, based on their morphology, at different phases of the hair cycle, were counted. Results With the increase of age, the hair density, diameters of hair shaft as well as hair bulb, the percentages of anagen follicles and grey hairs all decreased, while the percentages of telogen follicles and white hairs increased, and significant difference was found between the 60-group and other 3 groups. In each group, the difference between males and females was found only in some parameters. The diameter of hair bulb positively correlated with that of hair shaft. Conclusion This study suggests that the parameters of hair growth could be used to help rating the extent of aging.

Objective To investigate the impact of severity of psoriasis on quality of life in patients with psoriasis vulgaris.Methods A questionnaire interview was carried out to the outpatients with psoriasis vulgaris(n=504)from Dec.2000to Sept.2001.All the patients were more than18years old.The content of questionnaire included daily life and activities,work and school performance,social activities and personal relationships,and psychologic status.Disease severity was assessed with psoriasis area and severity index(PASI).498patients were included for the final analysis.Statistical analysis was performed with SPSS software package.Results63.3%patients were restricted in their food selection.40.2%had bad sleep,59.0%could not dress short clothes in the summer.26.5%were restricted in use of public traffic and services.15.1%were rejected in haircut and cosmetic service.31.2%had decreased income along with severity of the disease.58.8%felt uncomfortable in social activities and public places.25.8%avoided handshaking with others.43.3%were reluctant in social intercourse.29.0%were not willing to take part in social activities,especially for moderate and severe cases.54.9%felt that their self-esteem was injured.26.6%thought that other peoples always avoided to meet them.64.4%felt anxiety for their disease.83.1%often worried about relapse or exacerbation of psoriasis.15.9%showed a tendency to commit suicide.Conclusions The more severe the disease is the more impact it may have on the daily life,work and school performance,social activities and personal relationship,and psychologic status in patients with psoriasis vulgaris.It is reccommended that besides the conventional treatment bio-psychic and social medical management be given to the patients especially for moderate and severe cases.