Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

Objective:To examine the satisfaction and teaching effectiveness of Health Statistics among students majoring in Public Utility Administration,and to provide valuable insights for optimizing current teaching practices and enhancing teaching effectiveness.Methods:A survey questionnaire,specifically designed for this study,was administered to 56 students of grade 2021 majoring in Public Utility Administration in our school.The questionnaire covered topics such as the difficulty of teaching content,learning satisfaction,and the Student Evaluation of Educational Quality(SEEQ)scale.Results:Non-parametric testing was considered the most difficult knowledge point,and male students found statistical inference of quantitative data was the most challenging,while female students found non-parametric testing was the most difficult.In terms of satisfaction,the highest score was obtained for pre-class review,while the lowest score was given to improving learning interest in Rain Classroom.The overall score for teaching effectiveness,as measured by SEEQ,was good across seven dimensions.Teaching enthusiasm received the highest score(4.40±0.43),while homework volume received the lowest score(3.23±0.37).With the exception of homework grading,satisfaction was positively correlated with most dimensions of teaching effectiveness evaluation.Conclusions:Despite perceiving the course as generally difficult,students expressed high satisfaction and overall positive evaluation of teaching effectiveness.Therefore,it is recommended to actively explore new teaching reforms to cultivate well-rounded applied talents for public utilities.

Objective:Methamphetamine(METH)is an illicit psychoactive substance that can damage various organs,with the urinary system being one of its significant targets.This study aims to explore the role of microtubule affinity-regulating kinase 4(MARK4)in METH-induced acute kidney injury(AKI). Methods:A total of 10 healthy adult male C57BL/6 mice were randomly divided into a control group and a METH group,5 mice in each group.The METH group was administered METH(20 mg/kg,intraperitoneally,once daily for 3 consecutive days),while the control group received an equal volume of physiological saline.The mice were executed 24 hours after the final injection,and the success of the AKI model was detected by blood serum creatinine,blood urea nitrogen,and renal HE staining.Proteins differentially expressed between kidney tissues with METH-induced AKI and normal kidney tissues were screened by proteomics techniques and subjected to gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and bioinformatics analysis.The accuracy of proteomic data was validated using Western blotting,and the expression levels of MARK4 and cleaved caspase-3 in mouse kidneys were measured.We further explored the role of MARK4 in METH-induced AKI.Firstly,a METH toxicity model was established in BUMPT cells to screen the appropriate concentration and time of METH treatment;the viability of BUMPT cells after METH treatment and the expression of cleaved caspase-3 were detected by interfering with MARK4 expression through inhibitors. Results:The proteomic analysis of kidney tissues from METH and control groups screened for a total of 17 differentially expressed proteins,of which 11 were up-regulated and 6 were down-regulated(all P＜0.05).The expression levels of MARK4 and cleaved caspase-3 were elevated in the kidneys of METH-treated mice(both P＜0.05).The activity of BUMPT cells gradually decreased with increasing METH treatment concentration(all P＜0.05),where the viability of BUMPT cells decreased to about 60％after METH treatment at 4 mmol/L.Compared with the control group,expression levels of MARK4 and cleaved caspase-3 were increased with higher METH concentrations and longer exposure times in a concentration-and time-dependent manner(all P＜0.05).Inhibition of MARK4 expression improved METH-induced decrease in BUMPT cell activity,down-regulated the expression of cleaved caspase-3,and decreased the apoptosis of BUMPT cells induced by METH. Conclusion:MARK4 is highly expressed in a mouse model of METH-induced AKI,and MARK4 mediates METH-induced AKI by regulating cell apoptosis.

Objective:To explore the dynamics and directionality between perceived discrimination and inter-group trust in migrant children.Methods:Totally 69 migrant children from a primary school in Fuzhou were select-ed and followed up for two years.The Questionnaire on Perceived Discrimination among Migrant Children and the trust game task were used to measure migrant children's perceived discrimination and intergroup trust,respective-ly.Statistical analysis of the results was conducted using correlation analysis,cross-lagged regression analysis,and repeated measures ANOVA.Results:There was a significant decrease in perceived discrimination after 2 years(P＜0.05).From the cross-sectional data,the perceived discrimination negatively predicts the in-group and out-group trust in the same period(P＜0.05).However,in the longitudinal view,the predictive effect of pretest perceived dis-crimination on in-group trust selection rate within post-test is not significant(P＞0.05).There was no significant difference between in-group trust and out-group trust in the pre-test(P＞0.05).Conclusion:Change over time,the level of perceived discrimination in migrant children may decrease.Although the statistical results are not signifi-cant,there is still a potential negative predictive trend of perceived discrimination on in-group trust,and the migrant children may gradually shift to ingroup trust.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the effects of continuous blood purification (CBP) on mitochondrial function of peripheral blood mononuclear cells and clinical prognosis of patients with traumatic sepsis.Methods:A prospective cohort study was used to analyze the clinical data of 90 patients with traumatic sepsis admitted to the Intensive Care Unit of Shaoxing People′s Hospital from January 2023 to June 2024. Based on standard operating procedures (SOP), patients were divided into CBP group and non-CBP group according to whether they received CBP treatment. The mitochondrial DNA (mtDNA) copy number, activity of mitochondrial respiratory chain complex V, levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 in the mononuclear cells on ICU admission and at 12, 24 and 48 hours after treatment were compared between the two groups. Acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score on ICU admission and at 48 hours after treatment were detected in the two groups. The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were compared between the two groups.Results:A total of 90 patients with traumatic sepsis were included, comprising 56 males and 34 females, aged 18-82 years [51.3(38.7, 70.6)years], with injury severity score (ISS) of 16-54 points [36.2(17.0, 53.6)points]. There were 52 patients in the CBP group and 38 in the non-CBP group. All the patients were followed up for 7-14 days [10.0(8.0, 12.0)days]. On ICU admission, the mtDNA copy number was 638.5±124.0 in the CBP group and 634.7±122.1 in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the mtDNA copy number in the CBP group was 564.2±105.6, 415.7±83.5 and 303.7±77.0 respectively, significantly lower than 622.9±120.2, 581.5±113.6, 530.7±97.8 in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the mtDNA copy number in both groups continued to decrease compared with that on ICU admission ( P<0.05). On ICU admission, the activity of mitochondrial respiratory chain complex Ⅴ was (74.0±26.0)pg/ml in the CBP group and (72.8±25.3)pg/ml in the non-CBP group ( P>0.05); at 12, 24 and 48 hours after treatment, it was (69.4±24.2)pg/ml, (78.3±26.8)pg/ml and (91.5±33.5)pg/ml respectively in the CBP group, significantly higher than (65.3±23.6)pg/ml, (60.7±19.4)pg/ml and (53.8±16.9)pg/ml in the non-CBP group ( P<0.05 or 0.01); at 12 hours after treatment, it was decreased in both groups compared with that on ICU admission ( P<0.05); at 24 and 48 hours after treatment, it was gradually increased in the CBP group compared with those on ICU admission and at 12 hours after treatment ( P<0.05), while in the non-CBP group, it continued to decrease ( P<0.05). The levels of TNF-α, IL-6 and IL-10 on ICU admission were (51.6±17.1)pg/ml, (174.1±57.3)pg/ml and (67.6±16.2)pg/ml respectively in the CBP group and (49.5±16.7)pg/ml, (177.8±58.7)pg/ml and (65.7±16.6)pg/ml respectively in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the levels of TNF-α in the CBP group were (43.6±15.6)pg/ml, (29.4±12.5)pg/ml and (26.2±10.6)pg/ml respectively, the IL-6 levels were (122.4±41.7)pg/ml, (90.6±33.1)pg/ml, (75.6±24.7)pg/ml respectively and the IL-10 levels were (72.6±18.1)pg/ml, (80.7±20.6)pg/ml, (86.2±22.9)pg/ml respectively, which were significantly lower than (48.8±16.2)pg/ml, (46.5±15.5)pg/ml, (40.0±14.2)pg/ml at 12 hours after treatment, (168.4±51.6)pg/ml, (131.5±42.7)pg/ml, (112.7±35.8)pg/ml at 24 hours after treatment, and (78.6±19.3)pg/ml, (91.1±23.8)pg/ml, (99.4±26.6)pg/ml at 48 hours after treatment in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the levels of TNF-α and IL-6 in both groups continued to decrease, while the levels of IL-10 continued to increase compared with those on ICU admission ( P<0.05). On ICU admission, the APACHE Ⅱ and SOFA scores were (20.6±10.5)points and (6.2±1.9)points in the CBP group and (21.2±11.2)points and (6.7±2.1)points in the non-CBP group ( P>0.05). At 48 hours after treatment, the APACHE Ⅱ and SOFA scores were (13.5±6.6)points and (2.7±0.6)points in the CBP group, which were significantly lower than (18.3±9.3)points and (5.3±1.5)points in the non-CBP group ( P<0.01). At 48 hours after treatment, the APACHE II and SOFA scores in both groups were significantly decreased compared with those on ICU admission ( P<0.05 or 0.01). The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were (13.0±5.7)days, (20.4±8.6)days and 19.2% (10/52) respectively, which were significantly shorter and smaller than (17.6±6.6)days, (26.5±9.4)days and 31.6% (12/38) in the non-CBP group ( P<0.05 or 0.01). Conclusions:CBP treatment may reduce the release of mtDNA by alleviating the mitochondrial damage of the mononuclear cells in patients with traumatic sepsis so that the release of inflammatory factors and cellular apoptosis is reduced, and improve the state of cell energy metabolism and cellular immune function by increasing the activity of mitochondrial respiratory chain complex V in the mononuclear cells, and participate in the reconstruction of immune homeostasis of the body so the inflammatory state and clinical prognosis of the patients are improved.

Objective:To evaluate the risk factors for the complexity and surgical prognosis in patients with proliferative diabetic retinopathy (PDR).Methods:A historical cohort study of the CONCEPT trial, including 97 patients (97 eyes) who were diagnosed with PDR and requiring three-channel 23-gauge transconjunctival pars plana vitrectomy (PPV) from June 2017 to January 2018 at the First Affiliated Hospital of Nanjing Medical University.All patients received preoperative intravitreal injection of 0.5 mg conbercpet.Based on the PDR complexity score, patients were divided into >3 group or ≤3 group, and the systematic risk factors were compared between the two groups.The influence of sex, age, hypertension, renal insufficiency, duration of diabetes mellitus, and hemoglobin A1c level on the PDR complexity score was evaluated by multivariate logistic regression analysis.Based on age, patients were divided into <45 years group, 45-<60 years group, and ≥60 years group, and the differences in mean operative time, incidence of intraoperative hemorrhage, surgically induced lacrimation and silicone oil filling, and incidence of hemorrhage on color fundus photos and macular edema by optical coherence tomography at postoperative months 1 and 6 were analyzed among different age groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (No.2017-SR-283).Written informed consent was obtained from each subject.Results:The age of patients with PDR complexity score >3 was 46.5(36.0, 51.8) years, which was less than 54.0(45.5, 61.5) years for PDR complexity score ≤3, and the difference was statistically significant ( Z=1.835, P=0.002).Among the factors predicting PDR complexity score >3, logistic regression analysis indicated that only age was statistically significant ( P=0.005).For each 1-year increase in age, the risk of PDR complexity score >3 would increase by 7.4%( OR: 0.929, 95% CI: 0.883-0.977).Among the systemic factors, there were significant differences in age, history of diabetes, proportion of patients with hypertension and renal insufficiency among the three age groups (all at P<0.05).Among the ocular factors, there were significant differences in the proportion of patients with history of retinal laser treatment, fibrovascular membrane and complexity score >3 among the three groups (all at P<0.05).The proportion of patients with fibrovascular membrane and complexity score >3 in the <45 years group was significantly higher than that in the 45-<60 and ≥60 years groups (all at P<0.05).There were significant differences in the proportion of patients with intraoperative bleeding and silicone oil filling in the three age groups (all at P<0.017).The proportion of intraoperative bleeding and silicone oil filling in <45 years group was significantly higher than that in 45-<60 and ≥60 years groups (all at P<0.05).The macular edema on postoperative month 1 in the <45 years old group was significantly higher than that in the 45-<60 and ≥60 years groups (both at P<0.05). Conclusions:Among systemic factors, age has a significant impact on the increased PDR complexity and contributes to the poor prognosis of patients.There is a higher percentage of intraoperative complications and early postoperative macular edema in patients in the younger age group compared to the older age group.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective: To understand the status quo of school bullying among middle school students in Anhui Province and its correlation with family environment and education methods of students related to school bullying, so as to provide corresponding prevention and controlling measures against school bullying. Methods: The investigation has been conducted on the occurrence of school bullying among middle school students ranging from junior grade one to senior grade three in Hefei, Wuhu, Fuyang of Anhui Province, during which up to 1 826 students information has been gathered through Questionnaire Atar Platform using the school bullying scale and self designed questionnaire. SPSS 26.0 statistical software has been applied for data analysis. Results: The incidence of bullying was 41.40%, and among them, 14.46% were reported to bully others, 39.59% of them were of being bullied, and 12.65% of them were reported of bullying others and being bullied at the same time. Multivariate Logistic regression corrected model showed that quiet relationship with mother ( OR=1.76, 95%CI =1.22-2.53) was a risk factor for the bully, quiet relationship with father( OR=1.89, 95%CI=1.47-2.43 ), reorganized family ( OR=2.28, 95%CI =1.22-4.29) were the risk factors for the bullied, quiet/poor relationship between parents ( OR=1.52, 95%CI=1.06-2.17; OR=3.15, 95%CI =1.79-5.57) was a risk factor for the bully-bullied; Punishment and abuse( OR=1.45, 95%CI=1.10-1.90; OR=1.82, 95%CI=1.48-2.23; OR=1.47, 95%CI = 1.10- 1.96) were risk factors for the above three behaviors( P <0.05). Conclusion The incidence of school bullying is influenced by family environment and rearing style. In daily life, parents should be mindful of maintaining a good family relationship, fostering active communication with child, which can reduce the occurrence of school bullying.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a consanguineous Chinese pedigree affected with Congenital coagulation factor XII (XII) deficiency. METHODS: Members of the pedigree who had visited Ruian People's Hospital on July 12, 2021 were selected as the study subjects. Clinical data of the pedigree were reviewed. Peripheral venous blood samples were taken from the subjects. Blood coagulation index and genetic testing were carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: This pedigree has comprised 6 individuals from 3 generations, including the proband, his father, mother, wife, sister and son. The proband was a 51-year-old male with kidney stones. Blood coagulation test showed that his activated partial thromboplastin time (APTT) was significantly prolonged, whilst the FXII activity (FXII:C) and FXII antigen (FXII:Ag) were extremely reduced. The FXII:C and FXII:Ag of proband's father, mother, sister and son have all reduced to about half of the lower limit of reference range. Genetic testing revealed that the proband has harbored homozygous missense variant of c.1A>G (p.Arg2Tyr) of the start codon in exon 1 of the F12 gene. Sanger sequencing confirmed that his father, mother, sister and son were all heterozygous for the variant, whilst his wife was of the wild type. By bioinformatic analysis, the variant has not been included in the HGMD database. Prediction with SIFT online software suggested the variant is harmful. Simulation with Swiss-Pbd Viewer v4.0.1 software suggested that the variant has a great impact on the structure of FXII protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CONCLUSION The c.1A>G (p.Arg2Tyr) variant of the F12 gene probably underlay the Congenital FXII deficiency in this pedigree. Above finding has further expanded the spectrum of F12 gene variants and provided a reference for clinical diagnosis and genetic counseling for this pedigree.
Male ; Female ; Humans ; Middle Aged ; Factor XII/genetics* ; Pedigree ; Codon, Initiator ; East Asian People ; Mothers ; Factor XII Deficiency/genetics* ; Mutation