AIM: Toll-like receptor 4 (TLR4) was an important pathogen recognition receptor in the innate immune system. The aim of this study was to investigate the distribution of TLR4 polymorphisms in the general population of China. METHODS: Peripheral blood samples were collected from 191 unrelated healthy Chinese Cantonese individuals. The functional regions of TLR4 locus,including promoter region and all three exons with their surrounding intronic regions were amplified using polymerase chain reaction. After purified,the amplified products were directly sequenced on both strands. RESULTS: A total of eight single nucleotides polymorphisms (SNPs) were detected,five of which were novel. The most common SNP were -1607 C/T with the minor allele frequency of 0.283. Two nonsynonymous substitutions Asp299Gly and Thr399Ile,which were common in Caucasus,were not detected in Cantonese. Neutrality test revealed that TLR4 in Chinese Cantonese was not significantly deviated from the neutral model. CONCLUSION: This is the new finding on the distribution of TLR4 SNPs in the general population of China. It provides several ethnic specific SNPs for further disease association studies of TLR4 polymorphisms in Chinese populations.

Objective To prepare a new-type acellular dermal matrix (ADM) and research on its relevant performance,which would provide theoretical evidence for clinical application.Methods Skin of Bama suckling pig was taken as resource of skin,and technologies of physics,chemistry and biology were selected to prepare new-type ADM.To detect the external structure,physical and chemical property as well as biological property of the prepared new-type ADM,hematoxylin-eosin (HE) staining observation,scanning electron microscope observation,amino acid analysis,material porosity and hydrophilicity test,tensile strength and in vitro degradation experiment,cytotoxicity test,and animal experiment have been conducted.Results New-type ADM cells have been thoroughly removed and dermal matrix remains intact with collagen content of 95.55％,connective three-dimensional pore structure,(85.03 ± O.99) ％ of porosity,(24.56 ± 0.57) ° of contact angle implying new-type ADM was hydrophilic substance,(5.48 ± 0.44) Pa of tensile strength implying its moderate level of pulling force,in vitro degradation period reduced to (28.7 ± O.76) h,and ＞75％ relative growth rate (RGR).Cells grew and proliferated on new-type ADM and could be replaced by original tissue after degradation.Conclusions New-type ADM have overcome disadvantages of traditional preparation method in sabotaging dermal matrix structure and incompletely removing cells from matrix,which is qualified with higher level of collagen content and porosity.With improved biological property,greatly reduced inflammation immunoreactions,and accelerated degradation rate,new-type ADM is of higher level of clinical application value.

Objective: To understand the association between bullying and anxiety symptoms of boarding middle school students, and to provide a scientific basis for preventing bullying and promoting mental health of boarding middle school students. Methods: By using stratified cluster random sampling method, 2 823 students were selected from 10 schools in Anyang, Henan Province. Questionnaire survey using self-designed bullying items and Mental Health Scale of Chinese Middle School Students was administered. Results: The overall prevalence of school bullying was 37.9%， with boarding school students(38.9%) being higher than non-boarding school students (37.1%). The anxiety symptom reporting rate of boarding students (42.9%) was higher than that of non-boarding students (27.3%). Binary Logistic regression analysis showed that, compared with non-boarding students, bully victim and bully perpetuator/victim students were more likely to have anxiety symptoms (OR=2.30, 6.04，1.94, 4.23) (P<0.05). Conclusion There is a correlation between different roles of campus bullying and anxiety symptoms among boarding and non-boarding school students. Boarding school students have a higher risk of anxiety symptoms, especially among those with both experiences of bully perpetuator/victim.

Objective: To explore the relationship between bullying among middle school students and family factors in a city of central China, so as to provide support for the prevention and reduction of school bullying among middle school students. Methods: The stratified cluster random sampling method was used to investigate the bullying involvement and family factors of 2 996 middle school students from first grade in junior high school to third grade in high school in a city in central China. Chi-square test and Logistic-regression analysis were used to analyze the relationship between family factors and bullying participation of middle school students. Results: Among 2 996 students, 390 students(13.0%) were found of having bullying behavior, and 1 127 students(37.6%) were found of being bullied. Univariate analysis showed that there were statistically significant differences in family factors such as whether she or he is the only child, father-child relationship, mother-child relationship, marital status of parents, whether the mother work away from hometown, education level of father and mother(χ2=8.88, 56.49, 30.85, 30.91, 3.89, 10.36, 11.72；25.00, 69.33, 46.76, 57.09, 3.93, 23.19, 45.49, P<0.05). Logistic regression analysis showed that the only child and mother’s education degree was junior college and below were the risk factors for middle school students’ bullying involvement (OR=1.37，1.39). Parents’ harmonious marital status and father’s not working outside are the protective factors of middle school students’ bullying(OR=0.53, 0.83).The only child is the risk factor of bullying in middle school students (OR=1.42), and good father relationship is the protective factor of bullying in middle school students (OR=0.38). Conclusion Family factors have a certain impact on the involvement of middle school students in bullying in a city of central China, and corresponding preventive measures should be formulated from the perspective of family to focus on the intervention of high-risk groups.

Objective By taking usage of bioinformatics screening methods,this medical research aimed at exploring how the miRNAs in endothelial progenitor cell exosomes relate to the regulation of angiogenesis.Methods miRNAs in endothelial progenitor cells exosomes and angiogenesis-related miRNA was intersected from the existing database to obtain the candidates of miRNA molecules related to angiogenesis in endothelial progenitor exosomes.Results 160 and 50 miRNAs in endothelial progenitor cell candidates were obtained through experimental data analysis and literature searching respectively.600 candidates of angiogenesis-related miRNAs were obtained through literature searching;the top 20 with the highest frequency were selected out.Finally,9 miRNA candidates (miR-126,miR-21,miR-221,miR-92a,miR-199a,miR-210,miR-214,miR-155,miR-146a) that may be highly expressed in endothelial progenitor exosomes and associated with angiogenesis were obtained for the following research.Conclusions Based on data analysis and literature searching,bioinformatics could screen out the target miRNAs for follow-up studies easily and reliably,it is worthy to be widely applied and popularized.

Objective: To analyze epidemiological characteristics of campus bullying among primary and middle school students in central China to explore its relation with mental health problems, and to provide a reference for the campus bullying prevention. Methods: Stratified cluster sampling method was used to select primary and middle school 10 581 students from Anyang, Nanyang and Xinxiang cities of Henan Province, Middle School Students Mental Health Scale and the Self designed Scale of Adolescent Bullying Behavior were used to analyze the relationship between mental health problems with campus bullying behavior. Results: The total report rate of bullying penetrator was 12.5% among students in the three cities. Among primary and middle school students with mental health problems such as hostility, interpersonal stress, academic pressure and emotional imbalance, the detection rate of bullying behavior was 24.2%, 20.3%, 19.4% and 20.1%, respectively. The results of multivariate analysis showed that hostility symptoms ( OR =3.78, 95% CI =1.71-8.32), interpersonal stress ( OR =3.50, 95% CI = 1.62 -7.57), academic pressure ( OR = 1.62 , 95% CI =1.21-2.16) and emotional imbalance ( OR =2.80, 95% CI =1.41-5.56) showed a significant impact on campus bullying ( P <0.05). Conclusion Mental health problems of primary and middle school students are closely related to the occurrence of bullying behavior. It is necessary to pay attention to the mental health education of bullies and intervene bullying behaviors from the source.

Objective To propose an integrated management scheme for perineal pain after vaginal delivery.Methods Literature review and Delphi inquiry were conducted to propose the perineal pain management scheme after vaginal delivery from November 2022 to April 2023.A total of 21 experts were consulted with 2 rounds of correspondence.Results Questionnaires collected from the two rounds of correspondence consultations were both at 100.0%.The expert authority coefficients for the two rounds were 0.930 and 0.935,respectively,with the expert coordination coefficients of the two rounds at 0.109(P<0.001)and 0.392(P<0.001),full mark rate 100%.A total of 3 primary items,15 secondary items and 40 tertiary items were summarised for the perineal pain management scheme after vaginal delivery in relation to prenatal prophylaxis,intrapartum protection and postnatal treatment.Conclusions The developed perineal pain management scheme after vaginal delivery is scientific and reliable.It provides a scientific reference for the prevention and treatment of perineal pain after vaginal delivery.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.