Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

ObjectiveTo explore the efficacy and predictive indicators of stellate ganglion block （SGB） as an adjunctive intervention for chronic subjective tinnitus and accumulate experience for the application of SGB in the clinical treatment of tinnitus. MethodsA retrospective review was conducted on the data of chronic subjective tinnitus patients who received SGB intervention， with unsatisfactory outcomes otherwise. Pure tone audiometry （PTA）， tinnitus loudness evaluation and Pittsburgh sleep quality index （PSQI） were used. The tinnitus handicap inventory （THI） scores were compared before and after SGB intervention. Correlation analysis and linear regression equations were employed to identify the potential indicators predicting the effectiveness of SGB intervention. Statistical analysis was performed by SPSS 24.0 software. ResultsBy April 2023， a total of 107 patients with chronic subjective tinnitus had undergone SGB intervention， including 67 male and 40 female， with a mean age of （45.32±11.40） years old and an average tinnitus history of （20.32±24.64） months ［16 （12~20）］. Only 7 patients （6.54%） quitted the intervention for personal reasons， which demonstrated good compliance with the intervention. No patients experienced adverse reactions such as infection at the injection site， hematoma， nerve injury， local anesthetic intoxication and so on， which revealed good safety. After SGB intervention， THI scores decreased to below 36 points in 77 patients and decrease by 10 points or more in 12 of the remaining patients， with a total effective rate of 89%. A paired sample t-test showed a significant difference in THI scores before and after SGB intervention （t=15.575， P<0.001）， indicating good improvement. Pearson correlation analysis suggested that pre-intervention THI scores and subjective tinnitus loudness were significantly positively correlated with the improvement level of THI scores （P<0.05）. Further stepwise linear regression analysis found that "pre-intervention THI scores" had statistical significance （P<0.001）， with a regression coefficient of 0.308， predicting a 17.4% improvement level in THI scores. ConclusionsDue to its good and safe short-term effects， SGB intervention can be used as a supplementary option for chronic subjective tinnitus when other interventions are not ideal， especially for patients with higher THI scores. However， further research is needed to clarify the long-term efficacy and underlying mechanisms， in order to establish a more solid theoretical basis for SGB intervention in the treatment of subjective tinnitus.

AIM:To determine the link between infliximab,adalimumab,vedolizumab,ustekinumab and risk of lymphoma in order to provide reference for the safety of clinical application.METHODS:Dis-proportionality analysis and Bayesian analysis were used in data mining to screen the suspected lym-phoma after the use of four biological agents based on the FAERS data from October 2012 to June 2023.The fatality and hospitalization rates of this four biological agents associated lymphoma were also investigated.RESULTS:Totally 705 cases of four biological agents associated lymphoma were collected.Four biological agents associated lymphoma appeared to influent more young pa-tients and middle-aged patients than elderly pa-tients(25.11％vs.22.41％vs.12.2％).There were slightly more male than females(42.84％vs.35.60％).Infliximab has the highest reporting odds ratio[ROR3.40,95％CI=(3.03,3.82)],proportional ratio[PRR3.38,95％CI=(3.01,3.79)],information component(IC1.14,IC-2SD=1.02)and empirical Bayes geometric mean(EBGM2.21,EBGM05=2.01).Significant difference in the fatality rate and hospi-talization rate among four biological agents were not found.CONCLUSION:Infliximab showed a strongest lymphoma association than the other three biological agents.Lymphoma risk should be vigilant when using infliximab.

Objective:To explore the attitude of kidney transplant (KT) recipients towards xenotransplantation and explore its related influencing factors to provide auxiliary references for the clinical research of xenotransplantation in China.Methods:The questionnaire data of "Attitude survey of KT recipients towards xenotransplantation" were collected from 194 KT recipients followed up at Organ Transplant Center of Affiliated Tongji Hospital. Nonparametric tests were utilized for comparing score differences and χ2 tests for comparing responses to specific questions. Variables with statistical significance in non-parametric test were included into multifactor linear regression analysis for exploring the influencing factors of recipients' attitudes towards xenotransplantation. Results:KT recipients had a higher score (75 points) on attitude scale of xenotransplantation. "Cognitive preference" dimension scored the highest (85 points); "Fear of risk" dimension scored lowest (50 points). The results of univariate analysis indicated that gender ( P=0.020), medical background ( P=0.006) and knowledge of clinical trial cases ( P<0.001) were the influencing factors of score of cognitive preference. Educational background ( P=0.029) was the factor affecting the score of "risk concern" dimension. Age ( P=0.028) and knowledge of clinical trial cases ( P=0.001) were the factors influencing the score of "psychosocial" dimension. Whether medical background ( P=0.018) and knowledge of clinical trial cases ( P=0.008) were the factors influencing the score of "efficacy expectation" dimension; Gender ( P=0.010), medical background ( P=0.018) and knowledge of clinical trial cases ( P=0.008) were the factors influencing total score. The results of multi-factor analysis revealed that gender ( B=-0.821, 95% CI: -1.419~0.223, P=0.007), medical background ( B=0.938, 95% CI: 0.097~1.779, P=0.029) and knowledge of clinical trials of xenotransplantation in the United States ( B=1.498, 95% CI: 0.887~2.110, P<0.001) was the influencing factor of cognitive preference. Educational background (B=-0.693, 95% CI: -1.353~-0.034, P=0.040) was the influencing factor of score on "risk concern" dimension. Knowledge of clinical trials of xenotransplantation in the United States ( B=1.075, 95% CI: 0.418~1.731, P=0.001) was an influencing factor of score on "social psychological" dimension; Knowledge of clinical trials of xenotransplantation in the United States ( B=0.710, 95% CI: 0.063~1.358, P=0.032) was an influencing factor of score on "efficacy expectation" dimension; Gender ( B=-2.259, 95% CI: -4.094~-0.423, P=0.016), medical background ( B=2.799, 95% CI: 0.219~5.378, P=0.034) and knowledge of clinical trials of xenotransplantation in the United States ( B=3.237, 95% CI: 1.360~5.114, P=0.001) were the influencing factors of total score. Conclusions:KT recipients have a higher awareness rate of xenotransplantation and a better acceptance of xenotransplantation in general. Those males with medical background and knowing clinical cases of xenotransplantation demonstrate a better attitude towards xenotransplantation. More concerned about the risk of infection, respondents expect heterologous pig kidneys to achieve the same long-term survival as allogeneic kidneys.

Objective:To investigate the association between plasma uric acid and hypertension and the gender difference in community-dwelling middle-aged and elderly population.Methods:A community-based cross-sectional study was conducted in Beijing Tongzhou Yongshun Community Health Service Center from June to December 2021, among residents aged 45 years or older selected by cluster sampling method. According to plasma uric acid (UA) level in quartiles, the subjects were divided into 4 groups; and stratified by gender, the subjects were further divided into subgroups. Multivariate logistic regression model was used to analyze the related factors of hypertension, and restricted cubic spline fitting logistic regression model was used to analyze the nonlinear association between uric acid and hypertension and the cut-off values of uric acid.Results:A total of 6 229 residents with the age of (63.2±7.3) years were enrolled in the study. In 1 874 male participants (30.1%), 946 participants (50.5%) had hypertension, and the uric acid level was 359 (309, 418)μmol/L; in 4 355 female participants (69.9%), 2 003 participants (46.0%) had hypertension, and the uric acid level was 306 (261, 359)μmol/L. Multivariate logistic regression analysis showed that after adjusting for factors that were statistically significant in univariate analyses or potentially clinically relevant (including age, body mass index, diabetes mellitus, coronary heart disease, cerebrovascular disease, albumin, estimated glomerular filtration rate, and cholesterol), uric acid was independently associated with hypertension ( P<0.001), for total participants the risk of hypertension in Q4 group was 1.33 times of that in Q1 group ( OR=1.33,95% CI 1.13-1.56, P=0.001); while for females the risk of hypertension in Q4 group was 1.38 times of that in Q1 group ( OR=1.38,95% CI 1.13-1.68, P=0.002), but no significant association was observed for males ( P>0.05). The results of restricted cubic spline fitting logistic regression analysis showed that there was a linear association between uric acid level and hypertension in the total population and males, and the risk of hypertension increased with uric acid level ( P<0.001 for the total population, P=0.016 for male). However, there was a non-linear association in females. When uric acid>307 μmol/L in females, the risk of hypertension increased significantly as the level of uric acid increased ( P<0.001). Conclusions:Uric acid level was independently associated with hypertension in the community-dwelling middle-aged and elderly population, and there was a gender difference in the correlation. The association was nonlinear in females and the cut-off value of uric acid in females was 307 μmol/L.

Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methy-lomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyl-transferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution pat-terns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolu-tion on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

Objective:To identify the risk factors of cognitive dysfunction in patients with atrial fibrillation and to establish a risk prediction model.Methods:The convenience sampling method was used to evaluate 260 patients with atrial fibrillation who were hospitalized in the Department of Cardiology of the Affiliated Hospital of Jining Medical College from January to December 2020. The cognitive function of the patients was evaluated with the Montreal Cognitive Function Assessment Scale (MoCA). Univariate analysis was used to screen the independent variables that had influence on the occurrence of cognitive dysfunction, and the statistically significant variables were included in the multivariate Logistic regression model. According to the regression coefficients of statistically significant variables, a line map was drawn to construct the risk prediction model of cognitive dysfunction in patients with atrial fibrillation.Results:There were 209 cases with cognitive impairment and 51 cases without cognitive impairment. Univariate analysis showed that sex, age, smoking history, drinking history, education level, free thyroxine, hemoglobin, D-dimer and BMI ( χ2 values were 4.08-18.83, t values were -6.04-2.94, Z=-2.76) were significantly different between the patients with or without cognitive dysfunction. The results of multivariate Logistic regression analysis showed that age ( OR values were 1.13), education level ( OR=0.01-0.05), quit smoking history ( OR=0.36), drinking history ( OR=0.35) and free thyroxine( OR=1.14) had significantly statistical significance ( P<0.05). The area under ROC curve (AUC) = 0.878 and AUC>0.8, this model had good clinical prediction ability. Conclusions:The construction of cognitive dysfunction risk prediction model for patients with atrial fibrillation can prevent or intervene high risk factors in advance, facilitate clinical use, and provide data support for the improvement of cognitive function in patients with atrial fibrillation.

Objective:To explore the distribution of pathogenic bacteria during perioperative period of kidney transplantation(KT)patients and examine drug resistance of major clinical pathogens to commonly used antibiotics to provide references for empirical medication of pathogenic bacteria infection after KT.Methods:From January 1, 2020 to June 30, 2021, 251 patients undergoing deceased donation KT on kidney transplant ward were selected.Clinical samples were collected and distribution and drug resistance of pathogenic bacteria examined for analyzing the incidence of possible donor-derived infections and predicting prognoses.Results:The detection rate of pathogens was 12.18%(367/3 014). A total of 225 non-repetitive strains were isolated.Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 48.89%(110/225), 43.11%(97/225)and 8.00%(18/225). The proportion of lavage fluid in all isolated bacteria was 49.78%(112/225). And Staphylococcus epidermidis and Klebsiella pneumoniae predominated.Drainage fluid accounted for 24.88%(56/225)and Pseudomonas putida and Staphylococcus haemolyticus predominated.Urine accounted for 18.67%(42/225)with a dominance of Enterococcus faecium; blood accounted for 6.22%(14/225)with a dominance of S. epidermidis.All detected pathogens showed varying degrees of resistance.The resistance rates of E. faecium to ampicillin, vancomycin and linezolid were 93.33%(28/30), 6.45%(2/31)and 38.71%(12/31). The resistance rates of K. pneumoniae and Acinetobacter baumannii to carbapenems were 71.43%(20/28)and 80.00%(12/15). The incidence of possible donor-derived infection was 3.59%(9/251)and there was no mortality.Conclusions:The detection rate of pathogenic bacteria is high in KT patients during perioperative period.There is a diverse distribution of isolates of different specimen types and all detected pathogens show varying degrees of drug resistance.Clinicians should regularly analyze the distribution characteristics and causes of drug-resistant bacteria.And antibiotics should be optimized according to the results of drug sensitivity.

Objective:To explore the efficacy and safety of a novel Tripterygium preparation (Kunxian Capsules)in kidney transplant recipients developing refractory proteinuria after transplantation.Methods:A total of 59 kidney transplant recipients received regular follow-ups from August 2018 to July 2021.Severity of proteinuria, kidney graft function and adverse effects were retrospectively recorded before and at Month 1/2/3/6 months after Kunxian treatment.They were divided into two groups of effective and void to explore the potential effect-related factors.Results:Six-month treatment was completed in 57 patients except for 2 cases of discontinued treatment due to severe adverse effects.A significant reduction in amount of proteinuria was observed at Month 1 [1.09(0.42, 2.59 g/24 h)vs 1.82(1, 2.7 g/24 h, P<0.01)]and the trend continued during subsequent follow-ups.Twenty-nine patients(50.9%)responded remarkably.Eighteen patients(31.6%)showed no response.The overall effective rate was 68.4%.Inter-group comparison revealed strong correlations between treatment efficacy and baseline serum creatinine levels, early initiation of treatment and symptom duration from onset to treatment.Kidney graft IgA nephropathy demonstrated the highest effective rate(11/13, 84.6%). Furthermore, elevated blood concentration of tacrolimus hinted at a potential drug interaction. Conclusions:Kunxian Capsules is efficacious and safe for renal transplant recipients developing moderate-severe proteinuria and not responding to traditional medications.Early initiation of treatment before graft function decline is recommended.Reducing tacrolimus dose cautiously in advance and monitoring adverse events are also essential.

Objective:To understand the knowledge and skills of professional technicians in prevention and control of parasitic diseases in Shandong Province, and to provide a basis for further capacity building.Methods:On October 12 and 13, 2017, five professional technicians from each of 17 prefectures and cities in Shandong Province participated in the "Shandong Province Parasitic Diseases Prevention and Control Job Skills Competition in 2017". This competition included theoretical knowledge examination (written test) and operation skill examination (operation test). The written test included basic knowledge of parasites life history, pathogen, diagnosis, epidemic and prevention; the operation test included blood smear making, Kato-Katz thick smear making, microscopic examination of Plasmodium and Helminth eggs. The competition results of the competitors were statistically analyzed, and the pass rate, correct answer rate and accuracy of microscopic examination were calculated. According to the report of malaria cases from 2010 to 2017, 17 prefectures and cities in Shandong Province were divided into malaria classⅠreport area (≥100 cases) and malaria classⅡreport area (< 100 cases), and the competition results of the two types of areas were compared. Results:A total of 85 competitors in Shandong Province participated in the competition, including 19 males (22.35%) and 66 females (77.65%); the age was (34.67±6.04) years old, the youngest was 25 years old, and the oldest was 51 years old. The scores of written test and operation test were (67.06±12.73) and (59.31±14.23) points, respectively, and the difference between them was statistically significant ( t=4.949, P < 0.01). The pass rate of written test was 74.12% (63/85); the correct answer rates of morphology, life history, pathogenicity, diagnosis, epidemic and prevention were 71.76% (366/510), 71.61% (913/1 275), 67.94% (462/680), 71.18% (847/1 190), 66.91% (455/680) and 65.76% (1 062/1 615), respectively, there was statistically significant difference in the correct answer rates of different knowledge points (χ 2=18.185, P < 0.01). The pass rate of operation test was 55.29% (47/85); among them, the pass rates of blood smear making, Kato-Katz thick smear making, microscopic examination of Plasmodium and Helminth eggs were 98.82% (84/85), 98.82% (84/85), 70.59% (60/85) and 31.76% (27/85), respectively. Four Plasmodium species were examined, and the overall accuracy of microscopic examination was 61.41% (261/425), there was no statistically significant difference in the accuracy of microscopic examination between different Plasmodium species (χ 2=4.791, P > 0.05). Nine common Helminth eggs were examined, and the overall accuracy of microscopic examination was 47.29% (402/850), there was statistically significant difference in the accuracy of microscopic examination between different Helminth eggs (χ 2=180.064, P < 0.01). The scores [(28.27±3.74) and (23.20±3.39) points, n=30] of microscopic examination of Plasmodium and Helminth eggs in the malaria classⅠ report area were higher than those in the malaria classⅡreport area [(22.40±5.81) and (18.25±3.41) points, n=55], and the differences were statistically significant ( t=2.217, 2.860, P < 0.05). Conclusions:For professional technicians, the mastery of theoretical knowledge in prevention and control of parasitic diseases is better than operation skills in Shandong Province. So the training and assessment of prevention and control skills of parasitic diseases should be strengthened in areas with weak abilities.