[Genotype-phenotype analysis of Fabry disease caused by GLA gene variation in a pedigree].

Objective: To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A. Methods: It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 µmol/(L·h) or elavated Lyso-GL-3 level>1.10 µg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed. Results: The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband's father had knee joint pain. The proband's elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband's fifth aunt with a GLA variant had decreased vision. Conclusions: High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

[Effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation].

Objective: To investigate the effect of dexmedetomidine on the intraoperative and early postoperative complications of patients undergoing orthotopic liver transplantation. Methods: This is a retrospective cohort study. The clinical data of 399 patients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Nanjing Medical University from January 2016 to September 2020 were retrospectively collected. There were 319 males and 80 females, aged (50.9±10.2) years (range: 10 to 73 years). These patients were divided into the control group (369 cases) and the dexmedetomidine group (30 cases) according to whether dexmedetomidine was continuously pumped intravenously during the operation until the operation ended. The 1∶2 propensity score matching was used to match the preoperative and intraoperative conditions of the two groups of patients, and the caliper width was 0.2. Outcome indicators included intraoperative postreperfusion syndrome, acute kidney injury and pulmonary complications within 7 days after surgery, length of hospital stay, time of stay in ICU, duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival and recurrence-free survival rate after surgery. The independent sample t test, χ2 test, Mann-Whitney U test or Fisher exact test was used to statistically analyze the data of the two groups of patients, respectively. Survival curves of overall survival and disease-free-survival were plotted by Kaplan-Meier method, and the survival rate and recurrence-free survival rate were compared by Log-rank test. Results: A total of 78 patients were included after propensity score matching, including 26 in the dexmedetomidine group and 52 in the control group. The incidence of acute kidney injury in the dexmedetomidine group within 7 days after surgery was 0 (0/26), significantly lower than that of the control group (21.2%,11/52)(corrected χ2=4.776, P=0.029). There were no significant differences in the incidence of intraoperative postreperfusion syndrome and pulmonary complications within 7 days after surgery, length of hospital stay, ICU time, the duration of assisted mechanical ventilation, rate of reintubation, 6-month and 1-year survival, and recurrence-free survival rate after surgery between the two groups (all P>0.05). Conclusion: Continuous infusion of dexmedetomidine via intravenous pump during operation may be beneficial in reducing the incidence of acute kidney injury within 7 days after orthotopic liver transplantation.

[Initial experience of transcatheter edge-to-edge repair guided by only transesophageal echocardiography in the treatment of tricuspid insufficiency].

Objective: To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE). Methods: Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure. Results: A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P<0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P<0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P>0.05). Conclusion: It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

Circ-Slain2 Alleviates Cartilage Degradation and Inflammation of TMJOA.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with the cessation of matrix anabolism and aggravation of inflammation, which results in severe pain and impaired joint function. However, the mechanisms are not well understood. Circular RNAs (circRNAs) are reported to have various biological functions and participate in the development, diagnosis, prognosis, and treatment of different diseases. This study aimed to investigate the roles and mechanisms of circ-slain2 in TMJOA. We first established TMJOA mouse models and found circ-slain2 was lowly expressed in the cartilage of TMJOA through sequencing data. We observed that circ-slain2 is predominantly localized in the cytoplasm and downregulated in mouse condylar chondrocytes (mCCs) treated with tumor necrosis factor α (TNFα) and interferon γ (IFNγ). Micro-computed tomography and histological examination showed that intra-articular injection of circ-slain2 overexpressing adeno-associated virus could alleviate cartilage catabolism and synovial inflammation to relieve TMJOA in vivo. In addition, elevated circ-slain2 also showed anticatabolic and anti-inflammatory effects on IFNγ- and TNFα-stimulated mouse condylar chondrocytes (mCCs). Functional enrichment analysis indicated that protein processing in endoplasmic reticulum (ER) was associated with TMJOA, and further functional experiments confirmed that circ-slain2 could suppress ER stress in OA mCCs. RNA binding protein immunoprecipitation assay revealed an overt interaction between activating transcription factor 6 (ATF6) and circ-slain2. Inhibition of the expression of both ATF6 and circ-slain2 resulted in dilation of the ER and enhanced the expression of ER stress markers, whose ER stress level was higher than inhibition of ATF6 but lower than knockdown of circ-slain2 expression. Collectively, our research demonstrated that circ-slain2 could regulate ATF6 to relieve ER stress, reducing temporomandibular joint cartilage degradation and synovial inflammation. These findings provide prospects for developing novel osteoarthritis therapies based on circ-slain2 by focusing on reducing the inflammation of synovium and the imbalance between matrix synthesis and degradation.

[Epidemiological characteristics and risk factors of sepsis development and death in patients with extremely severe burns].

Objective: To explore the epidemiological characteristics and risk factors of sepsis development and death in patients with extremely severe burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, 135 patients with extremely severe burns who met the inclusion criteria were admitted to the Department of Burn and Wound Repair of the Second Affiliated Hospital of Zhejiang University School of Medicine, including 100 males and 35 females, aged 18-84 years. The incidence and diagnosis time of sepsis, the rate of positive microbial culture of blood samples (hereinafter referred to as positive blood culture), and the mortality rate of all patients, as well as the incidence of sepsis and the pathogen of infection in patients with positive blood culture were recorded (statistically analyzed with chi-square test or Fisher's exact probability test). According to the occurrence of sepsis, all patients were divided into sepsis group (58 cases) and non-sepsis group (77 cases), and the gender, age, body mass index, history of hypertension, history of diabetes, combination of inhalation injury, burn site, burn type, total burn area, and combined injury of patients were compared between the two groups. According to the outcome, all patients were divided into death group (37 cases) and survival group (98 cases), and the aforementioned data grouped according to sepsis as well as the stability of shock period and the combination of sepsis of patients were compared between the two groups. The aforementioned data between two groups were statistically analyzed with univariate analysis of independent sample t test, Wilcoxon rank-sum test, Mann-Whitney U test, chi-square test, or Fisher's exact probability test. Factors with P<0.1 were selected for multivariate logistic regression analysis to screen independent risk factors of sepsis and death in patients with extremely severe burns. Results: Among all patients, the incidence of sepsis was 42.96% (58/135), the diagnosis time of sepsis was 14 (7, 24) d after injury, the positive blood culture rate was 62.22% (84/135), and the mortality rate was 27.41% (37/135). The incidence of sepsis of patients with positive blood culture was 69.05% (58/84). The top 5 pathogenic bacteria in the detection rate of septic patients with positive blood culture were Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterobacter cloacae, ranking from high to low, and the proportion of Acinetobacter baumannii infected was significantly higher than that of non-septic patients with positive blood culture (χ2=7.49, P<0.05). Compared with those in non-sepsis group, the proportion of combination of inhalation injury, the proportion of perineal burns, and the total burn area of patients in sepsis group increased significantly (with χ2 values of 11.08 and 17.47, respectively, Z=5.68, P<0.05), while the other indicators did not change significantly (P>0.05). Multivariate logistic regression analysis showed that combination of inhalation injury, total burn area ≥80% total body surface area (TBSA), and perineal burns were independent risk factors for patients with extremely severe burns developing sepsis (with odds ratios of 3.15, 7.24, and 3.24, respectively, with 95% confidence intervals of 1.07 to 9.29, 1.79 to 29.34, and 1.21 to 8.68, respectively, P<0.05). Compared with those in survival group, the proportion of combination of inhalation injury, the proportion of perineal burns, and the proportion of combination of sepsis (with χ2 values of 6.55, 11.64, and 22.26, respectively, P values all <0.05), total burn area (Z=4.25, P<0.05), and proportion of instability of shock period (P<0.05) of patients in death group all increased significantly, while the other indicators did not change significantly (P>0.05). Multivariate logistic regression analysis showed that the instability of shock period and combination of sepsis were independent risk factors for death of patients with extremely severe burns (with odds ratios of 4.87 and 3.45, respectively, with 95% confidence intervals of 1.21 to 19.57 and 1.28 to 9.33, respectively, P<0.05). Conclusions: Patients with extremely severe burns have a high incidence of sepsis and a high mortality rate. The peak period of sepsis onset is 2 weeks after injury, with Acinetobacter baumannii as the most prominent infectious pathogen. Combination of inhalation injury, total burn area ≥80% TBSA, and perineal burns are independent risk factors for extremely severe burn patients complicated with sepsis, and combination of sepsis and instability of shock period are independent risk factors for death of patients with extremely severe burns.

Global, regional, and national time trends in myocarditis-related mortality, 1990-2019: An age-period-cohort analysis.

OBJECTIVE: The aim of this study was to analyze the tendency of myocarditis mortality in 204 countries and areas during the last three decades and its connection with age, epoch, and birth cohort. MATERIALS AND METHODS: The Global Burden of Disease 2019 Study acquired a cause-specific myocarditis mortality estimate. The net drift, as well as the influence caused by age, period, and birth cohort, were evaluated by the age-period-cohort model. Additionally, we analyzed the tendency in research intensity and international collaboration across countries using 3,983 myocarditis-related publications from four periods during 1990-2019. RESULTS: During the last three decades, 101 of 204 countries and areas experienced an increase (net drifts ≥0.0%) or stagnant declines (≥-0.5%) in the death rate. In particular, increasing death rate was generally discovered in most countries whose Socio-demographic indexes (SDIs) are high and middle-high, such as the United States [net drift=2.11% (95% CI 1.71-2.51)] and Italy [2.65% (1.24-4.08)]. Countries with a higher number of deaths were more active in this field of study, such as the United States (237 publications), China (120), and Italy (73). The United States and Italy, whose total link strengths were 209 and 135, respectively, were more active in international collaborative studies. CONCLUSIONS: Despite the global decrease in myocarditis death rate during the last three decades, negative period and cohort effects and elevated mortality were discovered in numerous countries, especially in those whose SDIs were high, and the age distribution of deaths shifted from adolescent to middle-aged and older populations. We also observed a decline in myocarditis research in some countries with increased mortality.

[Prevalence of syphilis in HIV-infected patients with transmission risk and influencing factors in Zhejiang Province].

Objective: To investigate the prevalence of syphilis in HIV-infected patients with transmission risk and influencing factors in Zhejiang Province. Method: The information about the HIV-infected patients, who were alive, had been diagnosed with HIV for >1 year, had received no antiviral treatment or had HIV viral load ≥50 copies/ml, and were aged ≥15 years, reported in Zhejiang as of December 31, 2018 were collected from China Information System for Disease Control and Prevention. The information included general demographic characteristics, sexual behavior characteristics and antiretroviral therapy and syphilis serological test results. The prevalence of syphilis and the influencing factors were analyzed by logistic regression model. The SPSS 19.0 software was used for statistical analysis. Results: A total of 2 275 HIV-infected patients were at risk of HIV transmission, and 75.5% (1 717/2 275) of them were tested for syphilis, the prevalence rate of syphilis was 8.7% (150/1 717). Among the HIV-infected patients with syphilis, 11.3% (17/150) received no antiviral treatment, 38.7% (58/150) had viral load of 50-999 copies/ml and 50.0% (75/150) had ≥1 000 copies/ml. Multivariate logistic regression analysis showed that being men (aOR=2.04, 95%CI:1.06-3.96), homosexual transmission (aOR=1.53, 95%CI:1.04-2.27), history of sexually transmitted diseases (STDs) before HIV diagnosis (aOR=1.98, 95%CI:1.35-2.92) and HIV viral load ≥1 000 copies/ml (aOR=1.90, 95%CI:1.09-3.30) were the risk factors for syphilis. Marriage (aOR=0.47, 95%CI: 0.29-0.76) was a protective factor for syphilis. Conclusions: The prevalence of syphilis was high in HIV-infected patients with transmission risk in Zhejiang. It is urgent to carry out classified management and targeted intervention in HIV-infected patients, explore multi-disease prevention and treatment mechanism, strengthen syphilis screening and treatment in HIV-infected patients to reduce the transmission of HIV and syphilis.

[A clustered epidemic investigation of non-marital non-commercial heterosexual contact of HIV in Zhejiang Province].

Objective: To identify the transmission relationship between HIV infection cases the non-marital non-commercial heterosexual contact in Zhejiang Province. Methods: When HIV positive was informed during January 2020 to January 2022, the staff conducted an epidemiological investigation to collect cases information on sociodemographic characteristics, mobility information, past HIV testing history, high-risk sexual behaviors, sexual partners, and etcetera. At the same time, 6-8 ml of blood from the new diagnosis of people infected with HIV before antiviral treatment was collected to separate the bleeding plasma. pol gene was amplified by nucleic acid extraction and PCR, sequenced by Sequencer 5.0 software, and Cytoscape 3.6.0 software was used to draw HIV molecular transmission network. Results: From January 2020 to January 2022, 88 HIV infected individuals were found in Pujiang County, of which 74 were transmitted through heterosexual transmission, of which 31 were infected through non-marital non-commercial heterosexual contact. Preliminary case studies have found that three female cases have engaged in unprotected non-marital non-commercial heterosexual contact with one male case. Among the 4 infected individuals, 2 of their spouses tested positive for HIV antibodies. Molecular transmission network monitoring was carried out on 65 newly diagnosed cases of heterosexual transmission with acquired sequences, forming 9 transmission clusters. The largest cluster contained 10 cases. A total of 11 HIV-infected individuals were involved in this HIV cluster epidemic. They were 3 males and 8 females, all over 50 years old and were farmers or rural housewives. They were traced to 7 sexual partners (6 negatives of HIV, 1 undetected). Among the 18 respondents' sexual social network relationships, there were 6 couples, 8 permanent partners, and 3 temporary partners. Among 11 HIV infected individuals, there were 9 cases of non-marital non-commercial heterosexual transmission and 2 cases of intramarital transmission. The epidemiological association between 7 non-married non-commercial heterosexual partners and case 2 (56-year-old male farmer), 3 cases confirmed by epidemiological investigation and molecular transmission cluster results, 3 cases confirmed by molecular transmission cluster and epidemiological investigation results, and 1 case confirmed by epidemiological investigation results. Conclusions: The transmission mode of this cluster epidemic was to spread HIV through heterosexual sex with a male case as the core, then cause the transmission within marriage and between fixed sexual partners. The combination of epidemiological investigation and molecular transmission network traceability survey supports the conclusion of this study.

Effect of Scarf and Chevron combined with Akin on postoperative balance in patients with moderate to severe foot bunion.

OBJECTIVE: The aim of this study was to analyze the effect of Scarf and Chevron combined with Akin on a postoperative balance of patients with moderate to severe foot bunion. PATIENTS AND METHODS: One hundred (100 feet) patients with moderate to severe bunion cysts treated at our hospital from January 2019 to January 2022 were retrospectively selected as subjects and divided into 2 groups according to their surgical procedure. The control group received Scarf combined with Akin, and the study group received Chevron combined with Akin. Oxidative stress mediators [late oxidized protein product (AOPP), lipid peroxide (LPO)], inflammatory factors [interleukin-1ß (IL-1ß), procalcitonin (PCT)], Hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal joint angle (DMAA) Angle, ankle-hind foot American Orthotic Foot and Ankle Association (AOFAS) score, pain visual analog scale (VAS) score and balance Berg Balance Scale (BBS) score were compared between the two groups before and after surgery. The effectiveness and safety of the operation were compared. RESULTS: The levels of AOPP and LPO in the study group decreased most significantly, t=1.081 and 10.850, p=0.001; the levels of IL-1ß and PCT in the study group increased most significantly, t=16.970 and 12.260, p=0.001; the indexes of HVA, IMA, and DMAA in the study group increased significantly, t=11.890, 11.550, and 12.670, p=0.001; the AOFAS and BBS scores in the study group increased significantly, while the VAS score in the study group decreased significantly, t=14.760, 13.580, 5.994, p=0.001; the total effective rate of treatment in the study group was the highest, χ²=6.960, p=0.00; the total incidence of complications in the study group was the lowest, χ²=1.834, p=0.175. CONCLUSIONS: Chevron combined with Akin is more effective than Scarf combined with Akin in treating moderate to severe foot bunion, the former is more minimally invasive and has a better effect in promoting postoperative balance recovery.

[Efficacy and safety of new systemic therapies in moderate-to-severe atopic dermatitis in the elderly: meta-analysis].

Objective: To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis. Methods: The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio (OR) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed. Results: A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients (OR=0.79, 95%CI:0.58-1.07, P=0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients (OR=0.79, 95%CI:0.55-1.14, P=0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients (OR=1.07, 95%CI:0.65-1.77, P=0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related. Conclusion: The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

[Comparison on the efficacy of Chinese-made novel-designed mechanical-locked and elastic self-locked transcatheter edge-to-edge repair system in the treatment of patients with functional mitral regurgitation].

Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P>0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) (P>0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.

[Enlightening from optimizing post-authorization safety monitoring system of SARS-CoV-2 vaccines in major economies worldwide].

Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.

[Puerarin alleviates lipopolysaccharide-induced acute kidney injury in mice by modulating the SIRT1/NF-κB pathway].

OBJECTIVE: To investigate the role of the SIRT1/NF-κB pathway in mediating the effect of puerarin against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). METHODS: Fifteen BALB/C mice were randomized into control group, LPS group and puerarin treatment group, and in the latter two groups, the mice were given an intraperitoneal injection of LPS (5 mg/kg), followed by daily injection of normal saline for 3 days or injection of puerarin (25 mg/kg) given 1 h later and then on a daily basis for 3 days. On day 5 after modeling, the kidney tissues were taken for histological observation and detection of cell apoptosis. The renal function indexes including urea nitrogen (BUN), serum creatinine (Scr) and kidney injury molecule 1 (KIM-1) and the levels of tumor necrosis factor (TNF-α) and interleukin 1ß (IL-1ß) were measured, and the expressions of SIRT1 and NF-κB-p65(acetyl K310) in the renal tissues were detected. RESULTS: Intraperitoneal injection of LPS caused obvious glomerular capillary dilatation, hyperemia, renal interstitial edema, and renal tubular epithelial cell swelling and deformation in the mice. The mouse models of LPS-induced AKI also showed significantly increased renal tubular injury score and renal cell apoptosis (P < 0.01) with increased serum levels of BUN, Scr, KIM-1, TNF-α and IL-1ß (P < 0.01), enhanced renal expressions of TNF-α, IL-1ß and NF-κB p65(acetyl K310) (P < 0.01) and lowered renal expression of SIRT1 (P < 0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score (P < 0.01) and renal cell apoptosis rate (P < 0.01), and decreased serum levels of BUN, Scr, KIM, TNF-α and IL-1ß (P < 0.01). Puerarin treatment significantly reduced TNF-α, IL-1ß and NF-κB p65 (acetyl K310) expression in the renal tissue (P < 0.05) and increased SIRT1 expression by 17% (P < 0.05) in the mouse models. CONCLUSION: Puerarin can effectively alleviate LPS-induced AKI in mice possibly by modulating the SIRT1/NF-κB signaling pathway.

[Investigation on health status of workers exposed to glyphosate].

Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively (P<0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine (r(s)=0.804, 0.238, P<0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine (r(s)=0.549, P<0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different (P<0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group (P<0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.

[Long-term outcome of transcatheter repair of paravalvular leak post surgical mitral valve replacement].

Objective: To explore the long-term clinical efficacy of transcatheter repair of mitral paravalvular leak (PVL) post surgical mitral valve replacement. Methods: This study is a retrospective study. Patients who completed transcatheter repair of paravalvular leak after surgical mitral valve replacement at Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine from March 2010 to December 2018 were included. Technical success was defined as the occluder being stably implanted in the paravalvular leak site without affecting the function of the mitral valve and surrounding tissues; and there were no intervention-related complications, such as new hemolysis or aggravated hemolysis, and echocardiography confirmed mitral paravalvular regurgitation reduced by more than 1 grade. Patients were followed up at 30 days, 1, and 3 years after the intervention. The main endpoints were all-cause death and re-surgery due to interventional failure or serious complications. The occurrence of occluder-mediated hemolysis and chronic renal insufficiency was recorded, and patients were monitored with echocardiography during follow up. Results: A total of 75 patients were included, aged (54.3±22.9) years old, and 38 patients were males. All patients had decreased cardiac function and/or hemolysis before intervention. Procedural success was achieved in 54 patients (72.0%). Incidence of device-mediated hemolysis was 18.7% (14/75). During the follow-up period, all-cause death occurred in 7 patients (9.3%), and 3 were cardiac deaths.The 3-year event-free survival rate was 81.3% (61/75). The need for cardiac surgery was 9.3% (7/75): 3 cases due to severe device-mediated hemolysis, 2 cases due to prosthetic valve failure and 2 cases due to moderate to severe residual regurgitation. The echocardiography follow-up results showed that the position of the occluder was stable, there was no impact on the artificial valve function and surrounding structures, and the residual regurgitation was stable without progressive increase in event-free patients. Compared with pre-intervention, the left ventricular end systolic diameter ((33.9±7.4)mm vs. (38.3±8.9) mm, P=0.036), end diastolic diameter ((53.7±8.3) mm vs. (58.4±9.1) mm, P=0.045) and left atrial diameter (59.3 (44.5, 90.7) mm vs. 64.3 (44.8, 96.6) mm, P=0.049) were significantly reduced, pulmonary artery systolic pressure was also significantly decreased ((36.5±15.8) mmHg vs. (46.3±14.9) mmHg, P=0.022, 1 mmHg=0.133 kPa). There was no significant difference between 3 years and 1 year after transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement (all P>0.05). Conclusion: Transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement is an effective treatment option in selective patients.

Two Schiff base iodide compounds as iodide ion conductors showing high conductivity.

Here, we reported the crystal structures, dielectric and conducting properties of two Schiff base iodide compounds [m-BrBz-1-APy]I3 (1) and [o-FBz-1-APy]I3 (2). The Schiff base cations build irregular channel frameworks, and the polyiodide anions are located in the channel. The impedance spectra demonstrated that the two compounds show intrinsic iodide ion conductance with higher conductivity of 1.03(4) × 10-4 S cm-1 at 343 K for 1 and 4.94(3) × 10-3 S cm-1 at 353 K for 2. The dielectric modulus analysis further confirmed that the conductance contributed to the migration of iodide ions.