Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

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.

Study of the effect of PU-H71 on increasing radiosensitivity of cervical cancer cells / 中华放射肿瘤学杂志

Objective:To investigate the effect of heat shock protein 90 (Hsp90) inhibitor PU-H71 combined with X-ray on radioresistant human cervical cancer cells.Methods:The expression levels of Hsp90 gene between cervical cancer tissues and adjacent tissues were analyzed by bioinformatics. Radioresistant cervical cancer cell lines HeLa RR and SiHa RR were obtained by fractional irradiations (2 Gy per fraction, 30 fractions). The cell lines were divided into the control group (treated with dimethyl sulfoxide), irradiation alone group, PU-H71 group (treated with 0.5 μmol/L PU-H71), and PU-H71+irradiation group (irradiation at 24 h after treatment with 0.5 μmol/L PU-H71). Cell survival was detected by clonal formation assay. Immunofluorescence assay was used to detect γH2AX foci at 1, 6, and 24 h after cell treatment. The expression level of Rad51 protein at 1, 2, 6, 12, and 24 h after cell treatment was detected using Western blot. The expression level of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) was measured at 2 h after cell treatment. Cell apoptosis at 48 h after cell treatment was assessed by flow cytometry. Results:PU-H71 enhanced the sensitivity of radioresistant cervical cancer cells to X-ray. Compared with the irradiation alone group, the radiation sensitization ratios (SER) of HeLa RR and SiHa RR cells at 10% survival were 1.36 and 1.27, and the apoptosis rates were increased by approximately 72.1% and 63.1% in the PU-H71+irradiation group, respectively. PU-H71 delayed the duration of γH2AX foci induced by X-ray, inhibited the phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), thus preventing non-homologous end joining (NHEJ) repair and delaying homologous recombination repair.Conclusion:PU-H71 increases the radiosensitivity of radioresistant cervical cancer cells by inhibiting the repair pathway of DNA double-strand break, which is expected to be a radiosensitizer to enhance the efficacy of radiotherapy for cervical cancer.

Analysis of related factors of emotional and behavioral abnormalities in children with overactivity of bladder / 现代泌尿外科杂志

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma / 医学前沿

Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.

GID complex regulates the differentiation of neural stem cells by destabilizing TET2 / 医学前沿

Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26+/- mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.

Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

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.

Effects of Ginkgo biloba on arsenic-induced lung injury in rats based on HMGB1/RAGE pathway / 中华地方病学杂志

Objective:To investigate the antagonistic and therapeutic effects of Ginkgo biloba on arsenic-induced lung injury in rats and its mechanism.Methods:A total of 42 healthy clean grade Wistar rats, half male and half female, weighing 120 - 130 g, were randomly divided into 7 groups with 6 rats in each group. Two intervention models of Ginkgo biloba antagonism and treatment were established, respectively. The specific treatments were as follows: (1) Experimental study on the antagonism of Ginkgo biloba (4 groups): the control A group was given deionized water; the Ginkgo biloba control (GBE) group was given Ginkgo biloba solution (50 mg·kg -1·bw); the arsenic-treated (As) group was given sodium arsenite solution (10 mg·kg -1·bw); the Ginkgo biloba antagonistic (As + GBE) group was treated with sodium arsenite solution (10 mg·kg -1·bw) and Ginkgo biloba solution (50 mg·kg -1·bw), and the above administration was by gavage for 6 days/week, for 4 months. (2) Experimental study on the treatment of Ginkgo biloba (3 groups): the control B group was given deionized water for 5.5 months; in the arsenism natural recovery (recovery) group, sodium arsenite solution (10 mg·kg -1·bw) was administered by gavage for 4.0 months and deionized water for 1.5 months; the Ginkgo biloba treatment (treatment) group was given sodium arsenite solution (10 mg·kg -1·bw) by gavage for 4.0 months and Ginkgo biloba solution (50 mg·kg -1·bw) for 1.5 months, and the above administration was for 6 days/week. Masson staining was used to evaluate collagen fiber deposition in lung tissue. Western blotting was used to detect the expression level of related proteins in lung tissue homogenates, including inflammatory cytokines matrix metalloproteinase-9 (MMP-9), interleukin (IL)-1β, IL-18; high mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) of the HMGB1/RAGE pathway; phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K), protein kinase B (AKT), phosphorylated AKT (p-AKT) of the PI3K/AKT pathway; transforming growth factor (TGF)-β1, SMAD2, p-SMAD2, SMAD3, p-SMAD3 and SMAD4 of the TGF-β1/SMAD pathway. Results:(1) Antagonistic effect of Ginkgo biloba: compared with the control A group, there was no significant change in protein expression and collagen fiber deposition in the lung tissue of GBE group ( P > 0.05); the levels of MMP-9, IL-1β and IL-18 protein expression and collagen fiber deposition in the lung tissue of As group were significantly increased ( P < 0.05); and the levels of HMGB1, RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, p-SMAD3 and SMAD4 protein expression were significantly increased ( P < 0.05). Compared with As group, the levels of MMP-9, IL-1β and IL-18 protein expression and collagen fiber deposition were significantly decreased in As + GBE group ( P < 0.05); and levels of HMGB1, RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, and p-SMAD3 protein expression were significantly decreased ( P < 0.05). (2) Therapeutic effect of Ginkgo biloba: compared with control B group, the levels of MMP-9, IL-1β, IL-18 protein expression and collagen fiber deposition were significantly increased in recovery group ( P < 0.05); and the levels of HMGB1, RAGE, PI3K, p-AKT, TGF-β1, p-SMAD2, p-SMAD3 and SMAD4 protein expression were significantly increased ( P < 0.05). Compared with recovery group, the levels of MMP-9, IL-1β, IL-18, HMGB1, RAGE, PI3K and p-AKT protein expression were significantly decreased in treatment group ( P < 0.05); and there was no significant change in collagen fiber deposition and TGF-β1, p-SMAD2, p-SMAD3 and SMAD4 protein expression levels in lung tissue ( P > 0.05). In both experiments, there was no significant difference in the protein expression levels of AKT, SMAD2 and SMAD3 between the groups ( P > 0.05). Conclusion:Ginkgo biloba intervention has ameliorated inflammatory injury and collagen fiber deposition in lung tissue of arsenic-treated rats possibly by inhibiting the expression levels of HMGB1/RAGE pathway-related proteins.

Role of LXRα/SREBP-1c in arsenic induced lipid metabolism disorders in rats / 中华地方病学杂志

Objective:To investigate the role of liver X-activated receptor (LXRα)/sterol-regulatory element binding protein (SREBP-1c) in arsenic induced lipid metabolism disorders in rats, and to provide a basis for study the mechanism of arsenic induced lipid metabolism disorders.Methods:Twenty-four healthy clean grade Wistar rats, were randomly divided into 4 groups according to body weight (80 - 100 g) by the random number table method, with 6 rats in each group, half male and half female. Rats in control group were given deionized water by gavage. The low, medium and high arsenic dose groups were given 2.5, 5.0 and 10.0 mg·kg -1·d -1 sodium arsenite solution by gavage, respectively. They were exposed to arsenic for 6 days a week for 4 months. At the end of the experiment, blood and liver samples of rats in each group were collected. The hepatic arsenic content was determined by inductively coupled plasma mass spectrometry (ICP-MS); the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by automatic biochemical analyzer. The mRNA expression levels of LXRα and SREBP-1c in liver tissues were determined by real-time PCR; the protein expression levels of LXRα, SREBP-1c, acetyl CoA carboxylase (ACC) and phospho-ACC (pACC) in liver tissues were determined by Western blotting. Results:The hepatic arsenic contents of rats in low, medium and high arsenic dose groups were (61.04 ± 4.98), (62.66 ± 6.71) and (87.86 ± 13.89) μg/g, respectively, which were higher than that in control group [(2.43 ± 0.63) μg/g, P < 0.05], and the hepatic arsenic content of rats in high arsenic dose group was higher than those in low and medium arsenic dose groups ( P < 0.05). The serum TG levels of rats in low, medium and high arsenic dose groups were (0.90 ± 0.17), (1.28 ± 0.24) and (1.82 ± 0.18) mmol/L, respectively, which were higher than that in control group [(0.50 ± 0.12) mmol/L, P < 0.05]; the serum LDL-C levels of rats in low, medium and high arsenic dose groups were (0.54 ± 0.04), (0.63 ± 0.07) and (0.69 ± 0.08) mmol/L, respectively, which were higher than that in control group [(0.27 ± 0.05) mmol/L, P < 0.05]; the serum TC levels of rats in medium and high arsenic dose groups were (1.88 ± 0.23) and (2.10 ± 0.10) mmol/L, respectively, which were higher than that in control group [(1.51 ± 0.14) mmol/L, P < 0.05]; the serum HDL-C levels of rats in medium and high arsenic dose groups were (0.84 ± 0.11) and (0.71 ± 0.14) mmol/L, respectively, which were lower than that in control group [(1.15 ± 0.08) mmol/L, P < 0.05]; and the serum levels of TG and LDL-C in medium and high arsenic dose groups were higher than those in low arsenic dose group ( P < 0.05), and the serum level of TG in high arsenic dose group was higher than that in medium arsenic dose group ( P < 0.05). The mRNA expression level of hepatic LXRα of rats in high arsenic dose group was higher than those in control group and low arsenic dose group ( P < 0.05); there was no significant difference in mRNA expression levels of hepatic SREBP-1c of rats between low, medium and high arsenic dose groups and control group ( P > 0.05). The protein expression levels of hepatic LXRα of rats in medium and high arsenic dose groups were higher than that in control group ( P < 0.05), and high arsenic dose group was higher than low arsenic dose group ( P < 0.05); the protein expression levels of hepatic SREBP-1c and ACC of rats in high arsenic dose group were higher than that in control group ( P < 0.05). There was a positive correlation between hepatic arsenic content in arsenic-exposed rats and the serum levels of TG, TC, LDL-C, the mRNA expression level of hepatic LXRα, the protein expression levels of hepatic LXRα, SREBP-1c and ACC ( r = 0.84, 0.62, 0.89, 0.55, 0.54, 0.64, 0.70, P < 0.05), and the serum level of HDL-C was negatively correlated with the hepatic arsenic content in arsenic-exposed rats ( r = - 0.75, P < 0.001). Conclusion:Sodium arsenite can increase the serum levels of TG, TC and LDL-C, decrease the serum level of HDL-C and increase the protein expression levels of LXRα and SREBP-1c in liver tissues, suggesting that arsenic induced lipid metabolism disorders in rats may be related to the upstream regulation mechanism of LXRα/SREBP-1c.

Focus on multimorbidity in arsenicosis, deepen study and prevention strategies in new era / 中华地方病学杂志

With the aging and lifestyle changes of the residents in arsenicosis area, the disease spectrum has also undergone significant changes, and coexistence of chronic diseases in arsenicosis has become a primary threat to residents health. In the future, basic study from a new perspective should be deepen, to explore new pathways for integrated prevention and treatment of chronic diseases of arsenicosis, and build a whole management model of "screening, management, prevention, treatment and study" to guarantee the prevention and treatment of chronic diseases of arsenicosis.

Evidence-based practice of the puncture management in hemodialysis patients with difficult new arteriovenous fistula / 中国实用护理杂志

Objective:To explore the puncture management in hemodialysis patients with difficult new arteriovenous fistula based on the finest evidence-based best practice evidence and evaluate the clinical effects.Methods:A team was formed, according to theoretical framework basing on the evidence of continuous quality improvement model, the best evidence-based interventions were obtained by adopting evidence-based practice. Formulated review indicators, evaluated obstacles and promoting factors in the process of practice, and took corresponding action strategies. From February 2020 to June 2020, 30 patients admitted to the dialysis center of Sir Run Run Shaw Hospital of Zhejiang University were recruited in the baseline review group by convenience sampling method. From September 2020 to January 2021, 30 patients from September 2020 to January 2021 were recruited in the after-effect evaluation group. The baseline review group adopted the original difficult new arteriovenous fistula puncture management scheme, and the after-effect evaluation group adopted the difficult autologous new internal fistula puncture management scheme based on the best evidence. The success rate of one puncture of fistula, the incidence rate of hematoma during puncture and dialysis, the incidence rate of discontinuation of treatment and the compliance with examination indexes were compared in the patients before and after applying for the evidences.Results:Compared with the baseline review group, the success rate of one-time puncture of internal fistula in the aftereffect evaluation group increased from 36.7% (11/30) to 73.3% (22/30), the incidence rate of hematoma during puncture and dialysis were decreased from 33.3%(10/30) to 6.67%(2/30) and 40%(12/30) to 0, the incidence rate of discontinuation of treatment were decreased from 40%(12/30) to3.33% (1/30), the difference was statistically significant ( χ2 values were 6.67-11.88, P<0.05). The implementation rate of review indexes in the aftereffect evaluation group was higher than that in the baseline review group, and the difference was statistically significant ( P<0.05). Conclusions:Evidence-based practice can improve the success rate of difficult new arteriovenous fistula, and reduce the incidence of arteriovenous fistula hematoma, reduce treatment interruption, and better maintain the lifeline of patients.

Research progress on Nrf2 in diabetic cardiomyopathy and intervention of traditional Chinese medicine / 中国临床药理学与治疗学

As a cardiovascular complication of diabetes, diabetic cardiomyopathy seriously affects the prognosis of patients with diabetes. The incidence and mortality of diabetic cardiomyopathy increase, and has emerged as a research hotspot in current years. The pathogenesis of diabetic cardiomyopathy is complex, involving a range of signaling pathways in its incidence and development. Nuclear factor NF-E2-related factor 2 (Nrf2), as a powerful antioxidant gene, enhances the capacity of the myocardium to withstand oxidative stress via interplay with different signaling elements and exerts anti-inflammatory response, anti-myocardial fibrosis, and anti-apoptosis effects. Researches have shown that certain ingredients of traditional Chinese medicine can alleviate the myocardial injury by affecting the relationship of Nrf2 with other signaling factors via enhancing the expression of Nrf2. Here we review the role of Nrf2 and therapy of traditional Chinese medicine in diabetic cardiomyopathy in hope of providing referential idea for the treatment of diabetic cardiomyopathy. A reference for the prevention and therapy of diabetic cardiomyopathy.

Residential elevation and its effects on hypertension incidence among older adults living at low altitudes: a prospective cohort study

BACKGROUND@#Research on the relationship between residential altitude and hypertension incidence has been inconclusive. Evidence at low altitudes (i.e., <1,500 m) is scarce, let alone in older adults, a population segment with the highest hypertension prevalence. Thus, the objective of this study is to determine whether hypertension risk may be affected by altitude in older adults living at low altitudes.@*METHODS@#This prospective cohort study collected data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We selected 6,548 older adults (≥65 years) without hypertension at baseline (2008) and assessed events by the follow-up surveys done in 2011, 2014, and 2018 waves. The mean altitude of 613 residential units (county or district) in which the participants resided was extracted from the Digital Elevation Model (DEM) of the National Aeronautics and Space Administration (NASA) and was accurate to within 30 m. The Cox regression model with penalized splines examined the linear or nonlinear link between altitude and hypertension. A random-effects Cox regression model was used to explore the linear association between altitude and hypertension.@*RESULTS@#The overall rate of incident hypertension was 8.6 per 100-person years. The median altitude was 130.0 m (interquartile range [IQR] = 315.5 m). We observed that the exposure-response association between altitude and hypertension incidence was not linear. The shape of the exposure-response curve showed that three change points existed. Hypertension risk increased from the lowest to the first change point (247.1 m) and slightly fluctuated until the last change point (633.9 m). The risk decreased above the last change point. According to the categories stratified by the change points, altitude was only significantly associated with hypertension risk (hazard ratio [HR] = 1.003; 95% confidence interval [CI] = 1.002-1.005) under the first change point (247.1 m) after adjusting for related covariates.@*CONCLUSION@#Our study found that the association between altitude and hypertension risk might not be linear. We hope the further study can be conducted to confirm the generality of our findings.

Correlation between the disease condition and dyslipidemia in patients with coal-burning-borne endemic arsenic poisoning / 中华地方病学杂志

Objective:To understand the relationship between the disease condition of patients with coal-burning-borne endemic arsenic poisoning (abbreviated as coal-burning-borne arsenic poisoning) and serum lipid metabolism indicators.Methods:Using a case-control study method, in the coal-burning-borne arsenic poisoning village of Yuzhang Town, Qianxinan Prefecture, Guizhou Province, 204 patients with arsenic poisoning diagnosed according to the standard of "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015) were included in case group, including 87 males and 117 females, aged(53.37 ± 8.06) years old; and they were divided into mild arsenic poisoning group (71 cases), moderate arsenic poisoning group (59 cases) and severe arsenic poisoning group (74 cases) according to the clinical grading. Another 63 residents were selected into control group in a non-arsenic-exposed village about 12 km away from the diseased village, including 23 males and 40 females, aged (53.78 ± 9.10) years old. A face-to-face questionnaire survey was conducted for each group of people, including basic information such as general demographic characteristics, smoking status, and drinking status; fasting peripheral blood was collected, and an automatic biochemical analyzer was used to detect serum total cholesterol (TC) and triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels.Results:There were significant differences of serum TC [(4.94 ± 1.00), (5.00 ± 0.99), (5.27 ± 0.94), (5.57 ± 1.07) mmol/L], TG [(2.17 ± 0.90), (2.25 ± 1.31), (2.66 ± 1.43), (2.78 ± 1.40) mmol/L], LDL-C [(2.51 ± 0.79), (2.74 ± 0.64), (2.97 ± 0.66), (3.15 ± 0.80) mmol/L], and HDL-C levels [(1.57 ± 0.55), (1.42 ± 0.43), (1.36 ± 0.42), (1.30 ± 0.38) mmol/L] in control group, mild, moderate and severe arsenic poisoning groups ( F = 5.83, 3.64, 9.72, 4.41, P < 0.01 or < 0.05). Among them, the serum TC level in severe arsenic poisoning group, serum TG and LDL-C levels in moderate and severe arsenic poisoning groups were significantly higher than those in control group ( P < 0.05); the serum HDL-C level in moderate and severe arsenic poisoning groups were lower than that in control group ( P < 0.05); the serum TC, TG and LDL-C levels in severe arsenic poisoning group were significantly higher than those in mild arsenic poisoning group ( P < 0.05). After linear trend test, serum TC, TG and LDL-C levels all showed an upward trend with the degree of arsenic poisoning ( Ftrend = 15.77, 10.14, 29.15, P < 0.05), and serum HDL-C level showed a downward trend with the degree of arsenic poisoning ( Ftrend = 12.75, P < 0.05). There were significant differences in the abnormal rates of serum TC, TG and LDL-C levels among control group and mild, moderate and severe arsenic poisoning groups (χ 2 = 21.16, 16.60, 8.29, P < 0.01 or < 0.05). Among them, the serum TC and TG levels abnormal rates in moderate and severe arsenic poisoning groups and serum LDL-C level abnormal rate in severe arsenic poisoning group were higher than those in control group ( P < 0.05), the serum TC, TG and LDL-C levels abnormal rates in severe arsenic poisoning group were higher than those in mild arsenic poisoning group ( P < 0.05). There was no significant difference of the serum HDL-C level abnormal rate among four groups (χ 2 = 2.11 , P > 0.05). The results of trend chisquare analysis showed that the abnormal rates of serum TC, TG and LDL-C levels presented an increasing trend with the degree of arsenic poisoning (χ 2trend = 19.90, 15.25, 7.63, P<0.05). The results of logistic regression analysis showed that the risk of abnormal serum TC level in patients with severe arsenic poisoning was 2.90 times that in control group [odds ratio ( OR) = 2.90, 95% confidence interval ( CI): 1.43 - 5.91], and the risk of abnormal serum LDL-C level in patients with severe arsenic poisoning was 2.87 times that in control group ( OR = 2.87, 95% CI: 1.22 - 6.71). Conclusion:There is a correlation between the disease condition of patients with coal-burning-borne arsenic poisoning and their dyslipidemia.

A new ECG sign for sudden death: Transient prolonged QT interval following premature contraction / 中南大学学报(医学版)

Early recognition and treatment for early warning electrocardiogram (ECG) of sudden death are very important to prevent and treat malignant arrhythmia and sudden death. Previous studies have found that R-on-T and T wave alternation, and QT interval prolongation are closely related to malignant arrhythmia or sudden death, which are included in the critical value of ECG.By analyzing the ECG characteristics of 4 patients with sudden death, we found that although the causes of the patients were different, there were transient prolongation of QT interval after premature contraction in 12 lead ECG, followed by malignant arrhythmia or sudden death. Thus, we thought that the transient prolongation of QT interval after premature contraction had a high value for warning malignant arrhythmia or sudden death. This phenomenon should be paid enough attention to reduce the risk of sudden death.

Expression and clinical significance of PRC1 in soft tissue sarcoma based on data mining and effect of PRC1 on the growth of liposarcoma / 西安交通大学学报(医学版)

Objective: To investigate the expression and clinical significance of protein regulator of cytokinesis 1 (PRC1) in soft tissue sarcoma (STS) and the effects of down-regulating the expression of PRC1 on the proliferation and cell cycle of human liposarcoma cell by data mining. Methods: Oncomine database was used to analyze the expression of PRC1 in STS tissue and normal tissue, which was then verified by TCGA database. The prognosis data downloaded from OncoLnc database were used to analyze the correlation between PRC1 expression and prognosis of STS patients. Meanwhile, to collect PRC1 expression in STS cells, we used publicly available data from the Cancer Cell Line Encyclopedia (CCLE) projects. String database was used to determine the co-expression molecules with PRC1 and map the gene co-expression network. The expressions of PRC1 in liposarcoma cell line SW872 and human subcutaneous preadipocytes (HPA-s) were detected by Western blotting and Real-time PCR. PRC1 was silenced in SW872 cell (SW872-siPRC1) by PRC1 target siRNA with SW872-NC cell as its control. MTT assay was used to detect the proliferation of SW872-siPRC1 and SW872-NC cells; flow cytometry was used to detect the cell cycle. Results: In the Oncomine database, 11 studies involved PRC1 expression in STS tissues and normal tissues. Compared with that of the control, the expression of PRC1 in STS tissues was significantly higher (P<0.05). The results were consistent with those in the TCGA database. The analysis using Oncomine database showed that the high expression level of PRC1 was associated with shorter overall survival (P<0.05). The analysis using CCLE database showed high expression of PRC1 in STS cells (P<0.05). The co-expression network of PRC1 was established by String database, including 11 nodes and 55 connections. PRC1 was over-expressed in liposarcoma cell line SW872. Cell proliferation curve showed that compared with that of SW872-NC cells in the control group, the proliferation of SW872-siPRC1 cells decreased significantly after 48 h and 72 h culture (P<0.05). Compared with SW872-NC cell in the control group, the G1 cell proportion of SW872-siPRC1 cells was (40.27±7.42)%, significantly lower than that of SW872-NC cells (62.01±4.89)%. The G2/M cell proportion of SW872-siPRC1 cells was (25.65±1.54)%, which was significantly higher than that of SW872-NC cells (8.17±0.96)% (both P<0.05). Conclusion: Tumor gene database mining shows that PRC1 is highly expressed in STS tissues and STS cells, which is associated with the patient's prognosis. Silencing PRC1 gene can inhibit the proliferation of liposarcoma SW872 cells and keep the cells staying in G2/M phase. PRC1 plays a role in promoting liposarcoma, which may provide a potential target for the clinical treatment and prognosis of soft tissue sarcoma, especially liposarcoma.

Meta-analysis of the relationship between arsenic exposure and pulmonary ventilation dysfunction / 中华地方病学杂志

Objective:To systematically evaluate the relationship between arsenic exposure and pulmonary ventilation dysfunction, so as to provide a basis for clarifying the mechanism of lung function injury caused by arsenic exposure and identifying at-risk populations of arsenic exposure.Methods:Pertinent studies were identified by searching PubMed, Embase, Web of Science, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP Database through March 2020. The studies that reported arsenic exposure and lung function dysfunction published at home and abroad were collected comprehensively. According to the inclusion and exclusion criteria, two reviewers independently screened and extracted the literatures. All of the Meta-analysis were performed by using Review Manager 5.3 software, the mean difference value ( MD) was used as the effect index, the fixed effect model or the random effect model were performed for comprehensive quantitative analysis according to the heterogeneity results, and subgroup analysis was conducted to explore the source of heterogeneity. Stata SE 15 software for funnel mapping and Egger's regression test were used to evaluate publication bias. Results:Totally 10 documents were included, all in English. The Meta-analysis showed that arsenic exposure could significantly reduce forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and the MD (95% CI) was - 23.82 ( - 39.93 -- 7.72) ml and - 47.47 (- 73.97 -- 20.98) ml, respectively. The differences were statistically significant ( Ζ = 2.90, 3.51, P < 0.01). FEV1/FVC was reported in three documents, and MD (95% CI) was - 4.72 (- 13.10 - 3.67). There was no evidence of an association between arsenic exposure and FEV1/FVC ( Ζ = 1.10, P > 0.05). The results of subgroup analysis showed that there were significant differences in FEV1 and FVC among subgroups by region (χ 2 = 6.80, 30.06, P < 0.01). Conclusion:Arsenic exposure is negatively correlated with vital capacity measurement indexes FEV1 and FVC, but not with FEV1/FVC, indicating that arsenic exposure may mainly lead to restrictive pulmonary ventilation dysfunction.

Inhibitory effects of miR-146a on retinal inflammation induced by high glucose in human retinal endothelial cells / 中华实验眼科杂志

Objective:To observe the effects of miR-146a on human retinal endothelial cell (HREC) under high glucose condition.Methods:Total of 57 cases diagnosed as diabetic mellitus and 40 cases with diabetic retinopathy (DR) in Wuxi People's Hospital Affiliated to Nanjing Medical University from October to December 2013.Forty-one healthy volunteers were enrolled and served as control group.The clinical data and venous blood samples of subjects were collected.HRECs were cultured in normal glucose (5.5 mmol/L) or high glucose medium (30 mmol/L). Real-time PCR was used to detect the expression of miR-146a.The cultured HRECs were transfected with miR-146a mimic, mimic negative control, inhibitor and inhibitor negative control by lipofectamine2000, respectively.The expression of miR-146a and intercellular cell adhesion molecule-1 (ICAM-1) mRNA was examined by real-time PCR and the expression of nuclear factor-кB (NF-кB) p65 and NF-кB p65 Ser536 was detected by Western blot assay. Results:The relative expression of miR-146a mRNA in the diabetic mellitus group and DR group was 0.36±0.08 and 0.27±0.08, respectively, which were significantly lower than 1.00±0.16 in the control group (both at P<0.01). The expression of miR-146a mRNA was 0.37±0.11 in the high glucose group, which was lower than 1.00±0.18 in the normal control group ( t=5.57, P<0.01). The relative expression of miR-146a mRNA in the miR-146a mimic group was 2 540.00±105.00, which was significantly higher than 61.00±17.90 in the miR-146a mimic control group; The relative expression of miR-146a mRNA in the miR-146a inhibitor group was 0.04±0.01, which was significantly lower than 0.88±0.04 in the miR-146a inhibitor control group ( t=23.23, 17.12; both at P<0.01). The relative expression of ICAM-1 mRNA in the miR-146a mimic group was 0.35±0.12, which was significantly lower than 1.00±0.13 in the miR-146a mimic control group; The relative expression of ICAM-1 mRNA in the miR-146a inhibitor group was 2.74±0.48, which was significantly higher than 1.00±0.16 in the miR-146a inhibitor control group ( t=3.58, 3.37; both at P<0.05). The relative expression of NF-кB p65 Ser536 in the miR-146a mimic group was 0.43±0.03, which was significantly lower than 1.07±0.09 in the miR-146a mimic control group ( t=6.74, P<0.01). The relative expression of NF-кB p65 Ser536 in the miR-146a inhibitor group was 2.08±0.12, which was significantly higher than 1.00±0.01 in the miR-146a inhibitor control group ( t=8.76; P<0.01). Conclusions:miR-146a can reduce inflammation of HREC in high glucose condition through inhibiting ICAM-1 expression and NF-кB phosphorylation.

Awareness, treatment and control of hypertension in 640 000 adults in eastern China / 中华流行病学杂志

Objective@#To understand the awareness, treatment, and control of hypertension in residents aged 35-75 years in eastern China, analyze the treatment mode for antihypertensive agents while identifying those factors affecting awareness, treatment and control.@*Methods@#The data collected in eastern China from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project were used to obtain the information about the awareness, treatment and control of hypertension in the residents and the antihypertensive medication treatment mode in this area. Multilevel mixed-effects model was used to explore the association of the demographic characteristics of hypertension patients with the rates of awareness, treatment and control of hypertension.@*Results@#A total of 640 539 participants aged 35-75 years, mean age (56.9±9.6) years, were included in the analysis, women accounted for 59.7% and 318 741 (49.8%) of the participants suffered from hypertension. Among those hypertensive patients, 46.5% were aware of their condition, 38.1% were taking prescribed antihypertensive medications, and 11.1% had achieved the control of hypertension, the differences were significant among provinces, between urban area and rural area and among different demographical groups. Calcium-channel blockers was the most commonly used medication (45.1%), and 78 735 hypertension patients (86.2%) took only one type of medication. Older age, higher household income, higher level of education, and histories of myocardial infarction, stroke and diabetes were associated with higher awareness, treatment and control of hypertension (P<0.05).@*Conclusions@#The rates of awareness, treatment and control of hypertension were low in residents in eastern China. The differences in hypertension management were significant among provinces and between urban area and rural area. Further efforts are needed to enhance the system of hypertension prevention, screening, diagnosis and treatment.

SOCS3 Attenuates GM-CSF/IFN-γ-Mediated Inflammation During Spontaneous Spinal Cord Regeneration / 神经科学通报·英文版

SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.

Value of ventricular tachycardia score in diagnosing pre-excited tachycardia / 中南大学学报(医学版)

To investigate the value of ventricular tachycardia (VT) score in diagnosing pre-excited tachycardia.
 Methods: Twelve-lead electrocardiograph results were obtained from 30 patients at pre-excited tachycardia attacking stage who were diagnosed by electrophysiology. We scored pre-excitation tachycardia based on the VT score. To analyze the electrocardiogram of pre-excited tachycardia using 7 diagnostic indicators of the VT score and calculate the specificity of 7 diagnostic indicators and right superior axis (-90º to ±180º), the differences were compared among VT score of 2 points and brugada, Wellens, and Vereckei algorithms in diagnosing pre-excited tachycardia. According to the specificity of Vereckei, Wellens, and Brugada algorithms, and VT scores from low to high, their prediction value and differences were analyzed.
 Results: Single indicator such as atrioventricular (AV) dissociation or right superior axis (-90º to ±180º) showed the highest specificity (100%) for identifying pre-excited tachycardia. No patient with VT score was ≥3 points, and the specificity was 100%. The specificity of VT score of 2 point was higher than that of Brugada, Wellens, or Vereckei algorithms in the diagnosing pre-excited tachycardia (76.7% vs 50.0%, 23.3% or 20.0%, P<0.05). The specificity of Vereckei, Wellens, and Brugada algorithms and VT score were gradually increased after each of stepwise individually eliminated VT (20.0%, 40.0%, 66.7%, 83.3%, P<0.05). However, there was no significant difference in the specificity in the remaining false positive cases between the 4 methods and VT score.
 Conclusion: VT score ≥3 points can identify pre-excited tachycardia and VT with 100% specificity. VT score of 2 points cannot completely distinguish pre-excited tachycardia from VT, but specificity of VT score with 2 points is obviously higher than that of Brugada, Wellens, and Vereckei algorithms.