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.

The effects of greenness exposure on hypertension incidence among Chinese oldest-old: a prospective cohort study.

BACKGROUND: Although the oldest-old (those aged over 80 years) are vulnerable to environmental factors and have the highest prevalence of hypertension, studies focusing on greenness exposure and the development of hypertension among them are insufficient. The aim of this study was to explore the association between residential greenness and hypertension in the oldest-old population. METHODS: This cohort study included data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The oldest-old were free of hypertension at baseline (2008), and hypertension events were assessed by follow-up surveys in 2011, 2014, and 2018. The one-year averages of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) at 500-m buffer before the interview year of incident hypertension or last censoring interview were collected at the level of 652 residential units (district or county). The linear or nonlinear association between greenness and hypertension incidence was analyzed using the Cox proportional hazards model with penalized splines. The linear links between greenness and hypertension incidence were determined using the Cox proportional hazards model included a random effect term. RESULTS: Among 5253 participants, the incidence rate of hypertension was 7.25 (95% confidence interval [CI]: 6.83-7.67) per 100 person-years. We found a nonlinear association between greenness exposure and hypertension risk, and the exposure-response curve showed that 1 change point existed. We examined the linear effect of greenness on hypertension by categorizing the NDVI/EVI into low and high-level exposure areas according to the change point. We found more notable protective effects of each 0.1-unit increase in greenness on hypertension incidence for participants living in the high-level greenness areas (hazard ratio (HR) = 0.60; 95% CI: 0.53-0.70 for NDVI; HR = 0.46; 95% CI: 0.37-0.57 for EVI). In contrast, no significant influence of greenness exposure on hypertension risk was found for participants living in the low-level greenness areas (HR = 0.77; 95% CI: 0.38-1.55 for NDVI; HR = 0.73; 95% CI: 0.33-1.63 for EVI). CONCLUSIONS: Greenness exposure is nonlinearly associated with hypertension risk among the oldest-old, presenting its relationship in an inverse "U-shaped" curve. Greenness is a protective factor that decreases the risk of hypertension.

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.

First and second SARS-CoV-2 waves in inner London: A comparison of admission characteristics and the effects of the B.1.1.7 variant

IntroductionA second wave of SARS-CoV-2 infection spread across the UK in 2020 linked with emergence of the more transmissible B.1.1.7 variant. The emergence of new variants, particularly during relaxation of social distancing policies and implementation of mass vaccination, highlights the need for real-time integration of detailed patient clinical data alongside pathogen genomic data. We linked clinical data with viral genome sequence data to compare cases admitted during the first and second waves of SARS-CoV-2 infection. MethodsClinical, laboratory and demographic data from five electronic health record (EHR) systems was collected for all cases with a positive SARS-CoV-2 RNA test between March 13th 2020 and February 17th 2021. SARS-CoV-2 viral sequencing was performed using Oxford Nanopore Technology. Descriptive data are presented comparing cases between waves, and between cases of B.1.1.7 and non-B.1.1.7 variants. ResultsThere were 5810 SARS-CoV-2 RNA positive cases comprising inpatients (n=2341), healthcare workers (n=1549), outpatients (n=874), emergency department (ED) attenders not subsequently admitted (n=532), inter-hospital transfers (n=281) and nosocomial cases (n=233). There were two dominant waves of hospital admissions, with wave one starting from March 13th (n=838) and wave two from October 20th (n=1503), both with a temporally aligned rise in nosocomial cases (n=96 in wave one, n=137 in wave two). 1470 SARS-CoV-2 isolates were successfully sequenced, including 216/838 (26%) admitted cases from wave one, 472/1503 (31%) admitted cases in wave two and 121/233 (52%) nosocomial cases. The first B.1.1.7 variant was identified on 15th November 2020 and increased rapidly such that it comprised 400/472 (85%) of sequenced isolates from admitted cases in wave two. Females made up a larger proportion of admitted cases in wave two (47.3% vs 41.8%, p=0.011), and in those infected with the B.1.1.7 variant compared to non-B.1.1.7 variants (48.0% vs 41.8%, p=0.042). A diagnosis of frailty was less common in wave two (11.5% v 22.8%, p<0.001) and in the group infected with B.1.1.7 (14.5% v 22.4%, p=0.001). There was no difference in severity on admission between waves, as measured by hypoxia at admission (wave one: 64.3% vs wave two: 65.5%, p=0.67). However, a higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029). ConclusionsAutomated EHR data extraction linked with SARS-CoV-2 genome sequence data provides valuable insight into the evolving characteristics of cases admitted to hospital with COVID-19. The proportion of cases with hypoxia on admission was greater in those infected with the B.1.1.7 variant, which supports evidence the B.1.1.7 variant is associated with more severe disease. The number of nosocomial cases was similar in both waves despite introduction of many infection control interventions before wave two, an observation requiring further investigation.

The Association Between Long-Term Exposure to Particulate Matter and Incidence of Hypertension Among Chinese Elderly: A Retrospective Cohort Study.

Background and Objectives: Studies that investigate the links between particulate matter ≤2. 5 µm (PM2.5) and hypertension among the elderly population, especially those including aged over 80 years, are limited. Therefore, we aimed to examine the association between PM2.5 exposure and the risk of hypertension incidence among Chinese elderly. Methods: This prospective cohort study used 2008, 2011, 2014, and 2018 wave data from a public database, the Chinese Longitudinal Healthy Longevity Survey, a national survey investigating the health of those aged over 65 years in China. We enrolled cohort participants who were free of hypertension at baseline (2008) from 706 counties (districts) and followed up in the 2011, 2014, and 2018 survey waves. The annual PM2.5 concentration of 706 counties (districts) units was derived from the Atmospheric Composition Analysis Group database as the exposure variable, and exposure to PM2.5 was defined as 1-year average of PM2.5 concentration before hypertension event occurrence or last interview (only for censoring). A Cox proportional hazards model with penalized spline was used to examine the non-linear association between PM2.5 concentration and hypertension risk. A random-effects Cox proportional hazards model was built to explore the relationship between each 1 µg/m3, 10 µg/m3 and quartile increment in PM2.5 concentration and hypertension incidence after adjusting for confounding variables. The modification effects of the different characteristics of the respondents were also explored. Results: A total of 7,432 participants aged 65-116 years were enrolled at baseline. The median of PM2.5 exposure concentration of all the participants was 52.7 (inter-quartile range, IQR = 29.1) µg/m3. Overall, the non-linear association between PM2.5 and hypertension incidence risk indicated that there was no safe threshold for PM2.5 exposure. The higher PM2.5 exposure, the greater risk for hypertension incidence. Each 1 µg/m3 [adjusted hazard ratio (AHR): 1.01; 95% CI: 1.01-1.02] and 10 µg/m3 (AHR: 1.12; 95% CI: 1.09-1.16) increments in PM2.5, were associated with the incidence of hypertension after adjusting for potential confounding variables. Compared to first quartile (Q1) exposure, the adjusted HRs of hypertension incidence for the Q2, Q3 and Q4 exposure of PM2.5 were 1.31 (95% CI: 1.13-1.51), 1.35 (95% CI: 1.15-1.60), and 1.83 (95% CI: 1.53-2.17), respectively. The effects appear to be stronger among those without a pension, living in a rural setting, and located in central/western regions. Conclusion: We found no safe threshold for PM2.5 exposure related to hypertension risk, and more rigorous approaches for PM2.5 control were needed. The elderly without a pension, living in rural and setting in the central/western regions may be more vulnerable to the effects of PM2.5 exposure.

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.

Supplementing the National Early Warning Score (NEWS2) for anticipating early deterioration among patients with COVID-19 infection

BackgroundThe National Early Warning Score (NEWS2) is currently recommended in the United Kingdom for risk stratification of COVID outcomes, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for severe COVID outcome and identify and validate a set of routinely-collected blood and physiological parameters taken at hospital admission to improve the score. MethodsTraining cohorts comprised 1276 patients admitted to Kings College Hospital NHS Foundation Trust with COVID-19 disease from 1st March to 30th April 2020. External validation cohorts included 5037 patients from four UK NHS Trusts (Guys and St Thomas Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID disease (transfer to intensive care unit or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. ResultsA baseline model of NEWS2 + age had poor-to-moderate discrimination for severe COVID infection at 14 days (AUC in training sample = 0.700; 95% CI: 0.680, 0.722; Brier score = 0.192; 95% CI: 0.186, 0.197). A supplemented model adding eight routinely-collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, CRP, estimated GFR, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI: 0.715, 0.757) and these improvements were replicated across five UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. ConclusionsNEWS2 score had poor-to-moderate discrimination for medium-term COVID outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID. KO_SCPLOWEYC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWMESSAGESC_SCPLOWO_LIThe National Early Warning Score (NEWS2), currently recommended for stratification of severe COVID-19 disease in the UK, showed poor-to-moderate discrimination for medium-term outcomes (14-day transfer to ICU or death) among COVID-19 patients. C_LIO_LIRisk stratification was improved by the addition of routinely-measured blood and physiological parameters routinely at hospital admission (supplemental oxygen, urea, oxygen saturation, CRP, estimated GFR, neutrophil count, neutrophil/lymphocyte ratio) which provided moderate improvements in a risk stratification model for 14-day ICU/death. C_LIO_LIThis improvement over NEWS2 alone was maintained across multiple hospital trusts but the model tended to be miscalibrated with risks of severe outcomes underestimated in most sites. C_LIO_LIWe benefited from existing pipelines for informatics at KCH such as CogStack that allowed rapid extraction and processing of electronic health records. This methodological approach provided rapid insights and allowed us to overcome the complications associated with slow data centralisation approaches. C_LI

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.