Globular adiponectin induces esophageal adenocarcinoma cell pyroptosis via the miR-378a-3p/UHRF1 axis.

BACKGROUND: Antiapoptosis is a major factor in the resistance of tumor cells to chemotherapy and radiotherapy. Thus, activation of cell pyroptosis may be an effective option to deal with antiapoptotic cancers such as esophageal adenocarcinoma (EAC). METHODS: Differential expression of ubiquitin-like versus PHD and ring finger structural domain 1 (UHRF1) in EAC and near normal tissues was analyzed, as well as the prognostic impact on survival in EAC. Also, the same study was done for globular adiponectin (gAD). Simultaneously, the mRNA expression of UHRF1 was observed in different EAC cell lines. Real time cellular analysis (RTCA) was used to detect cell proliferation, and flow cytometry and inverted fluorescence microscopy were used to detect pyroptosis. Biocredit analysis was conducted to observe the correlation between UHRF1 and key pyroptosis proteins. OD values and CCK8 assay were used to determine the effect of miR-378a-3p on EAC cells. Quantitative real-time polymerase chain reaction and Western blot were used to detect the correlation between UHRF1, gAD, and miR-378a-3p in EAC cells. Moreover, in vivo and in vitro experiments were performed to detect the relevant effects on tumor migration and invasion after inhibiting UHRF1 expression. RESULTS: UHRF1 was negatively correlated with the survival of patients with EAC, while miR-378a-3p showed the opposite effect. Additionally, gAD promoted EAC cell pyroptosis, upregulated miR-378a-3p, and significantly inhibited the proliferation of EAC cells. gAD directly reduced UHRF1 expression in EAC cells by upregulating miR-378a-3p. In cell migration and invasion assays, inhibition of UHRF1 expression significantly suppressed EAC cell metastasis. In animal experiments, we again demonstrated that gAD induced pyroptosis in EAC cells by inhibiting the expression of UHRF1. CONCLUSION: gAD-induced upregulation of miR-378a-3p significantly inhibited the proliferation of EAC by targeting UHRF1. Therefore, gAD may serve as an alternative therapy for chemotherapy- and radiation-refractory EAC or other cancers with the same mechanism of pyroptosis action.

The value of multimodal functional magnetic resonance imaging in differentiating p53abn from p53wt endometrial carcinoma.

BACKGROUND: Endometrial carcinoma (EC) is the sixth most common cancer in women. P53 gene expression in patients with endometrial cancer can predict the efficacy and prognosis of patients with neoadjuvant therapy. PURPOSE: To explore the value of multimodal magnetic resonance imaging (MRI) in differentiating p53 abnormal (p53abn) from p53 wild-type (p53wt) EC. MATERIAL AND METHODS: Data from 47 EC patients, including 14 p53abn cases and 33 p53wt cases, were retrospectively analyzed. The preoperative MRI sequences included amide proton transfer weighted (APTw) imaging, T2 mapping, mDIXON-Quant imaging and diffusion-weighted imaging (DWI). After post-processing, APT, T2, transverse relaxation rate (R2*), fat fraction (FF) and apparent diffusion coefficient (ADC) maps were obtained. The APT, T2, R2*, FF and ADC values for lesions of the two groups of cases were measured by two observers who were blind to the pathological data. RESULTS: The APT value and R2* value in the p53abn group were higher than those in the p53wt group, while the ADC value was lower (all P < 0.05). There was no statistically significant difference in T2 value and FF value between the two groups (all P > 0.05). The area under curve of APT, R2*, ADC and combined APT + R2*+ADC values for identification of p53abn and p53wt EC were 0.739, 0.689, 0.718 and 0.820, respectively (all P > 0.05). CONCLUSION: APTw, mDIXON-Quant and DWI techniques can be usedfor quantitative identification of p53abn and p53wt EC. The multimodal MRI provides a new way for preoperative quantitative evaluation of EC molecular typing, which has certain clinical application value.

Multi-step-ahead and interval carbon price forecasting using transformer-based hybrid model.

Accurate and stable carbon price forecasts serve as a reference for assessing the stability of the carbon market and play a vital role in enhancing investment and operational decisions. However, realizing this goal is still a significant challenge, and researchers usually ignore multi-step-ahead and interval forecasting due to the non-linear and non-stationary characteristics of carbon price series and its complex fluctuation features. In this study, a novel hybrid model for accurately predicting carbon prices is proposed. The proposed model combines multi-step-ahead and interval carbon price forecasting based on the Hampel identifier (HI), time-varying filtering-based empirical mode decomposition (TVFEMD), and transformer model. First, HI identifies and corrects outliers in carbon price. Second, TVFEMD decomposes carbon price into several intrinsic mode functions (imfs) to reduce the non-linear and non-stationarity of carbon price to obtain more regular features in series. Next, these imfs are reconstructed by sample entropy (SE). Subsequently, the orthogonal array tuning method is used to optimize the transformer model's hyperparameters to obtain the optimal model structure. Finally, after hyperparameter optimization and quantile loss function, the transformer is used to perform multi-step-ahead and interval forecasting on each part of the reconstruction, and the final prediction result is obtained by summing them up. Five pilot carbon trading markets in China were selected as experimental objects to verify the proposed model's prediction performance. Various benchmark models and evaluation indicators were selected for comparison and analysis. Experimental results show that the proposed HI-TVFEMD-transformer hybrid model achieves an average MAE of 0.6546, 1.3992, 1.6287, and 2.2601 for one-step, three-step, five-step, and ten-step-ahead forecasting, respectively, which significantly outperforms other models. Furthermore, interval forecasts almost always have a PICI above 0.95 at a confidence interval of 0.1, thereby indicating the effectiveness of the hybrid model in describing the uncertainty in the forecasts. Therefore, the proposed hybrid model is a reliable carbon price forecasting tool that can provide a dependable reference for policymakers and investors.

Papermaking wastewater treatment coupled to 2,3-butanediol production by engineered psychrotrophic Raoultella terrigena.

The simultaneous bioremediation and bioconversion of papermaking wastewater by psychrotrophic microorganisms holds great promise for developing sustainable environments and economies in cold regions. Here, the psychrotrophic bacterium Raoultella terrigena HC6 presented high endoglucanase (26.3 U/mL), xylosidase (732 U/mL), and laccase (8.07 U/mL) activities for lignocellulose deconstruction at 15 °C. mRNA monitoring and phenotypic variation analyses confirmed that cold-inducible cold shock protein A (CspA) facilitated the expression of the cel208, xynB68, and lac432 genes to increase the enzyme activities in strain HC6. Furthermore, the cspA gene-overexpressing mutant (strain HC6-cspA) was deployed in actual papermaking wastewater and achieved 44.3%, 34.1%, 18.4%, 80.2% and 100% removal rates for cellulose, hemicellulose, lignin, COD, and NO3--N at 15 °C. Simultaneously, 2,3-butanediol (2,3-BD) was produced from the effluent with a titer of 2.98 g/L and productivity of 0.154 g/L/h. This study reveals an association between the cold regulon and lignocellulolytic enzymes and provides a promising candidate for simultaneous papermaking wastewater treatment and 2,3-BD production.

Printable High-Efficiency and Stable FAPbBr3 Perovskite Solar Cells for Multifunctional Building-Integrated Photovoltaics.

Perovskite solar cells (PSCs) show great promise for next-generation building-integrated photovoltaic (BIPV) applications because of their abundance of raw materials, adjustable transparency, and cost-effective printable processing. Owing to the complex perovskite nucleation and growth control, the fabrication of large-area perovskite films for high-performance printed PSCs is still under active investigation. Herein, the study proposes an intermediate-phase-transition-assisted one-step blade coating for an intrinsic transparent formamidinium lead bromide (FAPbBr3 ) perovskite film. The intermediate complex optimizes the crystal growth path of FAPbBr3 , resulting in a large-area, homogeneous, and dense absorber film. A champion efficiency of 10.86% with high open-circuit voltage up to 1.57 V is obtained with a simplified device architecture of glass/FTO/SnO2 /FAPbBr3 /carbon. Moreover, the unencapsulated devices maintain 90% of their initial power conversion efficiency after aging at 75 °C for 1000 h in ambient air, and 96% after maximum power point tracking for 500 h. The printed semitransparent PSCs, with average visible light transmittance over 45%, demonstrate high efficiencies for both small devices (8.6%) and 10 × 10 cm2 modules (5.55%). Finally, the ability to customize the color, transparency, and thermal insulation properties of FAPbBr3 PSCs makes them high prospects as multifunctional BIPVs.

Apatinib combined with olaparib induces ferroptosis via a p53-dependent manner in ovarian cancer.

OBJECTIVE: PARP inhibitors combined with antiangiogenic drugs have been reported to improve outcomes in BRCA wild-type ovarian cancer patients, the mechanism of the combination is unclear. In this study, we explored the mechanism of apatinib combined with olaparib in the treatment of ovarian cancer. METHODS: In this study, human ovarian cancer cell lines A2780 and OVCAR3 were used as experimental objects, and the expression of ferroptosis-related protein GPX4 after treatment with apatinib and olaparib was detected by Western blot. The SuperPred database was used to predict the target of the combined action of apatinib and olaparib, and the predicted results were verified by Western blot experiment to explore the mechanism of ferroptosis induced by apatinib and olaparib. RESULTS: Apatinib combined with olaparib-induced ferroptosis in p53 wild-type cells, and p53 mutant cells developed drug resistance. The p53 activator RITA sensitized drug-resistant cells to ferroptosis induced by apatinib combined with olaparib. Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. CONCLUSION: This discovery revealed the specific mechanism of ferroptosis induced by apatinib combined with olaparib in p53 wild-type ovarian cancer cells and provided a theoretical basis for the clinical combined use of apatinib and olaparib in p53 wild-type ovarian cancer patients.

Chinese herbal injection for cardio-cerebrovascular disease: Overview and challenges.

Cardio-cerebrovascular diseases are the leading cause of death worldwide and there is currently no optimal treatment plan. Chinese herbal medicine injection (CHI) is obtained by combining traditional Chinese medicine (TCM) theory and modern production technology. It retains some characteristics of TCM while adding injection characteristics. CHI has played an important role in the treatment of critical diseases, especially cardio-cerebrovascular diseases, and has shown unique therapeutic advantages. TCMs that promote blood circulation and remove blood stasis, such as Salvia miltiorrhiza, Carthami flos, Panax notoginseng, and Chuanxiong rhizoma, account for a large proportion of CHIs of cardio-cerebrovascular disease. CHI is used to treat cardio-cerebrovascular diseases and has potential pharmacological activities such as anti-platelet aggregation, anti-inflammatory, anti-fibrosis, and anti-apoptosis. However, CHIs have changed the traditional method of administering TCMs, and the drugs directly enter the bloodstream, which may produce new pharmacological effects or adverse reactions. This article summarizes the clinical application, pharmacological effects, and mechanism of action of different varieties of CHIs commonly used in the treatment of cardio-cerebrovascular diseases, analyzes the causes of adverse reactions, and proposes suggestions for rational drug use and pharmaceutical care methods to provide a reference for the rational application of CHIs for cardio-cerebrovascular diseases.

Surprising leopard restoration in fragmented ecosystems reveals connections as the secret to conservation success.

The Chinese Loess Plateau has been the cradle of Chinese civilization and the main human settlement in China for thousands of years, where anthropogenic activities are believed to have deeply eroded natural landscapes. After decades of minimal leopard sighting in forests of northern China, due to serious human interference, we recently discovered that the leopard population is recovering. This finding provides hope for successful biodiversity conservation in human-dominated ecosystems. To understand the mechanism of leopard return into such a highly fragmented landscape, we applied the concept of ecological networks (ENs) to identify key factors promoting leopard restoration and quantify the ecological links among habitats. We first determined the existence of a healthy leopard population in the study area based on the size of its home range and presence of breeding individuals. We then innovatively used the relationship between species richness and top predators to generate ENs, and found that the connectivity of ENs had a significant positive interaction with leopard survival. Our study validates the effectiveness of establishing ecologically connected habitats for leopard protection, and highlights the importance of applying ENs for conservation planning in highly fragmented ecosystems. This study provides a successful case for the protection of top predators in human-dominated landscapes.

Evaluation of clinical efficacy and safety on phacoemulsification combined with gonioscopy-assisted angle plasty for primary angle-closure glaucoma with cataract / 中华实验眼科杂志

Objective:To evaluate the efficacy and safety of phacoemulsification combined with gonioscopy-assisted angle plasty (Phaco-GAAP) for primary angle closure glaucoma (PACG) with cataract.Methods:A case series study was carried out.Twenty-five eyes of 22 patients with PACG and cataract were enrolled in Beijing Tongren Hospital from April 2022 to August 2022.All of the patients received Phaco-GAAP surgery.During the operation, viscoelastic-assisted goniosynechialysis was performed at first, followed by a secondary angle plasty for residual peripheral anterior synechiae (PAS) based on the quantified assessment by gonioscopy, and the extent of PAS was recorded intraoperatively.The operated eyes were followed at 1 day, 1 week, 1 month and 3 months after surgery to evaluate intraocular pressure (IOP), PAS range, the number of anti-glaucoma drugs application, operation-related complications, and success rate.The qualified success rate was defined as medicine-controlled IOP ≤21 mmHg after surgery, and complete success rate was defined as IOP ≤21 mmHg without any anti-glaucoma medication.This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Tongren Hospital (TRECKY2021-136). Written informed consent was obtained from each patient prior to entering the research cohort.Results:The extent of PAS was [270(225, 360)°], [165(110, 215)°] and [100(35, 175)°] at preoperation, first and secondary angle plasty, respectively, showing a significant difference among them ( χ2 =40.742, P<0.001). The PAS range was significantly reduced at first angle plasty in comparison with preoperation and was significantly reduced at secondary angle plasty in comparison with at first angle plasty (both at P<0.001), and the proportion of the angle PAS range ≥180° decreased from 48% to 24% after second angle plasty.In 13 eyes finished gonioscopy, the PAS range was [240(195, 305)°], [60(25, 182.5)°], [170(120, 275)°]and [180(140, 280)°]at preoperation, at the end of operation, postoperative 1 month and 3 months, respectively, with a significant difference ( χ2 =23.631, P<0.001). The PAS range was significantly smaller at postoperative 1 month, 3 months than that at preoperation (both at P=0.004) and larger than that at the end of operation ( P=0.011, P=0.003). The IOP was (40.19±17.23), (15.80±7.98), (13.89±5.09), (12.80±3.79) and(13.24±2.78) mmHg before operation and 1 day, 1 week, 1 month and 3 months after operation, respectively, showing a significant difference ( F=44.031, P<0.001), and the IOP was significantly reduced after operation (all at P<0.001). The PAS range at the end of operation was positively correlated with preoperation ( rs=0.409, P=0.042). The complete and qualified success rates were 95.8%, 95.8% for postoperative 1 month, 95.8% and 100% for postoperative 3 months, respectively.The primary complication was intraoperative anterior chamber angle hemorrhage, with an incidence of 68%. Conclusions:Phaco-GAAP can intraoperatively quantify PAS range and guide secondary angle plasty, therefore, it is an effective and safe surgical intervention for PACG with cataract.

The predicting indices for the outcome of refractory septic shock in preterm infants / 中国新生儿科杂志

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

Research progress of palliative care for patients with lung transplantation / 中国实用护理杂志

This paper summarized the research progress of palliative care for lung transplantation patients, to summarize the necessity and influencing factors of palliative care for lung transplantation patients, and defined the research status of palliative care implementation mode for lung transplantation patients, with a view to providing ideas for further research of palliative care on lung transplantation patients in China.

Correlation between paroxysmal slow-wave events and cognitive impairment in patients with cerebral small vessel disease / 国际脑血管病杂志

Objective:To investigate the correlation between paroxysmal slow-wave events (PSWEs) and cerebral small vessel disease (CSVD) and CSVD-related cognitive impairment.Methods:Patients with CSVD visited Weihai Municipal Hospital from March 2021 to April 2022 were included, and sex- and age-matched healthy controls were recruited for cross-sectional analysis. The patients with CSVD were further divided into cognitive impairment group and non-cognitive impairment group. The self-developed Python script was used to detect the PSWE parameters in electroencephalogram records. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate cognitive function. Multivariate logistic regression analysis was used to determine whether PWSE parameters were the independent related factors of CSVD and CSVD-related cognitive impairment. Multiple linear regression analysis was used to determine the correlation between the PSWE parameters and overall cognitive function (MoCA total score) in patients with CSVD. Results:A total of 76 patients with CSVD (including 41 patients with cognitive impairment and 35 patients without cognitive impairment) and 45 healthy controls were included. Compared with the healthy control group, PWSEs in the F3 (left frontal area) and O1 (left occipital area) regions of the CSVD group occurred more frequently and lasted longer (all P<0.05). Multivariate logistic regression analysis showed that the frequency (odds ratio [ OR] 1.080, 95% confidence interval [ CI] 1.023-1.140; P=0.005) and duration ( OR 1.006, 95% CI 1.001-1.011; P=0.023) of PWSEs in the left frontal area, as well as the frequency ( OR 1.052, 95% CI 1.010-1.095; P=0.014) and duration ( OR 1.003, 95% CI 1.000-1.006; P=0.028) of PWSEs in the left occipital region were the independent related factors for CSVD. The frequency ( OR 1.106, 95% CI 1.033-1.183; P=0.004) and duration ( OR1.010, 95% CI 1.003-1.017; P=0.004) of PWSEs in the left frontal area were the independent risk factors for cognitive impairment in patients with CSVD. Multiple linear regression analysis showed that the frequency ( β= –0.242, P=0.045) and duration ( β= –0.235, P=0.046) of PWSEs in the left frontal region were negatively correlated with the overall cognitive function score in patients with CSVD. Conclusions:The frequency and duration of PSWEs in some brain regions of patients with CSVD increase, and there is an independent correlation between PSWEs and cognitive impairment, suggesting that the damage of blood-brain barrier may participate in the pathogenesis of cognitive impairment in patients with CSVD.

Progress on the impact of pathogenic gene mutations in epilepsy on treatment choices / 国际儿科学杂志

In the past decade, significant progress has been made in the study of epilepsy-causing genetic mutations and the molecular mechanisms of epilepsy clinical manifestations.A growing number of studies have shown that the mechanism of action of pathogenic genes related to clinical symptoms shows significant correlation.In the selection of antiepileptic drugs for patients with different gene mutation, early identification of pathogenic genes has guiding significance for the selection of antiepileptic drugs.This review summairzes common epilepsy pathogenic genes, including ion channels genes, cellular metabolism related genes and cell signaling pathway related genes, and research progress on therapeutic targets corresponding to pathogenic genes in recent years.As research deepens, specific gene defects and their machanisms of action provide a basis for studying new treatment methods.

Analysis of cytogenetic characteristics of primary childhood B-cell acute lymphoblastic leukemia and risk factors for first treatment response / 白血病·淋巴瘤

Objective:To investigate the cytogenetic characteristics and influencing factors associated with first treatment response in primary childhood B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 49 children with primary B-ALL who were admitted to the First Hospital of Xiamen University from April 2019 to September 2021 were retrospectively collected, and the clinical characteristics, cytogenetic and molecular biology findings and other clinical indicators before and after treatment were obtained. Genotyping, clinical risk stratification after the first induction chemotherapy and chemotherapy regimen development were performed according to the pediatric ALL treatment specification (2018 version). The relationship between different genotypes and clinical indicators in children with B-ALL was analyzed, and the correlation between clinical risk stratification and each indicator was analyzed by Spearman rank correlation analysis.Results:The median age of 49 children was 3.0 years old (interquartile range: 3.2 years old), 32 cases (65.3%) were male and 17 cases (34.7%) were female, with a male-to-female ratio of 1.88∶1. Thirty-five cases (71.4%) had gene mutations before treatment and 14 cases (28.6%) had no mutations. Among the 35 cases with mutations, E2A-PBX1 was found in 5 cases (10.2%), including 1 case with Philadelphia chromosome (Ph)-like; IKZF1 deletion was found in 8 cases (16.3%), including 4 cases with Ph-like, 1 case with Ph-positive, and 1 case with MLL rearrangement; MLL rearrangement was found in 3 cases (6.1%); Ph-like alone was found in 12 cases (24.5%); TEL-AML1 was found in 6 cases (12.2%), including 2 cases with Ph-like; 1 case (2.0%) with Ph-positive alone. The clinical risk stratification showed that 7 cases (14.3%) had high risk, 28 cases (57.1%) had intermediate risk, and 14 cases (28.6%) had low risk. The proportions of patients with high and intermediate clinical risk before induction chemotherapy [20.0% (7/35) vs. 0.0% (0/14), 62.9% (22/35) vs. 42.9% (6/14)] and the proportion of patients with altered mutation status on day 33 of induction chemotherapy [42.9% (15/35) vs. 0.0% (0/14)] were higher in patients with mutations before induction chemotherapy than those in patients without gene mutations before treatment (all P < 0.01). The gene mutation or not before treatment was not correlated with gender, white blood cell count at first diagnosis, hormone sensitivity, minimal residual disease (MRD) from the 15th to the 19th day of induction chemotherapy, and MRD on the 33rd day of induction chemotherapy (all P > 0.05). Clinical risk stratification of children was associated with white blood cell count at first diagnosis ( r = 0.392, P = 0.005), neutrophil count ( r = 0.453, P = 0.001), lymphocyte count ( r = 0.418, P = 0.001), monocyte count ( r = 0.359, P = 0.017), blood uric acid level ( r = 0.378, P = 0.007), and proportion of bone marrow naive lymphocyte count before treatment ( r = 0.316, P = 0.027) and from 15th to the 19th day of induction chemotherapy ( r = 0.399, P = 0.005) and the 33rd day of induction chemotherapy ( r = 0.408, P = 0.028), proportion of children with bone marrow MRD ≥ 0.000 1 on the 33rd day of induction chemotherapy ( χ2 = 15.42, P < 0.001), and proportion of children with gene mutations before treatment ( χ2 = 9.10, P = 0.005). Conclusions:High levels of leukocytes, neutrophils, lymphocytes, monocytes, naive lymphocytes, blood uric acid, and naive lymphocytes from the 15th to the 19th day and the 33rd day of chemotherapy, MRD on the 33rd day of chemotherapy and genotype in children with B-ALL may be associated with poor response to treatment. Clinical risk stratification is associated with gene mutation status, and gene mutation may be an important indicator of treatment response in children with B-ALL.

Prediction of concentration immediately dangerous to life or health of benzene and its derivatives based on quantitative structure-activity relationship / 环境与职业医学

Background With the increasing exposure to hazardous chemicals in the workplace and frequency of occupational injuries and occupational safety accidents, the acquisition of occupational exposure limits of hazardous chemicals is imminent. Objective To obtain more unknown immediately dangerous to life or health (IDLH) concentrations of hazardous chemicals in the workplace by exploring the application of quantitative structure-activity relationship (QSAR) prediction method to IDLH concentrations, and to provide a theoretical basis and technical support for the assessment and prevention of occupational injuries. Methods QSAR was used to correlate the IDLH values of 50 benzene and its derivatives with the molecular structures of target compounds. Firstly, affinity propagation algorithm was applied to cluster sample sets. Secondly, Dragon 2.1 software was used to calculate and pre-screen 537 molecular descriptors. Thirdly, the genetic algorithm was used to select six characteristic molecular descriptors as dependent variables and to construct a multiple linear regression model (MLR) and two nonlinear models using support vector machine (SVM) and artificial neural network (ANN) respectively. Finally, model performance was evaluated by internal and external validation and Williams diagram was drawn to determine the scopes of selected models. Results The ANN model results showed that \begin{document}$ {R}_{\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{i}\mathrm{n}}

Clinical Evidence of Oral Chinese Patent Medicines in Treatment of Chronic Kidney Disease： A Scoping Review / 中国实验方剂学杂志

ObjectiveTo review the information and clinical studies of oral Chinese patent medicines （CPMs） for chronic kidney disease （CKD）. MethodThe CPMs for treating CKD were retrieved from the Pharmacopoeia of the People's Republic of China， National Essential Drugs List， and Medicine List for National Basic Medical Insurance， Employment Injury Insurance and Maternity Insurance. China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， SinoMed， PubMed， Embase， Cochrane， and Web of Science were searched for the clinical trials of the treatment of CKD by CPMs from their inception dates to September 25， 2022. A database was established with the collected CPMs， and then the general conditions of the clinical trials were analyzed and presented visually. ResultA total of 16 CPMs for CKD were included in this study， including 5 classical traditional Chinese medicine （TCM） prescriptions involving Rehmanniae Radix and 11 new CPMs. The indications of the TCM prescriptions did not mention the corresponding western disease names， and those of the new CPMs mainly included chronic renal insufficiency， chronic renal failure， and chronic nephritis. Four CPMs were prepared with single Chinese medicine or active components. Specifically， Bailing Preparation and Jinshuibao Preparation were mainly prepared with the powder of Cordyceps， and the main components of Haikun Shenxi capsules and Huangkui capsules were fucoidan sulfate and the flower extract of Abelmoschi Corolla， respectively. The CPMs mainly exerted tonifying and eliminating effects on the lung， spleen， and kidney. A total of 892 clinical trials were screened out， covering all the areas in China and presented an increasing trend. Bailing Preparation was the most studied， followed by Niaoduqing Preparation. Among the 892 studies， 475 focused on single CPMs without combination with other CPMs or therapies. These studies mainly compared between conventional intervention and conventional intervention + CPM， which accounted for 75.58%. The 475 studies covered different kidney diseases， such as chronic kidney disease， chronic renal failure， nephrotic syndrome， diabetic kidney disease， IgA nephropathy， and membranous nephropathy， and involved a variety of populations including the elderly and children. Thirty-six studies evaluated TCM syndromes， reflecting the characteristics and advantages of TCM treatment. ConclusionThere are abundant oral CPMs for CKD， with varied efficacy and characteristics for different kidney diseases. However， the instruction manuals of the oral CPMs are not detailed or standard. According to the clinical research evidence in this field， the research on oral CPMs for CKD is characterized by a wide scope， rich study types， and wide disease coverage， while the sample size and quality remain to be improved.

Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.

Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

OBJECTIVE@#To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.@*METHODS@#Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.@*RESULTS@#A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.@*CONCLUSION@#The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

The role of the high-level public health school in the development of the Center for Disease Control and Prevention / 中华流行病学杂志

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.