TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism

Background@#Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. @*Methods@#In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. @*Results@#Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. @*Conclusions@#We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention / 中华肿瘤杂志

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention / 中华肿瘤杂志

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Effects of stress-induced protein Sestrin2 on necroptosis of dendritic cells induced by lipopolysaccharide / 中华危重病急救医学

Objective:To investigate the effect of stress-induced protein Sestrin2 (SESN2) on necroptosis of mouse dendritic cell (DC) induced by lipopolysaccharide (LPS) combined with zVAD, a panaspartate-specific cysteine protease (caspase) inhibitor.Methods:The DC2.4 cell line derived from the bone marrow of mouse in the 3rd to 10th generations was cultured. The cells were stimulated with LPS for 0 hour, 6 hours, 12 hours, and 24 hours, and grouped according to the stimulation time points. Western blotting was performed to determine the protein expression of SESN2 in each group. Overexpression empty lentivirus (NC), SESN2 gene overexpression RNA sequence lentivirus (SESN2 LV-RNA), small interfering empty lentivirus (NS), and SESN2 gene small interfering RNA sequence lentivirus (SESN2 siRNA) were transfected into DC2.4 cells. After 72 hours of transfection, cell fluorescence expression was observed under the inverted fluorescence microscope. Cells in each transfection group were stimulated with LPS for 24 hours. The blank control groups were set up and cultured with phosphate buffered saline (PBS) for 24 hours. Western blotting was performed to measure SESN2 protein expression. In the same groups as above, cells were stimulated with LPS+zVAD for 24 hours. The blank control groups were set up and cultured with PBS for 24 hours. Western blotting was used to determine the expression of mixed lineage kinase domain-like protein (MLKL) and phosphorylated-MLKL (p-MLKL). The p-MLKL levels and the number of positive cells were observed using laser scanning confocal microscopy. The necroptotic cell ratios were assessed by both flow cytometry and Hoechst staining.Results:Compared to the LPS 0 hour group, the expression of SESN2 in the LPS 24 hours group showed a significant increase. Therefore, 24 hours was chosen as the subsequent stimulation time point. After successful lentivirus transduction and 24 hours of cultivation, the MLKL phosphorylation level in the SESN2 siRNA+LPS+zVAD group was significantly higher than that in the NS+LPS+zVAD group. The MLKL phosphorylation in the SESN2 LV-RNA+LPS+zVAD group was significantly lower than that in the NC+LPS+zVAD group. The MLKL phosphorylation levels in both the NS+LPS+zVAD group and the NC+LPS+zVAD group were obviously higher than those in the NS+PBS group and the NC+PBS group, respectively. Laser scanning confocal microscopy showed that the trends in quantity and fluorescence intensity of p-MLKL protein expressions were consistent with the above results. The results from flow cytometry analysis and Hoechst staining showed that the rates of cell necrotic apoptosis in SESN2 siRNA+LPS+zVAD group were significantly higher than those in NS+LPS+zVAD group [flow cytometry analysis: (30.800±1.153)% vs. (20.800±1.114)%, Hoechst staining: (75.267±0.451)% vs. (46.267±3.371)%, both P < 0.05], indicating that knocking down SESN2 further exacerbated the occurrence of necroptosis. The necrotic apoptosis rates in SESN2 LV-RNA+LPS+zVAD group were significantly lower than those in NC+LPS+zVAD group [flow cytometry analysis: (7.160±0.669)% vs. (19.240±2.322)%, Hoechst staining: (32.433±3.113)% vs. (48.567±4.128)%, both P < 0.05], indicating that overexpressing SESN2 reversed such response and markedly reduced the proportion of necroptotic cells compared to the corresponding empty vector group. Conclusion:SESN2 exhibits an inhibitory effect on necroptosis of DC in sepsis. Targeted SESN2 expression may regulate the process of DC-mediated immune response in sepsis.

Chinesization of the HEMO-FISS-QoL questionnaire and its reliability and validity / 中华行为医学与脑科学杂志

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Study on value-based medical insurance access and pricing methods of multi-indication drugs / 中国药房

OBJECTIVE To discuss medical insurance access and pricing methods for multi-indication drugs. METHODS The access situation of multi-indication drugs in China’s medical insurance negotiation over the years was sorted out. Referring to the economic theory of value-based pricing and the relevant experience of other countries， five applicable pricing methods of 3 categories for multi-indication drug in China were summarized. Taking ceftazidime-avibactam（CAZ-AVI） as an example， cost- utility analyses were performed for different indications， and appropriate pricing methods were applied. RESULTS & CONCLUSIONS All multi-indication drugs in China adopted a single pricing method. The pricing methods that could be explored include product-based pricing， such as single pricing based on the lower-value indication or mixed/weighted single pricing； indication-based pricing， such as developing a new agreement for single pricing under different discounts and listing with different brands and pricing of the same medicine for different indications； and compensation for access restrictions. Each method has its advantages and limitations. The case of CAZ-AVI showed that it is necessary to estimate the value of each indication for multi- indication drugs， and comprehensively consider appropriate access conditions and pricing methods based on value. Although single pricing is simple to operate， it is different to reflect the value entirely. The indication-based pricing and compensation for access restrictions all depend on the information collection system and the cooperation of multiple departments. China is supposed to carry out the value-based pricing of multi-indication drugs and constantly explore reasonable access methods to improve overall social welfare.

Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment / 中国中药杂志

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

Treatment and factors associated with prognosis of hyperkalemia in the emergency department / 中华危重病急救医学

Objective:To survey treatment and prognosis of hyperkalemia patients in the emergency department and to analyze factors associated with all-cause in-hospital mortality.Methods:We implemented electronic hospital information system, extracted demographic characteristics, underlying diseases, laboratory findings, potassium lowering therapy and prognosis of hyperkalemia patients [age ≥ 18 years, serum potassium (K +) concentration ≥ 5.5 mmol/L] in the emergency department of Peking Union hospital in Beijing between June 1st 2019 to May 31st 2020. The enrolled subjects were divided into the non-survival group and the survival group according to their prognosis. Univariate analysis and Cox regression model were adopted to analyze factors affecting all-cause in-hospital mortality of hyperkalemia patients. Results:A total of 579 patients [median age 64 (22) years; 310 men (53.5%) and 269 women (46.5%)] with hyperkalemia were enrolled, among which, 317 (54.7%), 143 (24.7%) and 119 (20.6%) were mild, moderate, and severe hyperkalemia, respectively. 499 (86.20%) patients received potassium-lowering therapy, forty-four treatment regimens were administered. Insulin and glucose (I+G, 61.3%), diuretics (Diu, 57.2%), sodium bicarbonate (SB, 41.9%) and calcium gluconate/chloride (CA, 44.4%) were commonly used for the treatment of hyperkalemiain the emergency department. The combination of insulin and glucose, calcium gluconate/chloride, diuretics and sodium bicarbonate (I+G+CA+Diu+SB) was the most favored combined treatment regimen of hyperkalemia in the emergency department. The higher serum potassium concentration, the higher proportion of administrating combined treatment regimen and/or hemodialysis (HD) (the proportion of administrating combined treatment regimen in mild, moderate, and severe hyperkalemia patients were 58.4%, 82.5% and 94.8%; the proportion of administrating HD in mild, moderate, and severe hyperkalemia patients were 9.7%, 13.3% and 16.0%, respectively). The proportion of achievement of normokalaemia elevated as the kinds of potassium lowering treatment included in the combined treatment regimen increased. The proportion of achievement of normokalaemia was 100% in the combined treatment regimen including 6 kinds of potassium lowering therapy. Among various potassium lowering treatments, HD contributed to the highest rate of achievement of normokalaemia (93.8%). 111 of 579 (19.20%) hyperkalemia patients died in hospital. Cox regression model revealed that complicated with cardiac dysfunction predicted higher mortality [hazard ratio ( HR) = 1.757, 95% confidence interval (95% CI) was 1.155-2.672, P = 0.009]. Achievement of normokalaemia and administration of diuretics attributed to lower mortality ( HR = 0.248, 95% CI was 0.155-0.398, P = 0.000; HR = 0.335, 95% CI was 0.211-0.531, P = 0.000, respectively). Conclusions:Treatment of hyperkalemia in the emergency department were various. Complicated with cardiac dysfunction were associated with higher mortality. Achieving normokalaemia was associated with decreased mortality.

Bilateral hypertensive intracerebral hemorrhage in basal ganglia: a case report / 中华神经科杂志

Hypertensive intracerebral hemorrhage (ICH) is mostly single in basal ganglia, thalamus and pons. Simultaneous hemorrhage in other brain regions is relatively rare, accounting for only 5.6% of all hemorrhagic strokes, while bilateral symmetrical hemorrhage is extremely rare. A case of bilateral basal ganglia symmetrical hemorrhage is reported for clinical reference.

Changes in choroidal thickness: a potential indicator of inflammatory response / 中华实验眼科杂志

Choroidal thickness is susceptible to age, sex and hormone levels under normal physiological conditions.In addition, under pathological conditions, the choroid is also vulnerable to ocular and systemic inflammatory reactions, resulting in the corresponding vascular reactivity changes, so that hemodynamic disorders will occur.When the normal physiological function of choroid is disrupted, imaging examination will show abnormal choroidal thickness.Optical coherence tomography can directly measure the changes in choroidal thickness, and its non-invasive detection method is convenient for patient follow-up and provides the basis for evaluating the progression of the disease.In recent years, researchers in various fields have proposed that the changes in choroidal thickness can become a new potential inflammatory index to evaluate ocular inflammatory diseases and systemic inflammatory diseases.In the long-term chronic inflammatory reaction, such as recurrent uveitis, systemic lupus erythematosus, rheumatoid arthritis and other diseases, the choroidal thickness is significantly lower than the normal value.But in the acute inflammatory response, such as the acute phase of sympathetic ophthalmia and the acute phase of posterior scleritis, the choroidal thickness will increase significantly compared with the normal value, and with the control of the inflammatory response, the thickened choroid will also decrease.However, the changing pattern of choroidal thickness is not the same, for example, the choroid is thickened in keratoconus, diabetic retinopathy, ankylosing spondylitis and other chronic inflammatory reactions.This article reviews the changes in choroidal thickness in ocular and systemic inflammation and its potential as a marker of inflammation.

Analysis on Influencing Factors of Ethical Cognition of Nursing Staff in Intensive Care Unit / 中国医学伦理学

【Objective:】 To explore the influencing factors of ethical cognition of intensive care unit (ICU) nursing staff. 【Methods:】 The convenient sampling method was used to select 530 ICU clinical nursing staff from 4 grade A tertiary hospitals in a city from May 2019 to May 2021 as the subjects. Univariate analysis and multivariate analysis were used to determine the influencing factors of ethical cognition of ICU nursing staff. 【Results:】 The results of univariate analysis showed that there were statistically significant differences in ethics committee knowledge scores and research ethics knowledge scores of nursing staff with different education levels, professional titles, attitudes, and training experiences (P<0.05). Among them, nursing staff with a bachelor’s degree or above had a higher total score of ethical cognition than those with a specialized degree or below (P<0.05), the total score of ethical cognition among professor of nursing was higher than that of nurses, nurse practitioners, and nurses-in-charges (P<0.05), the total score of ethical cognition among nursing staff with positive attitudes was higher than that of general positive nursing staff (P<0.05), and the total score of ethical cognition of nurses with training experience was higher than that of those without training experience (P<0.05). The results of multivariate analysis showed that education level, professional title, attitude, and training experience were all influencing factors of the ethical cognition among ICU nursing staff (P<0.05). 【Conclusion:】 Education level, professional title, attitude, and training experience are all influencing factors affecting the ethical cognition of ICU nursing staff, and the above factors should be combined to improve the cognitive ability of ICU nursing staff through multiple ways.

Research progress on metabolic activation of indirect carcinogens by CYP1A1 / 中国职业医学

Cytochrome P450 enzyme 1A1 (CYP 1A1) is one of the main members of CYP1A subfamily, which participates in metabolizing and activating a variety of indirect carcinogens. CYP1A1 can induce carcinogenesis by participating in activating exogenous compounds to produce intermediates or active metabolites that bind to specific biomolecules. CYP1A1 plays a critical role in the metabolic activation of benzo(a)pyrene e ［B(a)P］, and plays a key role in activating the toxic and carcinogenic effects of B(a)P. CYP1A1 involves in the metabolic activation of 7,12-dimethyl benzanthracene and 2-amino-1-methyl-6-phenylimidazo［4,5-b］pyridine (PhIP), and plays an important role in PhIP-induced genotoxicity. CYP1A1 is the main enzyme to metabolize and activate 7H-dibenzo［c,g］carbazole (DBC), a key factor in the carcinogenic effect of DBC. CYP1A1 is also associated with metabolic activation of indirect carcinogens such as aflatoxin B1, 3-nitrobenzene, and naphthalene. Inhibition of the catalytic activity of CYP1A1 can decrease the CYP1A1-mediated activity of carcinogens, thus playing a role in the prevention and treatment of malignant tumors.

Effect of astaxanthin on blood brain barrier injury and cognitive impairment in db/db mice and its mechanism / 中国药理学通报

Aim To investigate the effect of astaxanthin (ASTA) on the blood brain barrier (BBB) injury and cognitive disorders in mice induced by hyperglycemia and the possible mechanism. Methods db/db mice aged eight weeks were administered ASTA (5, 10, 20 mg • kg

Luteolin regulates M1 macrophage polarization by inhibiting glycolytic pathway induced by HIF-1 / 中国药理学通报

Aim To investigate the effect of luteolin on M1 macrophages polarization through HIF-1α-mediated glycolytic pathway. Methods RAW264.7 cells were divided into control groups(M0)and LPS+IFN-γ groups(M1). M1 groups were further divided into luteolin group, 2-DG(glycolysis inhibitor)group, luteolin+2-DG group,luteolin+DMOG(HIF-1α agonist)group. The protein expression levels of iNOS, Arg-1 and HIF-1α were detected by Western blot. Macrophage phenotype was detected by flow cytometry. In addition, the expression levels of IL-6 and IL-10 were measured by ELISA. The gene expression levels of GLUT1, HK2, PFK1, PK and HIF-1α were quantified by quantitative real-time PCR. Results Compared with M1 groups, luteolin and luteolin+2-DG treatment groups decreased the expression levels of GLUT1, HK2, PFK1, PK and HIF-1α related to glycolysis. In addition, luteolin and luteolin+2-DG treatment group significantly inhibited the expression of M1 macrophage markers such as iNOS, CD86 and IL-6, whereas up-regulated M2 macrophage markers Arg-1, CD206 and IL-10. Notably, the inhibitory effects of luteolin on M1 macrophages were restored by DMOG. Conclusion Luteolin regulates M1 macrophage polarization by inhibiting the glycolytic pathway induced by HIF-1α.

Mechanism of BCL2L2-PABPN1 expression induced by sodium arsenite and its metabolites in 16HBE cells / 中国职业医学

@#Objective - - （BCL2L2）- （ ） To investigate the differential expression of the fusion gene BCL 2 like protein 2 poly A （PABPN1） （ ） binding protein nuclear 1 induced by sodium arsenite SA and its methylated metabolites in 16HBE cells and the Methods ） ， related mechanism. i The 16HBE cells exposed to SA at concentrations of 1.5 3.0 and 4.5 µmol/L were set as -， - - low medium and high dose arsenic exposure groups. The 16HBE cells exposed to 4.5 µmol/L monomethylarsonic acid （ ）， （ ） ， MMA dimethylarsonic acid DMA and SA were set as MMA group DMA group and SA group. The 16HBE cells without ， BCL2L2-PABPN1 toxic stimulation were set as control group. After the cells were cultured for 48 hours the expression of was - （ - ） ） （ ） detected by quantitative real time polymerase chain reaction qRT PCR . ii Two small interfering RNA siRNA silencing 基金项目：国家自然科学基金（ ）； 年云南省科技厅昆明医科大学应用基础研究联合专项面上项目 82160607 2021 （ ） 202101AY070001-054 作者简介：施雅（ —），女，在读大学本科生，主要从事劳动卫生与环境卫生学研究；尹锦瑶（ —），女，在读劳动卫生与环境卫 2001 1995 生学硕士研究生，主要从事劳动卫生与环境卫生学研究；施雅和尹锦瑶为共同第一作者 通讯作者：何越峰教授，博士研究生导师，- ： E mail heyuefeng@kmmu.edu.cn中国职业医学 年 月第 卷第 期 ， ， ， · · 2022 10 49 5 Chin Occup Med October 2022 Vol.49 No.5 523 BCL2L2-PABPN1， - fragments were designed and transfected into 16HBE cells to knockdown which were set as siRNA 1 group - - BCL2L2-PABPN1 and siRNA 2 group. Non transfected control group without knockdown of transfection was set up. After ， BCL2L2-PABPN1 - culturing for 48 hours the expression level of in the three groups of cells was detected by qRT PCR. The cell - survival rate and early apoptosis rate were detected by MTS method and JC 1 mitochondrial membrane potential detection ， （ ） ， method respectively. The apoptosis was detected by Hoechest33342/propidium iodide PI double staining and the expression - Results ） level of P53 signaling pathway related proteins was detected by Western blotting. i The relative expression of BCL2L2-PABPN1 （P ） BCL2L2- in 16HBE cells increased with the increasing SA doses <0.01 . The relative expression of PABPN1 - ， - - in high dose arsenic exposure was higher than that in control group low dose and medium dose arsenic exposure （ P ） BCL2L2-PABPN1 ， groups all <0.05 . The relative expression of in SA group was higher than those in control group MMA （ P ） BCL2L2-PABPN1 group and DMA group all <0.05 . The relative expression of showed no significant difference between ， （ P ） ） BCL2L2-PABPN1 control group MMA group and DMA group all >0.05 . ii The relative expression levels of and cell - - - （ P ） survival rate in siRNA 1 group and siRNA 2 group were lower than those in non transfected control group all <0.05 . ， （P ） However there was no significant difference in the early apoptosis rate among the three groups >0.05 . The results of - Hoechest33342/PI double staining showed that the number of nuclear shrinkage and early apoptotic cells in siRNA 1 group and - - ， - siRNA 2 group was higher than that in non transfected control group. The relative protein expression levels of P53 phospho ， - - ， - - （ P ） p53 BCL 2 associated death promoter P21 and cytochrome C in siRNA 1 group and siRNA 2 group were higher all <0.05 , - - P and the relative protein expression levels of P53 up regulated modulator of apoptosis were lower (all <0.05), when compared - Conclusion with the non transfected control group. SA may block the apoptosis of 16HBE cells by inducing the expression of BCL2L2-PABPN1 fusion gene . The mechanism may be related to the activation of P53 signaling pathway. The SA methylated BCL2L2-PABPN1 BCL2L2-PABPN1 - metabolites MMD and DMA had no effect on the expression of . may affect anti apoptosis BCL2L2 PABPN1 through affecting the synergistic effect of and genes.

The effect of ribophagy on lipopolysaccharide-induced apoptosis of dendritic cells / 中华急诊医学杂志

Objective:To investigate the role and significance of NUFIP-1-mediated ribophagy in apoptosis of dendritic cells (DCs) stimulated by lipopolysaccharide (LPS).Methods:Cultured mouse dendritic cell line DC2.4 were divided into the blank control group and LPS stimulation groups for 6, 12, 24, 48 and 72 h ( n=5). LPS subgroups were consistently cultured with 1 μg/mL LPS for the corresponding incubation time. Western blot was adopted to detect the expression levels of NUFIP-1 and autophagy-related proteins p62 and LC3B across groups. Laser scanning confocal microscopy (LSCM) was applied to detect the expression and cellular localization of NUFIP-1, with its co-localization with Lyso-tracker and LC3B, respectively. The silencing blank vector NS and silencing virus vector NUFIP-1 siRNA were transferred into DC2.4 ( n=3) and stimulated with 1 μg/mL LPS for 24 h. The apoptosis of DC2.4 was measured by flow cytometry analysis. The expression levels of apoptosis-related proteins were determined using Western blot, including cleaved caspase-3 and Bcl-2. One-way analysis of variance (ANOVA) was applied for comparison among multiple groups, and LSD-t method was used for subsequent pairwise comparison. A P<0.05 was considered statistically significant. Results:The results of Western blot showed that expression level of NUFIP-1 in DC2.4 revealed a trend of first increasing and subsequent decreasing upon LPS stimulation for different times (6, 12, 24, 48 and 72 h), and the expression level of NUFIP-1 in the LPS 24 h group was significantly higher than that in the blank control group [blank control group: (0.6786 ± 0.0820); LPS 24 h group: (1.4830 ± 0.1170); P<0.01]. Meanwhile, p62 expression in the LPS 24 h group was significantly lower than that in the blank control group [blank control group: (0.9087 ± 0.1235); LPS 24 h group: (0.3113 ± 0.5571); P<0.01]. Moreover, the conversion from LC3B-I to LC3B-II in the LPS 24 h group was significantly higher than that in the blank control group [blank control group: (0.5542 ± 0.1248); LPS 24 h group: (2.5310 ± 0.3119); P<0.01]. LSCM indicated that NUFIP-1 was predominantly located in the nucleus and perinuclear area in DC2.4. The fluorescence intensity of NUFIP-1 increased in a time-dependent manner from 6 h to 24 h after LPS stimulation, whereas a significant reduction could be observed at 48 h and 72 h after LPS stimulation. Meanwhile, the co-localization of NUFIP-1 with Lyso-tracker and LC3B was substantially reinforced in comparison with the blank control group. Transfection of NUFIP-1 siRNA through lentivirus transfection technology significantly down-regulated the expression level of NUFIP-1 in DC2.4, with statistical differences compared with the blank control group and empty vector group [blank control group: (0.6627 ± 0.1707); empty vector group: (0.6966 ± 0.1107); siRNA group: (0.1428 ± 0.0296); P<0.05]. Flow cytometry analysis revealed that the apoptotic rate of LPS-stimulated DC2.4 was significantly higher in the NUFIP-1 siRNA transfection group than that in the blank control group and empty vector group [blank control LPS 24 h group: (47.91% ± 1.006%); empty vector LPS 24 h group: (70.26% ± 1.011%); siRNA LPS 24 h group: (80.23% ± 2.094); P<0.01]. Western blot analysis of apoptosis-related protein further confirmed that the expression level of cleaved caspase-3 was significantly elevated in the NUFIP-1 siRNA transfection group compared to those of the blank control group and empty vector group under LPS challenge [blank control LPS 24 h group: (0.4748 ± 0.0876); empty vector LPS 24 h group: (0.2849 ± 0.0418); siRNA LPS 24 h group: (0.9733 ± 0.0525); P<0.01]. Likewise, expression of Bcl-2, an anti-apoptotic protein was significantly down-regulated in the siRNA LPS 24 h group [blank control LPS 24 h group: (0.7810 ± 0.0490); empty vector LPS 24 h group: (0.8292 ± 0.0729); siRNA LPS 24 h group: (0.3957 ± 0.0838); P<0.05]. Conclusions:NUFIP-1-mediated ribophagy is significantly activated in DC2.4 upon LPS stimulation, exerting an underlying protective effect on apoptosis.

Incidence and risk factors of ischemic stroke in patients with type 2 diabetes among urban workers in Beijing, China / 北京大学学报(医学版)

OBJECTIVE@#To explore the incidence of ischemic stroke after the onset of type 2 diabetes, and further analyze the risk factors, so as to provide a basis for further research.@*METHODS@#The data were obtained from the database of the Beijing Urban Employee Basic Medical Insurance Database. The study used a prospective design to describe the incidence of ischemic stroke in patients with type 2 diabetes. In our study, these patients were followed up for seven years. Multivariate Logistic regression models were used to analyze the risk factors of ischemic stroke in patients with type 2 diabetes.@*RESULTS@#A total of 185 813 newly diagnosed type 2 diabetes patients were enrolled, with an average age of (58.5±13.2) years, and 49.0% of them were males. A total of 10 393 patients with newly diagnosed ischemic stroke occurred in 7 years, with a cumulative incidence of 5.6% and an incidence density of 8.1/1 000 person-years. Ischemic stroke occurred in all age groups in patients with type 2 diabetes. The cumulative incidence was 1.5% (95%CI: 1.3%-1.6%) in group ≤44 years old, 3.6% (95%CI: 3.4%-3.7%) in group 45-54 years old, 5.4% (95%CI: 5.2%-5.5%) in group 55-64 years old, and 9.2% (95%CI: 9.0%-9.4%) in group ≥65 years old, and the cumulative incidence increased with age (P < 0.05). Cumulative incidence rate of the males (6.8%, 95%CI: 6.7%-7.0%) was higher than the females (4.4%, 95%CI: 4.3%-4.6%). Among the patients < 80 years old, the cumulative incidence rate of the males was higher than that of the females in all the age groups. In the patients ≥80 years of age, the cumulative incidence was higher in the females (9.2%) than in the males (7.9%). Further analysis revealed that complications, such as coronary heart disease (OR=3.18, 95%CI: 2.72-3.72), heart failure (OR=1.53, 95%CI: 1.32-1.79) and kidney failure (OR=1.45, 95%CI: 1.20-1.75) were associated with ischemic stroke in the patients with type 2 diabetes.@*CONCLUSION@#The incidence level of ischemic stroke in patients with type 2 diabetes is high. It is necessary to strengthen the management of risk factors in elderly patients, screen the complications of type 2 diabetes as early as possible, and take active preventive and control measures.

Comparative study on Sichuan yak pericardium and Australian cattle pericardium / 生物医学工程学杂志

Currently, as the key raw material of artificial biological heart valve, bovine pericardium is mainly depend on import and has become a "bottleneck" challenge, greatly limiting the development of domestic biological heart valve. Therefore, the localization of bovine pericardium is extremely urgent. In this study, the pericardium of Sichuan yak was compared with that of Australian cattle in terms of fundamental properties and anti-calcification performance. The results demonstrated that the appearance and thickness of yak pericardium were more advantageous than the Australian one. Sichuan yak pericardium and Australian cattle pericardium had comparable performance in shrinkage temperature, mechanical test and anti-calcification test. This study preliminarily verifies the feasibility of substitution of Australian cattle pericardium by Sichuan yak pericardium and promotes the progression of bovine pericardium localization with data support.

Repair fingertip defect and soft tissue defect of donor site with nerve anastomosed relay flap / 中华显微外科杂志

Objective:To explore the method and effect of repairing fingertip defect and soft tissue defect in donor area by relay flap with suture nerve.Methods:From January 2017 to May 2019, 11 cases of fingertip defects were repaired with reverse island fascial pedicle flap of dorsal digital artery sutured with nerve, with a flap area of 0.6 cm×1.2 cm-1.6 cm×2.0 cm, and the flap donor area was repaired with dorsal metacarpal artery cutaneous branch flap. The patients were followed-up by outpatient, reexamination and WeChat interviews.Results:Twenty-two flaps of 11 cases survived completely and the wound healed in stage I. The postoperative follow-up ranged from 3 to 36 months, with an average of 13 months. The flap and pedicle were not bloated, the shape of finger was satisfactory, the texture was soft, and the skin color was close to the skin of finger. Sensory recovery≥S 3. The TPD of the flap was 6-11 mm, with an average of 8.4 mm. Hand function was evaluated according to the Trial Standard of Upper Limb Function Evaluation of Chinese Medical Association: excellent in 10 cases and good in 1 case. The patients were satisfied with the repair effect and resumed their daily life and work. Conclusion:This operation is simple, does not need to sacrifice the main blood vessels and nerves, can restore the good shape and sensction of the affected finger, with the activity close to normal. It is an effective method to repair the fingertip defect.