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.

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.

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.

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.

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.

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

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.

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.

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.

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.

Study on the consistency and correlation of different methods for measuring energy consumption in patients with severe acute pancreatitis / 中华消化杂志

Objective:To analyze the consistency and correlation of indirect calorimetry (IC) and Harris-Benedict estimation method (H-B) in measuring energy consumption in patients with severe acute pancreatitis (SAP), as well as the characteristics of energy metabolism at resting state of SAP patients with different etiologies, and so as to guide the formulation of clinical energy nutrition support program.Methods:From February 1 to December 31, 2019, 61 SAP patients admitted into the intensive care unit of the First Affiliated Hospital of Nanchang University were enrolled. Collected relevant data of patients, such as the etiology of SAP, whether mechanical ventilation was needed, as well as the metabolic status. All SAP patients accepted IC test on the first day after admission to intensive care unit. According to the energy consumption measured by IC (hereinafter referred to as IC value) and the energy consumption measured by H-B (hereinafter referred to as H-B value), SAP patients were determined to be in high, normal or low metabolic state. Bland-Altman method and Pearson linear regression were used to analyze the consistency and correlation of the two methods in measuring energy consumption, and the linear equation was fitted. Paired t test was used for statistical analysis. Results:Among the 61 SAP patients, 13 cases were biliary SAP, 30 cases were hyperlipidemic SAP, 6 cases were alcoholic SAP, and 12 cases were SAP of other causes or unknown causes. Nineteen cases needed mechanical ventilation and 42 cases did not need mechanical ventilation. There were 70.5% (43/61) of SAP patients in high metabolic state, 13.1%(8/61) of SAP patients in normal metabolic state, and 16.4% (10/61) of SAP patients in low metabolic state. The IC value in 61 SAP patients was higher than H-B value((8 604.7±367.8) kJ/d vs. (6 491.2±133.7) kJ/d), and the difference was statistically significant ( t=5.95, P<0.001). The IC value in patients with hyperlipidemic, alcoholic and biliary SAP was (8 815.2±537.9), (7 631.2±890.5), and (8 108.0±933.1) kJ/d, respectively, and the H-B value was (6 869.6±204.5), (5 916.8±153.7), and (5 974.2±200.9) kJ/d, respectively. The IC value in patients with biliary or hyperlipidemic SAP were higher than H-B value, and the differences were statistically significant( t=2.29 and 3.38, both P<0.05). The IC value and H-B value in SAP patients with mechanical ventilation and without mechanical ventilation were (10 485.0±741.1) and (6 462.6±222.8) kJ/d, (6 595.1±364.7) and (6 503.2±166.7) kJ/d, respectively. The IC value in SAP patients with mechanical ventilation was higher than H-B value and the IC value in SAP patients without mechanical ventilation, and the differences were statistically significant ( t=4.71 and 5.20, both P<0.001). The consistency analyzed by Bland-Altman method showed that the two methods had obvious biases, and the average bias value was 92.2 kJ/d. The result of Pearson linear regression analysis indicated that there was a linear relationship between two methods ( r=0.44, P<0.001). The linear equation fitted by the univariate regression was Y=1.240 6 X+ 154.42, in which X was the H-B value and Y was the IC value. Conclusions:SAP patients are mostly in a hypermetabolic state in the early stages of the disease. The IC value is higher than H-B value, and it is recommended to use IC to measure energy consumption in SAP patients.

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.

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.

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.

Comparison of effects of Xuebijing injection and its component hydroxysafflor yellow A on coagulation and survival rates of septic rats / 中华危重病急救医学

Objective:To explore the effects of Xuebijing injection and its component hydroxysafflor yellow A on coagulation and survival rates of septic rats.Methods:① Assessment of coagulation: 144 male Sprague-Dawley (SD) rats were divided into four groups by random number table: sham group, cecal ligation and puncture (CLP) induced sepsis model group (CLP group), CLP+Xuebijing group, and CLP+hydroxysafflor yellow A group, with 36 rats in each group. CLP was used for reproducing septic models. The cecum of the rats in the sham group was exposed by laparotomy and then returned to the abdominal cavity without CLP, while the other steps were the same as those in the CLP group. Rats in the CLP+Xuebijing group and CLP+hydroxysafflor yellow A group were injected with Xuebijing (4 mL/kg, twice a day) or hydroxysafflor yellow A solution (0.378 g/L, 298 μg each time, twice a day) through caudal vein after operation. Levels of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), and D-dimer in peripheral blood were measured by automatic coagulation analyzer at 6, 12, 24 hours after operation. The enzyme linked immunosorbent assay (ELISA) was applied to determine levels of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and soluble thrombomodulin (sTM) in peripheral blood. ② Analysis of survival rates: 120 rats were divided into four groups by random number table (the same groups with those in the section of assessment of coagulation), with 30 rats in each group. The Kaplan-Meier survival curve was plotted, and the cumulative survival rates were observed and recorded for 7 days after CLP surgery.Results:① Results of coagulation assessment: compared with the sham group, septic rats in the CLP group showed significant dysfunction in coagulation early, as evidenced by prolonged PT at 6 hours after CLP (s: 8.9±0.2 vs. 8.4±0.4, P < 0.01), and significantly increased levels of Fib, D-dimer, TFPI and sTM [Fib (g/L): 2.8±0.3 vs. 2.3±0.1, D-dimer (ng/L): 1.8±0.2 vs. 1.5±0.1, TFPI (ng/L): 131.1±10.9 vs. 102.8±10.5, sTM (μg/L): 27.2±1.2 vs. 19.8±2.9, all P < 0.01]. The coagulation dysfunction became more and more serious at 12 hours after operation, and further deteriorated with time. The use of both Xuebijing and hydroxysafflor yellow A revealed significant improvement in coagulation of septic rats at 6 hours, as shown by shortened PT (s: 8.3±0.2, 8.3±0.1 vs. 8.9±0.2, both P < 0.01), and decreased Fib, D-dimer, TFPI and sTM as compared with those in the CLP group [Fib (g/L): 2.3±0.1, 2.3±0.2 vs. 2.8±0.3; D-dimer (ng/L): 1.5±0.1, 1.5±0.2 vs. 1.8±0.2; TFPI (ng/L): 109.5±10.2, 91.5±5.0 vs. 131.1±10.9; sTM (μg/L): 22.3±1.5, 21.1±1.8 vs. 27.2±1.2; all P < 0.01]. However, there was no significant difference in coagulation function between the two intervention groups. ② Results of survival rates analysis: the rats in the sham group all survived 7 days after operation. The 7-day cumulative survival rate of the CLP group was only 36.67% (11/30). Compared with the CLP group, the cumulative survival rates were significantly increased in rats of the CLP+Xuebijing group and CLP+hydroxysafflor yellow A group [66.67% (20/30), 66.67% (20/30) vs. 36.67% (11/30), both P < 0.05], but no significant difference was found between the CLP+Xuebijing group and CLP+hydroxysafflor yellow A group. Conclusion:Both Xuebijing and its component hydroxysafflor yellow A appear to be capable of alleviating coagulation disorders and improving survival rates of septic rats effectively, and the effects show no significant difference between them.

Prevalence and risk factors of osteoarthritis in patients with type 2 diabetes in Beijing, China from 2015 to 2017 / 北京大学学报(医学版)

OBJECTIVE@#To explore the prevalence and related factors of osteoarthritis in patients with type 2 diabetes mellitus, and provided a scientific basis for the prevention of the comorbidity.@*METHODS@#The data were obtained from the database of all designated medical institutions in Beijing from 2015 to 2017. Data of the adult patients with type 2 diabetes mellitus were collected for descriptive analysis, and a Logistic regression model was used to explore the related factors of osteoarthritis in the patients with type 2 diabetes mellitus.@*RESULTS@#A total of 1 046 264 diagnosed type 2 diabetes mellitus adult patients were included in our study, with an average age of 63.07 years, and 50.78% were males. Among the patients with type 2 diabetes mellitus, there were 341 561 cases with osteoarthritis, and the prevalence of osteoarthritis was 32.65%. The prevalence of females (38.05%) was higher than that of males (27.41%), and the difference was statistically significant (P < 0.05). Osteoarthritis occurred in all age groups among the patients with type 2 diabetes mellitus, with the highest prevalence of osteoarthritis in the age group of 65-69 years (36.76%), and the lowest prevalence in the age group ≤44 years (14.3%). Before the age of 70, the prevalence increased with age. Further analysis of related factors for osteoarthritis in the patients with type 2 diabetes mellitus showed that female (OR=1.62, 95%CI: 1.61-1.63), age (OR=1.01, 95%CI: 1.01-1.01), had other comorbidities (OR=1.19, 95%CI: 1.18-1.21), used hypoglycemic drugs (OR=0.79, 95%CI: 0.78-0.80), having the cardiovascular disease (OR=1.13, 95%CI: 1.11-1.15), having cerebrovascular disease (OR=1.25, 95%CI: 1.23-1.28), and having nephropathy (OR=1.61, 95%CI: 1.51-1.71) were associated with the osteoarthritis in the type 2 diabetic mellitus patients.@*CONCLUSION@#Our study revealed that the prevalence of osteoarthritis in patients with type 2 diabetes mellitus is high in Beijing area. Health education and disease monitoring should be strengthened in middle-aged and elderly patients. Screening for comorbidities should be carried out as soon as possible, with the focus on menopausal women.

Meta-analysis of Oral Chinese Medicine for Adjuvant Treatment of Primary Hepatic Carcinoma and Screening of Basic Chinese Herbs / 中国实验方剂学杂志

Objective:To systematically evaluate the efficacy of oral Chinese herbal prescriptions combined with transcatheter arterial chemoembolization （TACE） against primary hepatic carcinoma （PHC） and screen the basic Chinese herbs，in order to provide certain reference for clinical medication. Method:The randomized controlled trials concerning the treatment of PHC with oral Chinese herbal prescriptions plus TACE were retrieved from CBM，China National Knowledge Infrastructure （CNKI），Chongqing Weipu Database for Chinese Technical Periodicals （VIP），and Wanfang Data Knowledge Service Platform.The quality of the included trials was evaluated by Cochrane handbook，and the Meta-analysis was performed using RevMan 5.3.The enumeration data were expressed by odds ratio （OR），the measurement data by mean difference （MD） or standardized mean difference （SMD），and the effect size by 95% confidence interval （CI）.The data of oral Chinese herbal prescriptions involved in trials were sorted out and subjected to association rule analysis and frequency analysis based on the Traditional Chinese Medicine Inheritance Support System （TCMISS），for exploring the basic Chinese herbs and their dosages against PHC. Result:A total of 75 randomized controlled trials were included，involving 7 406 cases. As revealed by the Meta-analysis，oral Chinese herbal prescriptions combined with TACE was significantly better than TACE alone in improving the short-term curative effect ［OR=2.05，95%CI（1.83，2.29）］，decreasing alpha fetoprotein （AFP） ［MD=-59.02，95%CI（-79.03，-39.01）］，ameliorating liver function ［SMD=-1.23，95%CI（-1.58，-0.88）］，boosting immunity ［SMD=1.08，95%CI（0.84，1.32）］，adjusting Karnofsky Performance Status （KPS） scale score ［OR=2.7，95%CI（1.11，11.02）］，elevating survival rate ［OR=2.31，95%CI（1.96，2.71）］，and reducing adverse reactions ［OR=0.38，95%CI（0.34，0.43）］.Data mining results showed that the basic Chinese herbs against PHC were Bupleuri Radix，Paeoniae Alba Radix，Atractylodis Macrocephalae Rhizoma，Poria，and Glycyrrhizae Radix et Rhizoma，with their clinical dosages listed as follows：6-15 g for Bupleuri Radix，10-15 g for Paeoniae Alba Radix，9-15 g for Atractylodis Macrocephalae Rhizoma，10-15 g for Poria，and 3-10 g for Glycyrrhizae Radix et Rhizoma. Conclusion:The oral Chinese herbal prescriptions combined with TACE produce better effects in treatment of PHC as compared with TACE alone.These five basic Chinese herbs have anti-cancer effect，and their dosages are within the ranges stipulated in 2020 edition of <italic>Chinese Pharmacopoeia.</italic>This Meta-analysis has provided certain reference for clinical medication.

Surveillance of Culex mosquitoes in Jiangsu Province from 2018 to 2019 / 中国血吸虫病防治杂志

Objective To investigate the distribution and density of Culex mosquito populations and the resistance of Culex pipiens pallens to insecticides in Jiangsu Province in 2018 and 2019. Methods During the period from June to October in 2018 and 2019, six counties (districts, cities) were sampled in southern, northern and central Jiangsu Province as surveillance sites. The density of Culex mosquitoes was measured overnight using the light trapping technique. In addition, Culex pipiens pallens mosquitoes were collected from Hai’an of Nantong City and Yandu District of Yancheng City, central Jiangsu Province, and the sensitivity of female first filial generations to dichlorodiphenyltrichloroethane (DDT), malation, proposur, beta cypermethrin and deltamethrin was tested using the standard WHO insecticide susceptibility test assay. Results A total of 104 423 Culex mosquitoes were captured in six surveillance sites of Jiangsu Province in 2018 and 2019, and Culex quinquefasciatus (49.11%), Culex pipiens pallens (28.38%), and Culex tritaeniorhynchus (21.04%) were predominant species. The density of Culex mosquitoes started to increase since early June, peaked in July and tended to be low in late October. Culex pipiens pallens mosquitoes captured from Hai’an was susceptible to malation, while those from Yandu District were moderately resistant to malation. Culex pipiens pallens mosquitoes from both Yandu and Hai’an were moderately resistant to proposur, and were resistant to DDT, beta cypermethrin and deltamethrin. Conclusions Culex quinquefasciatus, Culex pipiens pallens and Culex tritaeniorhynchus are predominant Culex species in Jiangsu Province. Culex pipiens pallens is resistant to DT, beta cypermethrin and deltamethrin in central Jiangsu Province.

PSC-MSC-Derived Exosomes Protect against Kidney Fibrosis In Vivo and In Vitro through the SIRT6/β-Catenin Signaling Pathway

Background and Objectives@#Chronic kidney disease (CKD) has a major impact on the quality of life of patients, and renal fibrosis is a critical pathological change in the disease. It is very important to control the process of renal fibrosis to improve the quality of life of patients with CKD. The pathological mechanism of renal fibrosis is very complicated, and the current treatment strategy also has many flaws. @*Methods@#and Results: To explore a better treatment, we collected exosomes from pluripotent stem cell (PSC)-derived mesenchymal stem cells (MSC) and verified their therapeutic effect on renal fibrosis through In Vivo and In Vitro experiments. In this study, we found that PSC-MSC-derived comes could prevent the epithelial differentiation of NRK-52E cells, and with increasing exosome concentrations, the effect was improved. Furthermore, PSC-MSC-derived exosomes could reduce the pathological process of renal fibrosis, reduce inflammatory reactions and improve renal function in UUO mice. Moreover, the protective effect of exosomes against renal fibrosis may be achieved by increasing the expression of SIRT6 and decreasing the expression of β-catenin and its downstream products. @*Conclusions@#These findings suggest the possibility of PSC-MSC-derived exosomes as a new, effective therapeutic tool for kidney fibrosis.