Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
Animals ; Humans ; Male ; Mice ; Rats ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Phosphodiesterase 5 Inhibitors ; Plasminogen Activator Inhibitor 1

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.
Humans ; Female ; Receptors, Chimeric Antigen/genetics* ; Carcinoma, Non-Small-Cell Lung ; CD8-Positive T-Lymphocytes ; Interleukin-2/pharmacology* ; Tumor Necrosis Factor-alpha ; Cell Line, Tumor ; HEK293 Cells ; Lung Neoplasms ; Ovarian Neoplasms ; Immunotherapy, Adoptive

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans ; Bone Density ; Low Back Pain ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy*

Background: The common reference intervals (RIs) for thyroid hormones currently used in China are provided by equipment manufacturers. This study aimed to establish thyroid hormone RIs in the population of Lanzhou, a city in the subplateau region of northwest China, and compare them with previous reports and manufacturer-provided values. Methods: In total, 3,123 individuals (1,680 men, 1,443 women) from Lanzhou, an iodine-adequate area of China, perceived as healthy were selected. The Abbott Architect analyzer was used to determine the serum concentration of thyroid hormones. The 95% RI was estimated using the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. Results: The serum levels of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), antithyroglobulin (ATG) antibody, and antithyroid peroxidase (ATPO) antibody levels were significantly correlated with sex (P<0.05). TSH, total thyroxine (TT4), and ATPO levels were significantly correlated with age (P<0.05). The serum levels of TSH, ATG, and ATPO in men were significantly lower than in women; in contrast, the serum TT3 level was significantly higher in men than in women (P<0.05). Serum TSH, TT3, TT4, and ATG levels differed across age groups (P<0.05), but no such variation was observed for ATG levels (P>0.05). The established RIs of TSH, ATG, and ATPO in this study differed between sexes (P<0.05). The thyroid hormone RIs established herein were inconsistent with the manufacturer-provided values. Conclusion The RIs of thyroid hormones in the healthy population of Lanzhou were inconsistent with those in the manufacturer’s manual. Validated sex-specific values are required for diagnosing thyroid diseases.

Objective:To explore the value of vascular endothelial-cadherin (VE-cad) in evaluating the severity of sepsis.Methods:A prospective study was conducted to select 85 patients with sepsis treated in the emergency ward of the First Affiliated Hospital of Wenzhou Medical University from June 1, 2015 to November 1, 2017. The gender, age, medical history, first infection site, number of affected organs, laboratory indexes, acute physiology and chronic health evaluationⅡ(APACHEⅡ), simplified acute physiology score Ⅱ(SAPSⅡ), sequential organ failure assessment (SOFA) and the total length of stay, emergency intensive care unit (EICU) length of stay, 28-day at admission and survival during hospitalization were measured, and the VE-cad level within 24 hours at admission was measured. The patients were divided into sepsis group and septic shock group according to the progress of the disease. The patients were divided into multiple organ dysfunction syndrome (MODS) group and non MODS group according to whether they were accompanied by MODS. The differences of the above indexes in patients with different disease progression, MODS and different prognosis were analyzed and compared. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of VE-cad in evaluating the severity of sepsis.Results:A total of 85 patients were included, mainly respiratory tract infection. Among them, 38 cases were sepsis and 47 cases were septic shock, 39 cases had MODS, 46 cases had no MODS, 64 cases survived and 21 cases died within 28 days after admission. Compared with sepsis group, the number of affected organs in septic shock group was greater [3 (2, 4) vs. 1 (0, 2)], APACHE Ⅱscore [13 (10, 21) vs. 7 (5, 12)], SAPS Ⅱscore [35 (31, 55) vs. 7 (5, 12)], SOFA score [7.0 (5.0, 10.0) vs. 3.0 (0, 5.0)], blood lactic acid [Lac (mmol/L): 3.5 (2.4, 6.2) vs. 1.9 (1.2, 2.2)], C-reactive protein [CRP (mg/L): 90.0 (58.1, 90.0) vs. 50.5 (38.0, 90.0)] and VE-cad levels [mg/L: 1.427 (1.141, 2.150) vs. 1.195 (0.901, 1.688)] were significantly increased, while platelet count [PLT (×10 9/L): 113.4±67.2 vs. 202.5±109.5] and hemoglobin (Hb) levels (g/L: 106.3±36.3 vs. 118.6±18.0) were significantly decreased (all P < 0.05). Compared with non MODS group, APACHE Ⅱ score [14 (10, 22) vs. 8 (6, 13)], SAPS Ⅱ score [36 (32, 56) vs. 29 (24, 35)], SOFA score (7.9±3.9 vs. 4.0±3.8), in-hospital mortality [53.8% (21/39) vs. 0% (0/46)], Lac [mmol/L: 3.1 (2.3, 6.3) vs. 2.1 (1.4, 4.6)] and VE-cad levels [mg/L: 1.427 (1.156, 1.937) vs. 1.195 (0.897, 1.776)] in MODS group were significantly higher, the length of stay in EICU was significantly longer [days: 6 (3, 12) vs. 3 (0, 7)], and the PLT level was significantly lower (×10 9/L: 118.2±80.0 vs. 182.5±104.0, all P < 0.05). Compared with the death group, the number of affected organs in the survival group was fewer [2 (1, 3) vs. 3 (1, 5)], APACHE Ⅱ score [9 (6, 13) vs. 21 (13, 25)], SAPS Ⅱ score [31 (25, 36) vs. 55 (35, 63)] and SOFA score (4.7±3.7 vs. 8.9±4.5) were significantly reduced, and the length of stay in EICU [days: 4 (1, 8) vs. 8 (3, 15)] was significantly shorter (all P < 0.05). ROC curve analysis showed that area under the ROC curve (AUC) of VE-cad, SOFA score and VE-cad combined with SOFA score in evaluating the severity of sepsis were 0.632 [95% confidence interval (95% CI) was 0.513-0.750], 0.830 (95% CI was 0.744-0.916) and 0.856 (95% CI was 0.779-0.933), respectively. When the cut-off value of VE-cad was 1.240 mg/L, the sensitivity was 68.1% and the specificity was 55.3%, the sensitivity of VE-cad combined with SOFA score was 85.1%, the specificity was 73.7%. Conclusion:VE-cad has a certain evaluation value for the severity of sepsis, and the evaluation value of VE-cad combined with SOFA score is better than that of VE-cad single index.

ObjectiveTo explore the mechanism of Wutou Chishizhi Wan in regulating autophagy and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β） signaling pathway in rats with myocardial ischemia-reperfusion injury （MIRI）. MethodSixty male SD rats were randomly assigned into the normal group （normal saline）， model group （normal saline）， positive control （trimetazidine， 5.4 mg·kg^-1） group， and low-， medium-， and high-dose （1.63， 4.9， 14.7 g·kg^-1， respectively） Wutou Chishizhi Wan groups， with 10 rats in each group. The rats in other groups except the normal group underwent left anterior descending coronary artery ligation for modeling. Electrocardiogram was employed to detect the ST-segment elevation to evaluate the modeling. Hematoxylin-eosin （HE） staining was performed to reveal the damage of myocardial tissue. The levels of aspartate aminotransferase （AST） and creatine kinase （CK） were determined by colorimetry， and those of cardiac troponin T （cTnT） and myoglobin （MYO） by enzyme-linked immunosorbent assay （ELISA）. Western blot was carried out to determine the protein levels of microtubule-associated proteins 1 light chain 3 （LC3）， autophagy-related gene Beclin-1， PI3K， Akt， GSK-3β， p-GSK-3β， and p-Akt. ResultCompared with the normal group， the modeling elevated the serum levels of AST， CK， cTnT， and MYO （P<0.01）， destroyed the arrangement of myocardial cells abd nucle， twisted and broken myocardial fibers， up-regulated the protein levels of LC3Ⅱ/Ⅰ and Beclin-1 （P<0.01）， and down-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Compared with the model group， trimetazidine and Wutou Chishizhi Wan （all the doses） lowered the levels of AST， CK， cTnT， and MYO in serum （P<0.01）， restored the arrangement of myocardial cells and muscle fibers， reduced necrosis， down-regulated the protein level of Beclin-1 （P<0.01）， and up-regulated the protein levels of PI3K， p-Akt， and p-GSK-3β （P<0.01）. Additionally， Wutou Chishizhi Wan （all the doses） down-regulated the protein level of LC3Ⅱ/Ⅰ （P<0.05， P<0.01）. Compared with those in the trimetazidine group， the serum AST level rose in the low-dose Wutou Chishizhi Wan group （P<0.05） and declined in the high-dose group （P<0.01）， and the protein level of Beclin-1 was down-regulated in the medium-dose group （P<0.01）. Additionally， the trimetazidine group had higher protein level of LC3Ⅱ/Ⅰ than medium- and high-dose Wutou Chishizhi Wan groups （P<0.05， P<0.01）， higher protein level of PI3K than low-， medium-， and high-dose groups （P<0.01）， lower protein level of p-Akt than low- and medium-dose groups （P<0.01）， and higher p-GSK-3β protein level than the medium-dose group （P<0.01）. ConclusionDifferent doses of Wutou Chishizhi Wan can ameliorate MIRI， and the high dose has the best effect. Wutou Chishizhi Wan can reduce the activity of myocardial injury markers AST， CK， cTnT， and MYO， and alleviate the pathological damage of myocardial tissue. It can down-regulate the protein levels of beclin-1， LC3Ⅱ/Ⅰ， and up-regulate those of PI3K， p-Akt， and p-GSK-3β. In summary， Wutou Chishizhi Wan may inhibit excessive autophagy and regulate the PI3K/Akt/GSK-3β signaling pathway to exert protective effect on MIRI rats.

Objective: To evaluate the effectiveness of project based learning of COVID 19 prevention and protection among primary school students. Methods: In February 2020, all the participants were selected from grade one, grade three and grade six in a primary school in Hefei and were randomly assigned into the experimental group (532 students) and the control group (530 students). Project based learning methods was administered in health education of COVID 19 prevention and protection in the experimental group for two weeks, with the traditional health education for the control group. Questionnaire survey was conducted before and after experimental. Results: After carrying out project based learning, the awareness rate of COVID 19 protection knowledge in the project group was 99.43%, while that in the control group was 74.74% after traditional education methods, the proportion of excellent students was 96.43% in intervention group, and 45.11% in control group, with significant statistical difference( χ 2=346.62, P <0.01). Conclusion Project based learning is superior than traditional health education in terms of improvement in self protection against COVID 19 among students.