Physiological pacing,such as His bundle pacing and left bundle branch area pacing,could significantly enhance cardiac electromechanical synchrony.Compared to His bundle pacing,left bundle branch area pacing is associated with higher implantation success,lower and stable pacing thresholds,and lower complications.The feasibility,safety,and efficacy of left bundle branch area pacing in patients with chronic heart failure and concomitant left bundle branch block have been preliminarily confirmed,making this strategy as a gradually emerging research focus now.This article aimed to summarize relevant study results and advancements of left bundle branch area pacing in patients with combined left bundle branch block and heart failure.

Pemphigus vulgaris is the most common and serious type of pemphigus, and timely treatment can change its prognosis. This review comprehensively analyzes considerations in the treatment of pemphigus vulgaris during pregnancy and lactation as well as during the prevention and control of COVID-19 pandemic, including treatment particularities and comprehensive nursing care, in order to provide better guidance and treatment for patients.

Objective To investigate the efficacy of different doses of clopidogrel combined with aspirin in the treatment of high-risk non-disabling ischaemic cerebrovascular events(HR-NICE)under the precise guidance of point-of-care testing(POCT)of cy-tochrome P-450 2C19(CYP2C19)genotype.Methods The single-center,randomised,prospective,and blinded endpoint assess-ment was used.HR-NICE patients continuously enrolled in the stroke green channel and neurology ward of Xuzhou Central Hospital from January 2021 to January 2022,and all patients scraping of the buccal mucosa will be screened for CYP2C19 loss-of-function allele car-riers by POCT.According to the random number table method,they were divided into the intensive group(clopidogrel 150mg/d)and the conventional group(clopidogrel 75mg/d)combined with aspirin(100mg/d)dual antiplatelet for 21 days.Baseline information,acute stroke Org 10172 treatment trial(TOAST)staging and 90 days modified Rankin scale(mRS)score and occurrence of adverse events and severe adverse events were collected for the two groups.The primary efficacy outcome was new stroke within 90 days and the primary safety outcome was severe or moderate bleeding within 90 days.Results A total of 1301 patients were screened,of which 727 patients carried CYP2C19 loss-of-function allele,and 476 patients were included:236 patients in the intensive group and 240 patients in the conven-tional group.The differences between the two groups were not statistically significant at baseline(P>0.05);4 cases(1.7%)inthein-tensive group and 26 cases(10.8%)in the conventional group had a new stroke at 90 days.The differences between the two groups were statistically significant(χ2 = 16.827,P<0.001);0 case(0)in the intensive group and1 case(2.5%)in the conventional group had moderate to severe haemorrhage at 90 days.The differences between the two groups was not statistically significant(P>0.05).Conclu-sion In HR-NICE patients with CYP2C19 loss-of-function allele,the enhanced clopidogrel dose was more effective than the conven-tional dose in the treatment with the antiplatelet drug aspirin combined with clopidogrel,and had a consistent safety profile with no more adverse events such as bleeding.

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.

Objective:To investigate the association between pulse pressure(PP) and new-onset diabetes in overweight and obese people.Methods:A prospective cohort study was conducted in overweight or obese participants selected from Kailuan Study who underwent 2006-2007 annual checkup and met the inclusion and exclusion criteria. PP was calculated by blood pressure and participants were divided into 4 groups according to PP quartile. The cumulative incidence of new-onset diabetes of different PP groups was calculated by Kaplan- Meier method and compare by Log- Rank test. The multivariate Cox proportional hazards model was used to analyze the association between different PP groups and new-onset diabetes. Results:During an average follow-up of 8.45 years, 8 922 diabetes was identified. The cumulative incidence rate of the Q1, Q2, Q3, and Q4 groups were 22.12%, 24.48%, 27.97%, and 33.44% respectively, which were statistically different( χ2=368.16, P<0.01). Cox proportional hazards regression analysis showed that after adjusting for multiple confounding factors, compared with Q1 group, the hazard ratio for diabetes in Q2, Q3, and Q4 groups were 1.07(1.00-1.14), 1.13(1.05-1.21), and 1.17(1.09-1.27) respectively. And the HR of diabetes event in pulse pressure(per 1 SD increase) was 1.04(1.02-1.07). Similar results were found in participants who were over-weight, obese, with normal blood pressure or hypertensive without drugs use. Conclusion:PP is positively correlated with the new-onset diabetes. High PP is one of the risk factors for developing diabetes in overweight and obese people.

Objective:To observe the presence or absence of necroptosis in PC12 cells after radiation injury, and to detect the expression of receptor-interacting protein 3(RIP3) and evaluate its regulatory effect on necroptosis.Methods:PC12 cells were treated with different doses of irradiation and their necroptosis was detected by lactate dehydrogenase (LDH) release at different time points. After pretreatment with necroptosis inhibitor Necrostatin-1(Nec-1), the changes of cell necroptosis were detected by LDH. The expression level of RIP3 after irradiation intervention was detected by Western blot (WB). After pretreatment with the RIP3-specific inhibitor GSK′872, the changes of cell necroptosis were detected by LDH. The best transfection sequence of RIP3 knockout was screened by WB. The cells were divided into the control group, irradiation group, solvent control group, no-load control group and pretreatment group. WB, immunofluorescence staining, MTT, LDH and Annex V-fluorescein Isothiocyanate/Propidium Iodide (AnnexV-FITC/PI) flow cytometry were used for detection and analysis.Results:After 4 Gy irradiation, the degree of cell necrosis was the highest after 3 hours of culture, and the expression level of RIP3 protein was up-regulated. The cell necrosis was decreased after Nec-1, GSK′872 and RIP3 gene knockdown pretreatment.Conclusions:The radiation injury of 4 Gy can induce the necroptosis of PC12 cells, and the most significant effect can be observed when cultured for 3 hours after irradiation. RIP3 is involved in the process of necroptosis of PC12 cells induced by radiation injury, and plays a pivotal positive regulatory role.

Objective To evaluate the effects of problem-based learning (PBL) teaching mode and lecture-based learning (LBL) teaching mode applied in clinical teaching of dermatology in China.Methods All studies on PBL teaching mode and LBL teaching mode applied in clinical teaching of dermatology in China published from 1990 to 2015 were identified by searching in CNKI,VIP database,Wanfang data and so on.Meta-analysis was performed by RevMan 5.3 software.Results Six random controlled trials on 710 clinical students qualified for the meta-analysis according to our criteria.The students in PBL group got significant higher scores than those of the students in LBL group in theoretical scores [WMD=3.75,95％CI=2.58-4.92,P＜0.05],clinical skills tests [WMD=5.27,95％CI=4.60-5.94,P＜0.05] and total scores [WMD=7.93,95％CI=6.49-9.37,P＜0.05].Conclusion PBL teaching mode is an effective mode on teaching of dermatology in China,particularly for theoretical scores and clinical skills,compared with LBL mode.

Objective To investigate the role of human cytomegalovirus (CMV) in the occurrence of drug eruptions.Methods Peripheral blood samples were collected from 44 patients with drug eruptions (including 13 severe cases) and 50 healthy human controls.Taqman fluorescent real-time quantitative PCR (RT-PCR) was performed to determine the positive rate and load of CMV DNA in peripheral blood mononuclear cells (PBMCs).Enzyme-linked immunosorbent assay (ELISA) was conducted to detect anti-CMV IgM antibodies in sera.Results The positive rate of CMV DNA was significantly higher in the patients than in the controls (65.91％ (29/44) vs.28.00 ％ (14/50),x2 =13.552,P ＜ 0.05),significantly different among patients with severe drug eruptions (11/13),patients with mild drug eruptions (58.06％ (18/31)) and the controls (x2 =16.153,P ＜ 0.05).In addition,patients with severe drug eruptions showed a higher positive rate of CMV DNA compared with patients with mild drug eruptions (x2 =13.817,P ＜ 0.05) and the controls (x2 =7.237,P ＜ 0.05).CMV DNA load was significantly higher in the patients than in the controls ((28 183.829 ± 19 527.654) vs.(3 019.952 ± 1 760.952) copies,t' =8.517,P ＜ 0.05).No significant difference was found in CMV DNA load between patients with severe drug eruptions ((554 813.389 ± 722 642.498) copies),patients with mild drug eruptions ((13 290.558 ± 14 082.356) copies)) and the controls (P ＞ 0.05).The positive rate of anti-CMV IgM antibodies was similar between the patients and controls (13.64％ (6/44) vs.6.00％ (3/50),P ＞ 0.05),but significantly different among patients with severe drug eruptions (4/13),patients with mild drug eruptions (6.45％,2/31) and the controls (x2 =7.832,P ＜ 0.05),and significantly higher in patients with severe drug eruptions than in the controls (x2 =6.409,P ＜ 0.05).Conclusions CMV infection exists in patients with drug eruptions,and might be a factor associated with the initiation and aggravation of drug eruptions.

Objective To identify allergens in portunus trituberculatus responsible for atopic dermatitis (AD) in children.Methods Totally,145 child outpatients with AD were enrolled in this study from September 2013 to July 2014,and underwent the skin prick test (SPT) with crab proteins or crab-specific IgE determination assay.Then,the children with positive SPT or elevated IgE levels underwent an oral challenge with portunus trituberculatus.Serum samples were collected from 33 children with a positive oral food challenge (test group) and from 30 health check-up child examinees (control group).Total proteins were extracted from fresh portunus trituberculatus.Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot were conducted to identify the protein fragments of portunus trituberculatus responsible for AD among these children.Results The SDS-PAGE of crude protein extracts from portunus trituberculatus yielded 11 protein bands with relative molecular masses of 94 000,70 000,58 000,49 000,36 000,34 000,32 000,27 000,21 000,19 000 and 17 000 respectively.Of the 11 protein bands,only 4 with relative molecular masses of 70 000,58 000,49 000 and 36 000 respectively reacted with sera from the patients by Western blot,with the reaction rate being 93.9％,45.4％,39.4％ and 100％ respectively.None of these protein bands reacted with sera from the control group by Western blot.There were significant differences between the test group and control group in the reaction rates of the four proteins with relative molecular masses of 70 000,58 000,49 000 and 36 000 respectively to sera (x2 =55.483,17.898,14.891,63.000,all P ＜ 0.05).Conclusion The two proteins with relative molecular masses of 70 000 and 36 000 respectively are major allergens in portunus trituberculatus responsible for AD among children.

Objective To explore the role of viral infection in the development of drug eruption in patients with HIV infection, and to evaluate the efficacy of antiviral treatment. Methods This study enrolled 87 HIV-positive patients, including 11 with and 76 without drug eruption, all of whom received highly active antiretroviral therapy(HAART). Clinical data on, baseline CD4+ and CD8+ T cell counts and CD4/CD8 ratio in these subjects were retrospectively analyzed. Results The severity of drug eruption was mild in the 11 HIV-positive patients, with a mean latency period of (14.00 ± 8.10)(range, 8 - 34)days. Of the 11 patients with drug eruption, 7 had liver function impairment, which was not in accordance with the severity of skin lesions. Drug eruption was controlled in all the 11 patients after anti-anaphylactic treatment without withdrawal of antiviral drugs. Compared with 75 HIV-positive patients without drug eruption, the 11 HIV-positive patients with drug eruption showed significantly increased baseline CD4 + T cell counts (493.00 ± 245.68 (range, 42 - 810)/μl vs. 347.81 ± 167.00 (range, 11 - 814)/μl, t = 647.50, P < 0.05), but decreased proportion of patients with baseline CD4+ T cell counts below the lower limit of normal(3/11 vs. 48/75(64.00%), X2 = 3.95, P < 0.05). There were no significant differences between 10 patients with drug eruption and 69 patients without drug eruption in the baseline CD8+ T cell count(1472.30 ± 858.55/μl vs. 1356.59 ± 684.06/μl, P > 0.05), CD4/CD8 ratio(0.40 ± 0.27 vs. 0.29 ± 0.16, P > 0.05), or percentage of patients with a CD4/CD8 ratio below the lower limit of normal (9/10 vs. 68/69 (98.55%), P >0.05). Conclusions The latency period of drug eruption seems to be long in HIV-positive patients receiving HAART, and mild drug eruption can be complicated by liver function impairment in the patients. Relatively high CD4 + counts may be a risk factor for the development and aggravation of drug eruption in HIV-positive patients.