G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Objective To investigate the preventive effect of ipratropium bromide on sufentanil-induced cough during general anesthesia induction.Methods A total of 201 patients undergoing elective surgery under general anesthesia from June 2022 to September 2024 were selected and divided into the ipratropium bromide group(group P,n=100)and the normal saline group(group C,n=101).Thirty minutes before anesthesia in-duction,group P and group C received oral administration of ipratropium bromide inhalation aerosol(2 puffs,equivalent to 42 μg C20H30BrNO3·H2O)and 0.9%normal saline spray(2 puffs),respectively.Anesthesiolo-gists intravenously administered sufentanil(0.5 μg/kg)within 5 seconds,followed by propofol(2 mg/kg)and rocuronium(0.6 mg/kg)after 3 minutes.Endotracheal intubation was performed using a videolaryngo-scope after achieving satisfactory muscle relaxation.The occurrence of cough within 1 minute after sufentanil administration was recorded.Heart rate(HR),mean arterial pressure(MAP),and pulse oxygen saturation(SpO2)were measured at different time points.Results Within 1 min after sufentanil administration,the in-cidence of severe cough and total cough in group P was significantly lower than that in group C(P<0.05).There was no significant difference in HR,MAP,or SpO2 between the two groups at different times(P>0.05).No adverse reactions such as nausea,vomiting,or arrhythmia occurred in either group.Conclusion In-haling ipratropium bromide 30 min before anesthesia induction could effectively reduce sufentanil-induced cough and decrease the incidence of severe cough.

Objective To analyze the factors affecting the prevalence of hyperuricemia(HUA)in an island troop.Methods A total of 1 113 soldiers stationed on an island from December 2021 to December 2022 were selected as research objects by cluster sampling.Their lifestyle and health information were collected.Physical examination and laboratory detection were conducted.Multivariate logistic regression was used to analyze the influencing factors of HUA.Results The prevalence rate of HUA was 21.02%(234/1 113).There were significant differences in the body mass index(BMI),waist-to-hip ratio,triglyceride,alanine aminotransferase,and creatinine between the soldiers with hyperuricemia and the soldiers with normal blood uric acid(P<0.05).Multivariate logistic regression analysis showed that BMI≥24(OR=1.49,95%CI:1.09-2.05),abnormal liver function(OR=2.26,95%CI:1.31-3.92),and dyslipidemia(OR=1.46,95%CI:1.01-2.12)were positively correlated with hyperuricemia;age>30 years old(OR=0.59,95%CI:0.37-0.93)and exercise time>1 h per week(OR=0.46,95%CI:0.22-0.97)were negatively correlated with HUA.Conclusion The prevalence rate of hyperuricemia is at a high level in an island troop.BMI≥24,age≤30 years old,exercise time≤1 h per week,abnormal liver function,and dyslipidemia are the risk factors for HUA.Prevention and control measures should be taken as early as possible for the soldiers with these risk factors.

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.

Objective Analyze the temporal trend of ischemic stroke(IS)mortality among the residents of Tengzhou City of Shandong Province during the period of hypertension control from 2013 to 2021.Methods On January 1,2013,Tengzhou City,Shandong Province,began its hypertension control program.The IS mortality rate was calculated using the mortality data from January 1,2013 to December 31,2021,and analyzed for its time trend among residents with different characteristics.The registered population was derived from the Public Security Bureau of Tengzhou City,Shandong Province,and the age and sex standardized mortality rate was calculated using the data of China's 7th population census in 2020.The Chi-square test was used to compare the differences in mortality rate,and Cochran-Armitage trend test was used to compare the time trend and age trend of mortality rate.Results The overall crude and standardized mortality rates of IS in Tengzhou showed a temporal trend from 2013 to 2021(Z values were 12.647,7.305,respectively;all P＜0.001),and decreased by 23.77％and 30.99％(Z values were-7.393,-9.975,respectively;all P＜0.001)respectively in 2021 compared with 2019.The crude mortality rate of IS in male increased by 13.27％in 2019 compared with 2017,while the crude and standardized mortality rate in female decreased by 16.39％and 19.49％in 2018 compared with 2017,respectively,with statistical significance(x2 values were 7.160,9.789,and 15.109,respectively;all P＜0.05).Except the crude mortality rates in 2013 and 2015,the crude mortality rates and standardized mortality rates for males in other years were all higher than those for females,with statistically significant differences(x2 values:25.816-124.040,all P＜0.001).The crude mortality rate for IS increased with age in all years(Z values:42.604-61.025,all P＜0.001).The proportion of IS deaths among those aged≥65 was 85.85％.The overall crude mortality rates of the age group of male 45-54 years old showed a temporal trend from 2013 to 2021(Z=3.035,P＜0.01),while females in the same age group did not show a temporal trend(P＞0.05).The IS mortality rate in urban areas decreased from 62.61 per 100 000 in 2013 to 54.00 per 100 000 in 2021(Z=-2.097,P＜0.05).The rural areas increased by 213.15％in 2019 compared with 2013 and decreased by 22.75％in 2021 compared with 2019(Z values were 19.074,-6.390,respectively;all P＜0.001).Conclusions The IS mortality rate in Tengzhou City showed a decreasing trend in urban areas from 2013 to 2021,and a decreasing trend in rural areas after 2019.Compared to females,there is a trend of younger mortality among males in the age range of 45-54.Males and rural IS patients should be given special attention.

Objective This study aims to predict the coronavirus disease 2019(COVID-19)epidemic in Xi'an based on SEAIQR model and Dropout-LSTM model,and to provide a scientific basis for evaluating the effectiveness of the"dynamic zero-COVID policy".Methods Considering a large number of asymptomatic infections,the changing parameters,and control procedures,we developed a time-dependent susceptible-exposed-asymptomatic-infected-quarantined-removed(SEAIQR)model with stage-specific interventions.Considering the time-series characteristics of COVID-19 data and the nonlinear relationship between them,we constructed a deep learning Dropout-LSTM model.The data of newly confirmed cases in Xi'an from December 9th,2021 to January 31st,2022 were used to fit the model,and the data from February 1st,2022 to February 7th,2022 were used to evaluate the model performance of forecasting.We then calculated the effective reproduction number(Rt)and analyzed the sensitivity of the different measurement scenarios.Results The peak of newly confirmed cases predicted by the SEAIQR model would appear on December 26th,2021,with 176 cases,and the"dynamic zero-COVID policy"may be achieved in January 24th,2022,with R2=0.849.The Dropout-LSTM model can reflect the time-series and nonlinear characteristics of the data,and the predicted newly confirmed cases were highly consistent with the actual situation,with R2=0.937.The MAE and RMSE of the Dropout-LSTM model were lower than those of the SEAIQR model,indicating that the predicted results were more ideal.At the beginning of the outbreak,R0 was 5.63.Since the implementation of comprehensive control,Rt has shown a gradual downward trend,dropping to below 1.0 on December 27th,2021.With the reduction of effective contact rate,the early implementation of control measures and the improvement of immunity threshold,the peak of newly confirmed cases will continue to decrease.Conclusion The proposed Dropout-LSTM model forecasts the epidemic well,which can provide a reference for decision-making of the"dynamic zero-COVID policy."

Objective:To analyze the impact of hypertension prevention and control on the mortality rate of acute myocardial infarction (AMI) in Tengzhou City, Shandong Province from 2013 to 2021.Methods:This study was a cross-sectional study. The surveillance data of AMI deaths from January 1, 2013 (the time when hypertension prevention and control began in Tengzhou) to December 31, 2021 were collected in the coronary heart disease information management system, the mortality rate of AMI and its change trend were analyzed, and the distribution differences among residents with different characteristics were analyzed. The registered population information was obtained from Tengzhou Public Security Bureau, and the age and gender standardized mortality rate was calculated based on the data of the 7th national population census in 2020. The t test was used to compare the differences in blood pressure and laboratory items, chi-square test was used to compare the differences in mortality rate, and Cochran-Armitage trend test was used to compare the time trend and age trend of mortality rate, so as to analyze the impact of hypertension prevention and control on the mortality rate of AMI. Results:The overall crude and standardized AMI mortality rates in Tengzhou decreased from 50.87/100 000 and 63.82/100 000 to 41.08/100 000 and 38.70/100 000 from 2013 to 2021, respectively ( Z=-5.741, -10.884, both P<0.001), and double peaks were formed in 2014 and 2017. The first peak of crude and standardized mortality rate was formed in 2015 for males, which was 25.12% and 17.60% higher than that in 2013; and the first peak was formed in 2014 for females, which was 29.56% and 24.38% higher than that in 2013 ( χ2=13.200, 9.065, 14.862, 12.123) (all P<0.05). The second peaks of crude and standardized mortality were formed in 2017, with an increase of 18.17% and 17.17% for males and 25.73% and 22.34% for females from 2016 ( χ2=8.266, 9.182, 14.066, 11.105), the standardized mortality rate was 15.18%-29.01% higher in males than that in females ( χ2=6.239-19.326) (all P<0.05). The mortality rate of AMI increased with age ( Z=35.485-51.308) ( P<0.001). Compared with 2013, the mortality rate in males aged 55 to 64 years in 2015 increased by 64.29% from that in 2013, and that of females in 2017 increased by 108.48% from that in 2015; and that in females aged 35 to 44 years in 2016 increased by 373.51% from that in 2015 ( χ2=10.751, 12.805, 4.799); in 2021, the age group of male and female≥65 years decreased by 43.51% and 41.28% when compared with that in 2013, respectively ( Z=-7.333, -7.465) (all P<0.05). The mortality rate of AMI in urban areas decreased by 76.93% in 2021 when compared with that in 2016, and in rural areas it decreased by 30.28% than that in 2017. Both regions showed a downward trend ( Z=-7.560, -2.398) (both P<0.05). Conclusions:The mortality rate of AMI in Tengzhou City, Shandong Province from 2013 to 2021 shows a decreasing trend, and prevention and control of hypertension may be one of the reasons. The standardized mortality rate of males is higher than that of females, and the mortality rate decline rate in rural areas is lower than that in urban areas. The primary and secondary prevention of AMI in such populations should be strengthened.

Objective:To analyze the trends of coronary heart disease mortality in Tengzhou city of Shandong province from 2013 to 2021.Methods:The data of coronary heart disease (ICD-10: I20-I25) from January 2013 to December 2021 were obtained from the Chronic Disease Surveillance Information System-Coronary Heart Disease Management Module of Shandong province; the population data were provided by Tengzhou Public Security Bureau. The 95% confidence interval ( CI) of the rate was calculated using the binomial exact method. The age-standardized mortality rate (ASMR) was calculated based on 2020 National Population Census. The trends of mortality rate were analyzed using the Cochran-Armitage trend test. Results:During 2013 to 2021, there were 20 667 coronary heart disease deaths in Tengzhou city, with an average of 2 296 cases per year. The male-to-female ratio was 1.09∶1, and 80.98% (16 736/20 667) of the death cases were aged 65 years or older. The crude mortality rate and ASMR of coronary heart disease were 131.84/10 5 and 168.22/10 5 in 2013, respectively. The crude mortality rate increased by 13.67% from 2013 to 2021 ( P<0.001) with an average annual increase of 1.59%; while the ASMR decreased by 18.65% from 2013 to 2021 ( P<0.05) with an average annual decease of 2.34%. The crude mortality rate of coronary heart disease in men and women showed an upward trend, with the difference in the increase for women being statistically significant ( P<0.01); while the ASMR both in men and women showed a downward trend ( P<0.001). The crude death rates from 2013 to 2021 in age groups of 65 or older for men and women decreased by 22.40% and 19.73%, respectively (both P<0.001); while the crude death rate for age groups of 44 or younger in men showed an upward trend ( P<0.05). The crude death rate among urban residents decreased by 5.22% from 2013 to 2021 with an annual decrease of 0.67% ( P>0.05); while the crude death rate among rural residents increased by 19.29% with an annual increase of 2.18% ( P<0.001). The overall crude death rate among urban residents was higher than that among rural residents (all P<0.05). Conclusions:From 2013 to 2021, the crude mortality rate of coronary heart disease in Tengzhou city of Shandong province shows an increasing trend while the age-standardized mortality rate shows a decreasing trend. The crude mortality rate of coronary heart disease in people aged 65 and above shows a decreasing trend. In addition, the change trends are different between women and men, and between urban and rural areas.

Drowning is a common and serious injury worldwide, especially for children and young people. Drowning occurs frequently, resulting in heavy health and economic burdens to society. This paper summarizes the progress in the research of the epidemiology of drowning both at home and abroad, including the epidemiological characteristics, risk factors and intervention measures. Through analysis on existing research literature, it is found that there are large differences in the incidence characteristics of drowning in different regions. Men and children are at high risk for drowning. Age, being man, rural environment, lack of supervision, alcohol consumption, and underlying diseases are risk factors for drowning. It is suggested to pay more attention to the problem of drowning, improve people's awareness of drowning, take appropriate intervention measures and strengthen multi-sectoral collaboration to prevent and control the incidence of drowning.