AIM: G protein-coupled inwardly rectifier potassium (GIRK) channel are distributed widely in mammalian brain. In CNS, GIRK 1/2 seems to be the predominant heterotetramers which play a pivot role in the regulation of the excitability of neurons and may contribute to the resting potential by leading to a hyperpolarization of membrane potential and reduction of the action potential frequency. In the context, the Weaver mouse is the first neurological abnormality directly linked to a genetic point mutation in the GIRK2 protein which includes spontaneous seizure. GIRK2 knock out mice showed normal development but more susceptible than normal mice to seizure induced by GABA antagonist. Here, we report that the mRNA and protein expression of GIRK subunit 2 is altered in kainic acid(KA)-induced epileptic rat hippocampus. METHODS: Rats were injected with kainate 14 mg/kg intraperitoneally to establish an acute and chronic temporal lobe epilepsy model. At chronic spontaneous seizure stage, by using of in situ hybridization, immunocytochemistry and Western blotting, the GIRK 1,2 mRNA and protein were analyzed quantitatively in the dentate gyreus, CA1, CA3 regions of hippocampus. RESULTS: GIRK1,2 mRNA and proteins were expressed abundantly in all regions of hippocampus. KA induced seizures and caused a significant increase in GIRK2 mRNA abundance and immunoreacitivity; only GIRK1 mRNA was increased significantly, but no difference was found by Western blotting protocol. CONCLUSION: GIRK1,2 mRNA and protein expression in the hippocampus of epileptic rat brain is up-regulated, which may be an adaptive response to over-excitability of neuron networks and prevent the over-excitability spread in hippocampus (DG-CA3-CA1). [

Objective To evaluate the effect of high load application of atorvastatin on the clinical outcome of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).Methods Eighty patients diagnosed with AMI were continuously enrolled in this study and randomly divided into two groups:high dose group(n=40) and control group(n=40).Application of high load atorvastatin before operation in loading group.The levels of serum lipid and cardiac function were measured and analyzed.Results The levels of BNP((204±60.3) pg/mL vs.(328.3±67.5) pg/mL;t=1.938,P=0.0315) on 7 days after PCI and levels of LVEF((50.3±6.0)％ vs.(56.9±7.3)％;t=2.169,P=0.019) on 1 month after PCI in high dose group were significantly better than those in control group.Correlation analysis showed that the administration of statin was negatively associated with levels of BNP(r=-0.157,P=0.021) on 7 days after PCI and positively associated with LVEF(r=-0.328,P=0.026) on 1 month after PCI.Conclusion The treatment of high dose statin before PCI may reduce the ischemia-reperfusion injury and prevent the no-reflow development,which therefore improve the cardiac function of AMI patients.

Severe acute respiratory syndrome coronavirus（SARS-CoV-2）is highly infectious and people are generally susceptible to it. In this article,we reviewed current research into the epidemiological characteristics of coronavirus disease 2019（COVID-19）,introduced China's effective prevention and control experience,preliminarily summarized the phased Results of China's fight against the COVID-19,and reviewed the early measures taken by Singapore,Japan,Italy,Iran and South Korea. We recommended China’s prevention and control measures in response to COVID-19 to the world;appealed to pay attention to non-drug interventions,to strengthen the cooperation and sharing of COVID-19 epidemic data and research,to improve the global ability in respond to public health emergencies,and to reduce the impact of COVID-2019 on the sustainable development of economy and society.

Objective:To investigate the consistency and diagnostic efficiency of Chinese Thyroid Imaging Reporting and Date System (C-TIRADS) in thyroid nodule evaluation by different seniority sonographers.Methods:The preoperative ultrasonographic datum of 134 thyroid nodules in 112 patients from January to November 2020 were independently analyzed by sonographers with different seniority. According to the C-TIRADS guidelines, the C-TIRADS ultrasonographic indicators of each nodule were recorded and C-TIRADS classification was performed. Cohen′s Kappa (K) statistical method was used to analyze the consistency of ultrasonic indicators evaluated by different seniority sonographers. Using postoperative pathological results as the gold standard, the diagnostic efficacy of C-TIRADS classification for differentiating benign and malignant thyroid nodules by junior and senior sonographers was calculated respectively, and the Receiver Operating Characteristic (ROC) curves were drawn respectively.Results:The solid structure and vertical orientation of thyroid nodule judged by different seniority sonographers were very consistent ( K=0.84, 0.81). The consistencies of very hypoechoic and microcalcifications were substantial agreement ( K=0.80, 0.61), and moderate ( K=0.531) for the margin of the nodules. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of distinguishing benign and malignant thyroid nodules by junior and senior sonographers were 91.8%, 65.8%, 77.6%, 69.1%, 90.6% and 96.7%, 67.1%, 80.6%, 71.1%, 96.1%, respectively. The corresponding area under the ROC curves were 0.788 and 0.819, respectively ( Z=1.369, P=0.171). Conclusion:Ultrasonologists with different experience have good consistency in evaluating the C-TIRADS ultrasonic indicators of thyroid nodule, and the diagnostic efficacy of C-TIRADS classification in differentiating benign and malignant thyroid nodule was similar.

Objective:To analyze the value of the modified 5-factor frailty index in assessing postoperative complications and mortality in elderly hip fracture patients.Methods:In this retrospective study, clinical data were collected of hip fracture patients aged 60 years and above surgically treated at Beijing Luhe Hospital affiliated to Capital Medical University between January 2015 and December 2019.Patients' group assignment was based on whether the modified frailty index score was ≤1 or ≥2, and a post-surgery follow-up was conducted for survival at 30 days, 1 year, 2 years, and 4 years, which was analyzed by the Kaplan-Meier method.Multivariate Cox regression analysis was used to identify factors affecting death in elderly patients.Results:A total of 1 208 patients were included, with 890 in the group with the index score ≤1 and 318 in the group with the index score ≥2.There was no difference in mortality at 30 days(1.6% or 14/890 vs.1.9% or 6/318, P=0.707), 1-year(11.3% or 99/874 vs.11.6% or 36/310, P=0.917), 2-years(19.7% or 168/852 vs.24.3% or 73/300, P=0.099)and 4-years(44.0% or 238/541 vs.51.5% or 106/206, P=0.071). The incidence of postoperative complications in the group with the score ≥2 was higher(14.8% or 47/318 vs.9.7% or 86/890, P=0.012), including the incidence of stroke(6.3% or 20/318 vs.1.8% or 16/890, P<0.001)and the incidence of postoperative pneumonia(6.0% or 19/318 vs.3.1% or 28/890, P=0.029), and the differences were statistically significant.Multivariate Cox regression analysis showed that age, being female, the Charlson comorbidity index score and low hemoglobin at admission were risk factors for 1-year, 2-year and 4-year mortality post-surgery(all P<0.05), while the modified frailty index score had no correlation with postoperative mortality. Conclusions:A modified frailty index ≥2 is predictive of increased risk of postoperative pneumonia and stroke in patients with hip fractures, but is not correlated with the risk of postoperative mortality.

Objective:To analysis the incentive level of family doctors in primary medical and health institutions in Beijing, and to explore its influencing factors, so as to provide references for promoting family doctors′ contract service.Methods:From October to December 2021, 40 family doctors were randomly selected from 135 urban community health service centers in 8 districts of Beijing, and a survey was conducted on basic demographic information, institutional organizational capacity evaluation, and family doctor incentive level evaluation (including four dimensions of work value, organizational environment, personal development, and reward compensation), and the influencing factors of family doctor incentive level was analyzed. Chi-square test and Pearson correlation analysis were used for univariate analysis, and multiple linear regression analysis was used for multivariate analysis.Results:A total of 4 568 family doctors were included, and the score of family doctors′ incentive level was 3.75±0.81, among which the work value score was the highest(3.89±0.77), followed by the organizational environment score(3.69±0.92) and personal development score(3.75±0.90), and the lowest score was reward(3.75±0.90). Age, education, professional title, working years and average total working hours per week negatively affected the incentive level( P<0.05), while the average monthly income, the frequency of attending training and further study, and the organizational ability of the organization positively affected the incentive level( P<0.05). Conclusions:The overall incentive level of family doctors in primary medical and health institutions in Beijing needed improvement, and there were many factors that affect the incentive level of family doctors. It was recommended to appropriately increase the salary and benefits of family doctors, reasonably arrange the workload of family doctors, strengthen the training mechanism of family doctors, and strengthen the organizational capacity building of primary medical and health institutions.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

Objective:To evaluate the effectiveness and safety of phacoemulsification cataract extraction combined with intraocular lens implantation (PEI) plus goniosynechilysis (GSL) and goniotomy (GT) for advanced primary angle-closure glaucoma (PACG).Methods:An observational case series study was performed.Fifty eyes of 50 patients with advanced PACG were enrolled in Zhongshan Ophthalmic Center from August 2020 to June 2021.All the patients received PEI+ GSL+ GT and were followed up for over 6 months, with a mean follow-up of 7.5 (6, 10) months.Intraocular pressure (IOP) was measured with a Goldmann applanation tonometer.Best corrected visual acuity (BCVA) was examined with an ETDRS chart and converted to logarithm of the minimum angle of resolution (LogMAR) units for analysis.Types and number of anti-glaucoma medications applied before and after surgery, and the surgical complications were collected.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) with a reduction of 20% from baseline without anti-glaucoma medication, no vision-threatening complications, no loss of light perception, and no reoperation.Qualified success was defined as an IOP of 5-18 mmHg with a reduction of 20% from baseline with or without anti-glaucoma medication, no vision-threatening complications, no loss of light perception, and no reoperation.This study adhered to the Declaration of Helsinki.This research protocol was approved by an Ethics Committee of Zhongshan Ophthalmic Center (No.2021KYPJ177). Written informed consent was obtained from each subject before entering the cohort.Results:The mean preoperative IOP was (28.81±7.81)mmHg, and the IOP at the end of follow-up was (13.41±4.10)mmHg, showing a statistically significant decrease ( t=12.260, P<0.001). The postoperative IOP was decreased by 13.80 (9.10, 19.40)mmHg, with a percentage decrease of 51.1% (38.6%, 67.1%). The mean preoperative and postoperative BCVA was (0.92±0.11) LogMAR and (0.88±0.10) LogMAR, respectively, and no significant difference was found ( t=-0.560, P=0.580). The number of anti-glaucoma medications was reduced from 2 (1, 3) before operation to 0 (0, 0) after operation.The complete success rate of surgery was 80% (40/50), and the qualified success rate was 94% (47/50). Surgical complications mainly included hyphema in 7 eyes, IOP spike in 7 eyes, and corneal edema in 3 eyes.No vision-threatening complication occurred. Conclusions:PEI+ GSL+ GT is preliminarily effective and safe for advanced PACG by reducing IOP and application of anti-glaucoma medications with few complications.

Objective To identify signals of adverse events associated with vaccines in electronic medical record data. Methods Data cleaning was performed on electronic medical records and vaccination data in Gansu Province from 2020 to 2022. Signal identification was performed using Apriori algorithm and Empirical Bayes Gamma-Poisson Shrinker (GPS) with stratification by gender and age group. Results A total of 33 statistical signals were identified, with 7 signals identified by the Apriori method and 26 signals identified by the GPS method. No overlapping signals were found between the two methods at two different signal thresholds. Conclusion The vaccine safety signals identified by GPS and Apriori in electronic medical records are reliable and accurate, but further research is needed to determine the correlation between the vaccine safety signals recognized by GPS algorithms.