Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Objective To explore the anesthesia management experience in the interventional treatment of pediatric congenital heart diseases (CHD) percutaneously guided by transthoracic echocardiography (TTE) on a mobile operating platform. Methods From March to July 2023, a total of 13 patients from remote areas underwent interventional treatment for CHD on the mobile operating platform of Fuwai Yunnan Cardiovascular Hospital. Patients who received non-tracheal intubation general anesthesia were retrospectively included. Results Eight children who had difficulty cooperating with the surgery (due to young age, emotional tension, crying) received monitored anesthesia care with local anesthesia supplemented by sedative and analgesic drugs while maintaining spontaneous breathing under the monitoring and management of an anesthesiologist (i.e., non-tracheal intubation general anesthesia). Among them, there were 5 males and 3 females, with an age of (6.95±3.29) years and a body weight of (19.50±6.04) kg. Through transthoracic echocardiography, they were diagnosed with atrial septal defect (6 patients), residual shunt after patent ductus arteriosus ligation (1 patient), and severe pulmonary valve stenosis (1 patient). The surgery proceeded smoothly, with satisfactory anesthesia and surgical effects, complete analgesia, and satisfactory postoperative recovery. There was 1 patient of body movement and 1 patient of respiratory depression during the operation, and both patients completed the surgery successfully after treatment. All children had no serious surgery- and anesthesia-related complications. The anesthesia time was 40.5 (34.5, 47.5) min, the surgery time was 39.0 (33.0, 45.5) min, and the recovery time was 43.0 (28.0, 52.5) min Conclusion Interventional surgery for CHD guided by TTE at a mobile platform is a minimally invasive approach without radiation damage. Non-tracheal intubation general anesthesia with spontaneous breathing can be safely and effectively implemented in children who cannot cooperate.

Objective:To observe the clinical efficacy and safety of Tongren Niuhuang Qingxin Pills combined with telmisartan tablets in the treatment of hypertensive vertigo syndrome of phlegm-heat disturbance.Methods:Randomized controlled trial was conducted. Totally 80 patients with hypertension vertigo and phlegm-heat disturbance syndrome were selected from March 2021 to August 2022 at Beijing Tongrentang Hospital of Traditional Chinese Medicine as the observation objects. They were randomly divided into two groups using a random number table method, with 40 cases in each group. The control group received oral telmisartan tablets, while the experimental group received Tongren Niuhuang Qingxin Pills in addition to the control group. Both groups were treated for 28 days and followed up for 1 month. The patients' room blood pressure before and after treatment was measured, and TCM syndrome scores were evaluated. The dizziness assessment rating scale (DARS) was used to evaluate the severity of dizziness, adverse reactions during treatment were recorded, drug safety was observed, and clinical efficacy was evaluated.Results:The total effective rate of the experimental group was 85.0% (34/40), and that of the control group was 7.5% (3/40), with statistical significance between the two groups ( χ2=48.32, P<0.001). Compared with before treatment, the experimental group had SBP [(136.63 ± 6.01) mmHg vs. (159.30 ± 9.01) mmHg, t=-21.00] and DBP [(84.48 ± 4.36) mmHg vs. (95.30 ± 3.75) mmHg, t=-13.80] after treatment; after treatment, SBP [(137.34 ± 6.39) mmHg vs. (158.00 ± 10.06) mmHg, t=-5.28] and DBP [(86.08 ± 4.43) mmHg vs. (95.18 ± 6.61) mmHg, t=-8.09] decreased in the control group ( P<0.01), but there was no statistical significance between the two groups after treatment ( P>0.05). After treatment, the TCM syndrome scores in the experimental group (8.68 ± 3.39 vs. 15.12 ± 3.03, Z=-6.61) were lower than those in the control group ( P<0.001), and DARS score [(8.53 ± 3.93) vs. (12.20 ± 3.95), Z=-3.63] was lower than that in the control group ( P<0.001). After treatment, the therapeutic effect index of TCM syndromes in the experimental group improved compared to before treatment in the same group. The therapeutic effect index of each symptom, from high to low, was as follows: rotation of oneself or visual objects>numbness of limbs>dry stool>dizziness and dizziness>liking cold drinks>bitter and dry mouth>red urine>red tongue, yellow coating, and greasy tongue>vomiting sticky and turbid phlegm>tinnitus>smooth pulse. There were no significant adverse reactions during the treatment of the two groups. Conclusion:Tongren Niuhuang Qingxin Pills combined with telmisartan can reduce the blood pressure of patients with hypertensive vertigo syndrome of phlegm-heat disturbance, improve the vertigo symptoms and TCM syndromes of patients, and the efficacy evaluation is superior to that of telmisartan alone.

OBJECTIVE: To compare the parental acceptance of dental treatment under general anesthesia and deep sedation in children and assess the changes in postoperative oral health-related quality of life and treatment efficacy. METHODS: The parents of 131 children undergoing dental treatment in the Department of Stomatology of Sichuan Provincial People's Hospital from January, 2022 to June, 2022 were surveyed using a questionnaire of children's advanced oral behavior management, and 83 children receiving general anesthesia or deep sedation for dental treatment between January, 2018 and December, 2021 were also investigated for changes in quality of life after the treatment using a questionnaire. The treatment efficacy was assessed at the 1-year follow-up visit in 149 children who received dental treatment under general anesthesia or deep sedation during the same period. RESULTS: The survey of perantal acceptance showed that 62.6% of the parents preferred deep sedation, 29.01% preferred general anesthesia, and 8.4% preferred compulsory treatment. Dental treatments under general anesthesia and deep sedation both significantly improved oral health-related quality of life of the children. While dental surgeries under general anesthesia resulted in the most significant improvement of pain symptoms, deep sedation was associated with both obvious relief of the children's pain symptoms and reduction of the parents' pressure level. No significant difference was found in the efficacy of treatments under general anesthesia and deep sedation at the 1-year follow-up. CONCLUSION Dental treatment in children under deep sedation has the highest parental acceptance, followed by treatment under general anesthesia, and the acceptance of compulsory treatment is the lowest. The treatments under general anesthesia and deep sedation significantly improve the quality of life of the children and their parents and both have good treatment efficacy.
Humans ; Child ; Quality of Life ; Deep Sedation ; Child Behavior ; Treatment Outcome ; Anesthesia, General ; Parents ; Pain ; Dental Care ; Dental Caries

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Objective:To construct the standardized training curriculum system for head nurse leadership based on five forces model.Methods:The first draft of the standardized training curriculum system for head nurse leadership was determined through literature review and semi-structured interview. From April to June 2022, 18 clinical experts from 8 provinces/cities across the country were selected for Delphi expert consultation to form a standardized training curriculum system for head nurse leadership.Results:In both rounds of consultation, 18 questionnaires were collected, and the effective response rate were 100.0%. The expert authority coefficients were 0.914 and 0.892, respectively. Based on the results of the expert consultation, the training system content was revised and improved, and all indicators met statistical standards, with expert opinions tending to be consistent. Finally, a standardized training curriculum system for head nurse leadership was formed consisting of 5 training themes, 18 course names and 67 course knowledge points.Conclusions:The standardized training curriculum system for head nurse leadership is scientific and systematic, which can provide reference for the leadership training of head nurses.

ObjectiveTo investigate the prevalence rate and influencing factors of depression and anxiety in disabled people in Guang'an during the post-pandemic period， so as to provide references for promoting mental health of disabled people. MethodsFrom April to May 2021， the disabled people dwelling in low-risk areas for coronavirus infections in Guang'an for half a year and met the criteria outlined in Classification and Grading Criteria of Disability （GB/T26341-2010） were selected as the survey subjects， and their depression and anxiety symptoms were evaluated via the Patients' Health Questionnaire Depression Scale-9 item （PHQ-9） and the Generalized Anxiety Disorder Scale （GAD-7） through Wenjuanxing platform. Then binary Logistic regression analysis was performed to screen the risk and protective factors for depression and anxiety in disabled people. ResultsThe detection rates of moderate-to-severe and severe depressive symptoms were 9.05% and 8.35%， and the detection rates of moderate and severe anxiety symptoms were 9.40% and 11.25%. Regression analysis denoted that being laid-off and job-waiting were risk factors for depression and anxiety in disabled people （OR=2.354， 2.353， P<0.01）. Being unmarried （OR=0.418）， married （OR=0.414）， visual disability （OR=0.254）， limb disability （OR=0.460）， good family function （OR=0.241）， moderate family dysfunction （OR=0.288）， complete self-care （OR=0.062） and partial self-care （OR=0.416） were protective factors for depression in disabled people （P<0.05 or 0.01）. Visual disability（OR=0.382）， hearing disability（OR=0.143）， limb disability（OR=0.432）， good family function （OR=0.246）， moderate family dysfunction （OR=0.402）， complete self-care （OR=0.093） and partial self-care （OR=0.378） were protective factors for anxiety in disabled people （P<0.05 or 0.01）. ConclusionThe disabled people in Guang'an during the post-pandemic period suffer a high detection rate of depression and anxiety， and the detection rate is even higher among those being laid-off or job-waiting， while good family function and complete or partial self-care ability are conducive to protecting the mental health of the disabled.

The present study was designed to investigate the mechanisms by which P2X7 receptors (P2X7Rs) mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus (PVN) of the hypothalamus of rats with acute myocardial ischemia (AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG (brilliant blue G, a P2X7R antagonist), nelivaptan (a vasopressin V1b receptor antagonist), or diphenyleneiodonium (DPI) [an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species (ROS) and NADPH oxidase 2 (NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes. Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine (AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron-V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.

Objective:To investigate the risk factors of lower extremity venous thrombosis in elderly patients with femoral neck fracture during perioperative period after artificial bipolar femoral head replacement and the effect of Mailuoshutong in clinical prevention and treatment of thrombosis.Methods:A retrospective case-control study was conducted on the clinical data of 92 elderly patients with femoral neck fracture who were admitted to the Affiliated Hospital of North China University of Technology from January 2015 to January 2020.According to the treatment method, the patients were divided into an observation group (44 cases) and a control group (48 cases). Patients in the observation group were treated with the combination of Mailuoshutong Pill and low molecular weight heparin calcium.The control group was treated with low molecular weight heparin calcium.The patients in both groups started anti-coagulation therapy immediately after admission, and they stopped the drug one day before operation and continued to take the drug on the second day after operation.Venous ultrasound of both lower limbs was recorded at the time of admission, on the 7th day after admission, and 14 days after surgery.The changes in hemoglobin, red blood cell count and drainage volume before and after operation were recorded.Results:The incidence of thrombosis was 2 cases (4.54%) on the 7th day after admission in the observation group and 9 cases (18.75%) in the control group.The difference was statistically significant (χ 2=4.400, P=0.036). The incidence of thrombosis was 3 cases (6.82%) in the observation group and 11 cases (22.92%) in the control group 14 days after operation.The difference was statistically significant(χ 2=4.611, P=0.032). The hemoglobin changes of observation group and control group were (23.73±6.89) g/L and (22.10±5.18) g/L respectively on the first day before operation and 48 hours after operation.The red blood cell count changes were (0.67±0.32) × 1012/L and (0.56±0.36) × 1012/L respectively, and the drainage volume of drainage tube after operation was (100.27±23.73) ml and (102.40±20.90) ml, respectively.There was no significant difference in the above indexes between the two groups (all P>0.05). Multivariate Logistic regression analysis showed that only low molecular weight heparin calcium was used to prevent and treat thrombosis ( OR=10.281, 95% CI: 1.609-65.689, P=0.014); the elderly patients ( OR=1.190, 95% CI: 1.061-1.336, P=0.003) and the thrombosis at the time of admission ( OR=8.346, 95% CI: 1.773-39.281, P=0.007) were the risk factors for lower extremity venous thrombosis on the 14th day after surgery. Conclusion:Mailuoshutong pill combined with low molecular weight heparin calcium can safely and effectively treat lower extremity venous thrombosis in perioperative period of artificial femoral head replacement for femoral neck fracture in elderly patients.Mailuoshutong pill combined with low molecular weight heparin calcium was a protective factor for lower extremity venous thrombosis 14 d after operation, while advanced age and thrombosis at the time of admission were risk factors.