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 therapeutic effect of transumbilical single-port laparoscopic high uterosacral ligament suspension(HUS)and iliacpubic ligament fixation(ILF)in the treatment of pelvic organ prolapse(POP)mainly caused by middle pelvic defects.Methods Clinical data of 15 cases of POP with middle pelvic defects from June 2017 to June 2023 were analyzed retrospectively.The HUS and ILF were performed by transumbilical single-port laparoscopy.At one year after operation,gynecological examination(POP-Q system)and maximum straining pelvic MRI examination were performed for objective evaluation.The Pelvic Floor Distress Inventory Short Form(PFDI-20)and Pelvic Organ Prolapse-Urinary Incontinence Sexual Questionnaire(PISQ-12)were used for subjectiveevaluation.Results Theoperationtimewas 65-135 min(mean,102.9±16.3 min),thebleedingvolumewas 20-50 ml,and the postoperative hospital stay was 6-9 d.Follow-up time ranged from 6 to 72 months(mean,42.8±22.3 months),among which 14 cases were≥12 months.No pelvic pain,lumbosacral pain,urinary retention and thread exposure occurred.Stress urinary incontinence(SUI)occurred in 1 case at 1 year after operation.Surgical failure was noted in 1 case(degree Ⅱ),the objective success rate being 93.3%(14/15).At 1 year after operation,the distance from the anatomical landmarks of pelvic MRI to the pubococcygeal line(PCL)was significantly higher than that before operation(P<0.01),and the PFDI-20 and PISQ-12 scores were significantly better than those before operation(P<0.01).Conclusions Transumbilical single-port laparoscopic HUS and ILF is a safe and effective mutual aid procedure for the treatment of POP mainly caused by middle pelvic defects with surgical indications,which can improve pelvic floor function and quality of life.It is simple and easy to perform with low cost of consumables,which is suitable for primary hospitals.

Objective:To investigate the association between serum zinc levels and convulsive brain injury in infants with mild gastroenteritis complicated with benign infantile seizures (BICE) and febrile seizures (FC).Methods:A case-control study method was conducted. 120 children with mild gastroenteritis and convulsion admitted to the First Affiliated Hospital of Hebei North University from January 2020 to January 2022 were enrolled as the research subjects. They were divided into BICE group and FC group according to the type of convulsion. The serum zinc level, the frequency and duration of convulsion, and the occurrence of convulsive brain injury in the two groups were recorded. Multivariate Logistic regression analysis was used to screen the risk factors for convulsive brain injury. The Spearman correlation method was used to analyze the association between serum zinc levels, clinical characteristics of convulsion and convulsive brain injury.Results:A total of 120 children were enrolled, of which 81 developed to BICE and 39 developed to FC during hospitalization. The serum zinc level of children in the FC group was significantly lower than that in the BICE group (μmol/L: 39.24±6.50 vs. 48.65±7.21, P < 0.01). In the BICE group and FC group, the serum zinc level in children with more than 2 convulsions was significantly lower than that in the children with one convulsion (μmol/L: 37.65±6.50 vs. 53.17±7.55 in the BICE group, and 30.27±5.58 vs. 44.16±7.57 in the FC group, both P < 0.01). Serum zinc level in children with convulsion duration ≥5 minutes was significantly lower than that in the children with convulsion duration < 5 minutes (μmol/L: 38.75±6.74 vs. 51.21±7.58 in the BICE group, and 31.08±5.46 vs. 45.19±7.25 in the FC group, both P < 0.01). Moreover, the serum zinc level of children with different convulsion frequency and duration in the FC group was significantly lower than that in the BICE group (all P < 0.01). Among the 120 children, 9 cases of convulsive brain injury occurred, and the incidence rate was 7.50%. The incidence of convulsive brain injury in the BICE group was 1.23% (1/81), which was significantly lower than 20.51% in the FC group (8/39, P < 0.01). The serum zinc level of children with convulsive brain injury was significantly lower than that of children with non-brain injury (μmol/L: 28.50±5.00 vs. 60.22±7.31, P < 0.01), and the number of convulsion was significantly higher than that of non-cerebral injury (≥ 2 convulsions: 100.00% vs. 1.80%, P < 0.01), and the duration of convulsion in children with brain injury was significantly longer than that of non-brain-injured children (convulsion duration ≥5 minutes: 100.00% vs. 11.71%, P < 0.01). Multivariate Logistic regression analysis showed that decreased serum zinc level [odds ratio ( OR) = 2.147, 95% confidence interval (95% CI) was 1.354-3.403], increased number of convulsion ( OR = 3.452, 95% CI was 1.266-9.417), and prolonged convulsion duration ( OR = 3.117, 95% CI was 1.326-7.327) were independent risk factor for convulsive brain injury in children with mild gastroenteritis and convulsion (all P < 0.05). Spearman correlation analysis showed that serum zinc level, convulsion ≥2 times, duration of convulsion ≥5 minutes and convulsion ≥2 times + convulsion duration ≥5 minutes were significantly negatively correlated with the occurrence of convulsive brain injury in FC children ( r values were -0.546, -0.517, -0.522, and -0.528, all P < 0.01). There was no significant correlation between serum zinc level, convulsion ≥2 times, convulsion duration ≥5 minutes and convulsion ≥2 times+convulsion duration ≥5 minutes and convulsive brain injury in BICE children ( r values were -0.281, -0.129, -0.201, -0.243, all P > 0.05). Conclusions:Serum zinc level is related to the characteristics of convulsive symptoms in children with mild gastroenteritis complicated with FC, and has a strong negative correlation with the occurrence of convulsive brain injury. Active targeted intervention and treatment may help reduce the incidence of brain injury in children.

Objective:To evaluate the efficacy of high-flow nasal cannula (HFNC) oxygen therapy in optimizing painless transesophageal echocardiography in elderly patients.Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅱ patients, regardless of gender, aged 60-75 yr, with body mass index of 18.5-23.9 kg/m 2, were randomized into 2 groups ( n=30 each) by a random number table method: group HFNC and conventional ventilation group (group C). Pure oxygen 10 L/min was inhaled for 3 min preoxygenation using the HFNC device in group HFNC. Group C inhaled pure oxygen at 6 L/min for 3 min preoxygenation via a nasal cannula. Sufentanil 0.1 μg/kg and remazolam 0.25-0.30 mg/kg were intravenously injected in turn. Group HFNC was connected to a high-flow humidification oxygen therapy device and inhaled pure oxygen at 60 L/min (37℃, FiO 2 100%). The flow rate of pure oxygen was maintained at 6 L/min (FiO 2 100 %) in group C. The patients were placed in left lateral decubitus position, esophageal ultrasound was performed after the eyelash reflex disappeared, and remazolam 0.1 mg/kg was intravenously injected intermittently when bucking and body movement were induced by operation stimulation. The occurrence of hypoxia-related adverse events, mandibular intervention and ventilation-related adverse events was observed during examination. The operation time, time of emergence from anesthesia and consumption of remazolam were recorded. Results:Compared with group C, the incidence of severe hypoxia and rate of mandibular intervention were significantly decreased (7%/0 and 53%/17%, P<0.05), the lowest intraoperative SpO 2 was increased ( P<0.05), and no significant change was found in the operation time, time of emergence from anesthesia and consumption of remazolam in group HFNC ( P>0.05). No ventilation-related adverse events occurred in both groups. Conclusions:HFNC can markedly optimize the ventilation management of elderly patients undergoing painless transesophageal echocardiography.

Objective:To study the clinical characteristics and compliance of early-onset gout patients by case-control analysis.Methods:A total of 111 early-onset patients (onset age ≤35 years old) were included as Group A, and 111 non-early-onset patients (onset age >35 years old) with matched disease durationwere included as Group B. The differences ofclinical characteristics, causes of acute gout attack, dairy diet habits, compliance, and misunderstanding of the disease were compared.Results:Compared with the non-early-onsetgoutpatients, the early-onset patients had a higher proportion of obesity (63 cases vs 28 cases), family history (36 cases vs 20 cases) and tophus (39 cases vs 23 cases) and higher level of VAS scores (8.5±1.3 vs 7.6±1.7; χ2=22.988, P<0.01; χ2=5.749, P=0.016; χ2=5.729, P=0.017; t=4.639, P<0.01), lowerproportionof the first metatarsophalangeal joint involvement as the initial joint involvement (45.9%, 51 cases vs 59.4%, 66 cases; χ2=4.066, P=0.044), higher proportion of the ankle involvement as the initial joint involvement (34.2%, 38 cases vs 21.6%, 24 cases; χ2=4.386, P=0.036), higher proportion of alcohol drinkers and high fructose drinkers, which was more likely to relate to alcohol intake, strenuous exercise and high fructose intakeas trigger of the flare ( χ2=6.513, P=0.011; χ2=7.126, P=0.008; χ2=1.978, P=0.160), while the proportion of regular exercisers and on diet in the family was lower ( χ2=22.887, P<0.01; t=-4.917, P<0.01). The proportion of poor diet and medication compliance in Group A was higher than that in Group B(57.7%, 64 cases vs 38.7%, 43 cases; χ2=5.207, P=0.022; χ2=5.867, P=0.015). As for the reason for poor treatment compliance, early-onset gout patients were more worry about the side-effects of drugs than non-early onset patients ( χ2=4.190, P=0.041). There was no significant difference between the two groups in the main misunderstanding of gout. Conclusion:Although early onset gout patients are young, their condition is more serious, and compliance is poorer, this group of patients should be highly valued in clinical diagnosis and treatment.

Objective: To test the reliability and validity of the Chinese version of the Handoff Clinical Examination Exercise (Handoff CEX). Methods: The Chinese version of the Handoff CEX was composed of two parts, one to assess the nurse providing the handoff and another to assess the nurse receiving the handoff. A total of 80 handoffs was evaluated to test the reliability and validity of the Chinese version of the Handoff CEX. Results: A total of 320 evaluations of handoff was obtained. The Cronbach α coefficient was 0.85 for the handoff provider, and that was 0.80 for the handoff recipient. Weighted kappa scores for provider evaluations ranged from 0.31-0.52, and that for recipient evaluations ranged from 0.35-0.55. The correlation coefficients between each factor ranged from 0.23 to 0.62, and that between each factor and the total scale ranged from 0.33 to 0.64 (P<0.05). Experienced nurses (>5 years) received significantly higher mean scores than inexperienced nurses(≤5 years) in all domains except organizational efficiency and professionalism(P<0.05). Conclusion The Chinese version of the Handoff CEX is a reliable and valid tool to assess the nursing handoff, which is useful for educators, supervisors and clinical nurses to provide training, ongoing assessment and feedback to improve the quality of handoff.

Objective:To explore the association between snoring and prevalent hypertension among adults in Zhejiang with a cross-sectional study.Methods:After excluding participants with self-reported, physician-diagnosed heart diseases, stroke and cancer at baseline study, 56 728 participants aged 30-79 in the China Kadoorie Biobank study from Tongxiang, Zhejiang were included for the final analysis. Three multivariable logistic regression models were used to estimate the ORs for the associations of snoring with prevalent hypertension. Results:The proportion of participants who snored frequently, snored sometimes, and never snored were 24.55%, 23.94%, and 51.51%, respectively. The corresponding figures of males were 32.40%, 26.55%, and 41.05%, respectively. The corresponding figures of females were 19.00%, 22.08%, and 58.92%, respectively ( P<0.001). After adjusted socio-demographic factors, behavioral lifestyle, BMI, waist circumference, and sleep duration etc., in comparison with participants who never snored, the odds ratios (95% CI) of hypertension for those who snored frequently and snored sometimes were 1.17 (1.12-1.23) and 1.12 (1.07-1.18), respectively. The effects of snoring on hypertension were statistically significantly different between women and men, participants who were central obese and those who were not, and between premenopausal and post-menopausal women. Conclusion:Snoring was associated positively with hypertension among adults. The effect of snoring on prevalent hypertension were obvious, especially among people, being female, being central obese, and being premenopausal.

Objective:To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods:The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children′s hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children′s general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results:Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (β-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ 2=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ 2=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ 2=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10 9/L vs. (13±7)×10 9/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions:The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.

Objective To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on insulin-like growth factor-Ⅰ (IGF-Ⅰ) and insulin-like growth factor-Ⅰ receptor (IGF-IR) expression after transcervical resection of polyp (TCRP).Methods 100 cases of endometrial polyps were selected.The control group (n =50) was treated with TCRP only,while the observation group (n =50) was treated with LNG-IUS after TCRP.The scores of pictorial blood loss assessment chart (PBCA),endometrial thickness,recurrence rate,mRNA expression of IGF-Ⅰ and IGF-IR in endometrial tissue were compared between the two groups.Results At 1,3,6,12 months follow-up,the PBAC score and endometrial thickness of observation group were significantly lower than control group (P ≤ 0.05).At 12 months after operation,the mRNA expression levels of IGF-Ⅰ and IGF-IR in the endometrium of the observation group were significantly lower than those of the control group (P ≤ 0.05).After 12 months of follow-up,the recurrence rates of the control group and the observation group were 16.0％ (8/50) and 4.0％ (2/50),respectively.The recurrence rate of the observation group was significantly lower than that of the control group (P ≤ 0.05).Conclusions TCRP combined with LNG-IUS treatment can significantly reduce EP recurrence,and down-regulation of the mRNA expression of IGF-Ⅰ and IGF-IR maybe its possible mechanism.

Objective To observe the effect of Shenmai injection on hemodynamics and serum inflammatory factors in patients with septic shock. Methods One hundred and fifty patients with septic shock admitted to Tianjin Fourth Center Hospital from August 2015 to March 2017 were enrolled and they were divided into a western medicine routine treatment group and an integrated traditional Chinese and western medicine treatment group according to the random number table method, 75 patients in each group. Both groups were given symptomatic treatment of basic western medicine, and the integrated traditional Chinese and western medicine treatment group was additionally given intravenous infusion (IV) of 30 mL Shenmai injection on the basis of conventional treatment, both groups were treated for consecutive 14 days. The changes in hemodynamic parameters, serum inflammatory factors: tumor necrosis factor-α (TNF-α) and interleukin (IL-6, IL-1β) were observed before and after treatment in the two groups, and the clinical efficacies of the two groups were evaluated 14 days after treatment. Results After treatment in both groups, hemodynamic indexes were improved, heart rate (HR) was decreased, and mean arterial pressure (MAP), central venous pressure (CVP), cardiac output index (CI) and peripheral vascular resistance index (SVRI) were increased; after 14 days of treatment, HR in the integrated traditional Chinese and western medicine treatment group was significantly lower than that in the western medicine routine treatment group (bpm: 101.8±3.1 vs. 104.9±9.3), while MAP [mmHg (1 mmHg = 0.133 kPa): 71.2±4.3 vs. 67.3±3.5], CI (mL·s-1·m-2: 3.6±0.4 vs. 3.4±0.6) and SVRI (kPa·s·L-1·m-2:190.37±24.91 vs. 180.23±20.13) were significantly higher than those in the western medicine routine treatment group (all P < 0.05). TNF-α, IL-6 and IL-1β were decreased in both groups after treatment; after 14 days of treatment, the above indexes in the integrated traditional Chinese and western medicine treatment group were significantly lower than those in the western medicine routine treatment group [TNF-α (ng/L): 226.3±42.8 vs. 273.7±29.4, IL-6 (ng/L):223.7±31.2 vs. 259.3±51.3, and IL-1β (ng/L): 95.1±20.7 vs. 132.4±47.5]. The total clinical effective rate in the integrated traditional Chinese and western medicine treatment group was significantly higher than that in the western medicine routine treatment group [93.3% (70/75) vs. 54.7% (41/75), P < 0.05]. Conclusion Shenmai injection can improve hemodynamics and regulate inflammatory factors; the therapeutic effect for treatment of septic shock is significant.