The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

Objective: The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. Results: NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. Conclusion We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/immunology* ; Female ; Humans ; Kinetics ; Male ; Middle Aged ; Neutralization Tests ; SARS-CoV-2

OBJECTIVE: To observe the effect of Qiang Jin exercises on the muscle strength and activity of lumbar spine in patients with lumbar disc herniation. METHODS: From March 2016 to September 2017, at the Department of Orthopaedics, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, a total of 110 subjects were enrolled, and 98 eligible subjects were screened. The subjects were randomized by stratified randomization and divided into experimental group and control group, 49 cases in each group, 25 males and 24 females in the experimental group, 25 males and 24 females in the control group. The experimental group exercised with Qiang Jin exercises, one time each morning and evening, each time10 sets were made;the control group used classic rehabilitation training, training twice a week, and three months was a course of treatment. After 12 weeks of training, the muscle strength and activity of the lumbar spine were evaluated and compared with the muscle strength and activity of the lumbar spine before training. RESULTS: The experimental group and the control group had different muscle strength and activity of the lumbar spine before and after treatment ( CONCLUSION Qiang Jin exercises can effectively improve the muscle strength and activity of the lumbar spine and improve the daily living ability of patients.
China ; Female ; Humans ; Intervertebral Disc Degeneration ; Intervertebral Disc Displacement ; Lumbar Vertebrae ; Lumbosacral Region ; Male ; Treatment Outcome

OBJECTIVE: To compare the degeneration of lumbosacral multifidus muscle in patients with lumbar disc herniation. METHODS: Magnetic Resonance Spectroscopy was performed on the multifidus muscle of 35 healthy volunteers and 35 patients with unilateral L lumbar disc herniation. There were 20 males and 15 females in each group, aged from 25 to 55 years old. In healthy volunteers, the mean age was (35.66±8.73) years old and the BMI was (21.85±1.94) kg/m; in the patients, the mean age was (36.09±7.70) years old, the BMI was (21.50±1.78) kg/m, the VAS score was (4.40±0.88) points, the course of disease was (11.2±7.14) months. The proportion of fat in the L lumbosacral multifidus muscle and the proportion of fat-suppressed cross-sectional area were observed by MRI, the differences of the observation indexes of the two groups were compared through data analysis. RESULTS: In healthy volunteers, the proportion of fat on the left side of the multifidus muscle was (0.169± 0.035)%, the proportion of fat removal cross-sectional area on the left side of the multifidus muscle was (0.699±0.070)%, the proportion of fat on the right side of the multifidus muscle was (0.168±0.031)%, and the proportion of fat removal cross-sectional area on the right side of the multifidus muscle was (0.712±0.056)%, there was no significant difference between the two sides (>0.05). In patients, the proportion of fat on the healthy side of multifidus muscles was (0.173±0.021)%, the proportion of fat removal cross-sectional area on the healthy side of multifidus muscles was (0.695±0.054)%, the proportion of fat on the affected side of the multifidus muscle was (0.228±0.027)%, and the proportion of fat removal cross-sectional area on the affected side of the multifidus muscle was (0.629±0.048)%, the differences of the above indexes on both sides were statistically significant (<0.05). There was a statistically significant difference in the proportion of multifidus muscle fat and the ratio of fat-suppressed cross-sectional area between the affected side and volunteers (<0.05). There was no significant difference in fat ratio and fat-suppressed cross sectional area ratio between the left and right sides of healthy volunteers and healthy side of patients (>0.05). CONCLUSION There is degeneration of lumbosacral multifidus muscle on the affected side of patients with unilateral L intervertebral disc herniation, featuring multifidus muscular atrophy and fat infiltration.

OBJECTIVE: To compare the degeneration of lumbosacral multifidus muscle in patients with lumbar disc herniation. METHODS: Thirty-five healthy volunteers and 35 patients with unilateral L lumbar disc herniation from December 2015 to September 2017 were recruited. There were 20 males and 15 females in each group, aged from 25 to 55 years old. In healthy volunteers group, the mean age was (35.66±8.73) years old and the BMI was (21.85±1.94) kg /m. In patients with lumbar disc herniation, the mean age was (36.09±7.70) years old, the BMI was (21.50±1.78) kg /m, the VAS score was 4.40±0.88, the course of disease was (11.20±7.14) months. Surface electromyography analysis was performed on the multifidus muscle of the two groups. The average myoelectric amplitude of the multifidus muscle in the two groups were compared. RESULTS: The average myoelectric amplitude of the multifidus muscle of healthy volunteers was (48.84±7.77) µV on the left and (49.13±7.86) µV on the right. There was no significant difference between the two sides (>0.05). The average myoelectric amplitude of multifidus muscle in patients with lumbar disc herniation was(48.82±8.14) µV on the healthy side and (42.81±7.00) µV on the affected side, and the difference was statistically significant between two sides(<0.05). There was no significant difference in the average myoelectric amplitude of multifidus muscle between the healthy side of lumbar disc herniation and on the left of healthy volunteers, or between the healthy side of lumbar disc herniation and on the right of healthy volunteers (>0.05). There was significant difference in the average myoelectric amplitude of multifidus muscle between the affected side of lumbar disc herniation and on the left of healthy volunteers, and also between the affected side of lumbar disc herniation and on the right of healthy volunteers(<0.05). CONCLUSION Patients with chronic lumbar disc herniation have an imbalance in myoelectric activity, and the muscle strength of the multifidus muscle on the affected side is significantly reduced.
Adult ; Electromyography ; Female ; Humans ; Intervertebral Disc Degeneration ; diagnostic imaging ; Intervertebral Disc Displacement ; Lumbar Vertebrae ; Male ; Middle Aged ; Paraspinal Muscles

OBJECTIVE: To study the clinical characteristics, drug sensitivity of isolated strains, and risk factors of drug resistance in children with invasive pneumococcal disease (IPD). METHODS: The clinical characteristics and drug sensitivity of the isolated strains of 246 hospitalized children with IPD in nine grade A tertiary children's hospitals from January 2016 to June 2018 were analyzed. RESULTS: Of the 246 children with IPD, there were 122 males and 124 females. Their ages ranged from 1 day to 14 years, and among them, 68 (27.6%) patients were less than 1 year old, 54 (22.0%) patients were 1 to 2 years old, 97 (39.4%) patients were 2 to 5 years old, and 27 (11.0%) patients were 5 to 14 years old. Pneumonia with sepsis was the most common infection type (58.5%, 144/246), followed by bloodstream infection without focus (19.9%, 49/246) and meningitis (15.0%, 37/246). Forty-nine (19.9%) patients had underlying diseases, and 160 (65.0%) had various risk factors for drug resistance. The isolated Streptococcus pneumoniae strains were 100% sensitive to vancomycin, linezolid, moxifloxacin, and levofloxacin, 90% sensitive to ertapenem, ofloxacin, and ceftriaxone, but had a low sensitivity to erythromycin (4.2%), clindamycin (7.9%), and tetracycline (6.3%). CONCLUSIONS IPD is more common in children under 5 years old, especially in those under 2 years old. Some children with IPD have underlying diseases, and most of the patients have various risk factors for drug resistance. Pneumonia with sepsis is the most common infection type. The isolated Streptococcus pneumoniae strains are highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin, ertapenem, and ceftriaxone in children with IPD.
Anti-Bacterial Agents ; Ceftriaxone ; Child ; Child, Preschool ; Drug Resistance ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Pneumococcal Infections ; Streptococcus pneumoniae

BACKGROUNDPlasma transfusion is a common clinical practice. Remote ischemic preconditioning (RIPC) protects organs against ischemia-reperfusion (IR) injury. Whether preconditioned plasma (PP), collected at late phase after RIPC, could protect organs against IR injury in vivo is unknown. This study explored whether transfusion of PP could reduce myocardial infarct size (IS) after IR in rat in vivo.

METHODSEighty Lewis rats were randomized to eight groups (n = 10 for each group). Two groups of plasma donor rats donated plasma at 48 h after transient limb ischemia (PP) or control protocol (nonpreconditioned plasma [NPP]). Six groups of recipient rats received normal saline (NS; NS-IR 1, and NS-IR 24 groups), NPP (NPP-IR 1 and NPP-IR 24 groups), or PP (PP-IR 1 and PP-IR 24 groups) at one or 24 h before myocardial IR. Myocardial IR consisted of 30-min left anterior descending (LAD) coronary artery occlusion and 180-min reperfusion. The area at risk (AAR) and infarct area were determined by double-staining with Evans blue and triphenyltetrazolium chloride. IS was calculated by infarct area divided by AAR. This was a 3 × 2 factorial design study, and factorial analysis was used to evaluate the data. If an interaction between the fluid and transfusion time existed, one-way analysis of variance with Bonferroni correction for multiple comparisons was used to analyze the single effects of fluid type when the transfusion time was fixed.

RESULTSIS in the NPP-IR 1 and PP-IR 1 groups was smaller than in the NS-IR 1 group (F = 6.838, P = 0.005; NPP-IR 1: 57 ± 8% vs. NS-IR1: 68 ± 6%, t = 2.843, P = 0.020; PP-IR 1: 56 ± 8% vs. NS-IR 1: 68 ± 6%, t = 3.102, P = 0.009), but no significant difference was detected between the NPP-IR 1 and PP-IR 1 groups (57 ± 8% vs. 56 ± 8%, t = 0.069, P = 1.000). IS in the NPP-IR 24 and PP-IR 24 groups was smaller than in the NS-IR 24 group (F = 24.796, P< 0.001; NPP-IR 24: 56% ± 7% vs. NS-IR 24: 68 ± 7%, t = 3.102, P = 0.026; PP-IR 24: 40 ± 9% vs. NS-IR 24: 68 ± 7%, t = 7.237, P< 0.001); IS in the PP-IR 24 group was smaller than in the NPP-IR 24 group (40 ± 9% vs. 56 ± 7%, t = 4.135, P = 0.002).

CONCLUSIONTransfusion of PP collected at late phase after remote ischemic preconditioning could reduce IS, suggesting that late-phase cardioprotection was transferable in vivo.

Animals ; Blood Component Transfusion ; methods ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Infarction ; etiology ; prevention & control ; Myocardial Reperfusion Injury ; complications ; Plasma ; Rats

AIM:To evaluate the feasibility and advantages of two-port 27-gauge pars plana vitrectomy for treatment of recurrent retinal detachment in silicone oil dwelling eyes.METHODS:A retrospective study.Two-port 27-gauge pars plana vitrectomy was performed in 7 eyes with recurrent retinal detachment without remove of silicone oil.Proliferative membrane peeling, endolaser treatment, and drainage of subretinal fluid were performed.Scleral bulking was performed if necessary.RESULTS:Sucessful retina re-attachment was accomplishied in all eyes.No visually significant intraoperative complication occurred.All eyes expericend quick recoveray of visual acuity and mild postoperative irritation.One eye developed a recurrent inferior retinal detchment in 20d after the surgery using non-remove technique, and recovered after conventional silicone oil removal and retinal reattachment surgery.CONCLUSION:Two-port 27-gauge pars plana vitrectomy is an efficacious (and potentially cost-efficient) method to treat early stage recurrent retinal detachment in silicone oil dwelling eyes.