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*

Objective : To investigate the current status of hearing loss in a fastener manufacturing enterprise, and to analyze its influencing factors, so as to provide insights into occupational disease prevention and control. Methods: The occupational health examination data of noise exposed workers and the workplace occupational disease hazard factors detection data in a fastener manufacturing enterprise in Jiaxing City in 2022 were collected through the Occupational Disease and Occupational Health Hazard Factors Detection System of China Disease Prevention and Control Information System, and factors affecting the development of high-frequency noise-induced hearing loss (HFNIHL) and speech-frequency noise-induced hearing loss (SFNIHL) were analyzed. Results: Totally 625 workers were investigated, with a median age of 44.00 (interquartile range, 13.00) years and a median length of service of 8.00 (interquartile range, 9.00) years, and including 519 men (83.04%) and 106 women (16.96%). There were 309 workers with single noise exposure (49.44%) and 316 workers with joint noise exposure (50.56%), and 518 workers exposed to noise with the normalized continuous A-weighted sound pressure level equivalent to a 40 h working week (LEX,40 h) that exceeded the national standard (82.88%). The detection rates of HFNIHL and SFNIHL were 49.12% and 35.04%, respectively. Multivariable logistic regression analysis indicated that males (OR=10.528, 95%CI: 5.271-21.025), length of service of 10 years and longer (OR=2.451, 95%CI: 1.599-3.759), LEX,40 h of >85 dB (A) (OR=2.227, 95%CI: 1.318-3.764) and joint noise exposure (OR=3.002, 95%CI: 2.080-4.334) were associated with an increased risk of HFNIHL, and male (OR=9.400, 95%CI: 4.211-20.985), LEX,40 h of >85 dB (A) (OR=2.305, 95%CI: 1.345-3.951), and joint noise exposure (OR=3.880, 95%CI: 2.677-5.623) were associated with an increased risk of SFNIHL. Conclusion Gender, length of service, noise intensity and exposure mode are factors affecting the risk of HFNIHL, while gender, noise intensity and exposure mode are factors affecting the risk of SFNIHL.

Objective: To investigate the relationship between working duration and work-related musculoskeletal disorders (WMSDs) among Internet enterprise employees. Methods: Employees were randomly sampled from five Internet enterprises in Jiaxing City of Zhejiang Province using the cluster sampling method. Participants' demographics and working duration were collected using questionnaire surveys, and the fatigue accumulation and WMSDs were assessed using the Self-diagnosis Questionnaire for Fatigue Accumulation and the Musculoskeletal Disorders Questionnaire. The working duration per week was classified into 40 h and less, 40 to 48 h, 48 to 56 h and 56 h and longer, and more than 40 h working duration per week was defined as long working duration. The association between working duration and WMSDs was examined with a multivariable logistic regression model. Results: Among 334 questionnaires recovered, 280 were valid, with an effective recovery rate of 83.83%. The participants included 211 men (75.36%) and 69 women (24.64%), and there were 204 participants at ages of less than 36 years (72.86%) and 234 participants with long working duration (83.57%). The detection of fatigue accumulation and WMSDs was 33.21% and 65.36% among the participants, with the highest prevalence of WMSDs detected in the neck (52.50%). Multivariable logistic regression analysis showed that weekly working duration correlated with WMSDs (>40 to 48 h, OR=2.199, 95%CI: 1.083-4.468; >56 h, OR=6.688, 95%CI: 1.902-23.520) after adjustment for gender, marital status and sleep disorders. If fatigue accumulation was included in the model, there was no statistical correlation between weekly working duration and WMSDs (P>0.05). Conclusion Long working duration may increase the risk of WMSDs among Internet enterprise employees, and fatigue accumulation may play a mediating role.

Objective:To construct a prediction model for prognosis of severe pneumonia patients combined with sepsis.Methods:Clinical data of 318 severe pneumonia patients combined with sepsis admitted at Taizhou People’s Hospital affiliated to Nanjing Medical University from March 2019 to March 2022 were retrospectively analyzed. Patients were randomized into a modeling set ( n=233) and a validation set ( n=85) with a 3∶1 ratio. In the modeling set there were 180 survival cases and 53 fatal cases according to the clinical outcomes within 30 days of admission. Multivariate Cox regression analysis was used to evaluate the independent prognostic factors for patients in the modeling set. A nomogram prediction model was constructed by R based on these prognostic factors and further verified using the data of the validation set with receiver operating curve (ROC), decision curve analysis (DCA), and calibrated with calibration curve analyses. Results:Multivariate Cox regression analysis suggested that septic shock ( HR=2.32, 95% CI 1.37-3.89, P=0.013) and neutrophil/lymphocyte ratio (NLR) ( HR=2.52, 95% CI 1.23-5.61, P=0.017) were independent risk factors for mortality in severe pneumonia patients combined with sepsis within 30 days of admission, while albumin/fibrinogen ratio (AFR) ( HR=0.64, 95% CI 0.41-0.83, P=0.011) and prognostic nutritional index (PNI) ( HR=0.68, 95% CI 0.57-0.83, P=0.009) were independent protective factors. The area under ROC curve (AUC) of the nomogram model based on these four indicators in the modeling and validation sets were 0.875 and 0.880, respectively. The DCA curve analysis indicated that the clinical benefit of this model was better than "All" or "None" curves in both the modeling and verification sets.The calibrate curve analysis indicated that the actual and corrected curves fitted well and were close to the ideal curve. Conclusion:The constructed nomogram model based on septic shock, AFR, NLR and PNI has a well prognostic value in severe pneumonia patients combined with sepsis.

Objective:To observe the effect of mechanical vibration on the expression of microRNA-214-3p and serum interleukin-1β (IL-1β) in the broken ends of fractured bones in ovariectomized rats.Methods:Thirty 3-month-old female Wistar rats were randomly divided into a control group, a model group, and a vibration group, each of 10. An operation of ovariotomy was performed in those of the model and vibration groups to establish osteoporosis model. Five months later a model of mid femur fracture was made with animals in all the groups. Five days after their fracture, the vibration group received 20 minutes of whole-body vibration treatment at 35Hz for 5 days a week, while the control group and the model group received natural rearing without any additional intervention At 2 and 6 weeks after the operation, the Lane-Sandhu X-ray scoring system was used to evaluate the quality of fracture healing, and reverse-transcription polymerase chain reactions and enzyme-linked immunosorbent assays were used to detect miR-214-3p in the fractured bones and the serum levels of IL-1β.Results:At 2 weeks and 6 weeks after the operation the average growth score of the broken ends in the model group was significantly lower than that of the control group, while that of the vibration group was significantly higher than the model group′s average. Compared with the control group at the same time point, the average miR-214-3p content of the model and vibration groups was significantly higher 2 and 6 weeks after the surgery. Compared with the model group, the average level of miR-214-3p of the fractured ends of the vibration group was significantly lower at 6 weeks. Two and six weeks after the surgery, the average IL-1β of the model group was significantly higher than the control group′s average, and that of the vibration group was significantly lower.Conclusion:Mechanical vibration can promote osteoporotic fracture healing by inhibiting the expression of miR-214-3p and reducing the level of IL-1β at the broken ends of fractured bones.

Objective : To compare the clinical effect of the reconstruction of defects of the surgical area with the facial-submental artery island flap (FSAIF) after resection of oral cavity squamous cell carcinoma (OC-SCC) and oropharyngeal squamous cell carcinoma (OP-SCC). Methods: A total of 203 cases of oral cavity squamous cell carcinoma and 72 cases of oropharyngeal squamous cell carcinoma were treated with the FSAIFs. The complications and success rate of the two groups were observed. The swallowing and voice functions of the two groups were evaluated and compared 6 months after the operation. The survival of the two groups was followed up. Results: No significant differences were found in TNM stage, the skin paddle of the flap, the rate of flap failure, or local complications between the OC-SCC and OP-SCC groups (P > 0.05). Significant differences in swallowing and speech outcomes were observed between the groups (P < 0.05). No significant differences were found in survival outcome between the groups after 9-59 months of follow-up. Conclusion FSAIF can be used for reconstructing the defect in oral cavity or oropharynx, but the swallowing function of reconstructing the defect in oropharynx is poor.

OBJECTIVETo analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations.

METHODSThe child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members. Candidate genes were captured with Agilent SureSelect and sequenced on an Illumina platform. Suspected mutation was verified by Sanger sequencing.

RESULTSThe patient, a six-year-and-10-month old girl, presented with non-symmetrical short stature, dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and cataract of right eye, in addition with frequent respiratory infection and micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency (18.9 ng/mL). Spine X-ray showed multiple malformations with centrums. Her mother also featured short stature (138 cm). Her aunt had short stature (130 cm) and limb-length discrepancy. Her little brother was 2.5 years old, and his height was 81 cm (-3.4 SD). Exome sequencing revealed a heterozygous mutation c.184C to T (p.Arg62Trp) in the proband and her mother. The same mutation was not found in her father and brother.

CONCLUSIONThe patient was diagnosed with X-linked chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the disease in this family.

Objective: To evaluate the spatiotemporal relationship between the root apex of mandibular molars and the inferior alveolar nerve canal (IANC) in adults. Methods: Cone-beam computed tomography (CBCT) images were collected in 236 patients, and the distances from the root apexes of mandibular molars to the IANC were measured in NNT 4.6 software. The relationship between distance and gender was evaluated. Results: In two-rooted mandibular first molars, the distances from the mesial root and distal root to the IANC were 7.34 ± 2.07 mm and 6.69 ± 2.08 mm, respectively, in males and 6.47 ± 2.22 mm and 5.94 ± 2.11 mm in females. In three-rooted mandibular first molars, the distances from the mesial root, distobuccal root, and distolingual to the IANC were 7.29 ± 1.30 mm, 7.40 ± 2.33 mm, and 9.97 ± 2.19 mm, respectively, in males and 6.08 ± 2.57 mm, 6.35 ± 2.40 mm, and 9.01 ± 2.90 mm, respectively, in females. In one-rooted mandibular second molars, the distance from the root to the IANC was 4.09 ± 1.64 mm in males and 3.89 ± 1.76 mm in females. In two-rooted mandibular second molars, the distances from the mesial root and distal root to the IANC were 5.14 ± 2.08 mm and 4.39 ± 1.85 mm, respectively, in males and 3.78 ± 1.69 mm and 3.24 ± 1.72 mm, respectively, in females. There were no significant with in-gender differences between the left and right side in the distances from the root apexes to the IANC (P>0.05). The distances from the mandibular first molar were greater in males than in females. The longest average distance was from the distolingual root apexes of three-rooted mandibular first molars to the IANC, and the distances were longer from the distobuccal root apexes of three-rooted mandibular first molars to the IANC than from the distal root apexes of two-rooted mandibular first molars to the IANC (P<0.05). There was no within-gender difference in the distances from the root apexes of single-rooted mandibular second molars to the IANC (P>0.05), but the distances in two-rooted mandibular second molars were larger in males than in females (P<0.05). The distances from the root apexes to the IANC were smaller in mandibular second molars than in mandibular first molars (P<0.05). Conclusion There are significant differences between adult males and females in the distance from the root apex to the IANC for mandibular first molars and two-rooted mandibular second molars. The distances from the root apexes to the IANC were smaller in mandibular second molars than in mandibular first molars.

Objective To investigate the value of platelet, serum sodium and serum creatinine levels in the prognosis of patients with liver failure. Methods The clinical data of 155 patients with liver failure were retrospectively analyzed, and the patients were divided into improvement survival group (87 cases) and deterioration died group (68 cases) according to the prognosis. The hospitalization time of every patient was divided into 4 roughly equal time period, and observed at 5 points of time:T1-T5. The levels and abnormal rates of platelet, serum sodium and serum creatinine were compared. Results The T3 - T5 serum creatinine levels in deterioration died group were significantly higher than those in improvement survival group: (102.14 ± 75.67) μmol/L vs. (78.21 ± 26.68) μmol/L, (116.45 ± 110.64)μmol/L vs. (78.77 ± 29.25) μmol/L, (161.43 ± 153.23) μmol/L vs. (76.40 ± 27.26) μmol/L, and the T1 - T5 serum sodium and platelet levels were significantly lower than those in improvement survival group:(135.05 ± 6.24) mmol/L vs. (137.52 ± 5.26) mmol/L, (137.01 ± 4.99) mmol/L vs. (139.00 ± 3.89) mmol/L, (134.80 ± 16.74) mmol/L vs. (139.15 ± 3.77) mmol/L, (134.40 ± 11.69) mmol/L vs. (138.30 ± 8.75) mmol/L, (133.30 ± 8.93) mmol/L vs. (139.01 ± 9.10) mmol/L, and (122.46 ± 72.59) × 109/L vs. (149.70 ± 71.70) ×109/L, (110.18 ± 65.10) × 109/L vs. (152.09 ± 82.79) ×109/L, (107.32 ± 70.49) ×109/L vs. (169.32 ± 100.65) ×109/L, (97.06 ± 58.15) ×109/L vs. (183.57 ± 112.68) ×109/L, (94.66 ± 57.00) × 109/L vs. (191.36 ± 118.64) ×109/L, and there were statistical differences (P<0.05). The abnormal rates of T3-T5 serum creatinine, T2 - T5 serum sodium and T1 - T5 platelet in deterioration died group were significantly higher than those in improvement survival group, the serum creatinine: 22.06%(15/68) vs. 6.90% (6/87), 27.49% (19/68) vs. 8.05% (7/87) and 42.65% (29/68) vs. 10.34% (9/87), the serum sodium: 32.35% (22/68) vs. 13.79% (12/87), 39.71% (27/68) vs. 14.94% (13/87), 48.53% (33/68) vs. 12.64%(11/87) and 60.29%(41/68) vs. 11.49%(10/87), the platelet:45.59%(31/68) vs. 21.84%(19/87), 55.88% (38/68) vs. 24.14% (21/87), 54.41% (37/68) vs. 25.29% (22/87), 55.88% (38/68) vs. 21.84%(19/87) and 61.76% (42/68) vs. 20.69% (18/87), and there were statistical differences (P<0.05). Abnormal rate of platelet was highest in each time point. Conclusions In the course of pathological changes in deterioration and dead patients, the platelet is the first and most easily affected compare with serum sodium and serum creatinine; the platelet may be a sensitive marker for predicting clinical outcome in patients with liver failure.

Objective To explore fecal bacteria transplantation for the treatment of severe gastrointestinal disease caused by food allergy. Method The therapeutic process of fecal bacteria transplantation for treatment of severe food allergy gastrointestinal disease was retrospectively analyzed, and the related literature was reviewed. Results A 2-year-old boy had onset of intestinal infection and diarrhea was persistent even though he had received adequate anti-infection therapy and supportive treatment. Finally, the patient received the treatment of fecal bacteria transplantation and the symptoms were then improved. No adverse reactions were observed in 2 months of follow-up. In foreign literature, fecal bacteria transplantation in children is mainly applied to clostridium difficile infection (CDI) and inflammatory bowel disease (IBD), with efficiency of 90%- 100% and 55.6% - 100%, respectively. While in the domestic literature, fecal bacteria transplantation in children is mainly used in CDI and antibiotic associated diarrhea, and the effective rate is 100%. No serious adverse reactions were found in all the researches. Conclusion Fecal transplantation is safe and effective in the treatment of children with severe gastrointestinal disease caused by food allergy, but its application in children is not yet mature and needs more in-depth researches.