The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

Background and objective Both of lung cancer incidence and mortality rank first among all cancers in China.Previous lung cancer screening trials were mostly selective screening for high-risk groups such as smokers.Non-smoking women accounted for a considerable proportion of lung cancer cases in Asia.This study aimed to evaluate the outcome of community-based mass screening in Guangzhou and identify the high-risk factors for lung cancer.Methods Residents aged 40-74 years in Guangzhou were screened with low-dose computed tomography(LDCT)for lung cancer and the pulmonary nodules were classified and managed according to China National Lung Cancer Screening Guideline with Low-dose Computed Tomography(2018 version).The detection rate of positive nodules was calculated.Before the LDCT examination,residents were required to complete a"lung cancer risk factors questionnaire".The risk factors of the questionnaire were analyzed by least absolute shrinkage and selection operator(LASSO)penalized Logistic regression analysis.Results A total of 6256 residents were included in this study.1228 positive nodules(19.63％)and 117 lung cancers were confirmed,including 6 cases of Tis,103 cases of stage Ⅰ(accounting for 88.03％of lung cancer).The results of LASSO penalized Logistic regression analysis indicated that age ≥50 yr(OR=1.07,95％CI:1.06-1.07),history of cancer(OR=3.29,95％CI:3.22-3.37),textile industry(OR=1.10,95％CI:1.08-1.13),use coal for cooking in childhood(OR=1.14,95％CI:1.13-1.16)and food al-lergy(OR=1.10,95％CI:1.07-1.13)were risk factors of lung cancer for female in this district.Conclusion This study highlighted that numerous early stages of lung cancer cases were detected by LDCT,which could be applied to screen-ing of lung cancer in women.Besides,age ≥50 yr,personal history of cancer,textile industry and use coal for cooking in childhood are risk factors for women in this district,which suggested that it's high time to raise the awareness of early lung cancer screening in this group.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

Objective:To evaluate the laparoscopic sleeve gastrectomy combined with hiatal hernia repair surgery for weight loss and antireflux.Methods:This study included 21 obese patients with gastroesophageal reflux who underwent laparoscopic sleeve gastrectomy at the Weight Loss Metabolism Center of the Department of Hepatobiliary and Pancreatic Surgery of Zhejiang Provincial People's Hospital from Dec 2019 to Dec 2020. Patients were divided into simple bariatric surgery group (9 cases) and simultaneous combined surgery group (12 cases).Results:In the combined surgery group, 1 case had postoperative gastric leakage. The postoperative body weight, waist circumference, and BMI indexes of the two groups showed a downward trend ( F=5.154, P=0.013; F=14.319, P<0.001; F=6.725, P=0.004). There was a statistically significant difference in the excess weight loss in both the two groups at 6 months after the operation compared to 1 month after the operation ( t=8.927, P<0.001; t=8.926, P<0.001). There was no statistically significant difference in postoperative lower esophageal sphincter resting pressure and Gerd symptom score in the bariatric surgery group compared with preoperative ( t=-0.891, P=0.507; t=0.629, P=0.298). The postoperative Gerd symptom score of the patients in the combined surgery group was significantly lower than that before the operation, and the resting pressure of the lower esophageal sphincter was significantly higher than that before the operation, ( t=-10.539, P<0.001; t=5.066, P=0.038). Conclusion:Combined surgery have the same weight loss effect as in simple bariatric surgery in obese patients with gastroesophageal reflux, in addition to stronger anti-reflux effect.

OBJECTIVETo investigate the abnormal changes in the testes and semen parameters in patients with varicose veins and analyze the possible relationship between clinical varicocele and infertility.

METHODSWe retrospectively reviewed the records of 172 male patients consulting for varicocele in our hospital since 2003. All these patients were examined for the size of the testes with scrotal ultrasound. The semen samples of the patients with varicocele except for 5 under the age of 17 years were collected and analyzed, using the data of semen analyses of 163 healthy young male volunteers (aged 18-29 years) as control.

RESULTSAll the 172 patients had left-sided varicose veins. Sixty-three patients were found to have bilateral varicocele, and in most of them, the clinical grades of the left-sided varicose veins were higher than those of the right-sided ones. The mean volume of the left testis of the patients was 10.99∓3.71 ml, significantly smaller than that of the right one (11.86∓4.05 ml, P<0.01). The physiochemical indices of the patients, including the voiding volume, semen pH, liquefaction time and sperm concentration, were normal or similar with those of the healthy volunteers (P>0.05). Almost all the patients sperm motility and viability were significantly lower than those of the healthy volunteers (P<0.05). In addition, no significant difference was found in the sperm density, motility or viability between the patients with unilateral and bilateral varicocele (P>0.05).

CONCLUSIONVaricocele may decrease the testicular volume. Both unilateral and bilateral varicocele may have an effect on the bilateral testes to cause possible functional impairment of the testes manifested by decreased sperm motility and viability.

Adolescent ; Adult ; Child ; Humans ; Infertility, Male ; etiology ; Male ; Middle Aged ; Retrospective Studies ; Semen ; Sperm Count ; Sperm Motility ; Testis ; physiopathology ; Varicocele ; complications ; physiopathology ; Young Adult

OBJECTIVE: To compare the safety and efficacy of prone and modified recumbent positions on minimal invasive percutaneous nephrolithotomy. METHODS: A total of 62 patients with upper urinary calculi were grouped into two groups, one of which consisted of 27 patients who underwent the minimal invasive percutaneous nephrolithotomy with modified recumbent position, and the other 35 patients with prone position. There was no significant statistical difference in the age, gender and complications between the two groups before surgery (P>0.05). Duration of and blood loss during surgery, complications in the perioperative period, and the length of postoperative hospital stay were all recorded. The data were analyzed by SPSS 13.0. RESULTS: Surgery was successful in all cases. There was no failure to puncture nor need to resort to open surgery. Average operation duration for the modified recumbent position group was (85.1± 25.3) min vs (97.2±30.6) min for the prone position group. Mean blood loss during the operation was (117.5± 49.7) mL vs (149.3±53.1) mL. There were no severe complications during and after surgery in the modified recumbent position group. In the prone position group, s one patient suffered pneumothorax during the operation and two suffered selective renal artery embolization because of massive hemorrhaging following the operation. There were significant differences in blood loss during surgery, in complications during the perioperative period, and in length of postoperative stay in hospital (P<0.05) between the two groups. CONCLUSION The patients are safer and more easily tolerate the minimal invasive percutaneous nephrolithotomy in the modified recumbent position than in the prone position, though the treatment efficacy of these two kinds of operation is similar. It is recommended that the modified recumbent position should be used generally in the percutaneous nephrolithotomy.
Adult ; Aged ; Female ; Humans ; Kidney Calculi ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Nephrostomy, Percutaneous ; methods ; Posture ; Prone Position ; Supine Position ; Ureteral Calculi ; surgery