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.

New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.
Humans ; China ; Physicians ; Antineoplastic Agents/therapeutic use*

Objective: To investigate the effects of glutamate (Glu) injected into hypothalamic paraventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possible mechanism. Methods: Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th, 10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group), CVH + injection of saline into PVN group (NS group), CVH+ injection of Glu into PVN (3, 6, and 12 μg Glu, namely G3, G6, and G12, respectively), 6 rats in each group, and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold, abdominal withdrawal reflex (AWR) score, and abdominal external oblique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL. Results: Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups increased, and the AWR scores and EMG amplitudes decreased. The differences were statistically significant(Pain threshold: t=7.65, 16.31, 24.78, both P<0.05; AWR scores: t=-2.98, -4.77, -7.29, both P<0.05; EMG amplitudes: t=-3.06, -5.75, -8.92, both P<0.05). Compared with the Sham group, the expression of AVP in PVN of the CVH group and NS group decreased ((42.63±5.20) %, (18.67±2.94) %, (17.53±2.47) %; t=6.95, t=7.56, both P<0.05). The expression of AVP was increased after different doses of Glu into PVN, and the AVP level in G12 group ((18.15±6.49)%) was higher than that of NS group, the difference was statistically significant (t=-4.21, P<0.05). Compared with the Sham group, the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65.48±1.68) %, (18.39±1.67) %, (17.69±1.68) %; t=34.35, t=34.80, both P<0.05). The expression of PCNA was increased after different doses of Glu injected into PVN, and the PCNA level in G12 group ((59.91±5.63)%) was higher than that of NS group, the difference was statistically significant (t=-12.44, P<0.05). Compared with the Sham group, the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23.38±11.40)%, (83.79±3.57)%, (80.91±2.47)%; t=-8.77, t=-8.54, both P<0.05). The expression of apoptotic cells was decreased after different doses of Glu into PVN, and the G12 group was ((18.15±6.49) %). Compared with NS group, the difference was statistically significant (t=15.65, P<0.05). Conclusion Injection of Glu into hypothalamic PVN can alleviate the visceral pain behaviors in CVH rats, and its mechanism may be related to arginine vasopressin.

Objective: To explore the international development trends and research hotspots of outdoor activities affecting the progression of children’s myopia, and to provide a reference for researching on effective ways to prevent children’s myopia. Methods: Totally 291 relevant documents included in the "Web of Science" core set database were used as research objects, and CiteSpace software was used for visual analysis. Results: At present, the publications in this field were mainly in the United States(81), China(80), Australia(76), and Singapore(33); the top three research institutions were "Natl Univ Singapore"(29), "Australian Natl Univ"(27), "Capital Med Univ"(25); the main authors were "Saw SM", "Morgan IG", "Mitchell P". The field has been developed on the basis of "Ophthalmology", "Public, Environmental and Occupational Health", and has been integrated into 32 disciplines. The research content included "exploration of high risk factors for the progression of children’s myopia" and "outdoor activities", "intervention in children’s progression of myopia" and "longitudinal tracking of children’s vision development". Randomized clinical trials that longitudinally track the correlation between changes in eyeballs and the progression of myopia and the effects of outdoor activities on the biological characteristics of children’s eyeballs have become a hot topic in this field. Conclusion Research on the effects of outdoor activities on the progression of myopia in children has increased dramatically. The study of increasing outdoor activities to interfere with the progression of myopia in children and the vertical tracking of key factors affecting the biological characteristics of children’s eyeballs have become the current international trends.

Objective This is the first study to explore clinical application value of serum Dickkopf-1 (DKK-1) detection in diagnosis of heptocellular carcinoma (HCC) by magnetic solid phase chemiluminescent immunoassay.Methods The level of serum DKK-1 and AFP in 205 cases of HCC,40 cases of liver cirrhosis,and 200 cases of healthy control were quantitatively detected by Magnetic solid phase chemiluminescent immunoassay.The area under ROC curve,sensitivity and specificity of DKK-1 and AFP for diagnosing HCC were calculated.Results The serum level of DKK-1 in HCC group was significantly higher than those of the liver cirrhosis group and healthy control group (P<0.01).DKK-1 maintained diagnostic sensitivity for patients with HCC who were alpha-fetoprotein (AFP) negative (66.3%).ROC curves showed optimum diagnostic cut-off value was 2.4 ng/mL,area under curve (AUC) was 0.822 (95% CI:0.783-0.856),sensitivity 65.9%,and specificity 87.5%).Moreover,measurement of DKK1 and AFP together improved diagnostic accuracy for HCC versus all controls compared with either test alone [AUC 0.915,95%CI:0.886-0.940),sensitivity 81.5 %(P<0.05)].Conclusion Serum DKK-1 detection has an important clinical value for diagnosis of HCC,especially for HCC with AFP negative.The combined detection of serum DKK-1 and AFP can greatly increase sensitivity and accuracy for diagnosing HCC.

Objective To investigate the clinical effects of the stent-laparoscopy approach in treatment of elderly patients with malignant colorectal obstruction.Methods Clinical data of 55 elderly hospitalized patients with colorectal cancer-induced bowel obstruction in Wenzhou Central Hospital from January 2009 to January 2014 were evaluated retrospectively.All patients were treated with expandable metallic stents for remission of bowel obstruction.Patients were divided to laparoscopy surgeryobservation group (n =14) receiving laparoscopic surgery after decompression and the laparotomy surgery-control group (n=41) receiving conventional open colorectal cancer operation.The intraoperative information,postoperative complications and long-term curative effect were compared between the laparoscopy surgery-observation vs laparotomy surgery-control group.Results During laparoscopy surgery period,two patients operated by laparoscopy surgery were converted to laparotomy surgery.Surgical time was significantly longer in the laparoscopy surgery-observation group than in laparotomy surgery-control group[(178 ± 33) min vs.(145 ± 31) min,t =3.384,P =0.001],and bowel function recovery and postoperative hospital stay were significantly shorter in the laparoscopy surgery-observation group than in laparotomy surgery-control group[3.1 ± 0.9) d vs.(4.3 ± 1.3) d and (7.1±1.3) d vs.(12.6±5.7) d,t=3.193 and t=2.911,P=0.002 and P=0.005].Intraoperative blood loss was less in the laparoscopy surgery-observation group than in the laparotomy surgery-control group[(63 ± 29) ml vs (86 ± 37) ml,t =2.11,P =0.04],with no significant differences in postoperative complications between the two groups (0.0 vs 9.76 ％,x2 =1.47,P=0.225).Fifty-five patients were followed up for 2 years.All patients survived in the laparoscopy surgery-observation group,but one patient died from the cerebrovascular accident in the laparotomy surgery-control group.Conclusions The stent-laparoscopy approach to treat colorectal cancer (CRC) patients with acute colorectal obstruction is a safe,effective,recovery quick and minimally invasive option for elderly patients.Emergency surgery may be converted to a limited operation by this method.Laparoscopic radical surgery with one-stage anastomosis is feasible.

Objective To explore the clinical efficacy of modified single-portlaparoscopic radical prostatec-tomy(LRP) by atransperitoneal or extraperitoneal approach, and the impact of either approach on immune function in patients with prostate neoplasms. Methods The clinical data on 39 patients who had undergoneextraperitoneal LRP(group A) and 20 patients who had receivedtranperitoneal LRP (group B) in our department from January 2012 to December 2015 were retrospectivelyanalyzed. The prostate neoplasms were preoperatively diagnosed as cancer by ultrasound, CT or MRI, and pathological examinations. The clinical stage was T1-T2c , N0M0 in all patients.The efficacy was assessed by surgical duration, intraoperative blood loss, timeto intestinal function recovery, and post-operative hospital stay in both groups. The indicators for immune function including prostate specific antigen (TPSA and FPSA), immunoglobulin (IgG, IgA, lgM, C3, and C4) and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) in patientswith prostate neoplasms before and after surgery were detected. Results 59 patients were operat-ed successfully, without converting to open approach. The mean surgical duration, blood loss, time to intestinal function recovery, and postoperative hospital stay were (133.8 ± 68.6) min, (75.6 ± 51.3) mL, (2.2 ± 0.7) days, and (14.7 ± 3.6) days in group A, while (159.4 ± 78.1) min, (102.2 ± 70.8) mL, (2.9 ± 1.1) days, and (15.2 ± 4.1) days in group B. There were significant differences between the two groups (P<0.05). After surgery, levels of IgG, IgA, C3, C4, CD3+, CD4+and CD4+/CD8+were significantly higherin group Athan in group B (P < 0.05). There were no significant differences between the two groups in levels of TPSA, FPSA and lgM (P>0.05). Average postoperative follow-up was 15 months (range 3-36) in 36 patients. No recurrence or metastasis was found in all the patients by imaging studies,and no long-term complications were found. Conclusions Extraperitoneal LRP, as compared with tranperitoneal LRP, has clearer vision, fewer effects on abdominal organs, shorter surgical duration, less blood loss, faster postoperative recovery, and better protection of immune function. It is worth popularizing clin-ically.

Purpose This subject detected the expression of paper miRNA34a,c-myc gene and protein in adenocarcinoma of lung tissue,adjacent mucosa tissue and normal lung tissue exploring the relationship between the two and the clinical significance.Method The project mainly used the method of real-time fluorescent quantitative PCR (qRT-PCR),Western blot and immunohistochecical to detect the expression of miRNA34a and c-myc in normal tissue and adenocarcinoma of lung respectively.Result (1) lower expression of miRNA34a in lung adenocarcinoma tissue,lower than the adjacent and normal tissues (P ＜ 0.01),higher than the metastatic carcinoma group (P ＜ 0.01).C-myc is highly expressed in lung adenocarcinoma tissue,higher than the adjacent and normal tissues (P ＜0.01),lower than the metastatic carcinoma tissue (P ＜ 0.01).miRNA34a and c-myc beside carcinoma tissues and normal tissues also have significant difference between the statistical significance (P ＜ 0.05).(2) Differentiation of low and high there was no statistically significant difference between patients with lung adenocarcinoma (P ＞ 0.05).there were significant differences in the expression of miRNA34a and c-myc in the tissues of metastatic and non metastatic adnocarcinoma.(3)The positive expression of c-myc group of lung cancer patients was lower than that of the negative group (P ＜ 0.05),low expression of the survival time in miRNA34a group was significantly lower than that in high expression group,there was significant difference (P ＜ 0.01).Conclusion Expression of miRNA34a and c-myc both showed a negative correlation in adenocarcinoma of lung.