Influenza is an acute respiratory infection caused by influenza viruses (IFV), According to the World Health Organization (WHO), seasonal IFV epidemics result in approximately 3-5 million cases of severe illness, leading to about half a million deaths worldwide, along with severe economic losses and social burdens. Unfortunately, frequent mutations in IFV lead to a certain lag in vaccine development as well as resistance to existing antiviral drugs. Therefore, it is of great importance to develop anti-IFV drugs with high efficiency against wild-type and resistant strains, needed in the fight against current and future outbreaks caused by different IFV strains. In this review, we summarize general strategies used for the discovery and development of antiviral agents targeting multiple IFV strains (including those resistant to available drugs). Structure-based drug design, mechanism-based drug design, multivalent interaction-based drug design and drug repurposing are amongst the most relevant strategies that provide a framework for the development of antiviral drugs targeting IFV.

Abstract Oral health problems is one of major public health problems that threatens children s overall health. Children s oral health is closely related to family parenting styles. Currently, grandparenting is becoming increasingly common in China, and its impact on children s oral health should not be underestimated. This article reviews the impacts of the oral health knowledge level, behavior habits, gender, socioeconomic status, and other factors related to grandparenting on children s oral health, in order to reduce the negative impact of grandparenting involvement on children s oral health, and to provide theoretical basis and guidance.

OBJECTIVE：To establish the metho d for the content determination of 8 nucleosides in wild and cultivated Pinellia ternate，and to conduct the difference analysis. METHODS ：The contents of uracil ，uridine，inosine，xanthine，adenine， guanosine，β-thymidine and adenosine in 20 batches of P. ternate （wild product YS 1-YS8，cultivated product ZP 1-ZP12）were determined by HPLC method. Based on the contents of the above 8 nucleosides，cluster analysis ，principal component analysis （PCA），partial least squares analysis （OPLS-DA）were used to comprehensively evaluate the wild and cultivated P. ternata . RESULTS：The contents of uracil ，uridine，inosine，xanthine，adenine，guanosine，β-thymidine and adenosine in 20 batches of P. ternate were 0.02-0.24，0.01-0.24，0.06-0.37，0.02-0.14，0.04-0.22，0.14-0.42，0.01-0.09，0-0.32 mg/g，respectively. Cluster analysis，PCA and OPLS-DA showed that 8 batches of wild P. ternate （YS1-YS8）were clustered into one category ，and 12 batches of cultivated P. ternate （ZP1-ZP12）were clustered into one category. Main characteristic markers of wild P. ternate were guanosine，uridine，adenosine and adenine ，while the main characteristic markers of cultivated P. ternate were urinine ，xanthine， inosine，and β-thymidine. CONCLUSIONS：The method for the content determination of 8 nucleosides in P. ternate is established. Nucleosides as quality markers can effectively distinguish wild and cultivated P. ternata ，and the quality of the wild P. ternate was better than that of cultivated P. ternate .

OBJECTIVE: To investigate the long-term outcome of laparoscope-assisted transanal total mesorectal excision (taTME) for rectal cancer. METHODS: Clinicopathological data of 29 patients with mid-low rectal cancer undergoing laparoscope-assisted taTME at Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangzhou Medical University from May 2010 to December 2015 were collected for the retrospective case-series study. All the operations were performed with transabdominal and transanal procedure simultaneously or sequentially. Perioperative presentations, pathological examinations, and oncologic outcomes were retrospectively analyzed. Long-term recurrence, metastasis and survival were assessed during follow-up. Outpatient clinic and telephone survey were used for follow-up. The follow-up time ended in December 2018. The overall survival (OS) rate and disease-free survival (DFS) rate were calculated by the Kaplan-Meier method. RESULTS: The average intra-operative blood loss was (75.9±9.5) ml (range,20 to 200). The average operating time was (223.6±4.1) minutes (range, 165 to 280). The average number of harvested lymph node was 22.3±2.0. The average length of pathological specimen was (13.1±0.6) cm. The average distal resection margin was (2.9±0.2) cm. 89.7% (26/29) of specimens was complete and 10.3% (3/29) near complete. Two cases (6.9%) had positive cutting circumferential margin. Median follow-up was 56 (range, 22 to 91) months. Local recurrence rate, distant metastasis rate, 3-year OS rate, 3-year DFS rate, 5-year OS rate, 5-year DFS rate were 10.3% (3/29), 20.7%(6/29), 96.6%, 83.2%, 87.6% and 79.6%, respectively. No incisional hernia or adhesive intestinal obstruction was found. CONCLUSION Long-term outcomes of mid-low rectal cancer patients undergoing laparoscope-assisted taTME are satisfactory.
Humans ; Laparoscopes ; Neoplasm Recurrence, Local ; Rectal Neoplasms ; surgery ; Rectum ; Retrospective Studies ; Transanal Endoscopic Surgery

Objective: To evaluate the risk factors of postoperative upgrade to pT₃a of cT₁ renal cell carcinoma, and to establish a nomogram prediction model to improve the ability of predicting locally advanced renal cell carcinoma and provide a reference for clinical surgical decision-making. Methods: Clinical data of 1 376 patients with cT₁ (diameter ≤ 7 cm) renal tumor hospitalized for surgery from January 2010 to December 2016 were retrospectively analyzed. There were 979 males and 397 females, with the mean age of (57.65±10.92) years. The mean body mass index (BMI) was (25.47±3.27) kg/m² and the average tumor size was (4.02±1.52) cm. There were 711 tumors on the left and 665 on the right. There were 363 cases with clinical symptoms, 567 patients with smoking history , 732 cases with history of chronic disease. There were 289 cases with tumor necrosis, 636 cases with tumor protrusion, 822 cases with irregular tumor , and 738 cases with renal sinus compression. Partial nephrectomy and radical nephrectomy were performed in 396 cases and 980 cases respectively. Mann-whitney U test and chi-square test were used for univariate analysis, logistic regression analysis was used for multivariate analysis to analyze the predictors of upgrading, R software was used to construct the nomogram predictive model, C-index was used to evaluate the model discrimination, and calibration curve method was used to evaluate the consistency of the model. Results: Postoperative pathology of total 1 376 cases showed that there were 1 195 cases of clear cell carcinoma of kidney, 48 cases of papillary cell carcinoma, 57 cases of chromophobe cell carcinoma, and 76 cases of other types. Among the 1 376 patients with cT₁ renal tumor, 75 patients were upgraded to pT_3a, accounting for 5.5% of all patients. Univariate analysis showed that the patients who upgraded to pT_3a were older [(63.08±10.17) years old and (57.34±10.88) years old], and the tumor length and diameter were larger [(5.24±1.35) cm and (3.95±1.51) cm]. Patients with clinical symptoms [46.7% (35/75) vs. 25.2%(328/1 301)], patients with CT indication of tumor necrosis [40.0%(30/25 975) vs. 19.9% (259/1 301)], patients with irregular tumor contour [73.3%(55/76 775) vs. 59.0%(767/1 301)], and patients with radical nephrectomy were higher [(92.1% (70/91 075) vs. 70%(910/1 301)]. All the differences were statistically significant (P<0.01). Multivariate analysis showed that the independent predictors of upgrading were age (OR=1.046, P<0.001), larger tumor (OR=1.504, P<0.001), clinically symptom (OR=2.153, P=0.004), irregular tumor profile (OR=2.466, P=0.002), and tumor necrosis on CT (OR=2.588, P<0.001). The C-index was 0.808, the calibration curve of forecasting curve with the standard curve fit was good, and the prediction of renal cancer are better in predict consistency. Conclusions Based on the five preoperative predictors, including age, tumor size, clinical presence or absence of symptoms, tumor profile, and whether or not the tumor necrosis indicated by CT, this study developed a nomogram of cT₁ renal cancer upgrade to pT_3a. This nomogram has a good statistical significance, and this model can provide prognosis consultation for patients and provide reference for doctors to make decisions before treatment.

Objective: To investigate the effect of progressive early rehabilitation training in patients with severe acute pancreatitis. Methods: A total of 67 patients with severe acute pancreatitis requiring mechanical ventilation who were treated in the intensive care department of Shanghai first people's hospital from May 2015 to May 2018 were selected. According to the order of admission, they were divided into the control group (n=32) and the intervention group (n=35). On the basis of this nursing, the intervention group was jointly evaluated by the ICU rehabilitation team and adopted the progressive early rehabilitation nursing mode according to the different degrees of patients' conditions. The intervention effects of the two groups were compared. Results: The success rate of one-time weaning, mechanical ventilation time and ICU hospitalization time in the intervention group were 97.14% (34/35), (4.62±1.98) d, (8.76±1.02) d, and 78.12% (25/30), (9.01±2.15) d, and (14.01±2.87) d, respectively, in the control group. The difference between the two groups was statistically significant (χ² = 3.986, t=-5.012, -8.260, P < 0.05 or 0.01). The incidence of delirium, Barthel index (BI) scale score and grip strength score were 2.86% (1/35), 47.54±4.32, (34.05±10.68) kg, in the intervention group, 12.50% (4/32), 41.68±3.18, and (26.79±8.97) kg, in the control group, respectively. The difference between the two groups was statistically significant (χ²=4.024, t=7.651, 3.194, P < 0.05 or 0.01). Conclusions Progressive early rehabilitation training and nursing has a great influence on the prognosis of patients with severe acute pancreatitis, which can effectively improve the prognosis of patients, accelerate the recovery of patients, shorten the length of hospital stay and the duration of use of ventilator, reduce the incidence of delirium, help patients to restore muscle strength, and improve the Barthel index score of patients, which is worthy of promotion and application.

Objective·To investigate effect and the possible molecular mechanism of JQ1,a specific inhibitor of bromodomain containing protein 4,on human hypertropic scar.Methods·Primary fibroblasts were isolated from human hypertrophic scars and treated with JQ-1 of different concentrations (0.1,0.5,1.0,2.0,2.5,and 12.5μmol/L) for 48 h.Then CCK-8 kit and wound healing assay were used to measure proliferation and migration of the fibroblasts.ELISA was adopted to detect the levels of collagen type Ⅰ (COL Ⅰ) and TGF-β1 after JQ-1 treatment for 24 h.Thirty-six nude mice were used for hypertrophic scar models.Human hypertrophic scars (1.0 cm× 1.0 cm×0.5 cm) were grafted subcutaneously at the backs of nude mice to establish scar animal models.After 4 weeks,the nude mice were averagely divided into two groups,i.e.JQ-1 group and DMSO group,which were respectively injected with 0.5 μmol/L JQ-1 and 0.1％ DMSO each mouse every day.COL Ⅰ / Ⅲ and α-smooth muscle actin (α-SMA) were examined by immunohistochemical method and sirius red staining.Results·Cell experiments showed that JQ-1 with the concentration of 0.5 μmol/L and above significantly inhibited proliferation of fibroblasts (P＜0.01).JQ-1 inhibited migration of fibroblast (P＜0.01).JQ-1 inhibited secretion of COL Ⅰ and TGF-β1 of fibroblasts (P＜0.01).Animal experiments showed that concentration and proportion of COL Ⅰ / Ⅲ in JQ-1 group decreased compared to DMSO group (P＜0.05).α-SMA protein expression in JQ-1 group also decreased (P＜0.05).Conclusion·JQ-1 can inhibit proliferation,migration,secretion of COL Ⅰ,and production of TGF-β1 of human sear fibroblasts in vitro;it can also inhibit secretion of COL Ⅰ /Ⅲ and fibroblast-myofibroblast differentiation in the human hypertrophic scars in nude mice.

Aim To investigate the effects of ursolic acid from loquat leaves on proliferation inhibition and expression of PPAR-γ 、TGF-β1 in rat hepatic stellate cells, so as to explore the mechanism of anti-hepatic fibrosis of UA.Methods HSC-T6 cells were randomly divided into blank group, rosiglitazone control group, the low, medium and high concentration of UA group to detect the cell proliferation inhibition by CCK-8 after 24,48,72 h.The content of type collagen Ⅰ in cell culture supernatant of each group was examined by ELISA.The expression of PPAR-γ mRNA, TGF-β1 mRNA in HSC-T6 cells exposured were examined by real-time quantitative PCR.Effects on HSC-T6 PPAR-γ and TGF-β1 protein from each group were detected by immunocytochemical method.Results CCK-8 results showed that the inhibitory rate of UA on cell proliferation increased with the prolongation of drug action time(P<0.01).ELISA results showed that with the increase of the concentration of UA, the content of type Ⅰ collagen content decreased(P<0.01).Real-time PCR results showed that with the increase of the concentration of UA, and the expression of PPAR-γ mRNA increased, the expression of TGF-β1 mRNA decreased(P<0.01).The results of immunocytochemistry showed that the expression of PPAR-γ protein was increased, and the expression of TGF-β1 protein was decreased with the increase of the concentration of UA(P<0.01).All effects mentioned above were dose-dependent.Moreover, the effects in the high concentration groups were stronger than those in control group.Conclusion UA can inhibit the proliferation of HSC-T6 cells, Which may be associated with the up-regulation of PPAR-γ expression and the down-regulation of TGF-β1 expression.

Objective To explore the action of nurses etiquette scene assessment to clinical nurses carrying out the etiquette rules consciously .Methods An inspection team was established to assess the scene of nurses etiquette;scoring criteria , evaluation methods and evaluation of the program were set up for the assessment .At first weeks of every month , from September to November in 2015 , when the patients′nursing satisfaction was surveyed , nurses etiquette service status in hospital was tested using scoring criteria of nurses etiquette scene assessment privately which was assigned as the control group .As the observed group, during the period of the first weeks of December , 2015 to February, 2016, While nursing satisfaction questionnaires were implemented , all ward nurses etiquette was tested openly .All nurses of two groups received routine training and theory of etiquette training before coming to the wards .Results Scores of control group were lower than the observed group , and the total scores , the scores of nurse dressing code and communication behavior norms were different between the two groups (P <0.05).The nursing service satisfaction of control group was lower than the observed group (P<0.05).Conclusions Scene assessment of nurse etiquette can help nurses improve compliance with the norms of etiquette consciously and the patients′satisfaction of nursing service .

Objective To investigate the role of miR-203 in radiation-induced thymic lymphoma (RITL).Methods A 60Co irradiator was used for total-body irradiation.MicroRNAs(miRNAs) level was assayed by qRT-PCR.Cell proliferation was assayed by MTT assay.Cell apoptosis was examined by fluorescence activated cell sorter (FACS).Dual luciferase reporter assay system was used to detect the 3'UTR reporter.Results MiR-203 was down-regulated in RITL tissues.Overexpression of miR-203 strongly inhibited the proliferation of both NIH3T3 cells and EL4 cells and vice versa.MiR-203 inhibited cells proliferation and induced apoptosis via TANK-binding kinase (TBK1),SLUG (SNAI2) and Cyclin D1 (CCND1).Conclusions Radiation down-regulated the level of miR-203 in thymic,which promoted radiation-induced thymic lymphoma by targeting TBK1,SNAI2 and CCND1.