Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

BACKGROUND:Oxidative injury is considered to be one of the important factors of cerebral ischemia-reperfusion injury.Superoxide dismutase 2(SOD2)is a key mitochondrial antioxidant molecule,and fenofibrate can regulate the expression of SOD2 by activating peroxisome proliferator-activated receptor α. OBJECTIVE:To explore whether the mechanism of fenofibrate in the treatment of cerebral ischemia-reperfusion injury depends on the expression of SOD2. METHODS:The TALENs system was used to construct SOD2 transgenic mice.The transgenic mice were genotyped by PCR and DNA sequencing techniques.The expression of SOD2 protein in transgenic mice was detected by western blot assay.Wild-type and SOD2 transgenic mice were randomly divided into four groups:wild-type control group(n=6),wild-type fenofibrate group(n=6),SOD2 transgenic control group(n=5)and SOD2 transgenic fenofibrate group(n=5).A mouse model of middle cerebral artery occlusion was prepared using the suture-occlusion method.After 90 minutes of ischemia,the thread was removed to reperfuse cerebral blood flow for 30 minutes.A cerebral blood flow monitor was used to monitor local cerebral blood flow.Brain tissue slices were taken for 2,3,5-triphenyltetrazolium chloride staining to analyze the situation of cerebral infarction in each group. RESULTS AND CONCLUSION:After PCR and DNA sequencing analysis,nine SOD2+/+ transgenic mice were successfully constructed.After cerebral ischemia-reperfusion,the wild-type fenofibrate group showed partial recovery of cerebral blood flow and significantly reduced cerebral infarction volume compared with the wild-type control group(P<0.001).There was no significant difference in cerebral blood flow and cerebral infarction volume between the SOD2 transgenic fenofibrate group and the SOD2 transgenic control group.The SOD2 transgenic control was superior to the wild-type control group in terms of improving cerebral blood flow and cerebral infarction(P<0.001).There were also no significant differences in cerebral blood flow and cerebral infarction volume between the wild-type fenofibrate group and the SOD2 transgenic control group and between the wild-type fenofibrate group and the SOD2 transgenic fenofibrate group.To conclude,the expression of SOD2 is one of the mechanisms of fenofibrate in the treatment of cerebral ischemia-reperfusion injury.

Objective To explore the application of Plan-Do-Check-Act(PDCA)cycle management to continuously im-prove the service quality of outpatient pharmacy and enhance patient satisfaction.Methods To address the problem of long wait-ing time for patients in outpatient pharmacy,we applied PDCA cycle to investigate the factors affecting patients'waiting time in the process of medicine collection,analyze the current situation,determine the expected goals,formulate the service quality im-provement plan of outpatient pharmacy,implement the improvement plan,follow up and supervise,and summarize and analyse the problems regularly until it was solved.Results After implementing the PDCA cycle in the management,the service quality of outpatient pharmacy was improved,the waiting time was significantly shortened and the satisfaction of medical treatment was in-creased.Conclusion The application of PDCA cycle method is effective in improving the service quality of outpatient pharmacy.Therefore,it is recommended for broader implementation.

Objective:To assess the application value of low-dose contrast agent combined with bolus tracking technique in radiotherapy localization for nasopharyngeal carcinoma (NPC).Methods:One hundred patients with NPC for radiotherapy localization were enrolled prospectively and randomly divided into observation ( n = 50) and control ( n = 50) group using random number table. All patients in the control group underwent routine computerized tomography (CT) for radiotherapy localization with an intravenous bolus of 80 ml iodinated contrast media. Images were obtained at a fixed delay of 50 s from the beginning of contrast injection. Patients in the observation group underwent CT scan using a bolus tracking technique with an intravenous bolus of 50-60 ml iodinated contrast media. By observing the time-CT value monitoring curve, the scanning was manually triggered when the peak fell. The score of image quality, enhanced CT value, iodine contrast dose, and dose calculation variance of planning target volume were compared between the two different dose groups. The differences of dose were compared using independent sample t-tests and the differences in graph scores were compared using Wilcoxon rank sum tests. Results:The dosage of iodine contrast agent in the observation group was 28.75% less than that in the control group, and the difference achieved statistical significance ( t=-42.11, P<0.001). The enhanced CT value of carotid artery and jugular vein in the control group increased 32.58% and 21.02% compared with patients in the observation group, respectively ( t=-8.11 and -4.82, P<0.001 for both). No statistically significant differences in the enhanced CT value were found for the gross tumor volume (GTV) of nasopharynx or sternocleidomastoid between the two groups ( P>0.05). The images in both groups can met the requirements of target volume delineation, and the difference of subjective score was not statistically significant ( Z=-1.36, P=0.175). There were no significant differences in the signal-to-noise ratio (SNR) or contrast-to-noise ratio (CNR) of nasopharynx between the two groups ( P>0.05). The results of subjective score and GTV target area showed high consistency between the two doctors with a κ value of 0.77. The differences in dose calculation variance of planning target volume between the two different dose groups was also not statistically significant ( P>0.05). Conclusions:In the radiotherapy localization for nasopharyngeal carcinoma, the application of low-dose contrast agent combined with bolus tracking technique could obtain good images for target delineation and effectively reduce the intake of iodine contrast agent and the risk of adverse reactions. Based on these results, low-dose contrast agent combined with bolus tracking technique has wide range of application.

Objective To establish a model of combined injury of thermal radiation and blast wave of gas explosion in closed pipeline,and investigate the characteristics of important organ injury induced by burn-blast combined injury in rats.Methods A total of 72 male SD rats(aged 8～10 weeks,weighing 200～10 g)were randomly divided into control group and mild and severe injured groups.After the model rats were inflicted with blast wave and thermal radiation,their physical parameters were detected and measured.The respiratory function of the survival rats was tested.In 24 h later,arterial blood gas analysis,blood biochemical tests,and detection for serum inflammatory factors and lung injury related protein levels were performed,and the pathological changes in the lung tissue and trachea were observed.Results The peak range of explosive blast wave overpressure was 209～493 kPa,and the temperature was 152～258 ℃.The mortality rate was 8.3％in the mild group and 53.1％in the severe group.Compared with the control group,longer inspiratory time(Ti)and relaxation time(Tr)and larger tidal volume(TV)(P＜0.05),while lower respiratory frequency(f)were observed in the 2 injured groups within 6 h after injury(P＜0.05).At 24 h after injury,the values of partial pressure of carbon dioxide(PaCO2),residual base value(BE)and bicarbonate(HCO3-)were increased significantly(P＜0.05),while partial pressure of oxygen(PaO2)was decreased(P＜0.05).The serum levels of alanine transaminase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bilirubin(TBI)and total bile acid(TBA)were notably elevated(P＜0.05).So were the levels of IL-1 β,TNF-α and IL-6(P＜0.01).Various severities of hyperemia foci and inflammation in the tracheal mucosa were observed in the injured rats.The incidence of lung injury was high,and the pathological manifestations were dot-shaped hemorrhage to diffuse hemorrhage of the whole lobe,rupture of alveolar septum,thickening of septum,and infiltration of red blood cells and inflammatory cells.The levels of serum lung injury-related proteins were significantly increased(P＜0.05).Conclusion A rat model which can highly simulate mild to severe burn-blast combined injury is constructed,which can meet the needs for rat model in study of explosive burn-blast compound injury.The main characteristics of the injury are lung injury,respiratory dysfunction,liver damage and secondary infection.

Objective:To evaluate the safety and efficacy of amniotic membrane patching in the treatment of recurrent macular hole associated with retinal detachment of high myopia (MHRD).Methods:A prospective study. From March 2018 to January 2020, 11 patients (11 eyes) of recurrent macular hole associated with MHRD at the First Affiliated Hospital of Zhengzhou University were enrolled. Among them, there were 3 males (3 eyes), and 8 females (8 eyes). The average age was 63.64±5.82. The axis length (AL) was 29.10± 0.59 mm, and the logarithm of the minimum angle of resolution best corrected visual acuity (logMAR BCVA) was 2.23±0.57. Patients previously received pars plana vitrectomy (PPV) combined with internal limiting membrane stripping surgery, which was more than 1 time. All eyes underwent standard pars plana three-channel 23G PPV combined with amniotic membrane covering and silicone oil filling. The silicone oil was removed 6 months after surgery. Follow-up time was up to 3 months after silicone oil removal surgery. 1, 3, and 6 months after the operation, the same equipment and methods were used to conduct relevant examinations before the operation to observe the closure of the macular hole, retinal reattachment and changes in logMAR BCVA. The logMAR BCVA before and after surgery was compared by paired t test. Results:At 1, 3, and 6 months after the operation, the retinas of all eyes were anatomically repositioned, the macular holes were well closed, and the amniotic membrane was attached to the retina. At 3 months after the silicone oil removal operation, there was no recurrence of macular hole in all eyes; logMAR BCVA was 1.35±0.32. No serious complications occurred during and after surgery in all eyes.Conclusion:Amniotic membrane patching is a safe and effective method for recurrent macular hole associated with MHRD.

Objective:To investigate the epidemiological characteristics of COVID-19 caused by 2019-nCoV Delta variant in Shangyu district, Shaoxing of Zhejiang province in 2021, and provide evidence for the improvement of COVID-19 control and prevention measures.Methods:The incidence data of COVID-19 in Shangyu from December 7 to 21, 2021 was obtained from Shangyu District Center for Disease Control and Prevention. The epidemiological characteristics of the cases, i.e. the population, time and space distributions, were analyzed, and the incubation period and time-varying reproduction numbers ( R t) were calculated. Results:From December 7 to 21, 2021, a total of 380 COVID-19 cases caused by 2019-nCoV Delta variant were detected in Shangyu, the median age of the cases was 52 years, M ( Q1，Q3: 38, 61). The male to female ratio of the cases was 1∶1.25, and the cases were mainly workers (36.58%) and farmers (27.63%). The epidemic affected 9 townships (or community) of Shangyu, especially Caoe and Baiguan communities with the cases accounting for 57.10% and 31.53% respectively. The median incubation period of cases was 4.00 days, M ( Q1，Q3: 3.00, 5.75). The basic reproduction number ( R0) was 4.06, and the R t was 5.62 in early phase of the outbreak (the highest) and continuously decreased to less than 1.00 within 10 days after the detection of the outbreak. The number of COVID-19 cases decreased to 0 within 14 days after the outbreak (December 7-21), and the main detection methods were screening in centralized isolation (55.53%) and home isolation (40.00%). The infection rates of close contacts and secondary close contacts were 2.06% and 0.46% respectively. Conclusion:The epidemic of COVID-19 in Shangyu characterized by short incubation period, large number of infected people, and case clustering, suggesting the strong transmission of Delta variant (B.1.617.2). Comprehensive prevention and control measures, such as management of close contacts and secondary close contacts, and high-risk area, are essential for the rapid control of the epidemic.

Objective: To assess the effectiveness of seasonal influenza vaccine among children aged 6 to 72 months. Methods: The test-negative case control study was conducted based on available surveillance data which was from China Influenza Surveillance Information system (CSIS). From October 2016 to April 2017 and from October 2017 to April 2018,1 161 cases aged 6-72 months with influenza-like illness in Yongkang and Yiwu city, were selected as the study subjects, and the cases with influenza test-positive were selected as the case group (403 cases). Test-negative subjects were selected as control group (758 cases). The etiology and immunization data of the subjects were obtained from CSIS and Immune Information and Management System (IIMS) respectively. Vaccine effectiveness was estimated using multivariate logistic regression model,and the mixed effects of non-randomized control in TNCC study were equalized by using the propensity score (PS) method in the statistical analysis. Results: The age of the subjects was (2.44±1.60) years,and there were 681 boys (58.66%). The age of case group was (2.62±1.58) years, and there were 246 boys (61.04%). The case group was including of 237 cases (58.81%) of influenza A (H3N2), 92 cases (22.83%) of influenza A (H1N1) pmd09, 62 cases (15.38%) of influenza B(Victoria) lineage, 11 cases (2.73%) of influenza B (Yamagata) lineage and one case (0.25%) co-infection of influenza [A(H₃N₂)+B (Victoria)]. The mean age of the control group was (2.35±1.61) years,and there were 435 boys (57.39%). Overall vaccine effectiveness (VE) against all type influenza for two seasons combined was 58% (95%CI: 31%-74%). An analysis by age groups showed 68% (95%CI:41%-82%) of the VE estimate among children aged 36-72 months while it was 28%(95%CI:-80%-71%)of the VE estimate among children aged 6-35 months. The VE estimate value was 54% (95%CI:16%-75%) against all type influenza and 65% (95%CI:24%-83%) against influenza A (H₃N₂) during the 2016-2017 season. During the 2017-2018 season, the VE estimate value was 69% (95%CI:18%-88%) against all type influenza. Conclusion Influenza vaccine is effective in preventing influenza virus infection during the flu season,especially the effect among children aged 36-72 months is higher compared to that among children aged 6-35 months.

Objective: To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer. Methods: The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stage Ⅰa2-Ⅱa2 and 40 cases of normal cervical tissues by real-time PCR and Western blotting. Then, the cells were infected with lentivirus-mediated siRNA-targeting FABP5. CCK-8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on in vitro cell proliferation, migration and invasion. And in vivo xenograft model and lung metastasis model were used to observe the transplanted tumor growth and metastasis in female athymic nude mice. Furthermore, the total protein and RNA were extracted from the primary xenografts to determine the expression levels of FABP5, metalloproteinase-2 and metalloproteinase-9 using Enzyme linked immunosorbent assay (ELISA), real-time PCR and Western blotting. Results: FABP5 expression was found to be significantly unregulated in cervical cancer tissues than that in normal cervical tissues (P<0.05). Compared with the Siha-NC group and uninfected group, the expression of FABP5 mRNA and protein in Siha-FABP5-RNAi group was significantly inhibited along with the decrease of cell proliferation, colony formation, wound healing and invasion ability. The clone formation rates of Siha cells in uninfected group, Siha-NC group and Siha-FABP5-RNAi group were (84.6±4.5)%, (84.6±5.1)% and (21.2±2.6)%, respectively. Moreover, the transwell assay showed that invasive cells in three groups were (72.8±4.7)/HPF, (72.6±3.3)/HPF and (21.4±2.3)/HPF, respectively. All of the difference was statistically significant (P<0.05). Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in nude mice in vivo (P<0.001). The subcutaneously xenografted volume in uninfected group, Siha-NC group and Siha-FABP5-RNAi group was (921.4±63.0) mm^3, (1 021.4±56.0) mm³ and (139.6±36.0) mm^3, respectively. The real-time quantitative PCR results showed that the relative expression levels of MMP-2 and MMP-9 mRNA were 1.00±0.10 and 1.00±0.10, 1.00±0.10 and 1.00±0.10 as well as 0.34±0.13 and 0.38±0.17 in xenografted tumor tissues of uninfected group, Siha-NC group and Siha-FABP5-RNAi group, respectively. MMP-2 and MMP-9 was significantly downregulated after FABP5 inhibition(P<0.05). Additionally, the protein expression trend of MMP-2 and MMP-9 in three groups was consistent with the mRNA levels. Conclusion FABP5 might promote the carcinogenesis and metastasis of cervical cancer via up-regulating MMP-2 and MMP-9.

Objective To assess the effectiveness of seasonal influenza vaccine among children aged 6 to 72 months. Methods The test?negative case control study was conducted based on available surveillance data which was from China Influenza Surveillance Information system (CSIS). From October 2016 to April 2017 and from October 2017 to April 2018,1 161 cases aged 6-72 months with influenza?like illness in Yongkang and Yiwu city, were selected as the study subjects, and the cases with influenza test?positive were selected as the case group (403 cases). Test?negative subjects were selected as control group (758 cases). The etiology and immunization data of the subjects were obtained from CSIS and Immune Information and Management System (IIMS) respectively. Vaccine effectiveness was estimated using multivariate logistic regression model,and the mixed effects of non?randomized control in TNCC study were equalized by using the propensity score (PS) method in the statistical analysis. Results The age of the subjects was (2.44±1.60) years,and there were 681 boys (58.66%). The age of case group was (2.62±1.58) years, and there were 246 boys (61.04%). The case group was including of 237 cases (58.81%) of influenza A (H3N2), 92 cases (22.83%) of influenza A (H1N1) pmd09, 62 cases (15.38%) of influenza B(Victoria) lineage, 11 cases (2.73%) of influenza B (Yamagata) lineage and one case (0.25%) co?infection of influenza [A(H3N2)+B (Victoria)]. The mean age of the control group was (2.35±1.61) years,and there were 435 boys (57.39%). Overall vaccine effectiveness (VE) against all type influenza for two seasons combined was 58% (95%CI: 31%-74%). An analysis by age groups showed 68% (95%CI:41%-82%) of the VE estimate among children aged 36-72 months while it was 28%(95%CI : -80%-71%)of the VE estimate among children aged 6-35 months. The VE estimate value was 54% (95%CI:16%-75%) against all type influenza and 65% (95%CI:24%-83%) against influenza A (H3N2) during the 2016-2017 season. During the 2017-2018 season, the VE estimate value was 69% (95%CI: 18%-88%) against all type influenza. Conclusion Influenza vaccine is effective in preventing influenza virus infection during the flu season,especially the effect among children aged 36-72 months is higher compared to that among children aged 6-35 months.