Objective Resveratrol can improve nonalcoholic fatty liver disease , but its action mechanisms remain unclear . This study aimed to investigate the protective effect of resveratrol against the free fatty acid ( FFA)-induced apoptosis of human hepatic L02 cells and its possible mechanisms . Methods Human hepatic L02 cells were incubated with FFA and resveratrol for 24 hours.The prepared cells were divided into a blank control , an FFA ( 2 mmol/L) , and a resveratrol group ( 50 μmol/L resveratrol +2 mmol L/FFA).After treatment, we measured the triglyceride (TG), glutathi-one (GSH), and malonaldchyde (MDA) contents and caspase3 ac-tivity in the hepatocytes , determined the apoptosis of the cells by flow cytometry , and detected the protein expression of silent information regulator 1 (SIRT1) by Western blot as well as the mRNA expressions of catalase (CAT), Mn superoxide dismucase (MnSOD), Bcl-2, and Bax by qRT-PCR. Results The TG content and caspase 3 activity in the hepatocytes were significantly increased in the FFA ([3518.±64.2] μmol/L and [5.97 ±0.78] U/g) and the resveratrol group ([201.1 ±60.1] μmol/L and [3.60 ±0.73] U/g) as compared with those of the blank control ([40.2 ±7.4] μmol/L and [2.56 ±0.49] U/g) (both P<0.05), but the caspase3 ac-tivity was markedly decreased in the resveratrol group in comparison with that of the FFA group (P<0.05).Both early and late apop-tosis rates of the hepatocytes were remarkably higher in the FFA ([6.75 ±0.81]%and [8.52 ±0.54]%) and the resveratrol group ([4.94 ±0.44]%and [6.52 ±0.61]%) than those in the blank control ([3.38 ±0.33]% and [2.72 ±0.19]%) ( both P<0.05), with statistically significant differences between the former two groups (P<0.05).The resveratrol group showed significant differences in the GSH content ([100.2 ±8.8] nmol/g), the MDA level ([2.36 ±0.82] mg/g), and the relative expression of SIRT1 (0.84 ±0.04) from the FFA group ([73.8 ±13.1] nmol/g, [3.77 ±0.92] mg/g, and 0.61 ±0.07) and the control ([113.7 ±13.8] nmol/g, [1.85 ±0.41] mg/g, and 0.90 ±0.02) (all P<0.05).The resveratrol group also exhibited statistically significant differences in the relative expressions of the MnSOD , CAT, and Bax genes from the FFA and control groups (P<0.05). Conclusion Resveratrol attenuates FFA-induced apoptosis of human hepatic L 02 cells by activating SIRT1 and reducing the oxidative stress of hepatocytes .

Objective: To analyze the genetic characterization of glycoprotein M(gM.),glycoprotein L(gL) of varicella zoster virus. Methods: According to the program of "Ministry of Science and Technology of China" , Based on the 12 suspected VZV patients monitored in Beijing (1 case), Shanghai (5 cases), Jilin (2 cases), Qinghai (1 case), Guangdong (2 case) and Sichuan (case) in 2007-2015. A total of 12 Vesicle fluid and throat swab samples were collected. Positive samples were identified by Agarose gel electrophoresis and two glycoprotein genes were amplified by polymerase chain reaction (PCR). Nucleotide sequences were determined and analyzed by PCR amplification of VZV positive specimens V-OKA-BK of the domestic varicella attenuated live vaccine and the Varilrix-1 of the imported attenuated live vaccine. Nucleotide sequences of VZV positive specimens, vaccine strains (V-OKA-BK, varilrix-1) and GenBank foreign wild strains (41 strains), parent strains (P-oka), vaccine strains (V-oka, Varilrix, Varivax) were compared using BioEdit and MEGA 5.0. Results: 12 specimens were VZV positive. Compared with the vaccine strains and the parent strains, the GM gene of 1 positive specimen had radical mutation at 86686 sites, which resulted in amino acid mutation, 5 positive specimens had base mutation at 87844 sites, and 30 strains of foreign wild strains had the same variation at 87 844 sites. 1 positive specimens of gL gene in 101245 sites had base mutation, and led to amino acid mutation, 6 positive specimens at 101624, 101625, 101626 sites had base of loss and the foreign wild strains in these 3 sites had the same variation. Compared with the vaccine strains, the nucleotide and amino acid homology of gM of 12 VZV positive specimens were 99.2%-100% and 98.2%-100%, respectively, and gL of those were 99.3%-100% and 98.6%-100%, respectively. Compared with 41 strains of foreign wild strains, homology of gM's nucleotides and amino acid were 99.3%-100% and 98.5%-100%, respectively; 99.1%-100% and 98.6%-100% for gL. The results of phylogenetic analysis showed that 7 VZV positive samples were on the same branch with 4 vaccine strains and p-oka strain. Based on gL, 12 VZV positive samples were on the same branch as the vaccine strains and p-oka strain. Conclusion This study demonstrates that the genes of gM, gL are highly conserved and remain stable immunogen, which may be involved in the attenuation of VZV and need to be further researched.

Objective:To investigate the possible mechanism of learning and memory damage induced by arsenic exposure through studying the effects of arsenic exposure on levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinases B (TrkB) in hippocampus of offspring mice at different developmental stages.Methods:Twenty-four pregnant Kunming mice were divided into control (distilled water) group and 15, 30 and 60 mg/L sodium arsenite (NaAsO 2) groups according to random number table method, six mice in each group. The pregnant mice were exposed to NaAsO 2 until weaning. After weaning, the offspring mice were still exposed to NaAsO 2 through drinking water till postnatal day (PND) 40. Morris water maze was used to determine the effects of arsenic exposure on learning and memory ability in PND 40 mice. The body weight of the mice was measured at PND 10, 20 or 40, and brain tissues were taken after the mice were sacrificed and the hippocampus was isolated. The levels of BDNF and TrkB mRNA in the hippocampus of offspring mice were measured by Real-time PCR. Results:There was significant difference in body weight of PND 20 offspring mice among the control, 15, 30 and 60 mg/L NaAsO 2 groups [(14.42 ± 1.88), (13.50 ± 1.38), (13.00 ± 1.14), (11.75 ± 0.82) g, F = 4.000, P < 0.05], the body weight of offspring mice in 60 mg/L NaAsO 2 group decreased significantly than that in control group( P < 0.05); there was significant difference in body weight of PND 40 offspring mice among groups [(38.58 ± 2.35), (37.17 ± 1.78), (35.67 ± 1.69), (33.83 ± 1.47) g, F = 7.248, P < 0.05], the body weights of offspring mice in 30 and 60 mg/L NaAsO 2 groups were significantly lower than that in control group, and the body weight of PND 40 offspring mice in 60 mg/L NaAsO 2 group was significantly lower than that in 15 mg/L NaAsO 2 group ( P < 0.05); the results of Morris water maze showed that there were significant differences in the escape latency of offspring mice among groups since 3 - 5 days of training ( F = 3.380, 6.788, 7.240, P < 0.05), the escape latency of offspring mice in NaAsO 2 groups [(67.76 ± 6.45), (71.47 ± 12.19), (73.96 ± 10.42), (58.63 ± 9.24), (60.20 ± 3.74), (67.96 ± 15.41) s] was significantly longer than that in control group [(52.83 ± 8.33), (43.39 ± 8.98) s] since 4 - 5 days of training ( P < 0.05); on the other hand, in the probe trail, there was significant difference in time spent in the target quadrant of offspring mice among groups ( F = 5.709, P < 0.05), time spent in the target quadrant of offspring mice in 30 and 60 mg/L NaAsO 2 groups [(18.85 ± 3.97), (16.90 ± 1.62) s] was significantly less than that in control group [(24.48 ± 3.18) s, P < 0.05]; there was significant difference in BDNF mRNA levels (1.00 ± 0.05, 0.98 ± 0.06, 0.85 ± 0.06, 0.68 ± 0.03) of PND 20 mice among groups ( F = 9.368, P < 0.05), BDNF mRNA level of mice exposed to 60 mg/L NaAsO 2 was significantly lower than that in control, 15 and 30 mg/L NaAsO 2 groups ( P < 0.05); there was significant difference in BDNF mRNA levels (1.00 ± 0.03, 0.75 ± 0.02, 0.76 ± 0.03, 0.73 ± 0.06) of PND 40 mice among groups ( F = 3.998, P < 0.05), and that of PND 40 mice exposed to NaAsO 2 decreased significantly than that in control group ( P < 0.05); there was significant difference in TrkB mRNA levels (1.00 ± 0.08, 0.71 ± 0.02, 0.73 ± 0.02, 0.68 ± 0.09) of PND 20 mice among groups ( F = 16.158, P < 0.05), and that of PND 20 mice exposed to NaAsO 2 were significantly lower than that in control group ( P < 0.05). Conclusion:Arsenic exposure could decrease the mRNA levels of BDNF and TrkB in the hippocampus of offspring mice, which may affect the ability of learning and memory.

OBJECTIVE To explore wheth er there is a relationship between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence. METHODS By searching for medical damage liability disputes related to off-label drug use up to 2021 on pkulaw.cn ，documents were extracted to record objective factors ，subjective factors and judgment results ；whether there was evidence-based evidence was judged according to Off-label Drug Use List and Evidence-based Evaluation Standards for Off-label Drug Use of Guangdong Pharmaceutical Association ；univariate analysis was adopted to test the relationship between the judgment results and evidence-based evidence. RESULTS A total of 57 cases were included. Cases mainly occurred in the eastern China （63.2％）and tertiary hospitals （64.9％），the main appraisal agency was the appraisal center or institute（61.4％），and the most common type of off-label drug use was overdose drug use （45.6％）. Among the judgment results ， 23 cases（40.4％）of off-label drug use had a causal relationship with medical damage ，most of the responsibility of doctors was secondary responsibility （28.1％），and the actual compensation amount of the most cases were less than 100，000 yuan（54.4％）. There were 25 cases（43.9％）with evidence-based evidence. Univariate analysis found that for off-label drug use the claim amount of the case with evidence-based evidence was significantly higher than that of the case without evidence-based evidence （P＝ 0.040），and there was no significant correlation between evidence-based evidence and the actual compensation amount of the case （P＝0.741），causality determination （P＝0.256），liability type （P＝0.598）or appraisal agency （P≥0.260）. CONCLUSIONS There is no significant correlation between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence ，indicating that there may be certain differences between judicial trials and medical science. The off-label drug use should be regulated by establishing a complete off-label drug use management system and standardizing informed consent procedure for off-label drug use. 1610307322@pku.edu.cn

ObjectiveTo evaluate the clinical efficacy and adverse effects of Shugan Hewei prescription combined with vonoprazan in the treatment of refractory gastroesophageal reflux disease （RGERD） due to qi depression and phlegm obstruction. MethodEighty RGERD patients who met the inclusion criteria underwent 24-hour pH impedance and high-resolution esophageal manometry and electronic gastroscopy. The 80 patients were randomly assigned to an observation group （Shugan Hewei prescription， one bag each time， twice a day + vonoprazan， 20 mg each time， once a day） and a control group （vonoprazan， 20 mg each time， once a day） by the random number table method. The treatment in both groups lasted for 4 weeks. The clinical efficacy was examined. The scores of TCM symptoms （pharyngeal discomforts such as phlegm obstruction， retrosternal discomfort， and belching）， somatic symptoms， quality of life， and improvement of esophageal mucosa under gastroscopy were observed in both groups before treatment and after treatment for 2 and 4 weeks. ResultSeventy-five patients completed the trial were included in this study， including 38 patients in the observation group and 37 patients in the control group. The total response rate in the observation group was 89.47%（34/38）， which was higher than that （62.16%，23/37） in the control group （χ²=13.014， P<0.01）. After treatment， the scores of esophageal mucous membrane， reflux disease symptoms， TCM symptoms， gastroesophageal reflux disease health-related quality of life scale （GERD-HRQL）， and somatic self-rating scale （SSS） decreased in both groups（P<0.05）. Moreover， the observation group outperformed the control group in alleviating heartburn， acid reflux， throat discomforts， midnight coughing， nausea and dry vomiting， mucousy mouth， and insomnia in the patients with GERD （P<0.05，P<0.01）. However， the two groups showed no statistically significant differences in the improvement of esophageal mucosa after treatment. ConclusionThe combination of Shugan Hewei prescription with vonoprazan was superior to vonoprazan alone in treating RGERD regarding clinical symptoms， physical signs， quality of life， and somatic symptoms， without causing obvious adverse effects.

Objective: To compare the overall survival (OS), progression-free survival (PFS) and brain metastasis free survival (BMFS) between the chemo-radiotherapy and surgical treatment for patients with limited stage small cell lung cancer (LS-SCLC). Methods: Clinical data of 69 patients diagnosed with LS-SCLC undergoing surgery in Zhejiang Cancer Hospital between 2000 and 2016 were collected. According to T, N stage, treatment duration, age, gender and whether or not prophylactic cranial irradiation (PCI), 69 patients of 503 LS-SCLC patients who underwent standard radiochemotherapy were assigned into the radiochemotherapy group by using the pair-matched case-control method. Results: Among 138 patients, 69 cases were allocated into the surgery group (24 cases of stage Ⅰ, 14 cases of stage Ⅱ and 31 cases of stage Ⅲ) and 69 cases in the radiochemotherapy group (24 cases of stage Ⅰ, 14 cases of stage Ⅱ and 31 cases of stage Ⅲ). The median OS time was 37.1 months (95%CI: 24.1-50.2 months) in surgery group and 45.0 months (95%CI: 15.8-74.2 months) in the radiochemotherapy group. The 2-and 5-year OS rates were 60% and 45% in the surgery group, and 64% and 45% in the radiochemotherapy group (P=0.846). The median PFS time was 27.1 months (95%CI: 0.00-60.3 months) in the surgery group and 36.2 months (95%CI: 20.9-51.4 months) in the radiochemotherapy group. The 2-and 5-year PFS rates were 52%, and 38% in the surgery group, and 56% and 40% in the chemo-radiotherapy group (P=0.610). The 2-and 5-year BMFS rates were 81% and 76% in the surgery group, and 84% and 80% in the radiochemotherapy group (P=0.774). The 5-year OS rate (62% vs. 40%, P=0.038) and 5-year PFS rate (80% vs.40%, P=0.048) for patients with stage Ⅰ LS-SCLC in the surgery group were significantly higher than those in the radiochemotherapy group. However, the 5-year BMFS rate in patients with stage Ⅰ LS-SCLC did not significantly differ between two groups (92% vs.95%, P=0.816). The 5-year OS rate (41% vs.51%, P=0.946), 5-year PFS rate (65% vs.42%, P=0.280) and 5-year BMFS rate (75% vs.78%, P=0.720) for stage Ⅱ SCLC did not significantly differ between two groups. As for stage Ⅲ SCLC patients, the OS rate (25% vs.48%, P=0.220), 5-year PFS rate (28% vs.36%, P=0.333) and 5-year BMFS rate (76% vs. 74%, P=0.84) did not significantly differ between two groups. Conclusions Surgical treatment can bring survival benefits to patients with stage Ⅰ LS-SCLC. The survival prognosis of stage Ⅱ patients is equivalent between two groups. Patients with stage Ⅲ LS-SCLC receiving radiochemotherapy obtain better survival trend compared with those undergoing surgery. The conclusion remains to be validated by studies with larger sample size or prospective investigations.