[Effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant in Guangdong Province].

Objective: To evaluate the effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant. Methods: A total of 1 403 Omicron-infected patients admitted to 20 designated hospitals in Guangdong Province from January 1 to May 31, 2022, were selected as subjects in this study. A case-control study was conducted to collect the demographic data, underlying disease, vaccination status, last exposure date, gene sequencing of infected strains and clinical outcomes from the China Disease Prevention and Control Information System and Guangdong telemedicine platform. Pneumonia (common, severe and critical) and non-pneumonia (asymptomatic and mild) were selected as the case group and control group. The effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant was analyzed. Results: The median age [M (Q1, Q3)] of the subjects was 36 (27-47) years old, with males accounting for 52.25% (733 cases). The main outcome of the infection was non-pneumonia, accounting for 92.09% (1 292 cases), and the duration [M (Q1, Q3)] of the disease was 18 (14-22) days. There were 134 (9.55%), 39 (2.78%), 403 (28.72%), 437 (31.15%) and 390 (27.80%) cases with no or partial vaccination, within 90 days of primary vaccination, over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination, respectively. Multivariate logistic regression analysis showed that after adjusting for gender, age, underlying disease, and location of the report, compared with those with no or partial vaccination, the risk of developing pneumonia was lower in those with over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination [OR (95%CI) values were 0.52 (0.28-0.98), 0.39 (0.21-0.73) and 0.40 (0.21-0.77), respectively]. Cox proportional hazard regression model analysis showed that after adjusting for gender, age, underlying disease and location of the report, the duration of the disease was shorter in those who received booster vaccinated for more than 90 days compared with that in those who had no or partial vaccination [HR (95%CI): 1.26 (1.03-1.55)]. Conclusion: The inactivated SARS-CoV-2 vaccine affects the clinical outcomes of patients infected with the Omicron variant.

[Feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia].

Objective: To investigate the feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia. Methods: This was a retrospective analysis of all fetuses requiring intrauterine transfusion (IUT) in the Shanghai First Maternity and Infant Hospital between January 2010 and December 2019. According to the different ways of IUT, they were divided into intrahepatic venous transfusion group and umbilical venous transfusion group, fetal outcomes and the incidence of procedure-related complications between the two groups were compared. Results: A total of 97 IUTs were performed on 48 fetuses. Among them, 16 cases were performed in the intrahepatic vein (31 transfusions), 32 cases were performed in the cord of the umbilical vein (66 transfusions).There were no significant differences between the two groups in age, labor history and the proportion of fetal hydrops before the first transfusion. In the intrahepatic venous transfusion group, the posterior placenta was 14/16, which was significantly higher than 78% (25/32) in the umbilical venous transfusion group (P<0.01). The live-birth rates of the two groups were 13/16 and 75% (24/32). There was no significant difference between the two groups (P>0.05). Before intrahepatic venous transfusion, the proportion of fetal hydrops was significantly higher than that of umbilical venous transfusion [55% (17/31) vs 24% (16/66), P<0.05]. Puncture success rate of intrahepatic venous transfusion and umbilical venous transfusion were both 100%. In the umbilical venous transfasion group, the incidence of needle slippage (5%, 3/66) and the abnormality of fetal heart rate (11%, 7/66) were higher than those in the intrahepatic venous transfasion group [0 and 3% (1/31)], but there were no significant differences between the two groups (all P>0.05). There were no cases of fetal loss within 24 hours, premature rupture of membranes, infection within 7 days and emergency cesarean section after IUT in both groups. Conclusions: Fetal intravascular transfusion via the intrahepatic vein is safe and feasible in the treatment of fetal anemia. But the requirements of puncture technique are relatively high, so it is recommended to be carried out in experienced fetal treatment center.

Gastrodin protects against high glucose-induced cardiomyocyte toxicity via GSK-3ß-mediated nuclear translocation of Nrf2.

Diabetic cardiomyopathy (DCM) is one of the major complications of diabetes that causes mortality and morbidity in diabetic patients. Gastrodin (GSTD) is a bioactive phenolic glucoside component of an ancient Chinese herb Tianma (Gastrodia elata Bl.), which is widely used for cardiovascular and cerebrovascular diseases by ancient Chinese. Up to now, whether GSTD has a beneficial effect on DCM is unclear. Therefore, this study aimed to investigate the effect of GSTD on high glucose-induced injury in H9c2 rat cardiomyocytes and HL-1 mouse cardiomyocytes, and its underlying mechanisms. High glucose (33 mM) treatment caused cardiomyocyte toxicity, oxidative stress and apoptosis in both H9c2 and HL-1 cells. Under both normal (5.5 mM glucose) and high glucose conditions, GSTD showed protective effect against high glucose-induced cytotoxicity and promoted the nuclear translocation of Nrf2 in a concentration and time-dependent manner in H9c2 and HL-1 cells. Knockdown of Nrf2 expression using siRNA specifically targeting Nrf2 attenuated the protective effect of GSTD. Furthermore, GSTD promoted the nuclear translocation of Nrf2 via activating glycogen synthase kinse-3ß (GSK-3ß) signaling pathway. 4-benzyl, 2-methyl, 1, 2, 4-thiadiazolidine, 3, 5 dione (TDZD-8), an inhibitor of GSK-3ß, inhibited the nuclear translocation of Nrf2 induced by GSTD, and attenuated the protective effect of GSTD as Nrf2 knockdown did. In summary, GSTD could protect against high glucose-induced cardiomyocyte toxicity via GSK-3ß-mediated nuclear translocation of Nrf2.

[Perioperative maternal complications of twin-twin transfusion syndrome after fetoscopic laser photocoagulation].

Objective: To analyze the perioperative maternal complications of twin-twin transfusion syndrome (TTTS) after fetolascopic laser photocoagulation (FLP). Methods: A retrospective study was conducted among 182 cases with TTTS received FLP in Shanghai First Maternity and Infant Hospital from January 2010 to December 2018. The types, incidence and related factors of perioperative maternal complications as well as the changes of maternal laboratory parameters before and after FLP were analyzed. Results: The age of 182 TTTS pregnant women was (29.8±3.9) years old, body mass index (BMI) before pregnancy was (21.3±2.9) kg/m2. The median gestational week of FLP treatment was 22.0 weeks, the preoperative cervical length was (34.1±9.0) mm, and the median preoperative maximum vertical pocket was 12.0 cm. During the perioperative period of FLP treatment, 22 cases (12.1%, 22/182) presented maternal complications, among which 4 cases (2.2%, 4/182) presented severe postoperative maternal complications, including 3 cases of pulmonary edema and 1 case of pulmonary embolism accompanied with right cardiac insufficiency. There were 18 cases (9.9%, 18/182) of common maternal complications during the perioperative period, including 6 cases (3.3%, 6/182) of intraoperative hemorrhage, 5 cases (2.7%, 5/182) of intraoperative amniotic fluid leakage into the pelvic cavity, 5 cases (2.7%, 5/182) of premature rupture of membrane 72 hours after the operation, 1 case (0.5%, 1/182) of inevitable abortion, and 1 case (0.5%, 1/182) of infection. The analysis of related risk factors found that maternal complications were only related to BMI before pregnancy, and the BMI of TTTS pregnant women with complications was lower than that of those without complications, the difference was statistically significant (P<0.01). The hemoglobin level, hematocrit and albumin level of TTTS pregnant women were significantly decreased at 4-6 hours and 24 hours after FLP respectively, compared with those before surgery (P<0.01), and there were no significant correlations with the amount of amniodrainage during surgery (P>0.05 for all). Conclusions: The overall incidence of perioperative maternal complications in the treatment of TTTS by FLP is not high, among which the serious complications mainly include pulmonary edema and pulmonary embolism. Timely correction of maternal hemodilution that may occur in TTTS pregnant women could achieve a good prognosis after FLP.

[Analysis on the cluster epidemic of coronavirus disease 2019 in Guangdong Province].

Objective: Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province. Methods: The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared. Results: A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M (P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant (P=0.003). Conclusion: COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.

Simvastatin induces apoptosis of nasopharyngeal carcinoma cells through NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the mechanism of simvastatin-induced apoptosis in nasopharyngeal carcinoma (NPC) cells. MATERIALS AND METHODS: CNE1 and HK1 cell lines were treated with different concentrations of simvastatin for different time course. Subsequently, Cell Counting Kit-8 (CCK-8), colony formation assay, and flow cytometry were conducted to evaluate cell activity, colony formation ability, as well as cell cycle of NPC cells, respectively. The mRNA expressions of p21, Bim, and cyclin D1 were examined by qPCR. Meanwhile, the protein expression levels of apoptosis-related proteins (including caspase-3, Bax, Bcl-2) were detected by Western blot. Caspase-3 activity was determined to estimate cell apoptosis. An NPC xenotransplantation model was constructed to further determine the role of simvastatin in vivo. In addition, NF-κB activity was assessed through Luciferase reporter gene assay and Western blot. RESULTS: Simvastatin treatment lead to significantly reduced viability of NPC cells and the number of cell colonies dose-dependently and time-dependently. Meanwhile, simvastatin treatment caused cell cycle arrest in G0/G1 phase, remarkably downregulated expression of cyclin D1, and upregulated expressions of p21 and Bim. In addition, simvastatin induced apoptosis of NPC cells and enhanced the Luciferase activity of caspase-3. Western blot results indicated that simvastatin promoted the protein level of Bax and caspase-3, whereas suppressed the protein expression of Bcl-2. In vivo experiments showed that simvastatin was able to suppress the growth of NPC cells. Further studies demonstrated that simvastatin remarkably attenuated the Luciferase activity of pNF-κB-Luc, thereby specifically inhibiting the NF-κB signaling pathway. CONCLUSIONS: Simvastatin inhibits proliferation and promotes apoptosis of NPC cells by inhibiting the NF-κB pathway.

[Clinical outcomes of COVID-19 cases and influencing factors in Guangdong province].

Objective: To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods: We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results: Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1 049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days (P(25), P(75): 18, 31 days) and the median length of hospitalization were 20 days (P(25), P(75): 15,27 days). For severe cases, the median time of showing severe manifestations was on the 12(th) day after onset (P(25), P(75): 9(th) to 15(th) days), and the median time of severe manifestation lasted for 8 days (P(25), P(75): 4, 14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (aHR=1.87, 95%CI: 1.43-2.46), older age (aHR=1.67, 95%CI: 1.51-1.85), seeking medical care on day 2-3 after onset (aHR=1.73, 95%CI: 1.20-2.50) pre-existing diabetes (aHR=1.75, 95%CI: 1.12-2.73) and hypertension (aHR=1.49, 95%CI: 1.06-2.09). Conclusions: The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.

[Risk assessment and early warning of imported COVID-19 in Guangdong province].

Objective: To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods: Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results: A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions: Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.

Long non-coding RNA LINC01287 promotes breast cancer cells proliferation and metastasis by activating Wnt/ß-catenin signaling.

OBJECTIVE: Long noncoding RNA (lncRNAs) frequently exhibited abnormal levels in numerous tumors and other diseases in current biological researches. LINC01287, a newly discovered lncRNA, has been found to act as an oncogene in hepatocellular carcinoma. The aim of this research was to explore the expressions and functions of LINC01287 in breast cancer (BC). PATIENTS AND METHODS: The relative expressions of LINC01287 in BC tissues and cells were determined using RT-PCR. The associations between the LINC01287 expression, the clinicopathological factors, and the overall survival of BC patients were statistically examined. The apoptosis and proliferation abilities of MCF-7 and MDA-MB-468 cells were analyzed by MTT and flow cytometry assay after LINC01287 knockdown. The effects of LINC01287 in migration and invasion were determined using wound-healing and transwell assays. The protein expressions of the Wnt/ß-catenin pathway were determined using Western blot. RESULTS: We showed that the levels of LINC01287 were significantly upregulated in BC tissues and BC cell lines, and the abnormal expressions of LINC01287 were correlated with TNM stage and lymph node metastasis. A distinct difference was observed and indicated that BC patients with higher LINC01287 expressions had significantly shorter overall survival than patients with lower LINC01287 expressions. The multivariate analysis demonstrated that LINC01287 expression was independently correlated with the overall survival. Si-LINC01287 transfection significantly inhibited the proliferation and metastasis of BC cells, and further promoted apoptosis. Besides, the knockdown of LINC01287 suppressed Wnt/ß-catenin activation and affected the expressions of ß-catenin, cyclin D1, and c-myc. CONCLUSIONS: Our findings indicated that the new lncRNA LINC01287 was correlated with poor clinical outcome and may function as a novel prognostic biomarker and therapeutic target in the development of antineoplastic therapies for BC.

[An analysis of the serological characteristics of anti-mitochondrial M2 subtype in patients with drug-induced liver injury and primary biliary cholangitis].

Objective: To analyze the serological characteristics of anti-mitochondrial antibody M2 subtype (AMA-M2) in patients with drug-induced liver injury (DILI) and primary biliary cholangitis (PBC), in order to provide reference for clinical differential diagnosis. Methods: Laboratory data of 2802 DILI cases who visited the hospital between January 2011 and December 2017 were retrospectively collected. AMA-M2 positive patients were analyzed with respect to laboratorical findings, and serum data of 120 patients with primary biliary cholangitis (PBC) at the same period was taken as a control. A chi-square test was used for group comparisons. One-way ANOVA and rank sum tests was used for ALT, AST, ALP, GGT and three groups of immunoglobulin M. Results: Among 2802 DILI patients, AMA-M2 positive rate was 5.1% (144/2 802), 77.1% (111/144) was DILI alone, 22.2% (32/144) was DILI with PBC, and 0.7% (1/144) was DILI with Sjogren's syndrome. An AMA-M2 level in DILI alone group was mostly mild and moderate than the PBC group and the DILI combined with the PBC group. There was significant difference between the two groups (P < 0.05).There was no significant difference in AMA-M2 levels between DILI group combined with PBC group and PBC group (P > 0.05). ALT and AST levels of DILI alone group and DILI combined with PBC were (585.92 ± 653.04) U/L, (501.45 ± 512.67) U/L and (373.47 ± 502.60) U/L, (335.97 ± 513.96) U/L, respectively, which were significantly higher than PBC group [(106.33 + 134.08) U/L, (112.59 + 152.20) U/L]. There were statistically significant differences between the two groups (P < 0.05).The ALP level of DILI alone group was (152.58 + 81.46) U/L, which was lower than PBC group (237.86 + 215.09). The difference was statistically significant (P < 0.05). The level of immunoglobulin M in the DILI alone group was (1.76 ± 1.16) g/L, which was lower than PBC group (4.74 ± 5.74) g/L and the DILI combined with the PBC group (3.31 ± 1.68) g/L. There was significant difference between the two groups. During follow-up, 2.7% of patients with DILI had cirrhosis, 42.3% had lower AMA-M2 titer, 14.4% had lower AMA-M2 titer, 13.5% had higher AMA-M2 titer and five cases developed PBC. Conclusion: AMA-M2 is not only positive in patients with PBC, but also low-to-medium or even high-level AMA-M2 may be detected in DILI patients. For AMA-M2-positive DILI patients, it is necessary to identify whether they are associated with PBC. Secondly, the levels of ALT, AST and ALP should be analyzed, and the patients should be on regular follow up for early and timely detection of drug-induced PBC.

GAS5 promotes podocyte injury in sepsis by inhibiting PTEN expression.

OBJECTIVE: To investigate the potential role of long noncoding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) in sepsis-induced podocyte injury and its underlying mechanism. MATERIALS AND METHODS: The sepsis model was established by lipopolysaccharide (LPS) induction in podocytes. The expression levels of Nephrin and GAS5 were detected by quantitative Real-time polymerase chain reaction (qRT-PCR) after LPS induction in podocytes for 12 h, 24 h and 36 h, respectively. Western blot was used to detect the expression level of Nephrin in sepsis-induced podocytes. The mRNA expressions of GAS5 and Nephrin in podocytes were detected after transfection of GAS5 siRNA. Albumin influx in podocytes after GAS5 knockdown was detected by Transwell assay. Western blot was used to detect the protein expression of Snail in sepsis after GAS5 knockdown. The target gene of GAS5 was predicted by bioinformatics analysis. QRT-PCR and Western blot were used to detect the protein and mRNA levels of PTEN (phosphatase and tensin homolog deleted on chromosome ten). Nephrin expression and the albumin inflow after PTEN knockdown were then measured. The expression of PI3K/AKT/GSK3ß was also detected after GAS5 was downregulated while PTEN was upregulated. RESULTS: LPS stimulation downregulated the mRNA expression of Nephrin in podocytes and achieved the lowest level at 24 h. The protein expression change of Nephrin was consistent with its mRNA expression. In the septic state, the albumin influx of podocytes remarkably increased, but the function of podocyte barrier was weakened. Besides, GAS5 expression decreased in a time-dependent manner in LPS-induced podocytes. After GAS5 knockdown by siRNA, Nephrin expression and the function of podocyte barrier were significantly reduced. Snail expression was also upregulated in septic state, and GAS5 knockdown increased the expressions of phosphorylated Snail and PI3K/AKT/GSK3ß. After knockdown of GAS5, the mRNA and protein levels of PTEN significantly decreased, which was contract to the expression of Snail. However, overexpression of PTEN could reverse the promotive effect of GAS5 on PI3K/AKT activation. CONCLUSIONS: GAS5 expression decreased in sepsis-induced podocyte injury, and GAS5 was involved in regulating sepsis-induced podocyte injury by reducing PTEN expression.

[Perinatal outcomes of thoraco-amniotic shunting for severe primary fetal hydrothorax].

Objective: To evaluate the safety and perinatal outcomes of thoracoamniotic shunting in the treatment of fetuses with severe primary hydrothorax. Methods: 22 cases of suspected severe primary fetal hydrothorax which underwent thoraco-amniotic shunting in Shanghai First Maternity and Infant Hospital, Fetal Medicine Unit and Prenatal Diagnosis Center from January 2012 to December 2017 were analyzed retrospectively. Hydrothorax associated with structural or chromosomal abnormalities, infections and immune fetal hydrops were excluded. Results: Totally, 28 shunts were placed in 22 fetuses. The median gestational age at TAS was 31.3 weeks. Preterm membrane rupture within 7 days after the procedure occurred in 9.1% (2/22) cases. Catheter displacement occurred in 18% (4/22) cases. The interval from shunting to delivery was 26.0 days. One fetus ended in induced abortion; 21 (95%, 21/22) babies were born alive, and their median gestational age at delivery was 34.4 weeks. 62% (13/21) newborns required ventilator supports; 4 neonatal deaths were attributed to pulmonary hypoplasia. The overall perinatal survival rate was 81% (17/21) . The perinatal survival rate with hydrops and without hydrops were 10/13 and 7/8 respectively. Conclusion: Thoraco-amniotic shunting is a safe procedure for intrauterine therapy and could improve the perinatal outcomes of severe primary fetal hydrothorax.

[Epidemiological characteristics of outbreaks of norovirus-Gâ ¡.2, Gâ ¡.17 and Gâ ¡.4/Sydney in Guangdong province, 2013-2017].

Objective: To understand the epidemiologic characteristics of outbreaks, caused by norovirus-GⅡ.2、GⅡ.17 and GⅡ.4/Sydney in Guangdong Province from 2013 to 2017 and to provide scientific evidence for epidemic prevention and control. Methods: Incidence data of norovirus outbreaks in Guangdong from January 1(st) 2013 to November 30(th) 2017 were collected from Public Health Emergency Management Information System. RT-PCR was performed for every case of each outbreak to detect norovirus nucleic acid and gene sequencing was conducted to identify the genotype of norovirus. Characteristics of norovirus GⅡ.2, GⅡ.17 and GⅡ.4/Sydney outbreaks were analyzed. Directly standardized method was used to calculate the proportion of symtoms as diarrhea and vomitting. Results: From January 1(st) 2013 to November 30(th) 2017, a total of 167 norovirus outbreaks were reported in Guangdong, and 115 outbreaks were caused by norovirus GⅡ.2, GⅡ.17 and GⅡ.4/Sydney respectively. The outbreaks caused by norovirus GⅡ.2 accounted for 39.68% (25/63) in primary schools, 28.57% (18/63) in child care settings, 25.40% (16/63) in middle schools and 6.35% (4/63) in universities. Outbreaks caused by norovirus GⅡ.17 accounted for 41.03% (16/39) in middle schools, 20.51% (8/39) at workplaces, 15.38% (6/39) in primary schools, 12.82% (5/39) in universities, 5.13% (2/39) in communities and child care settings respectively. The outbreaks caused by norovirus GⅡ.4/Sydney accounted for 53.85% (7/13) in universities, 15.38% (2/13) in child care settings and at workplaces respectively, 7.69%(1/13) in primary schools and middle schools respectively. The outbreaks caused by norovirus GⅡ.2 had 77.78% (49/63) of contact transmission, 17.46% (11/63) of food-borne transmission. The outbreaks caused by norovirus GⅡ.17 showed 53.85% (21/39) of food-borne transmission, 15.38% (6/39) of contract transmission, 12.82% (5/39) of water-borne transmission. The outbreaks caused by norovirus GⅡ.4/Sydney had 53.85% (7/13) of food-borne transmission, 38.46% (5/13) of the contact transmission. In terms of the clinical manifestations, the standardized proportion of vomit was 73.76% and the proportion of diarrhea was 42.85% in cases infected with norovirus GⅡ.2, the proportion of standardized of vomit was 76.37% and the proportion of diarrhea was 51.40% in cases infected with norovirus GⅡ.17, with the standardized proportion of vomit was 54.10% and the proportion of diarrhea was 55.95% in cases infected with norovirus GⅡ.4/Sydney. Conclusions: The outbreaks caused by norovirus GⅡ.2 through contact transmission mainly occurred in primary schools, child care settings and middle schools. The outbreaks caused by norovirus GⅡ.17 through food-borne transmission mainly occurred in middle schools and at workplaces. The outbreaks caused by norovirus GⅡ.4/Sydney food-borne transmission and contact mainly occurred in universities.

[Analysis on epidemiological characteristics of enterovirus 71 cases of hand-foot-mouth disease based on the active monitoring in Guangdong Province in 2011-2015].

Objective: To analyze the hand-foot-mouth disease (HFMD) enterovirus 71 (EV-A71) infection epidemic characteristics of Guangdong Province from 2011 to 2015. Methods: We colleted data on common cases of hand-foot-mouth disease infected with EV-A71 reported from eight sentinel hospitals in Guangdong Province from January 2011 to December 2015, through the "Guangdong Province Acute Infectious Disease Surveillance Information Platform System" , including the age and incidence of cases. Time and etiological data, etc.We also collected data on the number of reported cases of HFMD disease and the number of laboratory-confirmed cases, through the "China Disease Prevention and Control Information System" , including data on common cases of HFMD disease, data on epidemics of severe cases and deaths, and the age, onset time, and pathogens of cases. Learning data, etc.The data from two sources were used to estimate the incidence of HFMD in EV-A71 and describe its distribution characteristics.Chi-square test was used to compare the positive rate of HF-A71 infection in hand-foot-mouth disease and the difference in estimated incidence among different age groups and months. Results: Eight sentinel hospitals from 2011 to 2015 reported a total of 1 855 common cases of EV-A71 infection, of which the highest was in 2014 (31.6%, 605/1 916) and the lowest was in 2015 (6.8%, 134/1 971) (χ(2)=521.85, P<0.001).According to the Disease Surveillance Reporting Information System, 1 772 516 cases of HFMD disease were reported from 2011 to 2015 in Guangdong Province, and 1 902 cases of severe and fatal cases of EV-A71 infection.The composition ratio of EV-A71 infected was 72.6% (1 775/2 444) and 97.0% (127/131) of severe HFMD disease in Guangdong province during 2011-2015.The average annual incidence of HF-A71 infection in all age groups showed a decreasing trend with age (χ(2trend)=990 273.20, P<0.001), and it was the highest in the 1-year-old group, which was 1 697.67/100 000, and the lowest in the 4-year-old group, which was 705.46/100 000. The difference of monthly average incidence of EV-A71 infection in HF-A71 in each month was statistically significant (χ(2)=401.23, P<0.001), the highest in May at 15.51 per 100 000, and the lowest in July at 9.42 per 100 000. Conclusion: EV-A71 infection rate of ordinary HFMD varies in different years. The most severe and death cases of HFMD were EV-A71 infected. 1 year old children were the high-risk group of infected with EV-A71 HFMD. April was the epidemic months of EV-A71 HFMD infection.

[Epidemiological characteristics of Coxsackie virus A16 caused hand foot and mouth disease cases in Guangdong province, 2012-2016].

Objective: To analyze the epidemiological characteristics of hand foot and mouth disease (HFMD) cases caused by Coxsackie virus A16 (Cox A16) in Guangdong province from 2012 to 2016. Methods: The data of mild HFMD cases caused by Cox A16 were collected from 8 sentinel hospitals in 8 prefecture-level cities in Guangdong to estimate Cox A16 infection status and its population and time distribution characteristics. Results: (1) The highest estimated incidence of Cox A16 infection was in 2014 (113.0/100 000), followed by 2016 (86.4/100 000) and 2012 (79.1/100 000), while the estimated incidence was lower in 2015 (29.0/100 000) and 2013 (28.8/100 000). (2) Cox A16 was confirmed to be the predominant pathogen causing HFMD outbreaks (54.6%, 89/163). The number of outbreaks in the year with high incidence (28 outbreaks) was 11.2 times higher than that in the year with low incidence (2.5 outbreaks). (3) Across all age groups, the annual estimated incidence of Cox A16 infection decreased with age (trend χ(2)=853 905.63, P<0.01). The incidence was highest in age group 1 year (1 449.2/100 000), followed by that in age group 3 years (1 097.0/100 000), in age group 2 years (1 083.5/100 000), in age group 4 years (687.8/100 000) and in age group 0 year (604.9/100 000). Among the age groups <12 months, the estimated incidence increased with age (trend χ(2)=5 541.77, P<0.01), which was highest in age group 11-months (2 105.1/100 000), followed by that in age groups 10-months (1 448.6/100 000), 9-months (938.3/100 000), 8-months (703.3/100 000) and 6-months (664.6/100 000). (4) The annual incidence peak was during May (143.9/100 000)-June (131.5/100 000). Conclusion: The prevalence of Cox A16 infection differed with year in Guangdong during 2012-2016. When the incidence of Cox A16 infection was high, more outbreaks occurred. The prevalence occurred mainly in nurseries and kindergartens from May to June each year. Children aged 0-4 years were the high risk group for Cox A16 infection, children aged 6-11 months were at high risk for Cox A16 infection.

Saccharomyces cerevisiae Hog1 MAP kinase pathway is activated in response to honokiol exposure.

AIM: The goal of the study was to investigate the cellular tolerance mechanism in response to honokiol exposure. METHODS AND RESULTS: The broth microdilution method was employed to test the sensitivity of different Saccharomyces cerevisiae strains to honokiol. Intracellular levels of reactive oxygen species (ROSs) were determined by DCFH-DA staining. The phosphorylation of Hog1 was evaluated by Western blot analysis. The mRNA expressions of genes involved in the Ras-cyclic AMP (cAMP) pathway were analysed by real-time reverse transcription polymerase chain reaction. We found that the sod1▵ mutant was hypersensitive to honokiol and produced more ROS compared with wild-type and sod2▵ cells. Hog1 was phosphorylated in response to honokiol exposure and deletion of HOG1 increased the sensitivity to honokiol. The expressions of genes involved in the Ras-cAMP pathway were down-regulated after honokiol exposure; exogenous cAMP significantly reduced the phosphorylation of Hog1, although the level was higher than the control level. CONCLUSIONS: In addition to SOD1, the Ras-cAMP cascade and Hog1 MAP kinase pathway is essential for protecting against honokiol-induced oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide insight into the understanding of the action mechanism of honokiol.

[Analysis on risk factors for norovirus outbreaks in Guangdong province, 2008-2015].

Objective: To analyze transmission factors of norovirus outbreaks in Guangdong province during 2008-2015 and provide evidence for the prevention and control of norovirus infection. Methods: Epidemiological analysis was performed on the data of norovirus outbreaks reported in Guangdong from January 1, 2008 to December 31, 2015, which were obtained from the Public Health Emergency Management Information System of Guangdong province. The samples collected from the norovirus outbreaks were detected for norovirus by RT-PCR and the gene sequencing of the positive PCR products were performed. Results: A total of 96 norovirus outbreaks were reported in Guangdong during 2008-2015. Sixteen outbreaks were reported during 2008-2012 and 80 outbreaks were reported during 2013-2015 (83.3%). Eighty-two outbreaks (85.4%) occurred in schools. The infection routes included foodborne transmission in 39 outbreaks (40.6%), person to person transmission in 23 outbreaks (24.0%) and waterborne transmission in 8 outbreaks (7.3%). The gene sequencing results showed that variant GⅡ.4/Sydney2012 was the predominant pathogen for 6 of the 20 outbreaks (30.0%) during 2012-2013. Variant GⅡ.17 was the predominant pathogens for 33 of the 53 outbreaks (62.3%) during 2014-2015. Conclusion: The norovirus outbreaks in Guangdong during 2008-2015 were caused by foodborne and person to person transmissions of two emerging variant: GⅡ.4/Sydney2012 and GⅡ.17.

Nivolumab effectively inhibit platinum-resistant ovarian cancer cells via induction of cell apoptosis and inhibition of ADAM17 expression.

OBJECTIVE: Nivolumab is an anti-PD-1 (anti-programmed death-1) monoclonal antibody. It has achieved an overall response rate of 17% in Phase 1 clinical trial for patient with platinum-resistant ovarian cancer (PROC). However, its underlying mechanism has not been fully explored yet. The aim of the study is to investigate the efficiency of nivolumab to inhibit PROC cells and its possible mechanism. MATERIALS AND METHODS: Firstly, methylthiazolyl tetrazolium bromide (MTT) assay was performed to determine the IC50 values of cisplatin in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The results showed that IC50 (half maximal inhibitory concentration) values of cisplatin were significantly decreased in a time-dependent manner in A2780, A2780/DDP, SKOV3, and SKOV3/DDP cells. Secondly, MMT assay was used once again to measure anti-tumor effects of nivolumab in A2780/DDP cells. The results showed that anti-tumor effects of nivolumab increased in a dose- and time-dependent manner. Thirdly, A2780/DDP cells were treated with nivolumab in combination with cisplatin for 48 h. RESULTS: The results demonstrated that nivolumab increased the anti-tumor effects of cisplatin in A2780/DDP cells. Notably, the combined treatment effectively reversed cisplatin resistance in PROC cells. Also, nivolumab induced cell apoptosis and cell-cycle arrest in G0/G1 phase in PROC cells. FACS and Western blot were performed to measure cell apoptosis and Bcl-2 and Bax expression respectively. The results showed that combined treatment significantly increased cell apoptosis rate, down-regulated Bcl-2, and unregulated Bax expression in PROC cells. Additionally, the expression levels of ADAM17 were significantly decreased in a dose-dependent manner in PROC cells, which were treated with nivolumab. CONCLUSIONS: Therefore, all the results demonstrated that the combined treatment with nivolumab and cisplatin effectively inhibited PROC cells via induction of cell apoptosis and inhibition of ADAM17 expression.

[Clinical value of anti-liver/kidney microsomal-1 antibody in patients with liver disease].

Objective: To investigate the clinical and laboratory features of patients with liver disease and positive anti-liver/kidney microsomal-1 (anti-LKM-1) antibody, and to provide a reference for clinical diagnosis and differential diagnosis. Methods: The clinical data of patients with positive anti-LKM-1 antibody who were treated in our hospital from 2006 to 2016 were collected, and clinical and laboratory features were analyzed and compared. An analysis was also performed for special cases. Results: The measurement of related autoantibodies was performed for about 100 thousand case-times, and 15 patients were found to have positive anti-LKM-1 antibody. Among the 15 patients, 7 were diagnosed with type 2 autoimmune hepatitis (AIH) with an age of 11.0 ± 9.0 years and were all adolescents with acute onset; 8 were diagnosed with hepatitis C with an age of 51.5 ± 9.0 years, among whom 7 were middle-aged patients and 1 was a child aged 12 years, and all of them had an insidious onset. Compared with the patients with hepatitis C, the AIH patients had significantly higher levels of alanine aminotransferase (1 003.9 ± 904.3 U/L vs 57.0 ± 84.1 U/L, P < 0.05), aspartate aminotransferase (410.7 ± 660.3 U/L vs 34.9 ± 42.9 U/L, P < 0.05), and total bilirubin (98.0 ± 191.0 µmol/L vs 15.4 ± 6.0 µmol/L, P < 0.05). There was a reduction in immunoglobulin G after the treatment with immunosuppressant, compared with the baseline. Of all 8 patients with hepatitis C, 6 received antiviral therapy with interferon and ribavirin, and 5 out of them achieved complete response, among whom 4 had a reduction in the level of anti-LKM-1 antibody after treatment; however, a 12-year-old child developed liver failure after interferon treatment and died eventually. Conclusion: Positive anti-LKM-1 antibody is commonly seen in patients with type 2 AIH or hepatitis C, but there are differences between these two groups of patients in terms of age, disease onset, liver function, and the level of anti-LKM-1 antibody. The hepatitis C patients with a confirmed diagnosis and exclusion of autoimmune hepatitis can achieve good response to interferon under close monitoring, even if anti-LKM-1 antibody is positive. As for adolescent patients with hepatitis C and positive anti-LKM-1 antibody, the possibility of AIH should be excluded.

Vena-venous hemofiltration in treating severe injury-induced multiple organ dysfunction syndrome.

Severe multiple injury (SMI) can induce multiple organ dysfunction syndrome (MODS) and easily result in complications, as well as having a high mortality rate. To explore the curative effect of continuous vena-venous hemofiltration (CVVH) in treating MODS and its effect on serum tumor necrosis factor (TNF)-α interleukin (IL)-10 and nitric oxide (NO), we selected 200 patients who suffered from SMI and received treatment in the First Affiliated Hospital of Zhengzhou University between April 2012 and April 2014 as research subjects. All patients were treated with CVVH. Vital signs, blood oxygen pressure (PaO(2)) and oxygenation index (OI) of artery, electrolyte and acid-base balance were observed before and after treatment. Before treatment, 1 h and 12 h after the start of treatment, and at the end of treatment, TNF-α and IL-10 concentrations in serum and ultrafiltrate were tested using enzyme linked immunosorbent assay, and NO concentration in serum and ultrafiltrate was detected using nitrate reduction method. After treatment, heart rate and respiratory rate of patients had significant decline (P less than 0.05) and average arterial pressure rose remarkably (P less than 0.05); blood urea nitrogen and creatinine decreased (P less than 0.05 or 0.01); PaO(2) and OI were both significantly increased (P less than 0.01); hyperkalemia and acidosis were effectively corrected (P less than 0.01); but differences of Na+, Ca2+ and Cl- before and after treatment had no statistical significance (P>0.05). Serum IL-10 concentration had a significant increase after treatment, while TNF-α and NO concentrations had a significant decline after treatment. A small quantity of IL-10, but not of TNF-α, was detected from ultrafiltrate. Concentration of NO in ultrafiltrate was higher. It can be concluded that CVVH can effectively relieve clinical symptoms of MODS patients, improve function of organs, correct electrolyte disturbance and acid-base imbalance and eliminate TNF-α and NO in serum, which is effective in improving the ratio of successful rescue of patients developing MODS.