Objective To evaluate the safety of human purified Vero cell rabies vaccine(PVRV)after exposure in China by Meta-analysis.Methods With rabies,vaccine and safety as key words,a systematic search was performed in PubMed,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI),supplemented by manual retrieval.A Meta-analysis was performed to analyze the incidence of adverse events of two immunization regimens Zagreb and Essen using Review Manager 5.4 software after literature screening and data extraction according to the inclusion and exclusion criteria.Results A total of 12 studies were included,of which 7 were prospective studies and 5 were retrospective studies.Most included in the studies showed a low risk of bias.The incidence of adverse events in Zagreb regimen was significantly higher than that in Essen regimen[relative risk(RR)= 1.01,95% CI = 0.90 ～ 1.14;I2= 73.00%,P<0.05],but there was a high degree of heterogeneity.The incidence of fever,pain and induration in Zagreb regimen was significantly higher than that in Essen regimen(RR = 1.14,0.92 and 0.86,95% CI = 0.82 ～ 1.60,0.73 ～ 1.14 and 0.29 ～ 2.51;I2= 73.00%,P<0.05],but there was a high degree of heterogeneity.The incidence of fever,pain and induration in Zagreb regimen was significantly higher than that in Essen regimen(RR = 1.14,0.92 and 0.86,95% CI = 0.82 ～ 1.60,0.73 ～ 1.14 and 0.29 ～ 2.51;I2= 81%,65% and 92%,respectively,P<0.01).Conclusion Two regimens of PVRV vaccination after exposure showed good safety.However,when adopting Zagreb regimen,attention should be paid to the physical conditions of children and the elderly with relatively poor immunity to avoid adverse events.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

AIM To observe the protective effects of Qigu Capsule-medicated serum on C2C12 myotube cell atrophy induced by dexamethasone.METHODS The Qigu Capsule-medicated serum was prepared.C2C12 cells cultured in vitro were divided into the normal control group,the dexamethasone group,the 10%blank serum group and the 10%Qigu Capsule-medicated serum group for 48 h,corresponding drug treatment,followed by 24 h culture with 10 μmol/L dexamethasone except the control group,and had cell viability detection by CCK-8 method.With their myotube cells intervened accordingly by the aforementioned regime following 6-7 days differentiation with 2%horse serum induction,the C2C12 cells had their myotube cells diameter measured;and the expressions of proteins related to MyHC,MuRF-1,Atrogin-1 and PI3K/Akt signaling pathway detected by Western blot.The impact of PI3K inhibitor LY294002 on the diameter of myotube cells and the expression of MuRF-1,Atorgin-1 and PI3K/Akt signaling pathway related proteins were detected as well.RESULTS Compared with the normal control group,the dexamethasone group and the blank serum group were observed with decreased viability of C2C12 cells(P<0.01),decreased diameter of myotube cells(P<0.01),increased protein expressions of MuRF-1 and Atrogin-1(P<0.01),and decreased expression of MyHC protein and phosphorylation levels of PI3K,Akt,mTOR and FoxO3a(P<0.01).Compared with the dexamethasone group,the Qigu Capsule-medicated serum group showed increased viability of C2C12 cells(P<0.01);increased diameter of myotube cells(P<0.01);decreased protein expressions of MuRF-1 and Atrogin-1(P<0.01);and increased expression of MyHC protein and phosphorylation levels of PI3K,Akt,mTOR and FoxO3a(P<0.05,P<0.01).The intervention of LY294002 upon the Qigu Capsule-medicated serum group offset the anti-muscular tube atrophy effect(P<0.01),increased the protein expressions of MuRF-1 and Atorgin-1(P<0.01),and decreased the phosphorylation levels of PI3K,Akt,mTOR and FoxO3a(P<0.05,P<0.01).CONCLUSION The Qigu Capsule-medicated serum can alleviate the atrophy of C2C12 myotubes induced by dexamethasone,and its mechanism may be related to the activation of PI3K/Akt signaling pathway.

Objective: To analyze the clinical characteristics of the neonates infected with SARS-CoV-2 during the Omicron outbreak in Shanghai 2022. Methods: In this retrospective case series study, all the 16 neonates with SARS-CoV-2 Omicron infection who were admitted to the neonatal unit in Shanghai Public Health Clinical Center from March 1^st to May 31^st, 2022 were enrolled. Their epidemiological history, clinical manifestations, nucleic acid cycle threshold (Ct) value and outcomes were analyzed. Based on maternal vaccination, they were divided into vaccinated group and unvaccinated group. Rank sum test and Chi-square test were used for the comparison between the groups. Results: Among the 16 neonates, 10 were male, and 6 were female. All the infants were full-term. The infection was confirmed at the age of 12.5 (8.0, 20.5) days. All the neonates had a history of exposure to infected family members, and thus horizontal transmission was the primary mode. Four infants were asymptomatic, 12 were symptomatic, and there were no severe or critical cases. The most common clinical manifestation was fever (11 cases), with the highest temperature of 38.1 (37.9, 38.3) ℃ and a course of 1-5 days. Other clinical manifestations included nasal obstruction (3 cases), runny nose (2 cases), cough (2 cases), poor feeding (2 cases), vomiting (1 case), and mild tachypnea (1 case). The complete blood counts of all neonates were within the normal range, and the C-reactive protein increased slightly in 1 infant. Chest imaging was performed in 2 infants, showing mild focal exudative changes. Nucleic acid turned negative (Ct value ≥35) within 7-15 days after diagnosis. All neonates fully recovered after supportive treatment, and the length of hospitalization was 13 (10, 14) days. In the telephone follow-up 2 weeks after discharge for all 16 cases, no infant showed reoccurrence of clinical manifestations or nucleic acid reactivation. Maternal vaccination was not significantly correlated with symptomatic infection or the persistence of positive nucleic acid result in neonates (all P>0.05). Conclusions: Horizontal transmission is the primary mode for neonatal SARS-CoV-2 Omicron infection. Neonatal infections are usually mild or asymptomatic, with good short-term outcomes. And their clinical manifestations and laboratory examinations are nonspecific.
Infant, Newborn ; Male ; Female ; Humans ; SARS-CoV-2 ; COVID-19 ; Retrospective Studies ; China/epidemiology* ; Fever ; Disease Outbreaks ; Nucleic Acids

【Objective】 To assess the status of HCV infection by analyzing the results of anti-HCV reactive blood samples detected by the current blood testing strategy, and discuss the viability of classified management of reactive blood donors. 【Methods】 The anti-HCV reactive samples (dual ELISA and once NAT), from May 2017 to October 2018, were divided into three groups: samples both anti-HCV and HCV RNA reactive, sole HCV RNA reactive, and sole anti-HCV reactive, and all of them were confirmed by recombinant immunoblot assay (RIBA). The positive predictive value (PPV) between groups were compared. The sensitivity, specificity and PPV for each reagent under different screening threshold (screening threshold for routine detection, optimal screening threshold, and corresponding screening threshold of the highest PPV) were analyzed. The group with low PPV were stratified by ELISA S/CO values, and PPV by different screening threshold was compared. 【Results】 There were 939 reactive samples (0.49%, 937/191 627). Confirmed by RIBA, the positive rate of anti-HCV reactive samples was 10.67%(100/937). Two samples were sole HCV RNA reactive (0.001%). Both anti-HCV+ HCV RNA reactive samples were 6.71%(63/939), with the PPV of 96.83%(61/63). Sole anti-HCV reactive samples were 93.08(874/939), with the PPV of 4.46%(39/874), among which PPV by dual and one ELISA reagent were 18.72% and 0.15%, respectively, showing statistically significant difference (P<0.05). The PPV between different S/CO values was statistically significant (P<0.05). The optimal screening thresholds of anti-HCV reagent were 9.29 and 3.97, according to the ROC curve, with significant difference noticed in PPV by different screening threshold (P<0.05). PPV in the sole anti-HCV reactive group increased from 4.46% (the routine screening threshold) to 49.35%(the optimal screening threshold), and the difference was statistically significant (P<0.05). 【Conclusion】 The blood donors with both anti-HCV and HCV RNA reactive can be determined as HCV infection and need to be permanently deferred. The S/CO value of sole anti-HCV reactive samples was positively correlated with RIBA confirmation results, and the higher the S/CO value, the greater the chances of positive confirmation are. With the current blood screening strategy, the HCV infection status of sole anti-HCV reactive blood donors can be determined by establishing a screening threshold with high PPV or adding confirmatory test.

【Objective】 To discuss the reliability and applicability of the current blood deferral strategy concerning anti-TPreactive blood donors (by ELISA). 【Methods】 TPPA confirmatory test was performed on the samples routinely detected by two different anti-TP ELISA reagents(reagent 1 and reagent 2), and the test data of dual reagent reactive and one reagent reactive blood donors were analyzed to determine the possibility of true positivity. 【Results】 1 624 anti-TP reactive samples(by ELISA) were collected, among which 1 467 were dual reagent reactive, 77 were reagent 1 reactive, and 80 were reagent 2 reactive. TPPA results showed that the positive predictive value (PPV) of dual reactive samples was 85.48%. Samples with high S/CO value (reagent 1≥13 and/or reagent 2 >17) were more likely to be true positive, with the PPV at 98.56% (reagent 1) and 99.13% (reagent 2), respectively, which were significantly higher than that when the S/CO value was≥1. Among the samples reactive to one reagent, 2 were confirmed positive in reagent 1 and 3 in reagent 2, with the PPV at 2.60% and 3.75% respectively, and had no correlation with high S/CO value. 【Conclusion】 Dual-reagent reactive donors with high S/CO value showed high possibility of true positivity, therefore should be deferred. TPPA test is helpful to identify true positivity in one-reagent reactive donors. Confirmatory test and follow-up should be a supplement to the current blood donor deferral strategy to ensure blood safety.

【Objective】 To explore the viability of classification management of HIV reactive blood donors based on test results in blood screening laboratory. 【Methods】 According to the HIV test results of blood donors (including twice ELISA and once NAT), the HIV reactive blood donors were divided into three groups. Group 1 was all-test reactive (both ELISA and NAT were reactive), group 2 serological reactive (only ELISA was reactive), and group 3 NAT reactive (only NAT was reactive). The HIV test results of 191 628 blood donors from May to December 2017 were analyzed. Samples with positive RIBA results and / or the repeated reactive NAT results were determined as HIV true positive. The yielding rates of HIV true positivity in each group were analyzed. Receiver operating characteristic curve (ROC curve) was used to elevate the S/CO limit under 99% specificity as the blood donor deferral limit for ELISA. 【Results】 A total of 180 HIV reactive samples were detected out of 191 628 blood donors, including 77 positive cases in group 1, 100 in group 2 and 3 in group 3. 1) The HIV reactive results were diverse. Among the 82 true positive blood donors, 4 were early HIV infection (3 HIV antibody+ antigen window period yield, 1 HIV antibody window period yield), 2 were suspected elite controllers, and 76 cases were both serology and NAT reactive. 2) The overall yielding rate of HIV was 47.67%, with group 1 (100%) = group 3 (100%) > group 2 (2.17%), showing statistically significant (P<0.01). 3) The blood donor deferral limit for ELISA1, ELISA2 was 5.40 and 9.69 (S/CO value), respectively, with the corresponding positive expective values of 98.73% and 91.14% (P>0.05). All true positive blood donors in group 1 and group 2 could be accurately screened by using the blood donor deferral limit for ELISA1 and ELISA2 simultaneously. 【Conclusion】 The composition of HIV results among blood donors is diverse and complex. It is necessary to continuously improve the awareness of HIV prevention and control. The classification of HIV reactive blood donors is conducive to conduct fine and scientific management. The blood donors in group 1 and group 3 should be permanently deferral, and the suspected HIV elite controllers in group 2 should be paid attention to and permanently deferral.

COVID-19 ; Female ; Humans ; Infectious Disease Transmission, Vertical ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy* ; Pregnancy Outcome ; Premature Birth ; Retrospective Studies ; SARS-CoV-2

Objective:This studu aims to investigate the effect of aqueous extract of modified Xiao Xianxiongtang on the epithelial mesenchymal transition（EMT） and the change of its invasion and migration ability of human gastric cancer MGC-803 cells mediated by transforming growth factor-β₁（TGF-β₁），and to explore the mechanism of regulating Wnt5a/Ca²⁺/ activated T-cell nuclear factor（NFAT） signaling pathway to inhibit EMT and invasion and metastasis of MGC-803 cells. Method:TGF-β₁（10 μg·L^-1）was used to induce EMT and the invasion and metastasis model of human gastric cancer MGC-803 cells. Transwell chamber experiment， scratchhealing experiment， Western blot and immunofluorescence assay were used to detect cell invasion and migration ability， expression of EMT marker protein and key protein expression of Wnt5a/Ca²⁺/NFAT signaling pathway， and intracellular Ca²⁺ concentration. Result:Compared with the blank group， TGF-β₁ could significantly enhance the invasion and migration ability of MGC-803 cells（P<0.01）， down-regulate the level of E-cadherin（P<0.01）， up-regulate protein expressions of N-cadherin， Snail and Vimentin（P<0.01）， and induce cell Wnt5a， calcineurin （CaN）， total protein of activated T-cell nuclear factor 1（NFAT1）， up-regulation of phosphorylated proteins p-NFAT1 and NFAT1 nucleoprotein and intracellular accumulation of Ca²⁺（P<0.01）. Compared with the TGF-β₁ group， modified Xiao Xianxiongtang （10， 20， 40 mg·L^-1） could significantly inhibit this phenomenon，and 40 mg·L^-1 had the best effect（P<0.05，P<0.01）.The specific inhibitors of Wnt5a/Ca²⁺/NFAT signaling pathway （R）-（+）-Bay-K-8644 and modified Xiao Xianxiongtang （40 mg·L^-1） could significantly inhibit theinvasion and migration of MGC-803 cells mediated by TGF-β₁， up-regulate the level of E-cadherin， and down-regulate expressions of N-cadherin， Snail， Vimentin， Wnt5a， CaN and NFAT1 proteins and reduce the intracellular accumulation of Ca²⁺（P<0.05，P<0.01）.Moreover， （R）-（+）-Bay-K-8644 combined with modified Xiao Xianxiongtang （40 mg·L^-1） had stronger inhibitory effect（P<0.05，P<0.01）. Conclusion:These results suggest that modified Xiao Xianxiongtang can inhibit the EMT mediated by TGF-β₁ via Wnt5a/Ca²⁺/NFAT signaling pathway，thereby reducing the invasion and migration ability of MGC-803 cells.

Tumor is one of the diseases that seriously endanger human health， and how to treat tumor effectively is still one of the important problems in the field of medicine. At present， most of the radiotherapies and chemical drugs for cancer have serious side effect despite of an obvious efficacy. With a unique syndrome differentiation treatment system and overall concept， traditional Chinese medicine has become the key research and development object of antitumor drugs due to many advantages， such as multiple channels， multiple levels， multiple links， multiple targets and less toxicity， and could can fully mobilize the immune and epidemic prevention mechanism of the body. A large number of studies have shown that Xiao Xianxiongtang and its effective ingredients have obvious antitumor effect. Many doctors have applied Xiao Xianxiongtang and modified formulas in clinical treatment of tumors， and relevant pharmacological studies have also confirmed the effectiveness of this formula， but with a lack of systematic summary of its effective ingredients and its mechanism of action. Now， with alkaloids， ketones， sterols and phenols in Xiao Xianxiongtang as the starting point， this study mainly focuses on inhibition of tumor cell proliferation， invasion and migration， induction of tumor cell apoptosis and autophagy， inhibition of tumor cell cycle， enhancement of tumor cell sensitivity， inhibition of tumor angiogenesis and regulation of immunosuppressive tumor microenvironment from two ways to sort out composition， function and mechanism of drugs. In this paper， effective components， main targets and mechanism of intervention in the tumor development of Xiao Xianxiongtang were reviewed， in order to provide a new idea for subsequent antitumor research and development of this prescription.