Epidemiological evaluation for vaccine effectiveness of varicella attenuated live vaccine among students in collective institutions in Jing an District, Shanghai from 2017 to 2019 / 中国学校卫生

Objective@#To understand the vaccination of varicella attenuated live vaccine (VarV) among students in collective institutions, to provide a basis for analying the protective effect of vaccination.@*Methods@#All collective institutions with chickenpox epidemic and post exposure vaccination in Jing an District from 2017 to 2019 were investigated. All students( n =6 473) in the affected class were included. Vaccination status and the incidence information of disease were collected to analyze vaccine effectiveness (VE).@*Results@#The proportion of study subjects without an immunization history decreased year by year, and 7.5% in 2017, 7.2 % in 2018, and 4.9% in 2019. The proportion with a history of one dose prior to exposure in cases was 90.0%, it was lower than 93.5% in the non cases ( χ 2=6.53, P <0.05). The proportion with one dose as post exposure prophylaxis in cases was 8.3%, it was much lower than 44.1% in the non cases ( χ 2=179.06, P <0.01). The proportion with one dose as post exposure prophylaxis in secondary cases was 28.6%, much lower than 44.1% in the non cases ( χ 2=9.44, P <0.01).Unvaccinated ones and the second dose as post exposure prophylaxis ones in cases had the highest rate of varicella development (11.0%), a history of one dose prior to exposure and one dose as post exposure prophylaxis in cases had the lowest varicella rate (1.0%).There was a clear protective effect within two years after one dose of VarV inoculation, VE was 63.1%(95% CI =11.0%-84.7%).@*Conclusion@#The vaccine effectiveness of one dose VarV was limited. Post exposure prophylaxis as early as possible was highly effective in decreasing secondary attack rate.

Research progress on metabonomic studies in periodontitis / 口腔疾病防治

@#Metabolomics reflects the endogenous metabolite changes in organisms through qualitative and quantitative detection of small molecules in biological samples, revealing the metabolic changes during disease development. Metabolomic studies of periodontitis further elucidate the etiology, diagnosis and predictive markers of periodontitis at the levels of metabolites and metabolic pathways. In this paper, the concept and research methods of metabonomics were summarized, and the current status of the metabonomics of saliva and gingival crevicular fluid in the study of periodontitis was reviewed. Previous studies have shown that metabolites such as short-chain fatty acids and amino acids and metabolic pathways such as glutamic acid and pyrimidine metabolism might promote the occurrence of periodontitis, and it was suggested that lactic acid, γ-amino-butyrate, butyric acid and lysophosphatidic acid might be potential diagnostic markers of periodontitis. The metabolomics study of periodontitis still faces challenges such as high heterogeneity of results and fluctuation of metabolites. In the future, its study could be optimized through multicenter prospective studies to provide fresh approaches for the etiology and diagnosis of periodontitis.

The neuroprotective effects of Lutongkeli in traumatic brain injury rats by anti-apoptosis mechanism

Purpose: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. Methods: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. Results: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. Conclusions: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Study on quality identification of Curcumae Rhizoma from different origins based on quantitative analysis of appearance color and content of main components / 中国中药杂志

L~*, a~* and b~* values of prepared slices of Curcumae Rhizoma were measured by spectrophotometer. SPSS 21.0 was used for discriminant analysis to establish the color range and mathematical prediction model of prepared slices of Curcumae Rhizoma. The values of L~*, a~* and b~* of kwangsiensis ranged from 58.09-62.40, 4.53-5.66 and 23.61-24.29, while the values of L~*, a~* and b~* of phaeocaulis were between 64.02-70.71,-0.89-4.13 and 44.59-54.52, respectively. The values of L~*, a~* and b~* of wenyujin were 68.55-70.99,-0.11-1.47 and 28.26-32.19, respectively. The mathematical prediction model was proved to be able to realize 100% identification of Curcumae Rhizome of different origins through original and cross validation and external samples validation. A dual wavelength HPLC was established; the contents of 9 sesquiterpenoids and 3 Curcumae Rhizomes were determined simultaneously; and the contents of Curcumae Rhizome of different origins were determined. The results showed that kwangsiensis had higher contents of neocurdione, β-elemene and isocurcumaenol, phaeocaulis curcumin, furadienone, demethoxycurcumin and curcumin; and wenyujin mainly contained curdione, furadienes and guimarone. Pearson correlation analysis on L~*, a~*, b~* value and content of 12 components showed that curcumin, furadienone, demethoxycurcumin and curcumin had a significant positive correlation with b~* value(P<0.01). There was a significant negative correlation between neocurdione, β-elemene and isocurcumaenol and L~* value(P<0.01). Curdione, furadienes and guimarone were significantly correlated with L~* value(P<0.01),indicating that the appearance co-lor of Curcumae Rhizoma could reflect the change of the content of the internal components. This study provided reference for the rapid recognition of Curcumae Rhizoma and the establishment of quality evaluation system.

Salidroside affects proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33Acells through JAK2/STAT3 pathway / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of salidroside on the proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33A cells and explore its possible mechanism. Methods: C33A cells were divided into 4 groups: control group, low-dose group (salidroside 50 μg/mL), high-dose group (salidroside 150 μg/mL), and AG490 group (inhibitor of JAK2/STAT3 signaling pathway, 50 μmol/L). Effects of salidroside and AG490 on the proliferation, invasion and apoptosis of C33A cells were detected by MTT method, EdU labeling experiment, Transwell assay, Rh123 staining and Flow cytometry, respectively. Western blotting was used to detect the effects of salidroside and AG490 on the expressions of JAK2/STAT3 pathway-related proteins (p-JAK2, p-STAT3) and apoptosis-related proteins (Bax, Bcl-2, caspase-3) in C33A cells. Result: Compared with the control group, the proliferation and DNA synthesis as well as the invasion of C33Acells in the low-dose group were significantly inhibited (all P<0.05), while the apoptosis was significantly enhanced (P<0.05); in the meanwhile, the fluorescence intensity of Rh123 was significantly reduced (all P<0.05) and the membrane structure of C33A cells were destroyed; moreover, the expressions of p-JAK2, p-STAT3 and Bcl-2 were significantly decreased while the expressions of Bax and caspase-3 were significantly increased (all P<0.05). Compared with the low-dose group, the effects of high-dose salidroside and AG490 on the proliferation, invasion, apoptosis and related protein expressions in C33A cells were more significant (all P<0.05), but there was no difference between the high-dose group and the AG490 group. Conclusion: Salidroside can inhibit the proliferation and invasion of C33A cells and promote cell apoptosis. Its mechanism may be related to inhibition of JAK2/ STAT3 signaling pathway.

Selective targeting p53WT lung cancer cells harboring homozygous p53 Arg72 by an inhibitor of CypA / 中国药理学与毒理学杂志

OBJECTIVE To explored the potential of pharmacological stabilization and reactivation of p53 for targeted cancer therapies. METHODS The cytotoxicity of a potent Cyclophilin A (CypA) inhibitor HL001 was tasted against a panel of cancer cell lines. The genotypes and activation of p53 were compared with the cytotoxicity profile of HL001. Two-dimensional (2D) PAGE analysis was performed to investigate differentially expressed proteins that involves in the anti-proliferation effects of HL001. Pull-down and Co-IP were used to confirmed the new identified PPI between CypA and G3BP1 and orthotopic animal model of lung cancer was used to tested the anti- tumor activity of HL001 in vivo. RESULTS We identify a novel CypA small molecule inhibitor HL001 that induces non-small cell lung cancer (NSCLC) cell cycle arrest and apoptosis via restoring p53 expression. We find that HL001 stabilizes p53 through inhibiting the MDM2-mediated p53 ubiquitination. Further mechanistic studies reveal that the downregulation of G3BP1 and the induction of reactive oxygen species and DNA damage by HL001 contribute to p53 stabilization. Surprisingly, HL001 selectively suppresses tumor growth in p53 wildtype NSCLC harboring Arg72 homozygous alleles (p53- 72R) through disrupting interaction between MDM2 and p53-72R in a CypA dependent manner. Moreover, combining HL001 with cisplatin synergistically enhance tumor regression in orthotopic NSCLC mouse model. CONCLUSION Pharma?cologic inhibition of CypA offers a potential therapeutic strategy via specific activation of p53-72R in NSCLC.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis / 中国药理学与毒理学杂志

OBJECTIVE Leukotriene B4 (LTB4) biosynthesis and subsequently neutrophilic inflam?mation may provide a potential strategy for the treatment of acute lung injury (ALI) or idiopathic pulmonary fibrosis (IPF). To provide a potential strategy for the treatment of ALI or IPF, we identified potent inhibi?tors of Leukotriene A4 hydrolase (LTA4H), a key enzyme in the biosynthesis of LTB4. METHODS In this study, we identified two known histone deacetylase (HDAC) inhibitors, suberanilohydroxamic acid (SAHA) and its analogue 4-(dimethylamino)-N-〔7-(hydroxyamino)-7-oxoheptyl〕benzamide (M344), as effective inhibitors of LTA4H using enzymatic assay, thermofluor assay, and X- ray crystallographic investigation. We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay. A murine experimental model of ALI was induced by lipopolysaccharide(LPS) inhalation. Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA. We next examined mRNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using qRT- PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA. We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin (BLM)-induced IPF model. RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H, signif?icantly decrease LTB4 levels in neutrophil, and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose. CONCLUSION Collectively, SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Assembly of a highly stable luminescent Zn5 cluster and application to bio-imaging / 中国药理学与毒理学杂志

OBJECTIVE To explore a novel pH-sensitive fluorescent probe for in vivo tumor imaging. METHODS Zn5 were obtained in 140℃ after mixed with MeOH, water, Zn(NO3)2 · 6H2O, H4L and trimethylamine. The fluorescence spectra of Zn5 with the same concentration in different pH aqueous solutions were detected. And the stability of Zn5 was investigated by time dependent fluorescence emission spectra of Zn5 in BSA aqueous solution and 5.0% serum solution. Then, the cytotoxicity of Zn5 was detected by MTT assays. To clarify whether a similar fluorescence response occurs in biological organisms, HeLa cells were pretreated with probe Zn5 (0.5 μmol·L- 1) and fluorescence imaging were collected for targeting lysosomes in living cells because of lysosomes' acidic microenvironment. The A375 tumor-bearing mice were used to assess the imaging ability of Zn5 in vivo. Mouse tumor xenografts were established by injection of A375 cells with 2×106 cells per flank. Probe (1 μg·g-1) was administered to mice by injection. Images were obtained using IVIS Spectrum CT Imaging System. RESULTS There is a 11-fold intensity increasing as the pH values changing from 8 to 2. The almost unchanged emission intensities suggest Zn5 is stable in both BSA and serum. Zn5 has negligible cytotoxicity for HeLa, 293T and CHO-K1 cells. Zn5 can selectively display lysosomes in living cells. Both the 2D and 3D images in vivo distinguish the tumor from other tissues with good fluorescence contrast. CONCLUSION The high chemical stability, emission in the Vis/NIR range, pH sensitivity, a pKa located in the tumor pH range, and low toxicity make Zn5 is suitable for application as a pH- sensitive fluorescent probe for bio-imaging.

Connexin 40-formed GJIC increases the phototoxicity of photodynamic therapy through ROS- and calcium-mediated pathways / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect of connexin (Cx) 40-formed gap junctional intercellular communication (GJIC) on Photofrin- photodynamic therapy (PDT) phototoxicity in Cx40- transfected HeLa cells and its potential mechanisms. METHODS HeLa cell line stably transfected to express Cx40 was seeded at high and low cell density, respectively, to assess in vitro photosensitivity using CCK8 assay. Western blot assay was performed to detect the expression of Cx40. The intracellular ROS and Ca2 +concentrations were determined using flow cytometer. 4-HNE and ceramide were measured using ELISA assay. RESULTS Cx40-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx40 is not expressed or Cx40 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx40-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS and calcium-mediated stress signaling pathways. CONCLUSION The work uniquely presents the ability of Cx40-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that mainte?nance or increase of Cx40-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency.

Anti-cancerous/Anti-bacterial Activities of Allicin Generated In situ from Diastereo Pure Alliins by Alliinase.

Aims: To facilitate allicin generation in-situ from pure diastereomers of alliin by enzymatic reaction of alliinase and assess its anti-cancerous/anti-bacterial activities. Study Design: Chemical synthesis and in-vitro assay of anti-cancerous/anti-bacterial activities. Place and Duration of Study: Protein Research Laboratory, Research Resources Center, University of Illinois at Chicago, between February 2014 and February 2015. Methodology: Cancer cell viability assay MTT assay, bacterial plate-diffusion growth inhibition assay, and flow cytometry cell cycle analysis have been used to demonstrate the anticancerous/ anti-pathogen activities of the in-situ allicin. Diastereomers of alliin are produced by H2O2 oxidation of deoxyalliin, which is prepared by mixing L-cysteine and allyl bromide. Deoxyalliin and diastereomers of alliin are purified to high purity with repeated fractional crystallization. In addition, fluorenylmethyloxycarbonyl (Fmoc) protected alliin and alliin methyl ester are synthesized and purified with RP-HPLC to test the importance of amino and carboxyl groups of alliin in alliinase enzymatic reaction. Alliinase is produced by a simple and effective method from an aqueous garlic extract Results: Results from spectrophotometric alliinase activity assay indicate that (+)-L-alliin is more reactive toward alliinase than (-)-L-alliin, and both amino and carboxyl groups of the cysteine portion of alliin are critical in alliinase enzymatic reaction. Results from cancer cell viability assay MTT assay, bacterial plate-diffusion growth inhibition, and flow cytometry cell cycle analysis confirm that the in-situ allicin is as active as allicin purified from aqueous garlic extract or allicin synthesized chemically in a dose-dependent manner. Conclusion: We describe here facile pathways to synthesize diastereomerically pure alliins and isolate allinase. The in-situ allicin conversed from alliin by allinase is very active. The data obtained here provide useful information on the design of the in-situ allicin strategy.

MALDI-TOF-MS combined with WCX technique in diagnosing pituitary adenoma / 中国应用生理学杂志

<p><b>OBJECTIVE</b>Application of matrix assisted laser desorption ionization time of flight mass spectrometry enhancement (MALDI-TOF-MS) combined with WCX nanometer magnetic bead technique, screening of the serum biomarkers in pituitary adenoma, to establish a serum protein fingerprint classification decision tree.</p><p><b>METHODS</b>Analyse the serum samples of 40 cases of pituitary adenoma and 60 cases of healthy adult and find the different protein peaks, then to establish the diagnosis model and the classification decision tree of pituitary adenomas.</p><p><b>RESULTS</b>A total of 42 differences in protein peaks were identified in the experimental and control group (P < 0.01). The diagnosis model of pituitary adenomas was established by three protein peaks (3382.0, 4601.9, 9191.2). The model could screen the pituitary adenoma out of the normal population. The sensitivity was 90.00% and the specificity was 88.30%. By the double blind experimental validation, the model could diagnose the pituitary adenoma and the sensitivity was 88%, the specificity was 83.30%.</p><p><b>CONCLUSION</b>Significantly different protein peaks can be screened out between pituitary adenoma cases and healthy controls using MALDI-TOF-MS combined with WCX technique, and these protein peaks may be used as a pituitary adenoma detection, follow-up indicator.</p>

The expression and significance of apoptosis related gene BAG-1 in meningioma / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To analyze the expressions of BAG-1 in meningioma for further understanding of biological behaviors of meningiomas.</p><p><b>METHODS</b>The specimens included in this study were collected from 158 meningioma cases. Streptavidin-peroxidase were used in immunohistochemical staining. The results of immunohistochemical score were depending on the positive ratio and intensity of the immunoreactivity. The expressions of BAG-1 in meningioma were analyzed in relationship with histopathologic grading, postoperative recurrence.</p><p><b>RESULTS</b>The difference in the expression degree of BAG-1 between each subtype in the same histopathologic grade and various subtypes between the grade of II to III were not statically significant (P > 0.05). The expression degree of BAG-1 between each subtype in the pathological grade I to the each subtype pathological grade I or III was different, the difference had statistical significance (P < 0.05 or P < 0.01). The immunohistochemical score of the expression of BAG-1 was decreased gradually with the pathologic grading of WHO increased, and the result was statistically significant (chi2 = 141.49, P < 0.01). As the immunohistochemical score of the expression of BAG-1 decreased the postoperative meningioma was easy to recur, the result was statistically significant (x2 = 55.13, P < 0.01).</p><p><b>CONCLUSION</b>The expression degree of BAG-1 is in close correlations with the WHO pathologic grading of meningioma. The lower the expressions of BAG-1, the more recurrent with postoperation of meningiomas will be.</p>

Wound infections secondary to snakebite in central Taiwan

There are very few microbiological data on wound infections following snakebites. The objective of this study was to investigate the treatment of secondary infection following snakebites in central Taiwan. Microbiological data and antibiotic sensitivity of wound cultures were retrospectively analyzed from December 2005 to October 2007 in a medical center in central Taiwan. A total of 121 snakebite patients participated in the study. Forty-nine (40.5%) subjects were bitten by cobra (Naja atra); 34 of them had secondary infection, and 24 of them (70.6%) needed surgical intervention. Cobra bites caused more severe bacterial infection than other snakebites. Morganella morganii was the most common pathogen, followed by Aeromonas hydrophila and Enterococcus. Gram-negative bacteria were susceptible to amikacin, trimethoprim/sulfamethoxazole, cefotaxime, cefepime, ciprofloxacin, and piperacillin/tazobactam. Enterococcus were susceptible to ampicillin, gentamicin, penicillin and vancomycin. It is reasonable to choose piperacillin/tazobactam, quinolone, second- or third-generation cephalosporin for empirical therapy following snakebite. Surgical intervention should be considered for invasive soft tissue infections.(AU)

Shewanella infection of snake bites: a twelve-year retrospective study

OBJECTIVE: Infections of snake bite wounds by Shewanella are rarely discussed in the medical literature. This study aims to characterize the presentation and management of Shewanella infections in snake bite wounds. METHOD: We retrospectively investigated the microbiology, clinical features, and outcomes of patients with Shewanella infected snake bite wounds admitted to a tertiary medical center from January 1998 to December 2009. RESULTS: Ten patients with Shewanella-infected snake bite wounds were identified. All of the snake bites were caused by cobras. The majority of patients had moderate to severe local envenomation and polymicrobial infections. Shewanella isolates are susceptible to ampicillin-sulbactam, piperacillin-tazobactam, third-and fourthgeneration cephalosporins, carbapenems, aminoglycosides, and quinolones but are resistant to penicillin and cefazolin. All of the patients examined had favorable outcomes. CONCLUSION: It is recommended that Shewanella infection be considered in snake bite patients, especially when patients present with moderate to severe local envenomation.