OBJECTIVETo study the effect of dimethoate on the expression of heat shock protein 70 (HSP70) in peripheral blood lymphocytes of human beings and to explore the feasibility of HSP70 in biomonitoring among workers exposed to organophosphorous pesticides.

METHODSPeripheral blood lymphocytes were isolated from subjects, comprising 11 people of the control group and 35 workers of the exposure group exposed to dimethoate. Flow cytometry was used for detecting both the basic level and the level of the dimethoate-induced expression of HSP70. The activity of whole blood acetylcholinesterase (AChE) was examined at the same time. Then the potential influential factors to HSP70 expression and AChE activity were analyzed.

RESULTSThe basic level of HSP70 expression in the exposure group and the control group was 41.24% +/- 10.45% and 23.97% +/- 4.29% respectively. The activity of AChE in these two groups were (125.23 +/- 7.97) and (145.36 +/- 8.78) U/ml respectively. Both differences were statistically significant (P < 0.01). Among the exposure group, the basic level of HSP70 expression of the two categories comprising operators and packers, were 47.34% +/- 11.87% and 38.05% +/- 8.20% respectively (P < 0.05), while there was no significant difference (P > 0.05) in AChE activity between these two categories. The factors that had significant influence on the HSP70 basic level of the exposure group were the health condition, the environmental concentration of dimethoate and the exposure time in order, according to their significance of influence. At least 88% variance of HSP70 could be explained by these factors. The only factor that could influence AChE activity significantly was the exposure time, and it could only explain about 12% variance of AChE activity. After the treatment of dimethoate in vitro, the level of the induced expression of HSP70 in the control group was significantly higher than that of the exposure group (P < 0.01). The increasing order was the control group, the group of packers and the group of operators according to the increasing extent and there were significant difference among them (P < 0.01). The factors that could significantly influence the change ratio of HSP70 expression were the environmental concentration and the exposure time.

CONCLUSIONHSP70 is a potential index that can reflect the individual and environmental conditions of workers exposed to dimethoate comprehensively.

Acetylcholinesterase ; blood ; Adult ; Cells, Cultured ; Dimethoate ; toxicity ; Female ; HSP70 Heat-Shock Proteins ; biosynthesis ; Humans ; Insecticides ; toxicity ; Lymphocytes ; drug effects ; metabolism ; Male ; Middle Aged ; Occupational Exposure

Objective We aimed to assess the association between urinary bisphenol A(BPA)concentrations and gestational age in pregnant women. Methods A total of 248 pregnant women were recruited from a maternal and child care hospital in Shanghai. A questionnaire survey was completed to collect socio-demographic information and spot urine samples were collected during pregnancy. Gas chromatography-tandem mass spectrometry(GC-MS/MS)was used to measure BPA concentrations in urine samples. Linear relationship between urinary BPA level and gestational age was assessed by using generalized additive models. Multivariate regression model was used to evaluate associations of prenatal BPA exposure with gestational age. Results BPA was detected in all the urine samples. Median value and geometric mean of urinary BPA levels were 0.85 μg/L and 1.21 μg/L, respectively. Linear relationship between urinary BPA concentration and gestational weeks was confirmed(non-linear P > 0.05). Positive association between urinary BPA level and gestational age was indicated(regression coefficient, β = 0.19;95%CI:0.04-0.35;P = 0.016). However, it was only observed in girls, stratified by sex of newborns(β = 0.18;95%CI:0.03-0.34;P = 0.020). After stratification by trimester, no significant association was found in the second or the third trimesters. Conclusion Pregnant women are extensively exposed to BPA. Urinary BPA exposure during pregnancy may extend gestational age, especially in girls.

OBJECTIVEContrast induced acute kidney injury (CIAKI) is a significant clinical problem. We, therefore, performed a prospective, randomized trial to investigate the role of probucol in the prevention of CIAKI in patients with unstable angina pectoris (UAP) undergoing percutaneous coronary angiography (CAG) and interventions (PCI).

METHODSWe studied 205 patients with UAP, who underwent CAG or PCI prospectively. Patients were randomly assigned to probucol group (n = 102) and control group (n = 103). In the probucol group, the patients received probucol tablets 500 mg b.i.d for 3 days before and after intervention. All the patients, after intervention, underwent hydration with intravenous saline at a rate of 1 ml per kilogram of body weight per hour for 12 hours.

RESULTSPatients were well-matched with no significant difference at baseline in majority measured parameters between two groups. CIAKI occurred in 23 of the 205 (11.22%) patients. Multivariate logistic regression was used to identify correlates of CIAKI and clinical data. CIAKI was most strongly associated with Scr > or = 132.6 micromol/L (OR = 21.11, 95%CI 1.95 - 56.06, P < 0.001), Ccr < 60 ml/min (OR = 4.19, 95%CI 1.94 - 9.05, P < 0.001), heart function > class II (OR = 6.23, 95%CI 2.73 - 14.21, P < 0.001), Diabetes (OR = 2.049, 95%CI 1.19 - 5.25, P < 0.001), age > or = 70 yrs (OR = 3.52, 95%CI 1.66 - 7.43, P < 0.001), coronary artery calcification shown by CAG (OR = 4.29, 95%CI 1.99 - 9.24, P < 0.001). The rate of CIAKI in probucol groups was slightly lower compared with control group (7.84% vs. 14.56%), without significant difference. The post-procedure mean peak of Scr [(101.62 +/- 42.98) micromol/L vs. (117.67 +/- 68.77) micromol/L, P = 0.047] and the post-procedure increasing Scr from baseline (DeltaScr) [(13.49 +/- 19.61) micromol/L vs. (22.50 +/- 18.31) micromol/L, P = 0.001] in the probucol group decreased significantly compared with that of control group.

CONCLUSIONProphylactic treatment with probucol 500 mg b.i.d during periprocedural stage in patients with UAP has preventing role against CIAKI after cardiac catheterization.

Acute Kidney Injury ; chemically induced ; prevention & control ; Aged ; Angina, Unstable ; diagnostic imaging ; Contrast Media ; adverse effects ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Probucol ; therapeutic use ; Prospective Studies

Abstract：Objective To improve the replication level of varicella⁃zoster virus（VZV）in human diploid cell line MRC⁃5 and increase the yield of VZV vaccine by reducing the expression of interferon（IFN）related genes via optimizing the cell line MRC⁃5. Methods Interferon receptor 1（IFNAR1）silenced MRC⁃5 cell line（MRC⁃5IFNAR1⁃）was constructed by CRISPR／Cas9 gene editing technology，which was determined for the relative expression of IFNAR1 mRNA，and for those of mRNA of IFN related genes IFNβ and OAS1 after VZV infection by qRT⁃PCR to evaluate the effect of gene silencing. Gene mutation sequences were further identified by sequencing of the silenced sites. The replication of VZV in MRC⁃5 and MRC⁃5IFNAR1⁃ cell lines was compared 168 h after VZV infection by using qRT⁃PCR and plaque formation unit（PFU）assay， to evaluate the effect of MRC⁃5IFNAR1⁃cell line on VZV replication. Results The growth status of MRC⁃5IFNAR1⁃ cell line wasconsistent with that of MRC ⁃ 5 cells，and the relative expression of IFNAR1 mRNA decreased by 73%；The relative expressions of IFNβ and OAS1 mRNA in MRC⁃5IFNAR1⁃ cell line were 61% and 90% lower than those in MRC⁃ 5 cells respectively after VZV infection；In addition，168 h after VZV infection，the level of DNA replication and the titer of VZV increased by 5. 7 folds and 4 folds respectively. Conclusion The successful establishment of MRC⁃5IFNAR1⁃ cell line may be a potential scheme to increase the yield of vaccines based on human diploid cells，and provided a reference for expanding production of VZV vaccine.

OBJECTIVE：To provid e reference for the medicinal resources and clinical application of Tibetan medicine “Dida”. METHODS：Delphi method was adopted. By reviewing literatures ，confirming consultation scope ，inviting experts engaged in clinical，scientific research ，teaching and production of Tibetan medicine. Two methods ，online inquiry and on-site questionnaire ， were used for expert consultation to evaluate the differences and problems existing in the utilization of “Dida”medicinal resources until a consensus was reached ，consensus on the medicinal resources and clinical application of Tibetan medicine “Dida”was determined finally. RESULTS & CONCLUSIONS ：A total of 33 experts participated in the two rounds of consultation. According to the results of literature research ，the first round set up 16 inquiry indicators ；and then according to expert opinions to modify the index system ，the second round set up 18 inquiry indicators. After two rounds of inquiry ，a consensus was finally reached on 16 items on the original name ，quality standards and clinical application of Tibetan medicine “Dida”，and 2 items related to the characteristics and compatibilities of “Dida”had not reach common views. The consensuses of 16 items mainly cover the original name of “Dida”and the evolution of geographic information ，the rational selection of “Dida”medicinal materials ，the effectiveness and safety of clinical use of “Dida”.

ObjectiveTo explore the effect of Xiao Xianxiongtang （XXXT） on the transforming growth factor （TGF）-β₁-induced invasion， metastasis， and epithelial-mesenchymal transition （EMT） of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells （NFAT） was performed by CB-DOCK （http：//clab.labshare.cn/cb-dock/）. The invasion and metastasis model of MGC-803 cells was established with 10 μg·L^-1 TGF-β₁. MGC-803 cells were classified into blank group， model group， 0.1 g·L^-1 XXXT group， 0.2 g·L^-1 XXXT group， and 0.4 g·L^-1 XXXT group. For further clarifying the key role of Wnt5a/Ca²⁺/NFAT signaling pathway in the inhibition of XXXT on gastric cancer， MGC-803 cells were transfected with Wnt5a overexpression plasmid， and then the cells were classified into blank plasmid group， Wnt5a-OE group， blank plasmid + XXXT （0.4 g·L^-1） group， and Wnt5a-OE + XXXT （0.4 g·L^-1） group. Cell viability was determined by cell counting kit-8 （CCK-8） assay， cell invasion and migration ability by Transwell invasion assay and wound healing assay， expression of EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail） and Wnt5a/Ca²⁺/NFAT signaling pathway-related key proteins ［Wnt5a， calcineurin （CaN）， NFAT1， and p-NFAT1］ by Western blot， and changes in intracellular Ca²⁺ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca²⁺/NFAT signaling pathway. XXXT （0.1， 0.2， 0.4 g·L^-1） significantly promoted the loss of MGC-803 cell viability （P<0.05，P<0.01）. It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner （P<0.05， P<0.01）. Moreover， it promoted the expression of E-cadherin while suppressed the expression of N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）. Further experiments showed that XXXT could inhibit the expression of Wnt5a， CaN， NFAT1， and p-NFAT1， and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1， so as to reduce the cellular Ca²⁺ concentration （P<0.05， P<0.01）. XXXT can reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionXXXT can attenuate the invasion， metastasis， and EMT of MGC-803 cells via the Wnt5a/Ca²⁺/NFAT pathway， thereby weakening the tumor-promoting effect of TGF-β₁. In summary， XXXT may exert therapeutic effect on gastric cancer by regulating the invasion， metastasis， and EMT of gastric cancer 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.

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.
Humans ; Cleft Palate/genetics* ; Cleft Lip/genetics* ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.
Humans ; Practice Guidelines as Topic