Objective:Methamphetamine(METH)is an illicit psychoactive substance that can damage various organs,with the urinary system being one of its significant targets.This study aims to explore the role of microtubule affinity-regulating kinase 4(MARK4)in METH-induced acute kidney injury(AKI). Methods:A total of 10 healthy adult male C57BL/6 mice were randomly divided into a control group and a METH group,5 mice in each group.The METH group was administered METH(20 mg/kg,intraperitoneally,once daily for 3 consecutive days),while the control group received an equal volume of physiological saline.The mice were executed 24 hours after the final injection,and the success of the AKI model was detected by blood serum creatinine,blood urea nitrogen,and renal HE staining.Proteins differentially expressed between kidney tissues with METH-induced AKI and normal kidney tissues were screened by proteomics techniques and subjected to gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and bioinformatics analysis.The accuracy of proteomic data was validated using Western blotting,and the expression levels of MARK4 and cleaved caspase-3 in mouse kidneys were measured.We further explored the role of MARK4 in METH-induced AKI.Firstly,a METH toxicity model was established in BUMPT cells to screen the appropriate concentration and time of METH treatment;the viability of BUMPT cells after METH treatment and the expression of cleaved caspase-3 were detected by interfering with MARK4 expression through inhibitors. Results:The proteomic analysis of kidney tissues from METH and control groups screened for a total of 17 differentially expressed proteins,of which 11 were up-regulated and 6 were down-regulated(all P＜0.05).The expression levels of MARK4 and cleaved caspase-3 were elevated in the kidneys of METH-treated mice(both P＜0.05).The activity of BUMPT cells gradually decreased with increasing METH treatment concentration(all P＜0.05),where the viability of BUMPT cells decreased to about 60％after METH treatment at 4 mmol/L.Compared with the control group,expression levels of MARK4 and cleaved caspase-3 were increased with higher METH concentrations and longer exposure times in a concentration-and time-dependent manner(all P＜0.05).Inhibition of MARK4 expression improved METH-induced decrease in BUMPT cell activity,down-regulated the expression of cleaved caspase-3,and decreased the apoptosis of BUMPT cells induced by METH. Conclusion:MARK4 is highly expressed in a mouse model of METH-induced AKI,and MARK4 mediates METH-induced AKI by regulating cell apoptosis.

Objective:To evaluate the in vitro cross-neutralization of serum antibodies in human and mice immunized with inactivated SARS-CoV-2 vaccine against Delta and Beta variants. Methods:Human serum samples after a second and a third dose of inactivated SARS-CoV-2 vaccine and mouse serum samples after a two-dose vaccination were collected. The neutralizing antibodies in the samples against SARS-CoV-2 strains of prototype, Delta and Beta variants were detected using micro-neutralization assay in biosafety level Ⅲ laboratory. The seroconversion rates and geometric mean titers (GMTs) of antibodies were calculated.Results:The seroconversion rates of antibodies in human serum samples against different SARS-CoV-2 strains were all above 95%. After two-dose vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 109, 41 and 15, respectively. The GMTs decreased by 2.7 folds and 7.3 folds for the Delta and Beta variants as compared with the prototype strain. After the booster vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 446, 190 and 86, respectively. The GMTs of neutralizing antibodies against Delta and Beta variants decreased by 2.3 folds and 5.2 folds as compared with that against the prototype strain. The seroconversion rates of antibodies against different SARS-CoV-2 strains in mouse serum samples were all 100%. The GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 2 037, 862 and 408, respectively. The GMTs decreased by 2.4 folds and 5.0 folds for the Delta and Beta variants.Conclusions:Inactivated SARS-CoV-2 vaccine could induce a certain level of neutralizing antibodies against Delta and Beta variants in both human and mouse models. Moreover, a third dose of vaccine induced higher levels of neutralizing antibodies against Delta and Beta variants in human. This study provided valuable data for the clinical application and protective evaluation of the inactivated SARS-CoV-2 vaccine.

【Objective】 To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. 【Methods】 The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. 【Results】 From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. 【Conclusion】 The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.

Objective: Abstract: Objective: cancer cells and its effects on the proliferation and migration of gastric cancer cells. Methods: The expression level of LINC00473 in gastric cancer cells was verified by qRT-PCR system. LINC00473 siRNA segment and overexpression vector were separately transfected into gastric cancer cells by the method of lipofection. The proliferation and migration abilities of gastric cancer cells with LINC00473 knockdown or overexpression in vitro were evaluated by cell counting kit-8 (CCK8) assay, colony formation assay and Transwell migration assay. The expression levels of proteins involved in epithelial-mesenchymal transition (EMT) were examined by western blot analysis. Results: The expression levels of LINC00473 were decreased in gastric cancer cells compared with that in human gastric epithelial cell strain GES-1 (P＜0.05). LINC00473 knockdown cells showed significant increased ability for cell growth (F=163.10, P＜0.01) and colony formation (t=3.29, P＜0.05) compared with the knockdown cells in scramble control. The results of Transwell migration assay showed that LINC00473-knockdown enhanced the migratory abilities of gastric cancer cells (t=4.68, P＜0.05). The knockdown of LINC00473 downregulated E-cadherin expression (t=4.08, P＜0.05) and upregulated N-cadherin (t=5.06, P＜0.01), Snail (t=7.69, P＜0.01) and Vimentin (t=3.82, P＜0.05) expression. Compared with the control group, LINC00473 overexpression cells showed significantly decreased cell growth (F=186.00, P＜0.01) and colony formation ability (t=3.22, P＜0.05). The results of Transwell migration assay showed that LINC00473-overexpression reduced the migratory ability of gastric cancer cells (t=5.52, P＜0.05). The overexpression of LINC00473 enhanced E-cadherin expression (t=2.90, P＜0.05) and reduced the expressions of N-cadherin (t=7.44, P＜0.01), Snail (t=2.78, P＜0.05) and Vimentin (t=4.64, P＜0.01). Conclusion The knockdown of LINC00473 may promote gastric cancer cell proliferation and migration in vitro by regulating EMT.

Background and objective Lung cancer is one of the most serious disease and the incidence of non-small cell lung cancer (NSCLC) is the highest in lung cancer. The main reason for the failure of chemotherapy is the tolerance to cisplatin. Transcriptional regulator SOX4 plays an important role in the occurrence and development of many tumors, and regulates Wnt signaling pathway by regulating the expression of β-catenin. We aimed to investigate the role of SOX4 on cisplat-in-resistance in NSCLC cell A549 cell. Methods The cisplatin-resistance lung cancer cell line A549/DDP was constructed by induction method in vitro, and cisplatin-resistance detected by CCK8 assay. Growth curves of A549 and A549/DDP was cal-culated. The expression level of SOX4 in A549 and A549/DDP cells were detected by Western blot. A549/DDP were knock-down of SOX4 by siRNA transfection, and the cisplatin-resistance of detected by CCK-8 assay, the expression level of β-catenin and Survivin were detected by real-time PCR and Western blot. Results The cisplatin-resistance cell line A549/DDP was constructed successfully, and its cisplatin-resistance is 13.7 times higher than in A549. There was no significance difference between A549 and A549/DDP in cell proliferation. The expression level of SOX4 is higher in A549/DDP than in A549. The cisplatin-resistance significantly decreased in A549/DDP cells after knockdown of SOX4 by siRNA transfection. The expres-sion level of β-catenin and Survivin significantly decreased in A549/DDP cells after knockdown of SOX4. Conclusion SOX4 can strengthen cisplatin-resistance of non-small cell lung cancer cell A549.

Background and objective It has been proven that chlorogenic acids can produce anticancer effects by regulating cell cycle, inducing apoptosis, inhibiting cell growth, Notch signaling pathways are closely related to many human tumors. The aim of this study is to study the mechanism of chlorogenic acid on apoptosis of non-small lung cancer through Notch1 pathway in animal level, and hope to provide theory basis on clinical treatment and research aimed at targeting Notch1 signaling in non-small cell carcinoma (NSCLC).Methods MTT assay was used to evaluate the A549 cell proliferation under the treatment of chlorogenic acid. The effect of chlorogenic acid on apop-totic and cell cycle were detected by flow cytometry. The animal model of A549 cell transplanted in nude was estab-lished, tumer size and weight were detected. The mRNA level of Notch1 signal pathway related facter were detected by RT-PCR; the expression of Notch1 signal pathway related facter in tumor tissue was detected by western blot.Results Chlorogenic acid inhibited the A549 cell proliferation. incresed cell apoptotic and cell percentagein G2/M (P<0.05), and in a dose-dependent manner. In animal model, tumer size and weight were lower than control group, the difference was statistically significant (P<0.05). The relative expression of mRNA of Notch1, VEGF, Delta4, HES1 and HEY1 were decreaced (P<0.05) in tumor tissue which treated with chlorogenic. The expression of Notch1 were decreaced, PTEN, p-PTEN, p-AKT were increced significantly in tumor tissue which treated with chlorogenic (P<0.05).Con-clusion Chlorogenic acid can regulate theapoptosis of non-small lung cancer through Notch pathway in animal level,which may be associated with the down-regulating the expression of VEGF and Delta4. Notch pathway may cross talk with PI3K/AKT pathway through PTEN in NSCLC.

Objective To explore the effect of reconstructing unilateral cleft lip by changing the arc-shaped incision, combined with the 3D reconstruction of upper lip muscles.Methods Twenty unilateral cleft lip patients were treated by using a new surgical operation, the 3D reconstruction of upper lip muscle, to restore normal anatomy and stress of the mucous membrane, muscle and skin.Operation scar was designed for straight line, located on the philtral ridges of the contour line;phitrum and philtral ridges were rebuilt, and postoperative scar reduced.Results A lot of 20 patients had no local infection, hemorrhage, complex crack, and were stage I incision healing.Followed up for 1-8 months postoperatively, the patient's lip bow line continuity was good, with symmetrical shape and good phitrum and philtral ridges;scar was hidden on the philtral ridges of the contour line, and no obvious upper lip scar contracture found through the follow-up period.Conclusions This improved method is simple in the incision design, and less scar hidden on the philtral ridges of the contour line after operation, which can maximize the recovery of the appearance of nose and upper lip with satisfactory effect.It is a feasible improvement method of repairing unilateral cleft lip.

Objective To improve the quality of aiye processed products, an eucalyptol content in commercially available aiye two processed products of chao aiye and aiye tan was investigated.Methods A capillary gas chromatography was used.The sample was prepared with n-hexane by reflux condensation.Chromatographic conditions: The separation was carried on an Ailgent DB-1 capillary column(30 mm ×0.320 mm ×0.25 μm). Inlet temperature was 200℃ and FID temperature was 250℃.The programmed column temperature was set as follows:maintained at 100℃ for 6 min and raised to 160℃ at the rate of 20℃/min followed by holding for 3min.The splitting-ratio was 5.0:1.The carried gas was nitrogen, flow rate was 1.0 mL/min.Injection volume was 1μL.Results In the given chromatographic conditions, the eucalyptol chromatographic separation had good, and the separation degree was greater than 1.5 between eucalyptol and other impurity peak.The linear range of eucalyptol was 11.4-114.0 mg/mL(r=0.999 5). Methods repeatability and recovery were good.The minimum limit of quantification was 0.5μg/mL.The results of determination of eucalyptol show that the eucalyptol content in the commercially available 11 batch of chao aiye was between 5.6-78.2 μg /g, and 12 batch of aiye tan had no eucalyptol. Conclusion The processing technology of current commercially available aiye processed products of chao aiye and aiye tan need to be improved, and the quality standard need to be improved.

OBJECTIVETo explore the expression pattern of Mus81 gene in Chinese Han patients with colorectal cancer and analyze its correlation with the clinicopathological parameters and the tumor markers.

METHODSMus81 expression was detected using nested quantitative real-time PCR in the colorectal cancer tissues and corresponding adjacent normal tissues from 43 Chinese Han patients. The correlations of Mus81 expression profile with the clinicopathological parameters and common tumor markers were evaluated.

RESULTSMus81 expression level was significantly lower in the colorectal cancer tissues than in the corresponding adjacent normal tissues (114.6 ± 68.0 vs 202.5 ± 109.0, P<0.001). Of the 43 patients, 32 (74.4%) showed down-regulated Mus81 expression, which correlated significantly with distant metastasis (P=0.043), high TNM stage (P=0.022) and high P53 protein expression (P=0.011) of the tumor.

CONCLUSIONDown-regulation of Mus81 in colorectal cancer is correlated with tumor metastasis and progression, suggesting the value of Mus81 as a potential marker for colorectal cancer in Chinese Han patients.

Biomarkers, Tumor ; Colorectal Neoplasms ; diagnosis ; genetics ; DNA-Binding Proteins ; genetics ; Disease Progression ; Down-Regulation ; Endonucleases ; genetics ; Humans ; Prognosis ; Real-Time Polymerase Chain Reaction

Objective To explore the expression pattern of Mus81 gene in Chinese Han patients with colorectal cancer and analyze its correlation with the clinicopathological parameters and the tumor markers. Methods Mus81 expression was detected using nested quantitative real-time PCR in the colorectal cancer tissues and corresponding adjacent normal tissues from 43 Chinese Han patients. The correlations of Mus81 expression profile with the clinicopathological parameters and common tumor markers were evaluated. Results Mus81 expression level was significantly lower in the colorectal cancer tissues than in the corresponding adjacent normal tissues (114.6 ± 68.0 vs 202.5 ± 109.0, P<0.001). Of the 43 patients, 32 (74.4%) showed down-regulated Mus81 expression, which correlated significantly with distant metastasis (P=0.043), high TNM stage (P=0.022) and high P53 protein expression (P=0.011) of the tumor. Conclusion Down-regulation of Mus81 in colorectal cancer is correlated with tumor metastasis and progression, suggesting the value of Mus81 as a potential marker for colorectal cancer in Chinese Han pateints.