Metastasis is the main risk factor for poor prognosis of laryngeal squamous cell carcinoma (LSCC) .Chemokines are closely related to metastasis in the tumor microenvironment.CXCL8 is a cyto-kine-like secreted protein that plays key roles in the malignant development of a variety of tumors,but has not been elucidated in LSCC.In this paper,we elucidated the role of CXCL8 in LSCC cells and found miRNAs that targeted CXCL8,which may become new targets for the diagnosis and treatment of LSCC.Firstly,the GEPIA showed that CXCL8 was highly expressed in head and neck cancer (P<0.05).The real-time fluorescence quantification (qRT-PCR) found that CXCL8 was highly expressed in LSCC cells.The enzyme-linked immunoassay also found that CXCL8 was highly secreted in the superna-tant of LSCC cells (P<0.001) .Then,the CCK8 assay confirmed that knockdown of CXCL8 significant-ly inhibited the proliferation of FD-LSC-1 and AMC-HN8 cells (the average inhibition rate was 34.0％and 19.5％,respectively);The EdU assay also confirmed that knockdown of CXCL8 significantly inhibi-ted the proliferation of LSCC cells (P<0.05) .The transwell assay confirmed that knockdown of CXCL8 also significantly inhibited the migration and invasion of FD-LSC-1 cell (average inhibition rate was 40.0％,38.5％,respectively);Knockdown of CXCL8 also significantly inhibited the migration and inva-sion of AMC-HN8 cell (average inhibition rate was 37.5％,53.5％,respectively ) .The analysis of bioinformatics predicted that CXCL8 may be a target of miR-513b-5p.The dual luciferase reporter assay confirmed that miR-513b-5p could bind to the CXCL8-3'UTR.QRT-PCR assay also confirmed that over-expression of miR-513b-5p could decrease the 60％ of the CXCL8 expression (P<0.01) .Cell function rescue assays found that overexpressed of CXCL8 could effectively reversed proliferation,migration and invasion of LSCC cells weakened by miR-513b-5p (P<0.05) .In summary,miR-513b-5p inhibited the proliferation,migration and invasion of LSCC cells by targeting CXCL8.

Objective:To examine the application of a novel pedagogical approach multidimensional supportive psychological intervention(MSPI)in the clinical practice teaching of andrological nursing care.Methods:Using the Hamilton Depression Scale(HAMD),we assessed the psychology of 100 nursing interns about to enter clinical practice in the Department of Andrology from De-cember 2021 to December 2022.We equally randomized the subjects into an experimental and a control group,the former receiving MSPI and the latter trained on the conventional teaching model without any psychological support intervention.Results:Compared with the baseline,the HAMD scores were significantly decreased in the experimental group after intervention(12.4±2.1 vs 8.9±2.4,P＜0.01),but increased in the controls(13.1±1.8 vs 14.7±1.9,P＜0.01);the skill scores dramatically increased in the experimental group(82.6±4.7 vs 91.2±2.4,P＜0.01),but decreased in the control group after intervention(81.0±3.5 vs 80.4±2.7,P=0.28).Conclusion:MSPI can significantly enhance the learning enthusiasm of nursing students in a short period,re-duce their psychological stress and improve teaching outcomes.This approach,combining psychology with teaching,can also strength-en the mental resilience of nursing students and better confront them with future professional challenges.

Hypertrophic cardiomyopathy is an autosomal dominant disease,which can be divided into obstructive type and non-obstructive type.Hypertrophic obstructive cardiomyopathy is a common cause of sudden death in young people and athletes,and is also an important cause of sudden cardiac death.Currently,the treatment of hyper-trophic obstructive cardiomyopathy mainly includes drug therapy,surgical septal myectomy,interventional therapy and cardiac resynchronization therapy.This paper is the review of research progress of the comprehensive treatment of hypertrophic obstructive cardiomyopathy,in order to provide theoretical basis and reference for the selection of the treatment scheme of hypertrophic obstructive cardiomyopathy.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Squalene epoxidase (SQLE) is a potential target for the treatment of liver cancer. Bioinformatics analysis indicated that the high expression of SQLE was closely related to the clinical stage and poor prognosis of patients with liver cancer. However, the existing inhibitors against SQLE 195 tyrosine residue (Y195) cannot be used clinically due to severe side effects. In this study, 35 small-molecule compounds targeting SQLE 335 tyrosine residue (Y335) were selected by computer virtual screening. Combined with MTT assay, 3 candidate compounds (19^#, 31^# and 35^#) with significant inhibitory effects on the proliferation of Huh7 cell line were obtained. Further studies showed that these 3 compounds could inhibit the migration of Huh7 cells, reduce the contents of total and free cholesterol, up-regulate the expression of tumor suppressor gene PTEN, and down-regulate the expression of PI3K and AKT proteins. The results showed that the novel inhibitors 19^#, 31^# and 35^# targeting SQLE Y335 could reduce cholesterol content, inhibit the proliferation and migration of Huh7, thus playing an anti-liver cancer role.

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.
Animals ; Humans ; Bufonidae ; Powders ; Bufanolides/pharmacology* ; Quality Control ; Chromatography, High Pressure Liquid ; Pain/drug therapy*

ObjectiveTo analyze the correlation between complete blood count （CBC）， glycosylated hemoglobin（GHbA1c）and thyroid function in late pregnancy on Tibetan Plateau. MethodsA retrospective analysis was performed on 374 patients of single pregnancies who had delivered in the department of Obstetrics and Gynecology， Chaya People's Hospital， Changdu City， Tibet Autonomous Region， between January 1， 2021 and December 31， 2021. All subjects completed CBC， GHbA1c and total triiodothyronine（TT3）， total thyroxine（TT4）， thyroid stimulating hormone（TSH）before delivery. According to the altitude of long-term residence， they were divided into three groups： the altitude of group A is <3500 m； the altitude of group B is 3 500~4 000 m； and the altitude of group C is ＞4 000 m. The anemia of Tibetan pregnant women in late pregnancy before and after adjustment， the levels of CBC， GHbA1c and thyroid function in different altitudes， and their correlations were analyzed. Results① The mean actual hemoglobin（HB）was 120.0（108.0~130.0）g/L， and the prevalence of anemia was 27.8%（104/374）. After adjustment， the mean HB was 93.0（80.0~104.0）g/L， and the prevalence of anemia was 84.3 %（315/374）； ② Actual HB levels increased with the rise of altitude， but the difference was not statistically significant（P>0.05）， and there was no difference among the three groups in the prevalence of anemia. After adjustment， HB levels showed a downward trends， while the prevalence of anemia increased with the rise altitude， and the difference was statistically significant（P＜0.001）. ③ Red blood cell count（RBC）and mean erythrocyte hemoglobin concentration（MCHC）increased， while TSH decreased with the rise of altitude， and the difference was statistically significant（P＜0.05）. ④ The actual HB and MCHC were positively correlated with TT4， GHbA1c was negatively correlated with TT4， and positively correlated with Platelet count （PLT）； spearman correlation analysis showed statistical significance（P＜0.05）. ConclusionsThe actual HB of Tibetan Plateau pregnant women in late pregnancy does not increase significantly with the rise of altitude. The prevalence of anemia increases significantly after adjustment according to the altitude. TSH decreases with the rise of altitude， and the altitude may have an effect on thyroid function in late pregnancy. Actual anemia in late pregnancy is associated with low T4， and low T4 and high PLT might be associated with increased GHbA1c. Actual HB， PLT and T4 in late pregnancy are expected to be predictors of thyroid disease and GDM.

This study aims to acetylate Rehmannia glutinosa polysaccharides by acetic anhydride method, optimize process parameters and evaluate their antioxidant activity. With the degree of substitution(D_s) as a criterion, the effects of reaction time, acetic anhydride-to-polysaccharides ratio and temperature were investigated. Process parameters were optimized by single-factor experiment and response surface methodology. The infrared spectroscopy(IR) and scanning electron microscopy(SEM) proved the successful acetylation and were employed to preliminarily analyze the structural characteristics of acetylated derivatives. The results showed that the D_s was 0.327 under the optimal technological conditions, including m(acetic anhydride):m(R. glutinosa polysaccharides)=2.70, reaction time 3.0 h and temperature 48 ℃. Further, the antioxidant properties of acetylated derivatives were investigated in vitro and acetylation was found effective to improve the antioxidant activity of R. glutinosa polysaccharides. This study provides a reference for the further development and application of R. glutinosa polysaccharides.
Acetylation ; Antioxidants/pharmacology* ; Polysaccharides/pharmacology* ; Rehmannia/chemistry*

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.