Research Progress of Granulocytic Myeloid-derived Suppressor Cells in Non-small Cell Lung Cancer / 中国肺癌杂志

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.
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2023 Report on satisfaction with graduate education of recent medical graduates in China / 中华医学教育探索杂志

Objective:To investigate the current situation of satisfaction with graduate education among recent medical graduates in China, and analyze the differences between different populations, and to propose countermeasures and suggestions.Methods:From June to July 2023, a self-made questionnaire was used to survey 16 903 medical graduates who had recently earned a post-graduate degree from 78 institutions about their satisfaction with curriculum sessions, practical sessions, research training, tutoring, and institutional management. The degrees of satisfaction with education among different populations were compared through the t test and analysis of variance with the use of SPSS 26.0. Results:The scores of satisfaction of the graduates with tutoring, curriculum sessions, practical sessions, institutional management, and research training were 4.44, 4.03, 4.02, 3.90, and 3.82, respectively. Satisfaction scores for individual dimensions were significantly higher for males, doctors, non-transfers, comprehensive universities, non-agricultural household registration, moderate-to-high annual household income per capita, parents with high educational levels, and parents with mid- or senior-level occupations ( P<0.05). Conclusions:There is room for improvement in students' satisfaction with medical graduate education. To improve the quality of medical graduate education, attention should be paid to key populations, education policies, school management, and tutoring to provide appropriate education for different students.

HIV antiretroviral therapy among blood donors: the impact on blood safety / 中国输血杂志

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Analysis of Cumulative Live Birth Rate of Selective Single Embryo Transfer by Time-lapse Monitoring System and Conventional Morphological Assessment in IVF/ICSI-ET / 实用妇产科杂志

Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P＞0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P＞0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21％accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.

Cartilage protective effect of swimming exercise in aged mice with knee osteoarthritis / 中国组织工程研究

BACKGROUND:Swimming is an important non-pharmacological treatment for knee osteoarthritis,which can effectively alleviate the disease.However,the effect and mechanism of swimming on senile knee osteoarthritis are still unclear. OBJECTIVE:To investigate the effect of swimming exercise on the articular cartilage of aged mice with knee osteoarthritis. METHODS:Six 3-month-old male C57BL/6 mice were selected as the young group,and twelve 18-month-old male C57BL/6 mice were randomized into the aged group and the swimming group,with six mice in each group.Mice in the swimming group received adaptive swimming for 1 week and formal swimming for 8 weeks.After the intervention,stride length analysis and sampling were performed in each group.The total number of leukocytes and lymphocytes in peripheral blood was detected by blood routine examinations.The morphology of the articular cartilage was observed by hematoxylin-eosin and safranin O-fast green staining.Chondrocyte counts and the modified Mankin's score were used to evaluate the degree of articular cartilage damage.The protein and mRNA expressions of type Ⅱ collagen,aggrecan and matrix metalloproteinase 13 in articular cartilage were detected by immunohistochemical staining and RT-qPCR. RESULTS AND CONCLUSION:Compared with the young group,the mice in the aged group showed significantly decreased stride length(P＜0.05),significantly increased numbers of peripheral leukocytes and lymphocytes(P＜0.05),significantly decreased count of chondrocytes(P＜0.05),significantly increased modified Mankin's score(P＜0.05),significantly decreased protein and mRNA expression of type Ⅱ collagen and aggreca(P＜0.05),and significantly increased matrix metalloproteinase 13 expression(P＜0.05).Moreover,hematoxylin-eosin and safranin O-fast green staining showed the uneven surface of the articular cartilage,abnormal chondrocytes,and proteoglycan loss in the aged group.Compared with the aged group,swimming exercise significantly improved the stride length of mice(P＜0.05),decreased the count of peripheral blood lymphocytes(P＜0.05),increased the count of chondrocytes(P＜0.05),decreased the modified Mankin's score(P＜0.05),increased the protein and mRNA expression of type Ⅱ collagen and aggrecan(P＜0.05),and decreased the expression of matrix metalloproteinase 13(P＜0.05).Hematoxylin-eosin and safranin O-fast green staining showed that the articular surface of mice in the swimming group was smooth,chondrocytes were normal,and proteoglycan loss was less.All these findings indicate that swimming exercise can reduce the number of inflammatory cells in the blood of aged mice,improve articular chondrocytes,matrix composition and cartilage tissue morphology;thus,it has a protective effect on the cartilage of aged mice with knee osteoarthritis.

Research Progress on the Combination Therapy of EGFR-TKIs and Metformin in Acquired Resistance to EGFR-TKIs in Non-small Cell Lung Cancer / 中国肺癌杂志

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR are effective in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. With the application and expansion of individualized and combined therapy, more and more studies have shown that combined administration of Metformin effectively solves the problem of acquired drug resistance to EGFR-TKIs in clinical treatment and prolongs the survival of patients with NSCLC. EGFR-TKIs combined with Metformin is expected to be the treatment method of choice for NSCLC patients with EGFR-TKIs resistance. This paper intends to summarize the research progress of EGFR-TKIs combined with Metformin in the treatment of EGFR-TKIs acquired resistance in NSCLC, in order to provide a new idea for the treatment of NSCLC patients with acquired resistance to EGFR-TKIs.
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Relationship between parents attitudes towards sexual education and their proactive adolescent sexual education for primary and secondary students in Baoshan City of Yunnan Province / 中国学校卫生

Objective@#To understand parents attitudes towards adolescent sexual education in Baoshan City of Yunnan Province, and to explore the correlation between attitudes and their proactive behavior in adolescent sexual education, so as to provide reference for improving parents initiative in adolescent sexual health education.@*Methods@#From November to December 2022, a stratified random cluster sampling method was used to select 7 389 parents of students from 35 primary, middle, and high schools in Baoshan City of Yunnan Province for a questionnaire survey on adolescent sexual health education in parents schools. Chi-square tests were conducted to compare the attitudes of parents towards sexual health education among different groups and their proactive behavior in providing sexual health education to their children. A multivariate Logistic regression model was used to analyze the correlation between parents attitudes towards sexual education and proactive sexual health education.@*Results@#Totally 43.17% ( 3 190 ) of parents had a more open attitude towards sex education for their children, with parents of girls, parents of elementary school students, mothers, <30 years old, junior high school education, workers, service personnel, married, harmonious relationships with their children and democratic parents had a higher rate of actively providing sex education for their children ( χ 2=4.65, 401.92, 23.53 , 197.50, 38.18, 13.65, 6.54, 8.07, 32.17, 96.58, P <0.05). Parents with a more conservative attitude towards sex education and parents of boys were negatively correlated with parents actively providing adolescent sexual health education to their children ( OR =0.86, 0.38, P <0.05). Parents who were <30, 30-<40, 40-50 years old, individuals/businesses, married, divorced, had a good and decent relationship with their children were positively correlated with their parents proactive adolescent sexual health education for their children ( OR =1.50, 1.90, 1.37, 1.22, 1.60, 1.32, 1.94, 1.53, P <0.05).@*Conclusion@#A more open attitude towards adolescent sexual health education can serve as a predictive factor for proactive adolescent sexual health education. In order to increase the rate of family sexual health education, it is recommended to enhance parents awareness of their responsibility for their children s sexual health education, promote harmonious parent-child relationships between parents and children, and communicate with their children with an open attitude.

Expression of BmSPI38 tandem multimers in Escherichia coli and its antifungal activity / 生物工程学报

The aim of this study was to prepare tandem multimeric proteins of BmSPI38, a silkworm protease inhibitor, with better structural homogeneity, higher activity and stronger antifungal ability by protein engineering. The tandem multimeric proteins of BmSPI38 were prepared by prokaryotic expression technology. The effects of tandem multimerization on the structural homogeneity, inhibitory activity and antifungal ability of BmSPI38 were explored by in-gel activity staining of protease inhibitor, protease inhibition assays and fungal growth inhibition experiments. Activity staining showed that the tandem expression based on the peptide flexible linker greatly improved the structural homogeneity of BmSPI38 protein. Protease inhibition experiments showed that the tandem trimerization and tetramerization based on the linker improved the inhibitory ability of BmSPI38 to microbial proteases. Conidial germination assays showed that His6-SPI38L-tetramer had stronger inhibition on conidial germination of Beauveria bassiana than that of His6-SPI38-monomer. Fungal growth inhibition assay showed that the inhibitory ability of BmSPI38 against Saccharomyces cerevisiae and Candida albicans could be enhanced by tandem multimerization. The present study successfully achieved the heterologous active expression of the silkworm protease inhibitor BmSPI38 in Escherichia coli, and confirmed that the structural homogeneity and antifungal ability of BmSPI38 could be enhanced by tandem multimerization. This study provides important theoretical basis and new strategies for cultivating antifungal transgenic silkworm. Moreover, it may promote the exogenous production of BmSPI38 and its application in the medical field.

Application of spherical lens with 0.05 D intervals in optometry for small incision lenticule extraction in myopic eyes / 中华实验眼科杂志

Objective:To investigate the clinical value of spherical lens with 0.05 D intervals in optometry for small incision lenticule extraction (SMILE) in myopic eyes.Methods:A randomized controlled clinical study was conducted.Sixty patients (120 eyes) with low to moderate myopia and myopic astigmatism who underwent SMILE in the 989th Hospital of the PLA from June 2021 to February 2022 were enrolled.The patients were randomly divided into 0.05 D interval group (optometry with spherical lens at 0.05 D interval) and 0.25 D interval group (optometry with spherical lens at 0.25 D interval), with 30 cases (60 eyes) in each group.There was no significant difference in matched age, sphericity, cylindricity, and best corrected visual acuity (BCVA) (all at P>0.05). The preoperative monocular red-green balance, 1- and 3-month postoperative monocular red-green balance, uncorrected visual acuity and spherical equivalent of both groups were compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the 989th Hospital of the PLA (No.WZLL-2021-034). Written informed consent was obtained from each subject before any medical examination. Results:The preoperative red-green balance rate in 0.05 D interval group was 95.00%(57/60), which was higher than 35.00%(21/60) in 0.25 D interval group, showing a statistically significant difference ( Wald χ2=17.642, P<0.001). The 1- and 3-month postoperative red-green balance rates in 0.05 D interval group were 63.33%(38/60) and 56.67%(34/60), which were higher than 23.33%(14/60) and 21.67%(13/60) in 0.25 D interval group respectively, showing statistically significant differences ( Wald χ2=9.137, P=0.003; Wald χ2=7.483, P=0.006). The 1- and 3-month postoperative visual acuity in 0.05 D interval group were -0.1(-0.1, -0.1) and -0.1(-0.1, -0.1), which were higher than 0.0(-0.1, 0.0) and -0.1(-0.1, 0.0) in 0.25 D interval group respectively, showing statistically significant differences ( Wald χ2=11.624, P=0.001; Wald χ2=12.841, P<0.001). The 1- and 3-month postoperative spherical equivalent were -0.07(-0.25, 0.13)D and -0.13(-0.25, 0.13)D in 0.05 D interval group, which were higher than -0.13(-0.38, 0.25)D and -0.13(-0.38, 0.25)D in 0.25 D interval group respectively, showing no statistically significant difference between the two groups ( Wald χ2=0.029, P=0.866; Wald χ2=0.189, P=0.664). Conclusions:Compared with spherical lens at 0.25 D interval, 0.05 D interval can improve the accuracy of preoperative and postoperative red-green balance rate and postoperative visual acuity in patients with low to moderate myopia who undergo SMILE.

Ethyl Acetate Extract of Qigesan Intervenes in Migration and Invasion of Esophageal Cancer Cells via Inhibiting TGF-β1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Qigesan （QGS） in intervening in the migration and invasion of esophageal carcinoma TE-1 cells. MethodMicroarray technology was used to screen differentially expressed genes （DEGs） in the normal group and the QGS group， and the ontological functions and signaling pathways of DEGs were analyzed. The thiazolyl tetrazolium （MTT） assay was used to detect the effect of QGS on the viability of TE-1 cells. In the subsequent experiments for verification， a blank group， a transforming growth factor-β1 （TGF-β1） group， a TGF-β1 + QGS group， and a TGF-β1 + SB431542 group were set up. The cell morphology in each experimental group was observed by microscopy. The migration and invasion abilities of cells were detected by wound healing assay， and the mRNA expression levels of E-Cadherin， vimentin， Smad2， and Smad7 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of E-Cadherin， vimentin， p-Smad2/3， Smad2/3， and Smad7 was detected by Western blot. ResultThere were 1 487 DEGs between the QGS group and the blank group， including 1 080 down-regulated ones （accounting for 72.63%） and 407 up-regulated ones. The down-regulated genes were mainly involved in biological processes such as cytoskeletal protein binding， ATP binding， adenylate nucleotide binding， and adenylate ribonucleotide binding， and the involved Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways included TGF-β signaling pathway， cell cycle， extracellular matrix-receptor interaction protein， tumor pathways， and oocyte meiosis. The up-regulated genes were mainly involved in RNA binding， DNA binding， transcriptional regulator activity， transcriptional activator activity， and nucleotide binding， and the KEGG pathways involved mainly included mitogen-activated protein kinase （MAPK） signaling pathway， bladder cancer， renal cell carcinoma， cancer pathways， and p53 signaling pathway. Compared with the blank group， the inhibition rate of cell viability of TE-1 cells increased after QGS （20， 30， 40， 60， 80 mg·L-1） intervention for 12， 24， 36， 48， 60 h （P<0.05）， and the inhibition rate was time- and dose-dependent. Compared with the blank group， the TGF-β1 group showed lengthened cells with fibroblast phenotype. Compared with the TGF-β1 group， the TGF-β1 + QGS group showed shortened cells with normal morphology and epithelial phenotype. The cell morphology in the TGF-β1 + SB431542 group was similar to that of the TGF-β1 + QGS group. Compared with the blank group， the TGF-β1 group showed potentiated ability of cell migration and invasion （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group showed inhibited and weakened migration and invasion abilities of cells （P<0.05）. However， there was no significant difference in migration and invasion abilities between the TGF-β1 + QGS group and the TGF-β1 + SB431542 group. The mRNA expression levels of vimentin and Smad2 in the TGF-β1 group were higher （P<0.05）， and the mRNA expression levels of E-Cadherin and Smad7 were lower （P<0.05） than those in the blank group. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1+ SB431542 group exhibited decreased expression levels of vimentin and Smad2 mRNA （P<0.05）， and elevated expression levels of E-Cadherin and Smad7 mRNA （P<0.05）. Compared with the blank group， the TGF-β1 group showed up-regulated protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and reduced protein expression levels of E-Cadherin and Smad7 （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group displayed decreased protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and increased protein expression levels of E-Cadherin and Smad7 （P<0.05）. ConclusionThe ethyl acetate extract of QGS inhibits the epithelial-mesenchymal transition （EMT） of TE-1 cells through the TGF-β1 pathway to reduce the migration and invasion of TE-1 cells.

Public health emergency response capacity in primary and secondary schools / 中国学校卫生

Objective@#To understand the public health emergency response capacity in primary and secondary schools, and to explore the problems and challenges in the prevention and control of public health emergency in primary and secondary schools for specific strategies.@*Methods@#By using the stratified group sampling method, a questionnaire survey on general situation, knowledge, attitude and training, as well as public health emergencies response capacity among 2 988 teachers or leaders responsible for school emergency response in primary and secondary schools from Beijing, Chongqing and Yunnan.@*Results@#Participants varied on their positions, titles, educational background and knowledge accuracy. Higher knowledge accuracy was associated with higher educational background ( χ 2=50.73-203.36, P < 0.05 ). The implementation of regular public health emergency related programs was poorly conducted in high schools (50.0%). Urban schools (42.0%) had higher proportion of qualified health care professionals than rural schools (18.2%), and private schools (48.5%) was higher than public schools (24.7%). The primary challenges included the shortage of guidance from professionals and the lack of related testing equipment (84.91%, 74.03%).@*Conclusion@#Although the ability of emergency handling of public health emergencies in schools in the three regions is advancing with the times, there are still many deficiencies, some omissions in the mastery of knowledge. It is suggested to inerease pre service and special training of school health work CDC should strengthen technical guidance and work supervision of infectious disease management in schools.

Enhancing the sensitivity of HIV DNA detection: a magnetic bead-based method / 中国输血杂志

【Objective】 To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). 【Methods】 Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4+ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. 【Results】 CD4+ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4+ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/106 CD4+ T cell′s respectively. 【Conclusion】 The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

Molecular epidemiological characterization of hypervirulent carbapenem-resistant Klebsiella pneumoniae in a hospital in Henan Province from 2020 to 2022 / 中华预防医学杂志

Objective: The study investigated the clinical distribution, antimicrobial resistance and epidemiologic characteristics of hypervirulent Carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) in a hospital in Henan Province to provide a scientific basis for antibiotic use and nosocomial infection prevention and control. Methods: A retrospective analysis of the clinical data from the cases was carried out in this study. Clinical data of patients infected with the CRKP strain isolated from the clinical microbiology laboratory of Henan Provincial Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were retrospectively analyzed. A string test, virulence gene screening, serum killing, and a G. mellonella infection model were used to screen hv-CRKP isolates. The clinical characteristics of hv-CRKP and the drug resistance rate of hv-CRKP to twenty-five antibiotics were analyzed using WHONET 5.6. Carbapenemase phenotypic characterization of the hv-CRKP was performed by colloidal gold immunochromatographic assay, and Carbapenemase genotyping, multi-locus sequence typing (MLST) and capsular serotyping of hv-CRKP isolates were performed by PCR and Sanger sequencing. Results: A total of non-duplicate 264 CRKP clinical isolates were detected in the hospital from 2020 to 2022, and 23 hv-CRKP isolates were detected, so the corresponding detection rate of hv-CRKP was 8.71% (23/264). The hv-CRKP isolates in this study were mainly from the intensive care unit (10/23) and neurosurgery department (8/23), and the main sources of hv-CRKP isolates were sputum (10/23) and bronchoalveolar lavage fluid (6/23). The hv-CRKP isolates in this study were highly resistant to β-lactam antibiotics, fluoroquinolones and aminoglycosides, and were only susceptible to colistin, tigecycline and ceftazidime/avibactam. The detection rate of the blaKPC-2 among 23 hv-CRKP isolates was 91.30% (21/23) and none of the class B and class D carbapenemases were detected. Results of MLST and capsular serotypes showed that ST11 type hv-CRKP was the dominant strain in the hospital, accounting for 56.52% (13/23), and K64 (9/13) and KL47 (4/13) were the major capsular serotypes. Conclusion: The hv-CRKP isolates from the hospital are mainly from lower respiratory tract specimens from patients admitted to the intensive care department and the drug resistance is relatively severe. The predominant strains with certain polymorphisms are mainly composed of the KPC-2-producing ST11-K64 and ST11-KL47 hv-CRKP isolates in the hospital.

Molecular epidemiological characterization of hypervirulent carbapenem-resistant Klebsiella pneumoniae in a hospital in Henan Province from 2020 to 2022 / 中华预防医学杂志

Objective: The study investigated the clinical distribution, antimicrobial resistance and epidemiologic characteristics of hypervirulent Carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) in a hospital in Henan Province to provide a scientific basis for antibiotic use and nosocomial infection prevention and control. Methods: A retrospective analysis of the clinical data from the cases was carried out in this study. Clinical data of patients infected with the CRKP strain isolated from the clinical microbiology laboratory of Henan Provincial Hospital of Traditional Chinese Medicine from January 2020 to December 2022 were retrospectively analyzed. A string test, virulence gene screening, serum killing, and a G. mellonella infection model were used to screen hv-CRKP isolates. The clinical characteristics of hv-CRKP and the drug resistance rate of hv-CRKP to twenty-five antibiotics were analyzed using WHONET 5.6. Carbapenemase phenotypic characterization of the hv-CRKP was performed by colloidal gold immunochromatographic assay, and Carbapenemase genotyping, multi-locus sequence typing (MLST) and capsular serotyping of hv-CRKP isolates were performed by PCR and Sanger sequencing. Results: A total of non-duplicate 264 CRKP clinical isolates were detected in the hospital from 2020 to 2022, and 23 hv-CRKP isolates were detected, so the corresponding detection rate of hv-CRKP was 8.71% (23/264). The hv-CRKP isolates in this study were mainly from the intensive care unit (10/23) and neurosurgery department (8/23), and the main sources of hv-CRKP isolates were sputum (10/23) and bronchoalveolar lavage fluid (6/23). The hv-CRKP isolates in this study were highly resistant to β-lactam antibiotics, fluoroquinolones and aminoglycosides, and were only susceptible to colistin, tigecycline and ceftazidime/avibactam. The detection rate of the blaKPC-2 among 23 hv-CRKP isolates was 91.30% (21/23) and none of the class B and class D carbapenemases were detected. Results of MLST and capsular serotypes showed that ST11 type hv-CRKP was the dominant strain in the hospital, accounting for 56.52% (13/23), and K64 (9/13) and KL47 (4/13) were the major capsular serotypes. Conclusion: The hv-CRKP isolates from the hospital are mainly from lower respiratory tract specimens from patients admitted to the intensive care department and the drug resistance is relatively severe. The predominant strains with certain polymorphisms are mainly composed of the KPC-2-producing ST11-K64 and ST11-KL47 hv-CRKP isolates in the hospital.

Research on cellular damages and astrocyte activation after cerebral ischemia and reperfusion / 中国药理学通报

Aim To observe cellular damage and astrocyte activation at different time points of cerebral ischemia and reperfusion. Methods The middle cerebral artery of male SpragueDawley rats was occluded for 90 min followed by different time points of reperfusion. Eighty-five SPF male SD rats were randomly divided into control group (Sham), IR3, 6, 12, 24 and IR48h (MCAO followed by 48 h of reperfusion) group. Cerebral ischemia and reperfusion injury was observed by HE staining, and the structure of astrocytes was estimated with transmission electron microscopy (TEM). GFAP expression was detected by immunofluorescence staining and Western blot. Results Cerebral ischemia following by different time points of reperfusion led to different degrees of cellular damage, which was the most serious at 24 h of reperfusion. TEM showed destruction of astrocytes structure, swollen organelles and broken mitochondrial ridge. After cerebral ischemia-reperfusion, the expression levels of GFAP were significant up-regulated in the ischemic penumbra cortex and the highest was at 48 h of reperfusion, indicating astrocytes were activated. In addition, the results showed the gradual decrease in GFAP expression in the infarct core. Conclusions After cerebral ischemia-reperfusion, cellular damage is aggravated, and astrocytes are gradually activated in the ischemic penumbra. With the extension of reperfusion time, the boundaries of infarct area and ischemic area are gradually clear, and scarring may occur.

METTL3-mediated m6A modification involved in electrical remodeling of atrial cardiomyocytes under high hydrostatic pressure / 中国药理学通报

To investigate the regulation of N6- methyladenosine ( m6A ) modification on L-type calcium channels in atrial myocytes under high hydrostatic pressure, mediated by methyltransferase-like protein 3 ( METTL3 ). Methods C57BL/6J mice were randomly assigned to the control group and the hypertension group ( treated with continuous administration of angiotensin for four weeks ). Masson staining was used to observe the fibrosis of mouse atrial tissue, while dot blot assay and Western blot were used to detect the levels of m6A, METTL3, and Cavi1 2 in the atrial tissue. A high hydrostatic pressure model was constructed using the HL-1 cell line cultured in vitro, and METTL3 was intervened to observe changes in m6A expression levels, METTL3 and Cavi1 2 levels in cells,and action potential duration ( APD ) and L-type calcium current ( I

Study on the mechanism of oridonin to reverse drug resistance of breast cancer cell MCF- 7 to fulvestrant / 中国药房

OBJECTIVE To explore the mechanism of oridon in（Ori）reversing the drug resistance of breast cancer cell MCF-7 to fulvestrant （Ful）. METHODS Ful-resistant breast cancer cell strains MCF- 7/Ful were induced and constructed in vitro . The relative cell viability of MCF- 7 cells and MCF- 7/Ful cells was detected by MTT assay ，inhibitory rate of Ori to MCF- 7/Ful cells was also detected. CompuSyn software was used to analyze the synergistic effect of Ori and Ful. MCF- 7/Ful cells were randomly divided into blank control group ，Ful group （5 μmol/L），Ori group （8 μmol/L），Ful（5 μmol/L）+Ori（8 μmol/L）group. The phosphorylation of phosphatidylinositol 3 kinase（PI3K）/protein kinase B （Akt）signaling pathway related protein in each group was detected by Western blot. MCF-7/Ful cells were used to prepare drug resistance model of transplanted tumor in nude mice，and they were randomly divided into blank control group ，Ful group （80 μmol/g），Ori group （50 μmol/g），Ful（80 μmol/g）+ Ori（50 μmol/g）group. The tumor weight and tumor inhibition rate were calculated ，to verify the reversal effect of Ori and Ful in vivo. RESULTS MTT assay showed that when Ful ≥10 μmol/L，the relative cell viability of MCF- 7/Ful cells was significantly higher than that of MCF- 7 cells（P＜0.05），and the drug resistance was significantly enhanced ；Ori had a significant inhibitory effect on MCF- 7/Ful cells ，the inhibition rate of Ori combined with Ful to MCF- 7/Ful cells was significantly increased （P＜0.05 or P＜0.01），and the effect of reversing drug resistance was significantly increased . The results of Western blot showed that compared with Ful group ，the phosphorylation levels of PI 3K and Akt protein in Ful+Ori group were significantly decreased （P＜0.05 or P＜ 0.01）. In vivo results showed that the tumor volume and mass of Ful+Ori group were significantly decreased ，and the tumor inhibition rate was （63.90±4.11）％，which was significantly higher than that of Ful group （P＜0.01）. CONCLUSIONS Ori can reverse drug resistance of breast cancer cell MCF- 7 to Ful ， and this effect may be through regulating PI 3K/Akt signaling pathway.

New eudesmane sesquiterpenoids from Atractylodis Macrocephalae Rhizoma and their inhibitory activities against SREBPs / 中国中药杂志

Three sesquiterpenoids were isolated and purified from the 95% ethanol extract of Atractylodis Macrocephalae Rhizoma by column chromatography on silica gel, Sephadex LH-20, ODS, and high-performance liquid chromatography(HPLC). Their chemical structures were identified on the basis of spectroscopic analysis and physiochemical properties as(7Z)-8β,13-diacetoxy-eudesma-4(15),7(11)-diene(1), 7-oxo-7,8-secoeudesma-4(15),11-dien-8-oic acid(2), and guai-10(14)-en-11-ol(3). Compounds 1 and 2 are new compounds and compound 3 was obtained from Compositae family for the first time. Compounds 1, 2, and 3 showed weak inhibitory activities against sterol regulatory element-binding proteins(SREBPs).

Mechanism of Kaixinsan on Learning and Memory Ability and Synaptic Function of APP/PS1 Mice / 中国实验方剂学杂志

Objective:To explore the underlying protective mechanism of Kaixinsan on learning， memory， and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group， a donepezil （2 mg·kg^-1·d^-1） group， and low- （0.7 g·kg^-1·d^-1）， medium- （1.4 g·kg^-1·d^-1）， and high-dose （2.8 g·kg^-1·d^-1） Kaixinsan groups， and the wild-type mice of the same age in the same litter were assigned to the normal group， with 12 mice in each group. After continuous intragastric administration for two months， the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine （ACh）， choline acetyltransferase （ChAT）， acetylcholinesterase （AChE）， and levels of hippocampal reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Real-time fluorescence-based quantitative polymerase chain reaction （Real- time PCR） was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor （BDNF）， beta-nerve growth factor （NGFB）， discs large homolog (DLG)2， DLG4， and synaptophysin （SYP）. Result:Compared with the normal group， the model group showed prolonged escape latency， reduced number of crossing platforms， shortened stay in the target quadrant （<italic>P</italic><0.01）， decreased number of mitochondria with different shapes and irregular arrangement， some swollen and deformed mitochondria with broken mitochondrial cristae， endolysis， and cytoplasm vacuole， and more cell debris. Additionally， the model group also displayed reduced serum levels of ACh and ChAT， increased AChE （<italic>P</italic><0.01）， elevated hippocampal ROS and MDA （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining SOD and GSH-Px （<italic>P</italic><0.01）， and diminished hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the donepezil group， and the medium- and high-dose Kaixinsan groups showed shortened escape latency， increased number of crossing platforms， prolonged stay in the target quadrant （<italic>P</italic><0.05，<italic>P</italic><0.01）， improved mitochondrial damage with a regular shape （mainly oval shape）， relieved mitochondrial swelling and deformation， and clear mitochondrial cristae. Furthermore， the donepezil group， and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels （<italic>P</italic><0.05，<italic>P</italic><0.01）， blunted AChE activity （<italic>P</italic><0.05）， reduced hippocampal ROS level （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining MDA level （<italic>P</italic><0.05）， potentiated SOD and GSH-Px activities， and up-regulated hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. In the low-dose Kaixinsan group， the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly （<italic>P</italic><0.05）. There was no statistical difference in swimming speed between the groups. Conclusion:Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins， reducing the ultrastructural damage to hippocampal neurons， resisting oxidative stress， and regulating cholinergic neurotransmitters， thereby exerting neuroprotective effects.

Epidemiological characteristics of hemorrhagic fever with renal syndrome in Xi'an from 2009 to 2018 / 中华地方病学杂志

Objective:To analyze the epidemiological characteristics and tendency of hemorrhagic fever with renal syndrome (HFRS) in Xi'an, master its popular and development laws, and provide scientific basis for formulating targeted prevention and control measures.Methods:The retrospective method was used to collect HFRS epidemic data and demographic data from 2009 to 2018 in Xi'an. The descriptive epidemiological method was used to analyze the three distributions (time, region, population distributions) of HFRS.Results:There were 8 710 HFRS cases in Xi'an from 2009 to 2018, with an average annual incidence of 10.13/100 000 and an average annual mortality rate of 0.08/100 000; the incidence of HFRS had decreased year by year since the peak incidence in 2010 (19.46/100 000), and had rebounded in 2017 (9.14/100 000), 2018 (9.04/100 000). The time distribution of the onset of HFRS was bimonthly, with peak in autumn and winter (October to January of following year) each year, accounting for 74.08% (6 452/8 710) of the total number of cases; the peak in spring and summer (May to July) accounted for 14.33% (1 248/8 710). HFRS cases were mainly concentrated in Chang'an District (2 446 cases), Zhouzhi County (1 494 cases), Hu County (1 170 cases), and Lintong District (940 cases), accounting for 69.46% (6 050/8 710). The age of onset of HFRS cases was mainly concentrated in 15-59 years old, accounting for 74.06% (6 451/8 710); the incidence rate in males was 14.77/100 000, in females was 5.25/100 000, the difference was statistically significant between gender (χ 2=1 921.42, P < 0.05); the occupational distribution was mainly farmers, accounting for 68.38% (5 956/8 710). Conclusions:From 2009 to 2016, the HFRS epidemic situation in Xi'an has showed a downward trend, and the incidence of HFRS has rebounded in 2017-2018. Xi'an should continue to take active and effective comprehensive measures to intervene to further realize effective control of HFRS.