Taking Kunming Medical University as an example, we explore the mechanism for the separation and coordination of supervision, management, and evaluation, establish and implement a course quality rating system, and strengthen the course quality evaluation. The course quality rating system mainly consists of merit evaluation for courses of grades A and B and admittance evaluation for courses of grades C and D. Through the course quality rating, courses are diagnosed and compared, with the aim to improve course connotation construction (labeling, setting an example, promoting excellent courses, and removing inferior courses), achieve "good pay for good courses", encourage the faculty to strengthen curriculum quality, and measure ourselves with our own ruler. We discussed the problems about the difference in evaluation indicators, the professionality of evaluators, and the incentive effect of evaluation results, and also proposed strategies for improving course quality rating in medical colleges from the perspectives of deepening the content of evaluation indices, ensuring the effectiveness after evaluation, and ascertaining the main body of course construction in daily work.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

AIM:To investigate the effects of Panax notoginseng compound formula(PN)on endometrial fibro-sis by regulating inflammatory reaction and intestinal flora(IF)in a rat model of intrauterine adhesion(IUA).METHODS:The rat IUA model was established by following the mechanical injury method.A total of 50 rats were randomly divided in-to sham group,model group,low-dose(210 mg/kg)PN group,medium-dose(420 mg/kg)PN group and high-dose(840 mg/kg)PN group.After 8 weeks of intragastric administration,the uterus was collected to observe morphological changes with naked eye.The degree of uterine tissue damage and fibrosis was evaluated through hematoxylin-eosin(HE)and Mas-son staining.The collagen type Ⅰ(Col Ⅰ)was detected by immunohistochemistry.The interleukin-6(IL-6)and IL-10 pro-tein expression was detected by Western blot.The levels of IL-6,IL-1β,tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor B(VEGFB)were detected by enzyme-linked immunosorbent assay(ELISA).The IF diversity and population structure were observed by 16S amplicon.RESULTS:Compared with the sham group,the uteruses of rats in the model group showed:reduced elasticity,accompanied by congestion and edema;decreased number of glands and blood vessels,and thinned endometrium(P<0.01);increased collagen fibers and Col Ⅰ protein expression(P<0.01);sig-nificantly increased IL-1β,IL-6,TNF-α and VEGFB levels in the uterine tissue(P<0.01);decreased IL-10 level(P<0.01);and reduced IF diversity(P<0.05).Compared with the model group,the drug intervention groups exhibited:re-covered elasticity of the uterus and relieved congestion and edema;increased number of endometrial glands and blood ves-sels(P<0.05);decreased collagen fibers and Col Ⅰ protein expression(P<0.01);reduced IL-1β,IL-6,and TNF-α lev-els to varying degrees in the uterine tissue(P<0.05);elevated IL-10 level(P<0.01);and improved IF diversity(P<0.05).CONCLUSION:The PN is able to significantly improve the endometrial tissue fibrosis in IUA rats.The under-lying mechanisms may be related to the inhibition of IL-6,IL-1β and TNF-α expression,up-regulation of IL-10,and im-provement of IF diversity.

AIM: To investigate the effect of repeated intravitreal injection of anti-vascular endothelial growth factor(VEGF)on the vitreomacular interface(VMI)and its related risk factors in patients with diabetic macular edema(DME).METHODS: The clinical data of 31 patients(55 eyes)with DME who received intravitreal injections of Conbercept(3+PRN)in the ophthalmology department of the First People's Hospital of Zunyi from January 2018 to December 2021 were analyzed retrospectively. There were 9 cases(13 eyes)in the group that has changes in VMI and 22 cases(42 eyes)in the other group that has no changes in VMI. The best corrected visual acuity(BCVA), central retinal thickness(CRT), and central choroidal thickness(CCT)of the two groups were compared, and the risk factors of VMI change were analyzed.RESULTS: The patients were followed up for an average of 9.58±8.32mo, received an average of 4.07±2.17 times of anti-VEGF therapy, and the number of intravitreal injections in VMI changed group was more than that in VMI unchanged group(5.77±2.09 times vs. 3.55±1.93 times, P=0.001). At the last follow-up, compared with before treatment, the BCVA of both patients improved significantly after treatment(both P<0.05), while CCT had no significant change(both P>0.05). CRT of patients in the VMI unchanged group decreased significantly(P=0.039), but there was no significant change in patients of VMI changed group(P=0.627). Logistic regression analysis showed that BCVA was a risk factor for VMI change before treatment(P=0.049, OR=6.210, 95%CI 1.006～38.346).CONCLUSIONS: The VMI of DME patients may change during repeated intravitreal injections of anti-VEGF drugs. The worse the BCVA before treatment, the higher the risk of change in VMI, and the patients with VMI change have a poor response to anti-VEGF treatment.

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma

Objective To investigate the current situation of the construction of geriatrics in second and third level gen-eral hospitals in Guangxi,analyze the existing problems,and propose suggestions.Methods A self-developed"Survey on the Current Situation of Geriatrics Construction"was used to conduct a questionnaire survey on 250 second and third level general hospitals in Guangxi from April to September 2021.Results A total of 98 geriatrics were established in 196 general hospitals,and the overall number met national requirements.Among them,36 are independent institutions,including 24 tertiary hospitals and 12 secondary hospitals,with 2 172 beds and 1 764 medical staff.Conclusion In the future,Guangxi should ensure the high-quality construction of geriatrics,reasonably allocate geriatric human resources,enhance disciplinary medical service capa-bilities,strengthen overall two-way health connections,and vigorously promote the construction and development of geriatrics in Guangxi.

OBJECTIVE: To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations. METHODS: Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA). RESULTS: Among the 35 145 subjects, 635 were found to be carriers of SMN1 E7 deletion (586 with heterozygous E7/E8 deletion, 2 with heterozygous E7 deletion and homozygous E8 deletion, and 47 with sole heterozygous E7 deletion). The carrier frequency was 1.81% (635/35 145), with 1.59% (29/1 821) in males and 1.82% (606/33 324) in females. There was no significant difference between the two genders (χ² = 0.497, P = 0.481). A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8, and was verified to have a SMN1∶SMN2 ratio of [0∶4], none of her three family members with a [0∶4] genotype had clinical symptoms. Eleven carrier couples had accepted prenatal diagnosis, and one fetus was found to have a [0∶4] genotype, and the pregnancy was terminated. CONCLUSION This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples. The data can provide a reference for genetic counseling and prenatal diagnosis, which has important clinical implications for the prevention and control of birth defects associated with SMA.
Humans ; Child ; Pregnancy ; Male ; Female ; Adult ; Homozygote ; Sequence Deletion ; Prenatal Diagnosis ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Survival of Motor Neuron 1 Protein/genetics* ; Genetic Carrier Screening

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.
Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction ; Reactive Oxygen Species/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Endothelium, Vascular ; Oxidative Stress ; Endothelial Progenitor Cells ; RNA, Messenger/metabolism* ; Abietanes

Purpose: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. Materials and Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. Results: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. Conclusion This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.