Objective:To investigate the situation of continuing medical education (CME) among obstetricians and gynecologists from Beijing's general hospitals at the secondary level or above in 2018 and 2023, and to provide a reference for standardizing CME for obstetricians and gynecologists in the future.Methods:We performed questionnaire surveys and interviews with 164 obstetricians and gynecologists in Beijing to investigate the status of completion of CME, the reasons for incompletion, the preferred modes to complete CME, and the preferred contents and forms of CME. SPSS 26.0 software was used for data analysis. The rate was compared using the chi-squared test.Results:Due to the impact of coronavirus disease 2019, the 2023 survey showed that 79 (48.17%) participants completed CME in an online mode, and 76 (46.34%) participants completed CME in an mostly online mode, with a significantly increased degree of satisfaction with CME compared with the 2018 survey ( P<0.05); 49 (29.88%) participants believe that online education is superior to traditional CME, and 69 (42.07%) participants believe that online education is comparable to traditional CME. The main advantages of the online education mode are flexible time and location and cost savings. "Hoping to improve my professional level" is the main purpose to participate in CME in both 2018 and 2023 surveys [124 (75.61%) vs. 127 (77.44%)]. "Professional skills and techniques" and "New advances in the specialty" are the contents of most interest. Conclusions:Obstetricians and gynecologists should raise the awareness to participant in CME. Relevant departments should establish a standardized system and an effective supervision and management mechanism, and take flexible education modes with the use of the Internet. Online education can achieve similar teaching effects and also improve learners' satisfaction.

Objective:To investigate the effect of miR-369-3p targeting ACTN4 expression on proliferation and apoptosis of hepatocellular carcinoma cells.Methods:Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expression levels of miR-369-3p and ACTN4 in hepatocarcinoma tissues and adjacent tissues. MiR-369-3p mimics, miR-negative control (NC), si-ACTN4, and si-NC were transfected into hepatocellular carcinoma MHCC97H cells by liposome method. Cell proliferation was detected by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dipheny-ltetrazolium bromide (MTT) assay. Flow cytometry was used to detect cell cycle and apoptotic rates. The dual luciferase reporter assay was used to verify the targeted regulation of ACTN4 by miR-369-3p. Western blot was used to detect the expressions of cyclin D1, p21, Bcl-2 and Bax.Results:The expression level of miR-369-3p in liver cancer tissue was lower than that in adjacent tissues [(0.46±0.04) vs (1.00±0.08), P<0.001)], while the expression level of ACTN4 was higher than that in adjacent tissues [mRNA (3.12±0.29) vs (1.01±0.09); protein (0.61±0.06) vs (0.25±0.03), P<0.001]. Overexpression of miR-369-3p significantly decreased the cell viability[(0.71±0.06) vs (1.26±0.11), P<0.001)], increased cell apoptosis rate [(20.16±2.11)% vs (6.25±0.64)%, P<0.001], increased the proportion of cells in G 1 phase [(31.14±3.36)% vs (51.56±5.23)%, P<0.001], decreased the proportion of cells in S phase [(32.44±3.56)% vs (14.33) ±1.45)%, P<0.001], increased the levels of p21 and Bax protein ( P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein ( P<0.001). Inhibition of the expression of ACTN4 significantly reduced the cell viability [(0.78±0.07) vs (1.24±0.12), P<0.001], increased the apoptosis rate [(6.58±0.66)% vs (18.32±1.82)%, P<0.001], increased the proportion of cells in G 1 phase [(48.69±4.21)% vs (30.33±3.01)%, P<0.001], decreased the proportion of cells in S phase [(36.21±3.42)% vs (18.54±1.61)%, P<0.001], increased the protein levels of p21 and Bax ( P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein ( P<0.001). Compared with the miR-369-3p+ pcDNA group, overexpression of ACTN4 increased the proliferation ability of hepatocellular carcinoma MHCC97H cells at 72 hours of culture[(1.12±0.11) vs (0.68±0.06), P<0.001], significantly reduced the proportion of cells in G 1 stage [(38.81±3.24)% vs (51.80±4.57)%, P<0.001], significantly increased the proportion of S-phase cells [(31.65±3.11)% vs (15.69±1.44)%, P<0.001], decreased cell apoptosis rate [(13.86±1.37)% vs (22.69±2.24)%, P<0.001], increased protein expressions of cyclin D1 and Bcl-2 ( P<0.001), decreased the protein expressions of p21 and Bax ( P<0.001). Conclusion:MiR-369-3p can induce cell cycle arrest in G 1 phase, inhibit the proliferation and promote apoptosis of liver cancer cells by regulating the expression of ACTN4.

Objective:To investigate the effect of miR-369-3p targeting ACTN4 expression on proliferation and apoptosis of hepatocellular carcinoma cells.Methods:Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expression levels of miR-369-3p and ACTN4 in hepatocarcinoma tissues and adjacent tissues. MiR-369-3p mimics, miR-negative control (NC), si-ACTN4, and si-NC were transfected into hepatocellular carcinoma MHCC97H cells by liposome method. Cell proliferation was detected by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dipheny-ltetrazolium bromide (MTT) assay. Flow cytometry was used to detect cell cycle and apoptotic rates. The dual luciferase reporter assay was used to verify the targeted regulation of ACTN4 by miR-369-3p. Western blot was used to detect the expressions of cyclin D1, p21, Bcl-2 and Bax.Results:The expression level of miR-369-3p in liver cancer tissue was lower than that in adjacent tissues [(0.46±0.04) vs (1.00±0.08), P<0.001)], while the expression level of ACTN4 was higher than that in adjacent tissues [mRNA (3.12±0.29) vs (1.01±0.09); protein (0.61±0.06) vs (0.25±0.03), P<0.001]. Overexpression of miR-369-3p significantly decreased the cell viability[(0.71±0.06) vs (1.26±0.11), P<0.001)], increased cell apoptosis rate [(20.16±2.11)% vs (6.25±0.64)%, P<0.001], increased the proportion of cells in G 1 phase [(31.14±3.36)% vs (51.56±5.23)%, P<0.001], decreased the proportion of cells in S phase [(32.44±3.56)% vs (14.33) ±1.45)%, P<0.001], increased the levels of p21 and Bax protein ( P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein ( P<0.001). Inhibition of the expression of ACTN4 significantly reduced the cell viability [(0.78±0.07) vs (1.24±0.12), P<0.001], increased the apoptosis rate [(6.58±0.66)% vs (18.32±1.82)%, P<0.001], increased the proportion of cells in G 1 phase [(48.69±4.21)% vs (30.33±3.01)%, P<0.001], decreased the proportion of cells in S phase [(36.21±3.42)% vs (18.54±1.61)%, P<0.001], increased the protein levels of p21 and Bax ( P<0.001), and decreased the levels of cyclin D1 and Bcl-2 protein ( P<0.001). Compared with the miR-369-3p+ pcDNA group, overexpression of ACTN4 increased the proliferation ability of hepatocellular carcinoma MHCC97H cells at 72 hours of culture[(1.12±0.11) vs (0.68±0.06), P<0.001], significantly reduced the proportion of cells in G 1 stage [(38.81±3.24)% vs (51.80±4.57)%, P<0.001], significantly increased the proportion of S-phase cells [(31.65±3.11)% vs (15.69±1.44)%, P<0.001], decreased cell apoptosis rate [(13.86±1.37)% vs (22.69±2.24)%, P<0.001], increased protein expressions of cyclin D1 and Bcl-2 ( P<0.001), decreased the protein expressions of p21 and Bax ( P<0.001). Conclusion:MiR-369-3p can induce cell cycle arrest in G 1 phase, inhibit the proliferation and promote apoptosis of liver cancer cells by regulating the expression of ACTN4.

Objective:To explore the incidence and risk factors of parastomal hernia after colostomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 145 patients undergoing colostomy in Xinxiang Central Hospital from January 2015 to January 2019 were collected. There were 86 males and 59 females, aged(59±11) years. Patients received pelvic and abdominal computed tomography once every 6 months after colostomy to detect the occurrence of parastomal hernia. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers, and chi-square test or Fisher exact probability was used for comparison between groups. Kaplan-Meier method was used to analyze the cumulative annual incidence of parastomal hernia. Logarithmic rank test was used to analyze the cumulative incidence based on clinical variables. COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Incidence of parastomal hernia after colostomy. All the 145 patients were followed up for 86(range, 60?108)months after colostomy, of which 46 cases had parastomal hernia and 99 cases had no parastomal hernia. There were significant differences in gender, age, body mass index (BMI) and chronic liver disease between patients with and without parastomal hernia after colostomy ( χ2=23.28, t=13.27, χ2=6.17, 5.82, P<0.05). (2) Annual cumulative incidence of parastomal hernia after colostomy. The 1-, 3-, and 5-year cumulative incidence of parastromal hernia after colostomy was 8.5%, 26.4% and 42.7%, respectively. When the follow-up time is more than 5 years, the incidence of parastromal hernia tended to be stable. The 5-year incidence of parastomal hernia after colostomy in female patients was higher than that in male patients (70.7% vs 20.3%, χ2=12.37, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients≥60 years old was higher than that in patients under 60 years old (49.8% vs 20.0%, χ2=10.52, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with BMI >28 kg/m 2 was higher than that in patients with BMI ≤28 kg/m 2 (55.3% vs 33.2%, χ2=11.76, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with chronic liver disease was higher than that in patients with non-chronic liver disease (45.2% vs 32.4%, χ2=15.32, P<0.05). (3) Analysis of risk factors for parastomal hernia after colostomy. Results of multivariate analysis showed that female, age >60 years old, BMI ≥28 kg/m 2 and chronic liver disease were independent risk factors for parastomal hernia after colostomy ( hazard ratio=2.70, 2.51, 1.85, 5.88, 95% confidence intervals as 1.39?6.74, 1.01?4.59, 1.02?4.87, 1.05?8.24, P<0.05). Conclusions:The incidence of parastomal hernia after colostomy is increasing year by year, and tends to be stable after 5 years. Female, age >60 years old, BMI≥28 kg/m 2, and chronic liver disease are independent risk factors for parastomal hernia after colostomy.

OBJECTIVETo explore the immuno-effect of plasmacytoid dendritic cells (pDC) on bacteria infection induced spontaneous remission (SR) of leukemia.

METHODSBoth pDC and myeloid dendritic cells (mDC) were isolated and purified from leukemic patient with SR and healthy donor by combination of immunomagnetic beads and flow cytometry. pDC were cultured in RPMI1640 medium and stimulated with different bacteria. The T cells proliferation was detected by MTT, and cytokine production by ELISA kits.

RESULTSThe human bacterial pathogen Staphylococcus aureus and Pseudomonas aeruginosa stimulation for 48 h resulted in the maturation of pDC with production of high quantity of IFN-α at (15.34 ± 2.91) ng/ml and (10.38 ± 1.41) ng/ml, respectively, comparing with that of negative group at (1.36 ± 0.13) ng/ml (P<0.01). Activated pDC could promote the differentiation of naive CD4⁺ T cells to Th1 cells with secretion of IFN-γ at (2.16 ± 0.37) ng/ml and (2.73 ± 1.11) ng/ml, respectively, comparing with that of positive control at (2.55 ± 0.23) ng/ml (P > 0.05). Activated pDC showed higher T cell stimulatory capacities [proliferation index (PI) was 4.36 and 4.05, respectively] than that of non-activated pDC (PI was 1.23 and 0.13, respectively) (P < 0.01).

CONCLUSIONStaphylococcus aureus and Pseudomonas aeruginosa activated pDC may play a key role in SR of leukemia following severe infections.

CD4-Positive T-Lymphocytes ; Dendritic Cells ; immunology ; Flow Cytometry ; Humans ; Interferon-alpha ; Leukemia ; diagnosis ; immunology ; Lymphocyte Activation ; Pseudomonas aeruginosa ; immunology ; Remission, Spontaneous ; Staphylococcus aureus ; immunology

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.