BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective To preliminarily analyze the efficacy of laparoscopic surgery versus open surgery in patients with intrahepatic cholangiocarcinoma(ICC).Methods A retrospective analysis was conducted on 84 patients with ICC who underwent surgical resection from September 2010 to March 2023,including 45 cases in the laparoscopic surgery group and 39 in the open surgery group.By using propensity score matching,34 matched pairs were successfully identified.The study compared intraoperative blood loss,proportion of achieving≥6 lymph nodes dissection,R0 resection rate,complication,postoperative hospital stay,survival,and recurrence between the two groups.Results In the laparoscopic group,intraoperative blood loss was significantly less than that in the open surgery group(median:250 ml vs.750 ml,Z=-3.406,P=0.001).The proportion of achieving≥6 lymph node dissection in the former was lower than that in the latter,but the difference was not statistically significant(5.9%vs.17.6%,χ2=1.275,P=0.259).There was no statistical difference in R0 resection rate between the laparoscopic group and the open surgery group[88.2%(30/34)vs.82.4%(28/34),χ2=0.469,P=0.493].The complication rate in the laparoscopic group was 17.6%(6/34),significantly lower than 47.1%(16/34)in the open surgery group(χ2=6.719,P=0.010);however,the rate of severe complication was the same in both groups at 2.9%(χ2=0.000,P=1.000).Laparoscopic surgery significantly shortened the postoperative hospital stay(median:7 d vs.10 d,Z=-3.021,P=0.003).The median overall survival in the laparoscopic group was 60.6 months,significantly longer than 15.9 months in the open surgery group(log-rank χ2=5.788,P=0.016).The median recurrence-free survival was 26.4 months in the laparoscopic group,significantly longer than 7.6 months in the open surgery group(log-rank χ2=4.532,P=0.033).Conclusions Compared to open surgery,laparoscopic surgery for ICC offers advantages such as less blood loss,lower complication rate,shorter postoperative hospital stay and longer survival.It achieves comparable R0 resection rate and adequate lymph node dissection.

Purpose: Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear. Materials and Methods: We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC. Results: Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression. Conclusion Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To assess the application effect of "internet + mobile medicine" on the process management of standardized residency training of obstetrics and gynecology.Methods:A total of 43 teachers including 14 administrators and 29 instructors who were not directly responsible for management, and 41 residents who participated in the standardized training in our base were enrolled as research objects. The data of process management were sorted by internet technology, and combined with personal wishes and casting lots, the residents were divided into two groups: the control group ( n=21) adopted traditional way while the observation group ( n=20) used mobile medicine for process management. By conducting multi-dimensional questionnaire and data comparison, we analyzed the evaluation of teachers and residents, the scores of different stage of residents, and the satisfaction of cervical cancer postoperative patients to medical care under different process management mode. SPSS 22.0 software was used for t test and chi-square test. Results:The application of "internet + mobile medicine" in standardized residency training obtained positive evaluation both by teachers and residents, and the ratio of considering "necessary" to reform the traditional residency training management mode in residents [95.1%(39/41)] and administrators [92.9%(13/14)] were both higher than that in instructors [62.1%(18/29)]. And 78.6%(11/14) of the administrators believed that cloud data management took less time. After 6 months of process management by different modes, the clinical diagnosis and treatment ability and skill operation ability scores of observation group were higher than those of control group [(93.6±5.6) vs. (89.4±5.7); (89.6±8.8) vs. (84.0±8.7)]. The "overall medical satisfaction rate" of cervical cancer patients was relatively high in both groups [100%(30/30) vs. 93.3%(28/30)], and the "very satisfied rate" of patients in the mobile medical group was higher than that in the traditional group [86.7%(26/30) vs. 63.3%(19/30)].Conclusion:The application of "internet + mobile medicine" is conducive to strengthening the process management and optimizing the quality of standardized residency training management of obstetrics and gynecology.

Objective:To explore the teaching effect of individualized teaching based on problem-based learning (PBL) that applied in gynecology practice teaching under the background of conflicts between postgraduate examination preparation and clinical internship for medical undergraduates.Methods:A total of 157 medical students of the five-year program who started gynecology internship and meanwhile prepared for the postgraduate entrance examination in 2018 were enrolled in the study and divided into two groups randomly. One group received traditional teaching (control group), and the other group received individualized teaching mode based on PBL (observation group). After the internship, the two groups of students were assessed for their theoretical and clinical skills, and the students' evaluation of the teaching effect was acquired through a questionnaire survey. SPSS 22.0 was used to perform chi-square test.Results:The students in observation group had statistically significant higher scores in theory and skill tests than those in the control group ( P<0.001). The evaluation of boosting their enthusiasm for internship, advancing self-learning ability, conducing to improving learning methods in the future, and enhancing clinical skills and thinking ability in the observation group was significantly better than that in the control group ( P<0.05). Conclusion:The individualized teaching model based on PBL could efficiently alleviate the conflicts between internship and postgraduate entrance examination preparation and improve the effect of gynecology practice teaching.

Objective:To explore the risk factors of paralytic ileus (PI) after simultaneous pancreas-kidney (SPK) transplantation.Methods:From January 2017 to December 2019, clinical data were reviewed retrospectively for 115 cases of SPK transplantation. The risk factors of PI after SPK were analyzed. According to the occurrence of PI, they were divided into two groups of occurrence and non-occurrence. One-way analysis of variance was utilized for analyzing such influencing factors as gender, age, body mass index (BMI), diabetic type, duration of diabetes, mode of dialysis, duration of dialysis, diabetic gastroenterology, history of open surgery, bowel preparation, operative duration, hemorrhagic volume, immunosuppressant and hypoproteinemia. Multivariate Logistic regression analysis was performed for screening the suspected risk factors.Results:Among them, 19 patients (16.5%) had PI. Univariate analysis showed that PI was associated with diabetic gastroenterology, operative duration, history of open surgery, no bowel preparation and hypoproteinemia ( P<0.05). Multivariate Logistic regression analysis revealed that the risk factors of PI after SPK included diabetic gastroenterology, operative duration time, history of open surgery and no bowel preparation ( P<0.05). Conclusions:Diabetic gastroenterology, operative duration, history of open surgery and no bowel preparation are risk factors for PI after SPK. Clinical interventions for the above factors are necessary.

To summarize the clinical experience regarding a patient with early recurrence of atypical hemolytic uremic syndrome (aHUS) after renal transplantation. AHUS is a rare disease with high recurrence rate and poor prognosis. Although the patient was treated with plasma exchange, intravenous gamma globulin, rituximab block B lymphocyte, hormone shock and so on, he still suffered renal transplantation failure. The risk of aHUS recurrence after renal transplantation should be fully evaluated.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

ObjectiveTo verify the reliability of the mouse model of cerebral cortical microinfarct induced by two-photon microscopy and to explore its pathological changes.MethodsSeventeen male C57BL/6J mice were randomly divided into a microinfarct group (n=11) or a sham operation group (n=6).A thinned cranial window of 3 mm diameter was performed over the cerebral cortex with a high-speed micro-drill until the small blood vessels were clearly observed under a dissecting microscope.Then, a permanent single cortical penetrating arteriole occlusion was induced with a gradually enhanced ultrashort laser irradiation through the thinned cranial window with two-photon microscopy.At 7 days after modeling, the cerebral microinfarct volume was measured with HE staining, and the neuron loss, activation of glial cells and deposition of 3-nitrotyrosine were assessed using immunohistochemistry.ResultsThe target vessels of cerebral cortex in 8 (72.7%) mice were occluded and the microinfarcts formed in the microinfarct group, and the average microinfarct volume was 317.23±20.29 μm3.There were remarkable neuron loss and microglia infiltration in the infarcted core, a large number of reactive astrocytes surrounding the infarcted lesion, and massive deposition of 3-nitrotyrosine in the peri-infarct area.No infarcts were observed in the sham operation group.The deposition of 3-nitrotyrosine in the sham operation group was significantly less than that in the microinfarct group (8.00±1.48 vs.98.38±9.10;t=23.962, P<0.001).Conclusions The mouse model of cerebral cortical microinfarct induced by two-photon microscopy is reliable, and its histopathologic changes are consistent with the pathologic features of cerebral microinfarct.