[ABSTRACT]AIM:Toexploretheeffectoftheelasticmodulusandsizesofliquidcrystal(LC)phasesonosteo-genic differentiation based on OPC/PU composite substrate by mimicking the microenvironment in rat bone mesenchymal stem cells (rBMSCs).METHODS: A series of composite substrates with different elastic modulus were constructed via modulation of LC content in the composites .The surface phase structure was observed by polarized microscopy , and the mechanical property was measured by a universal material testing machine .Furthermore, the laser confocal microscope was employed to observe the spreading , polarization and the cytoskeleton arrangement of the rBMSCs .The proliferation of rBM-SCs was evaluated by CCK-8 assay.The specific mRNA expression of osteogenic differentiation such as collagen Ⅰ, and osteopontin on the composite membranes was detected by real-time PCR.RESULTS:The size and number of LC phase in-creased and the elastic modulus of the composite substrates decreased with the increase of the LC content .The rBMSCs ex-hibited better characteristics of initial adhesion , spreading and proliferation on the OPC 10-PU and OPC30-PU in the early and medium culturing .The rBMSCs displayed higher expression of collagen Ⅰ and osteopontin on the OPC10-PU in the early and medium osteogenic induction , while the high expression of these osteogenic genes occured on the OPC 30-PU and OPC50-PU in later osteogenic induction .The emphasis of genetic expression was switched from collagen Ⅰin the early and medium osteogenic induction to osteopontin in the later stage .CONCLUSION:When the content of LC remained low in the composite substrates , rBMSCs mainly responded to the mechanical stimuli induced by substrate stiffness and exhibited distinguished cellular behaviors;with the increase in the LC content , rBMSCs had strong interactions with LC by sensing the viscoelasticity of LC , probably resulted from the contribution of both substrate stiffness and the viscoelasticity of LC phase .

Objective: To investigate the clinical significance of the monocyte count/high-density lipoprotein cholesterol ratio(MHR)in evaluating imperfect ST-segment resolution in elderly patients with acute ST-elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI). Methods: This was a retrospective cohort study.A total of 274 elderly patients with STEMI underwent PCI in our hospital from December 2015 to December 2018 were enrolled.Based on the extent of the ST-segment resolution of the postoperative electrocardiogram, patients were divided into an imperfect ST-segment resolution group(observation group, n=79)and a favorable ST-segment resolution group(control group, n=195). General clinical data were compared between the two groups, and logistic regression equation was used to analyze the association of MHR with ST-segment resolution.Receiver operating characteristic(ROC)curve was performed to assess the predictive value of MHR for imperfect ST-segment resolution. Results: Compared with patients in the control group, patients in the observation group were associated with a significantly higher proportion of anterior wall myocardial infarction and heart failure(≥Killip 2), A longer duration of chest pain to balloon expansion, higher levels of creatine kinase isoenzyme, N-terminal pro-brain natriuretic peptide, hypersensitive C-reactive protein, blood sugar, blood uric acid, fibrinogen, triglyceride and mononuclear cell count, and lower levels of high density lipoprotein cholesterol and lymphocyte count(all P<0.05). Meanwhile, there was a significant difference in MHR between the observation group and the control group [(0.75±0.22)vs.(0.48±0.19), t=9.831, P=0.001]. Multivariate Logistic regression analysis showed that MHR was an independent risk factor for imperfect ST-segment resolution(OR=1.950, 95%CI: 1.646-5.430, P=0.003)and ROC curve showed the threshold value of MHR at 0.67, the area under the curve at 0.867, the sensitivity at 79.72%, and the specificity at 79.61%. Conclusions MHR may be an independent risk factor and a good predictive index for imperfect ST-segment resolution in elderly patients with STEMI after PCI.

This paper introduces various measures of actively developing online teaching in Shanghai Medical College of Fudan University, on the basis of in-depth analysis of the development trend of educational informatization and the large-scale online teaching in China during the COVID-19 epidemic. According to the requirement of Ministry of Education —— "Suspended Class, Ongoing Learning", our university has actively carried out online teaching, promoted the multi-platform blended online teaching, established a quality assurance system with multi-role linkage and regular feedback, focused on improving ideological and political education efficiency of online courses at the same time. By analyzing the characteristics of medical education, together with the benefits and limitations of online medical teaching, this paper demonstrates the application and development of online teaching resources and platforms in medical education, and looks into the future of online medical education as well.

Oral and maxillofacial malignant tumors threaten the life and health of patients, and seriously affect their swallowing, language function and face. 125I seeds brachytherapy for oral and maxillofacial malignant tumors has been widely concerned and studied because of its advantages such as less surgical trauma, large and uniform dose distribution in the target tissue, little damage to the surrounding normal tissue, and reducing radiation exposure of medical staff. Low-dose brachytherapy with 125I seeds can effectively reduce the tumor volume and prolong the survival time of patients. This article reviews the clinical application of 125I seeds brachytherapy in oral and maxillofacial malignant tumors.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Target trail emulation is an observational research method, which can use real-world data (such as observational data and historical data) to carry out research design according to the design principles of randomized controlled trials (RCT) when RCT cannot be carried out. The intervention group and the control group were classified by simulating random grouping. Finally a high-reliable conclusion similar to RCT can be obtained. This paper summarizes the basic concepts and application process of target trail emulation based on the effect of statins on the prognosis of myocardial infarction in diabetic patients to provide reference for the application of this method in real world.

Objective:To introduce our experience on dealing with the internal carotid artery (ICA) during the resection of lateral skull base tumors, and to explore the reference values for using radiological findings to make a rational surgical plan.Methods:A retrospective study of patients who underwent resection of lateral skull base tumors involving ICA at Peking Union Medical College Hospital from May 2015 to May 2021 was conducted. The demographic information, preoperative examinations, diagnosis, surgical details and follow-ups were collected. A total of 41 patients were enrolled [24 (58.5%] females, 17 (41.5%) males], with an average age of 47.9 years. According to the preoperative imaging findings, the relationships between the tumors and ICA were divided into four types: adjacency, compression, invasion and ICA aneurysm.Results:The ICA was preserved in 32 (78.0%, 32/41) cases and was reconstructed in nine (22.0%, 9/41) cases. All the 27 (65.9%, 27/41) tumors adjacent to ICA were successfully separated from the artery. Among the 11 tumors compressing the ICA, six were resected with the involved ICA segment and vascular reconstruction was conducted. One (2.4%, 1/41) tumor invading ICA and two (4.9%, 2/41) ICA aneurysms required revascularization. The mean follow-up time was (26.1±2.9) months. There was no recurrence, except one case of adenoid cystic carcinoma which had brain metastases one year after surgery.Conclusions:According to the preoperative imaging, lateral skull base tumors adjacent to ICA can be detached from the vascular surface. Separation should be attempted first for tumors compressing ICA, and revascularization should be followed if separation failed. Vascular reconstruction is usually needed in the removal of tumors invading ICA and ICA aneurysms. Preoperative radiology can provide good references for planning a surgery for lateral skull base tumors.

Objective:To explore the strategy of prostate biopsy in patients with prostate specific antigen(PSA)gray zone based on prostate imaging reporting and data system (PI-RADS).Methods:The clinical data of 427 patients who underwent transperineal prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. The median age was 66 (61, 72) years old. The median PSA was 6.62 (5.46, 8.19) ng/ml. The median PSA density (PSAD) was 0.15 (0.11, 0.21) ng/ml 2. The median prostate volume (PV) was 43.68 (31.12, 56.82) ml. PSA velocity (PSAV) data were available in 65 patients with negative MRI examination(PI-RADS <3), and the median PSAV was 1.40 (0.69, 2.89) ng/(ml· year). Among the patients with positive MRI(PI-RADS≥3), there were 174 patients with only 1 lesion and 83 patients with ≥2 lesions. A total of 170 patients with negative MRI underwent systematic biopsy, and 257 patients with positive MRI underwent systematic combined targeted biopsy. The PI-RADS score, regions of interest(ROI), PSAD, f/tPSA and PSAV were analyzed to explore the biopsy strategy for patients with PSA gray area based on bpMRI imaging. Results:Of the 427 patients included in the study, 194 were positive and 233 were negative. Among the patients with positive biopsy pathology, 140 cases were clinically significant prostate cancer (CsPCa). Among the MRI-negative patients, there were 33 cases with PSAV ≥1.4 ng/(ml·year), and 10 cases of prostate cancer and 6 cases of CsPCa were detected by systematic biopsy.In 32 cases with PSAV <1.4 ng/(ml·year), 3 cases of prostate cancer and 0 case of CsPCa were detected by systematic biopsy. The sensitivity of systematic biopsy for the diagnosis of prostate cancer and CsPCa in patients with PSAV≥1.4 ng/(ml·year) were 76.9% (10/13) and 100.0% (6/6) respectively, the specificity were 55.8% (29/52) and 54.2% (32/59) respectively, the negative predictive value were 90.6% (29/32) and 100.0% (32/32) respectively, and the positive predictive value were 30.3% (10/33) and 18.2% (6/33) respectively. In MRI-positive patients with PI-RADS 3, the prostate cancer detection rates of targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 41.7% (45/108), 32.4% (35/108) and 35.2% (38/108), respectively ( P=0.349). The detection rates of CsPCa were 27.8% (30/108), 21.3% (23/108) and 25.0% (27/108), respectively ( P=0.541). In patients with PI-RADS 4-5 and PSAD > 0.15 ng/ml 2, the detection rates of CsPCa in targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 67.8% (61/90), 58.9% (53/90) and 67.8% (61/90), respectively ( P=0.354). Conclusions:For MRI-negative patients, all CsPCa could be detected by perineal systematic biopsy when PSAV ≥1.4 ng/(ml·year), and active observation could be performed when PSAV <1.4 ng/(ml·year). For MRI-positive patients, targeted combined systemic biopsy was required when PI-RADS score was 3, and targeted biopsy only could be performed when PI-RADS score ≥4 and PSAD >0.15 ng/ml 2, otherwise targeted combined systemic biopsy was required.

Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs). However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biological rhythms in adult somatic cells disappear when they are reprogrammed into induced pluripotent stem cells (iPSCs). These studies indicated that the development of biological rhythms in ESCs might be closely associated with the maintenance and differentiation of ESCs. The core circadian gene Clock is essential for regulation of biological rhythms. Its role in the development of biological rhythms of ESCs is totally unknown. Here, we used CRISPR/CAS9-mediated genetic editing techniques, to completely knock out the Clock expression in mouse ESCs. By AP, teratoma formation, quantitative real-time PCR and Immunofluorescent staining, we did not find any difference between Clock knockout mESCs and wild type mESCs in morphology and pluripotent capability under the pluripotent state. In brief, these data indicated Clock did not influence the maintaining of pluripotent state. However, they exhibited decreased proliferation and increased apoptosis. Furthermore, the biological rhythms failed to develop in Clock knockout mESCs after spontaneous differentiation, which indicated that there was no compensational factor in most peripheral tissues as described in mice models before (DeBruyne et al., 2007b). After spontaneous differentiation, loss of CLOCK protein due to Clock gene silencing induced spontaneous differentiation of mESCs, indicating an exit from the pluripotent state, or its differentiating ability. Our findings indicate that the core circadian gene Clock may be essential during normal mESCs differentiation by regulating mESCs proliferation, apoptosis and activity.
Animals ; Apoptosis ; Base Sequence ; CLOCK Proteins ; genetics ; metabolism ; CRISPR-Cas Systems ; Cell Differentiation ; Cell Proliferation ; Cellular Reprogramming ; Circadian Clocks ; genetics ; Gene Editing ; Gene Expression Regulation ; Gene Knockout Techniques ; Hepatocyte Nuclear Factor 3-beta ; genetics ; metabolism ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mice ; Mouse Embryonic Stem Cells ; cytology ; metabolism ; SOXB1 Transcription Factors ; genetics ; metabolism

OBJECTIVE: To compare the long-term survival outcomes of Siewert II adenocarcinoma of esophagogastric junction (AEG) between transthoracic (TT) approach and transabdominal (TA) approach. METHODS: The databases of Gastrointestinal Surgery Department and Thoracic Surgery Department in West China Hospital of Sichuan University from 2006 to 2014 were integrated. Patients of Siewert II AEG who underwent resection were retrospectively collected. INCLUSION CRITERIA: (1) adenocarcinoma confirmed by gastroscopy and biopsy; (2) tumor involvement in the esophagogastric junction line; (3) tumor locating from lower 5 cm to upper 5 cm of the esophagogastric junction line, and tumor center locating from upper 1 cm to lower 2 cm of esophagogastric junction line; (4)resection performed at thoracic surgery department or gastrointestinal surgery department; (5) complete follow-up data. Patients at thoracic surgery department received trans-left thoracic, trans-right thoracic, or transabdominothoracic approach; underwent lower esophagus resection plus proximal subtotal gastrectomy; selected two-field or three-field lymph node dissection; underwent digestive tract reconstruction with esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis above or below aortic arch using hand-sewn or stapler instrument to perform anastomosis. Patients at gastrointestinal surgery department received transabdominal(transhiatal approach), or transabdominothoracic approach; underwent total gastrectomy or proximal subtotal gastrectomy; selected D1, D2 or D2 lymph node dissection; underwent digestive tract reconstruction with esophagus-single tube jejunum or esophagus-jejunal pouch Roux-en-Y anastomosis, or esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis; completed all the anastomoses with stapler instruments. The follow-up ended in January 2018. The TNM stage system of the 8th edition UICC was used for esophageal cancer staging; survival table method was applied to calculate 3-year overall survival rate and 95% cofidence interval(CI); log-rank test was used to perform survival analysis; Cox regression was applied to analyze risk factors and calculate hazard ratio (HR) and 95%CI. RESULTS: A total of 443 cases of Siewert II AEG were enrolled, including 89 cases in TT group (with 3 cases of transabdominothoracic approach) and 354 cases in TA group. Median follow-up time was 50.0 months (quartiles:26.4-70.2). The baseline data in TT and TA groups were comparable, except the length of esophageal invasion [for length <3 cm, TA group had 354 cases(100%), TT group had 44 cases (49.4%), χ²=199.23,P<0.001]. The number of harvested lymph node in thoracic surgery department and gastrointestinal surgery department were 12.0(quartiles:9.0-17.0) and 24.0(quartiles:18.0-32.5) respectively with significant difference (Z=11.29,P<0.001). The 3-year overall survival rate of TA and TT groups was 69.2%(95%CI:64.1%-73.7%) and 55.8% (95%CI:44.8%-65.4%) respectively, which was not significantly different by log-rank test (P=0.059). However, the stage III subgroup analysis showed that the survival of TA group was better [the 3-year overall survival in TA group and TT group was 78.1%(95%CI:70.5-84.0) and 46.3%(95%CI:31.0-60.3) resepectively(P=0.001)]. Multivariate Cox regression analysis revealed that the TT group had poor survival outcome (HR=2.45,95%CI:1.30-4.64, P=0.006). CONCLUSION The overall survival outcomes in the TA group are better, especially in stage III patients, which may be associated with the higher metastatic rate of abdominal lymph node and the more complete lymphadenectomy via TA approach.
Adenocarcinoma ; classification ; mortality ; pathology ; surgery ; China ; Databases, Factual ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; methods ; Esophagogastric Junction ; pathology ; surgery ; Gastrectomy ; methods ; Humans ; Laparotomy ; Lymph Node Excision ; methods ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms ; classification ; mortality ; pathology ; surgery ; Survival Analysis ; Thoracic Surgical Procedures