Objective To explore the mechanism of ubiquitin specific peptidase 21 (USP21) increasing the stability of forkhead box protein M1 (FOXM1) and promoting M2 polarization of macrophages in endometriosis (EM). Methods Eutopic endometrial stromal cells (EESC) collected from patients and normal endometrial stromal cells (NESC) from routine health examiners were cultured in vitro, and the expression levels of USP21 and FOXM1 were detected using RT-qPCR and Western blot. EESCs were co-cultured with macrophages. M1 polarization markers of interleukin 6 (IL-6) and CXC chemokine ligand 10 (CXCL10) and M2 polarization markers of CD206 and fibronectin 1 (FN1) were tested using RT-qPCR. M2 marker CD206 was further detected by flow cytometry. IL-6, tumor necrosis factor-alpha (TNF-α), IL-10, and transforming growth factor-beta (TGF-β) levels in cell supernatant were detected by ELISA. Co-immunoprecipitation was used to assess the interaction between USP21 and FOXM1, and the ubiquitination level of FOXM1. FOXM1 protein stability was detected through cycloheximide (CHX) assay. Results USP21 and FOXM1 expression levels in the EESC group were significantly increased compared with those in the NESC group; compared with the NESC + M0 group, the EESC + M0 group showed no significant difference in the expression of M1 polarization markers (IL-6 and CXCL10), but increased expression of M2 polarization markers (CD206 and FN1), along with notably increased number of M2 macrophages; there was no significant difference in IL-6 and TNF-α levels, but increased levels of IL-10 and TGF-β in the cell supernatant. The above findings indicated that the deubiquitinase USP21 was highly expressed in EM, promoting M2 polarization of macrophages. Knocking down USP21 or FOXM1 can inhibit M2 polarization of EM macrophages. USP21 interacted with FOXM1 in EESC, leading to a decrease in FOXM1 ubiquitination level and an increase in FOXM1 protein stability. Overexpression of FOXM1 reversed the inhibitory effect of knocking down USP21 on M2 polarization of EM macrophages. Conclusion The deubiquitinase USP21 interacts with FOXM1 to increase the stability of FOXM1 and promote M2 polarization of EM macrophages.
Humans ; Forkhead Box Protein M1/genetics* ; Female ; Macrophages/cytology* ; Endometriosis/genetics* ; Ubiquitin Thiolesterase/genetics* ; Cells, Cultured ; Endometrium/metabolism* ; Ubiquitination ; Adult ; Interleukin-10/metabolism* ; Interleukin-6/metabolism* ; Protein Stability ; Stromal Cells/metabolism*

In recent years,with the development of the bio-psycho-social medical model,more and more attention has been paid to the relationship between psycho-emotional factors and liver.According to traditional Chinese medicine theory,the liver is mainly responsible for catharsis and regulating emotion,which is closely related to emotion.Epidemiological studies have shown that all kinds of liver diseases are accompanied by different degrees of mental disorders,and mental and emotional abnormalities may promote the occurrence of liver diseases and affect the prognosis.Liver and emotion have a common pathogenesis in pathology,involving the dysfunction of nervous,endocrine and immune systems.Based on the basic theory of traditional Chinese medicine and modern medical research,this review analyzes the correlation between emotions and liver.At the same time,neurotransmitters,inflammatory cytokines,brain-derived neurotrophic factor(BDNF),soluble epoxide hydrolase(sEH),intestinal microecology,hypothalamic-pituitary-adrenal(HPA)axis and hypothalamic-pituitary-thyroid(HPT)axis,which summarizes the potential mechanisms of liver disease complicated with emotional disorders,and provides certain reference value for future theoretical research and clinical treatment.

Objective·To explore the role of advanced platelet-rich fibrin(A-PRF)in osteochondral regeneration.Methods·Bone-marrow mesenchymal stem cells(BMSCs)and knee joint chondrocytes were obtained from New Zealand rabbits.A-PRF was obtained by low-speed centrifugation of the heart blood of rabbits.The histological structure of A-PRF was observed by an optical microscope.The release of growth factors in A-PRF was detected by ELISA,including platelet-derived growth factor,transforming growth factor-β,insulin-like growth factor,vascular endothelial growth factor,epidermal growth factor and fibroblast growth factor.A-PRF's cytotoxicity and capability for promoting the proliferation of rabbit BMSCs were detected by live/dead double staining and MTT methods.The effect of A-PRF on the gene expression of type Ⅱ collagen,aggrecan,alkaline phosphatase(ALP)and osteocalcin(OCN)in rabbit BMSCs was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Transwell chambers were used to determine the effect of A-PRF on the migration ability of rabbit BMSCs and the chondrocytes.Rabbit knee osteochondral defect models were established,and 18 rabbits were randomly divided into 3 groups.The A-PRF group(n=6)was implanted with A-PRF in the defect,the A-PRF+BMSCs group(n=6)was implanted with rabbit BMSCs on A-PRF,and the control group(n=6)did not undergo implantation.The rabbits were sacrificed 12 weeks after surgery and the knee joint specimens were stained with hematoxylin-eosin(H-E),toluidine blue and safranin O/fast green.Based on the surface morphology and histology of the knee joints,the International Cartilage Repair Society(ICRS)scoring system was used for macroscopic and histological scoring.Results·A-PRF had a loose network structure and can slowly release growth factors.No cytotoxicity to rabbit BMSCs was observed after adding A-PRF,and the the capability for promoting the proliferation of rabbit BMSCs was significantly increased at 24,48 and 72 h after adding A-PRF(all P<0.05).Chondrogenesis-related gene Ⅱ collagen and aggrecan,as well as osteogenesis-related genes ALP and OCN were significantly up-regulated(all P<0.05).After adding A-PRF,the migration abilities of rabbit BMSCs and chondrocytes were significantly enhanced(both P<0.05),and the migration ability of rabbit BMSCs was significantly higher than that of chondrocytes(P=0.025).The joint surface morphology in the rabbit knee joint defect models was observed.It can be seen that the defects in the A-PRF group and the A-PRF+BMSCs group were basically restored,while the the defects in the control group were only covered by soft tissue.In the ICRS macroscopic score,there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group,but the scores of the two groups were all significantly higher than those of the control group(all P<0.05).According to the histological results,both the A-PRF group and the A-PRF+BMSCs group formed osteochondral repair,but the cartilage in the A-PRF group was more mature,while the control group formed fibrous repair.In the ICRS histological score,there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group,but the scores of both the groups were significantly higher than those of the control group(both P<0.05).Conclusion·Autologous A-PRF has good biocompatibility and the capability for promoting the proliferation of BMSCs.It can promote the repair of cartilage and subchondral bone both in vitro and in vivo.

Objective To investigate the effects of microRNA-26a-5p(miR-26a-5p)on high glucose-induced retina Müller activation and apoptosis by regulating PTEN/PI3K/Akt signaling pathway,and the potential mechanism of diabetic retinal neurodegeneration.Methods Various concentrations of high glucose were added into rMC-1 culture.CCK-8 and flow cytometry was used to examine cell proliferation and apoptosis respectively.The regulatory effects of miR-26a-5p on the expressions of PTEN,PI3K and Akt were observed by real-time PCR;the expression levels of IL-1β and IL-6 in Müller cells were examined by ELISA.The data were processed by Graphpad 8.0 software.Results Müller cells grew actively in high-glucose stimulation culture.Compared with the control group,the activity of Müller cells stimulated by 50 mmol/L glucose increased gradually at 12 h and 24 h,but decreased at 48 h after stimulation,when Müller cells apoptosis increased.The difference between the groups was statistically significant(P＜0.05).The expression of miRNA-26a-5p decreased,that of PTEN increased,and those of PI3K and Akt decreased.Meanwhile,IL-1β and IL-6 levels were significantly increased in Müller cells.miR-26a-5p over-expression alleviated injuries to high glucose stimulated retinal Müller cells by inhibiting PTEN,which upregulated the expression of PI3K/Akt and downregulation of IL-1β and IL-6(P＜0.01).Conclusion Upregulating miR-26a-5p protects Müller cells against apoptosis,probably through regulation of PTEN/PI3K/Akt and affecting the production of inflammatory factors.

[Objective] To analyze the characteristics of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 allele polymorphisms among cord blood donors in Guangdong population. [Methods] According to HLA high resolution genotyping data of 32 717 samples of cord blood donors from Guangdong Cord Blood Bank from January 2009 to December 2023, the allele frequencies were calculated by direct counting and the haplotype frequencies were calculated by using Arlequin software 3.5.2.2. [Results] A total of 102 HLA-A alleles, 160 HLA-B alleles and 96 HLA-DRB1 alleles were detected in 32 717 samples. Among them, 46 HLA-DPB1 alleles were detected in 5 377 samples, and 66 HLA-C alleles and 35 HLA-DQB1 alleles were detected in 13 310 samples. The most common alleles were HLA-A^*11∶01 (28.96%), HLA-B^*40∶01 (15.23%), HLA-DRB1^*09∶01 (15.72%), HLA-C^*01∶02 (19.40%), HLA-DQB1^*03∶01 (20.85%) and HLA-DPB1^*05∶01 (40.79%). The most common 3 loci haplotype and 6 loci haplotype were HLA-A^*02∶07-B^*46∶01-DRB1^*09∶01 (1.55%), HLA-C^*07∶02-DQB1^*03∶01-DPB1^*05∶01 (1.77%), HLA-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (3.31%) and HLA-A^*02∶07-B^*46∶01-C^*01∶02-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (0.30%). [Conclusion] In this study, the allele and haplotype frequencies of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 were obtained in the cord blood donors in Guangdong, which can provide important reference data for HLA gene related research and the selection of donors for clinical application.

Objective To compare the superiority of total arterial revascularization in patients with coronary artery disease (CAD) complicated with left ventricular dysfunction. Methods This retrospective study included the patients who were diagnosed with CAD and the left ventricular ejection fraction (LVEF) of ≤40% and underwent coronary artery bypass grafting (CABG) at our hospital from January 2016 to July 2019. The patients were divided into two groups according to the different types of bypass vessels: a total arterial revascularization group (TAR group) and a conventional group (a CON group). The clinical data were compared between the two groups to explore the incidence of important complications and evaluate the safety of total arterial revascularization and its protective effect on cardiac function. Results Finally 75 patients were enrolled including 52 males and 23 females with a mean age of (61.58±7.93) years. There were 35 patients in the TAR group and 40 patients in the CON group. The operation time and the drainage volume at 24 hours after operation in the TAR group were longer or more than those in the CON group (P<0.001), but there was no statistical difference in hospital stay, postoperative complications (such as respiratory failure, mediastinal infection, renal failure), intra-aortic balloon pump or extracorporeal membrane oxygenation use rate (P>0.05). After 2 years of follow-up, compared with the CON group, the cardiac function of the TAR group was significantly improved, the LVEF was higher, the left ventricular end diastolic diameter was reduced, and the graft stenosis rate was lower (all P<0.05). Conclusion Total arterial revascularization is a safe and feasible surgical method, which is helpful to improve the cardiac function and improve the quality of life.

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P<0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.

Since the occurrence of the first case of "egg freezing for single women" in China, it has aroused different discussions and thoughts from all walks of life. Through the ethical analysis of the four principles of bioethics, this paper found a reasonable ethical basis for single women’s egg freezing. From the perspective of favorable principle, egg freezing could temporarily preserve women’s fertility, which is conducive to women’s better realization of their own personal value and social values. From the perspective of no harm principle, no harm is relative, and the harm brought by egg freezing technology is within the acceptable and permissible range. From the perspective of justice principle, whether there is gender discriminatory in that men could freeze their sperm but women have many restrictions on egg freezing. From the principle of respect for autonomy, whether to choose egg freezing is a manifestation of women’s autonomy rights, which should be respected. This paper tried to propose corresponding solutions to the ethical and legal issues caused by the permission of egg freezing from the legal perspective, the medical ethics committee’s responsibilities, and the ethical level.

Objective:To develop a risk prediction lineogram of neooperative atrial fibrillation in patients with esophageal cancer.Methods:The clinical data of 1 509 patients undergoing esophageal cancer surgery admitted to the department of esophageal surgery of our hospital from December 2019 to April 2022 were gathered, and they were divided into two layers according to whether they had new atrial fibrillation after surgery. In each layer, they were randomly divided into training set and test set in a ratio of 7∶3. In the training population, the multi-factor logistic regression method was used to establish the prediction model, and the line graph of the prediction model was drawn. The ROC curve and calibration curve were drawn to assess the differentiation ability and calibration ability of the prediction model. The test set population is used to validate the prediction model. Results:A total of 1 509 patients with esophageal cancer were included in the study, and the incidence of new atrial fibrillation after surgery was 247 patients(16.4%). A total of 1 039 patients(68.9%) were enrolled in the training set. The multivariate logistic regression model indicated that age, gender, BMI, pulmonary infection, the use of invasive ventilator, and the need for additional drainage of fluid accumulation were the influencing factors for new postoperative atrial fibrillation. The AUC of the training set prediction model under ROC curve was 0.775(95% CI: 0.737-0.812, P<0.001), indicating that the model has high predictive discrimination ability. Calibration curve and Hosmer- Lemeshow test results P=0.796, indicating that the model has good consistency of prediction ability. There were 470 subjects(31.1%) in the test set. The results showed that the AUC of the prediction model under the ROC curve was 0.773(95% CI: 0.719-0.826, P<0.001), indicating that the prediction model still has a high discriminative ability in the test set population. Conclusion:Patients with age, gender, BMI, pulmonary infection, the use of invasive ventilator, and the need for additional drainage of effusion are at higher risk of new atrial fibrillation after surgery. The timely prediction, prevention and management of POAF are crucial to improve the prognostic quality of postoperative patients with esophageal cancer by constructing clinical prediction models.

OBJECTIVE: To investigate the effect of body mass index (BMI) on the short-term effectiveness of high tibial osteotomy (HTO) in the treatment of varus knee arthritis. METHODS: The clinical data of 84 patients (84 knees) with varus knee arthritis treated with HTO between May 2016 and August 2020 were retrospectively analyzed. According to BMI, the patients were divided into normal group (32 patients in group A, BMI<25 kg/m ²), overweight group (27 patients in group B, BMI>30 kg/m ²), and obese group (25 patients in group C, BMI>30 kg/m ²). The BMI of groups A, B, and C were (23.35±0.89), (26.65±1.03), and (32.05±1.47) kg/m ², respectively. There was no significant difference ( P>0.05) in gender, age, surgical side, disease duration, and preoperative Hospital for Special Surgery (HSS) score, visual analogue scale (VAS) score, knee range of motion, and hip-knee-ankle angle (HKA) between groups. The operation time, intraoperative dominant blood loss, and the decrease of hemoglobin on the 3rd day after operation were recorded and compared between groups. The improvement of knee joint function and pain status were evaluated by knee joint HSS score, knee range of motion, and VAS score before and after operation, and measuring the HKA of patients on X-ray film. During the follow-up, the X-ray films of the knee joint were reexamined to observe the position of the internal fixator and the healing of osteotomy. RESULTS: All patients completed the operation successfully and were followed up 8-40 months (mean, 19.3 months). There was no significant difference in follow-up time, operation time, intraoperative dominant blood loss, and the decrease of hemoglobin on the 3rd day after operation between groups ( P>0.05). No operative complications such as severe vascular or nerve injury occurred. After operation, deep venous thrombosis of lower extremities occurred in 1 case in groups A and B respectively, and fat liquefaction of surgical incision occurred in 2 cases in group C. There was no significant difference in the incidence of perioperative complications between groups (3.1% vs. 3.7% vs. 8.0%) ( P=0.689). During the follow-up, there was no bone nonunion, plate fracture or loosening. At last follow-up, HSS score, VAS score, knee range of motion, and HKA significantly improved in the 3 groups when compared with those before operation ( P<0.05), but there was no significant difference in the differences of the above indexes between groups before and after operation ( P>0.05). CONCLUSION BMI does not affect the short-term effectiveness of HTO in the treatment of varus knee arthritis. HTO can be selected for overweight and obese patients after standard medical treatment is ineffective.
Humans ; Osteoarthritis, Knee/surgery* ; Body Mass Index ; Overweight ; Retrospective Studies ; Treatment Outcome ; Knee Joint/surgery* ; Obesity/complications* ; Osteotomy ; Blood Loss, Surgical