BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

BACKGROUND: Hemorrhagic stroke (HS) is associated with significant disability and mortality. However, the relationship between meteorological factors and hemorrhagic stroke, as well as the potential moderating role of these factors, remains unclear. METHODS: Daily data on HS, air pollution, and meteorological conditions were collected from January 2015 to December 2021 in Ganzhou to analyze the relationship between meteorological factors and HS admissions. This analysis employed a time-stratified case-crossover design in conjunction with a distributional lag nonlinear model. Additionally, a bivariate response surface modelling was utilized to further investigate the interaction between meteorological factors and particulate matter. The study also stratified the analyses by gender and age. To investigate the potential impact of extreme weather conditions on HS, this study defined the 97.5th percentile as representing extremely high weather conditions, while the 2.5th percentile was classified as extremely low. RESULTS: In single-day lags, the risk of admissions for HS was significantly associated with extremely low temperature (lag 1-2 and lag 13-14), extremely low humidity (lag 1 and lag 9-12), and extremely high precipitation (lag 2-7). Females exhibited greater susceptibility to extremely low temperature than males within the single-day lag pattern in the subcomponent layer, with a maximum relative risk (RR) that was 7% higher. In the cumulative lag analysis, the risk of HS admissions was significantly associated with extremely high temperature (lag 0-8∼lag 0-14), extremely low humidity (lag 0-2∼lag 0-14), and extremely high precipitation (lag 0-4∼lag 0-14). Within the cumulative lag day structure of the subcomponent layer, both extremely low and extremely high temperature had a more pronounced effect on females and aged ≥65 years. The risk of HS admissions was positively associated with extremely high barometric pressure in the female subgroups (lag 0-1 and lag 0-2). The highest number of HS admissions occurred when high PM_2.5 concentrations coexisted with low precipitation. CONCLUSIONS Meteorological factors were significantly associated with the risk of hospital admissions for HS. Individuals who were female and aged ≥65 years were found to be more susceptible to these meteorological influences. Additionally, an interaction was observed between airborne particulate matter and meteorological factors. These findings contributed new evidence to the association between meteorological factors and HS.
China/epidemiology* ; Humans ; Female ; Male ; Aged ; Middle Aged ; Cross-Over Studies ; Hospitalization/statistics & numerical data* ; Adult ; Hemorrhagic Stroke/etiology* ; Meteorological Concepts ; Weather ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Aged, 80 and over ; Young Adult

Objective:To evaluate the three-dimensional choroidal vascularity index (3D-CVI) and choriocapillaris blood flow density (CCD) changes in patients with high myopia using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA), and to investigate the relationship between axial length (AL) and choroidal vascular structure changes in high myopia.Methods:A cross-sectional study was performed.A control group of 168 eyes of 168 normal subjects, and a high myopia group of 182 eyes of 182 high myopia patients were enrolled from November 2021 to October 2022 at the Peking University People's Hospital.All subjects underwent an ultra-widefield SS-OCTA scan with an area of 24 mm × 20 mm.Full-field average and central area 3D-CVI and CCD were compared between the two groups.Correlation analysis and receiver operating characteristic curve analysis were used for 3D-CVI, CCD and AL, respectively.The AL cut-off values were determined when 3D-CVI and CCD were reduced.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2021PHB058-001).All participants voluntarily signed an informed consent form.Results:The mean 3D-CVI and central 3D-CVI in the high myopia group were (31.37±7.85)% and (29.63±9.00)%, respectively, which were significantly lower than (32.86±4.25)% and (35.01±3.96)% in the control group ( t=2.241, 7.337; both at P<0.05).The mean CCD in the high myopia group was (45.59±3.63)%, which was significantly lower than (46.47±1.36)% in the control group ( t=3.038, P=0.003).Correlation analysis showed that mean 3D-CVI and CCD were negatively correlated with AL in the high myopia group ( r=-0.547, -0.657; both at P<0.001).Receiver operating characteristic curve analysis of 3D-CVI, CCD and AL suggested that the AL cut-off value of mean 3D-CVI-reduction was 28.93 mm and the area under the curve of 0.883 ( P<0.001, sensitivity=0.690, specificity=0.944).The AL cut-off value of mean CCD-reduction was 28.26 mm and the area under the curve was 0.884 ( P<0.001, sensitivity=0.793, specificity=0.832). Conclusions:3D-CVI and CCD are both reduced in patients with high myopia.As AL increases, CCD changes earlier than 3D-CVI.

Objective:To analyze the associations between the choroidal vasculature and submacular fluid (SMF) in central serous chorioretinopathy (CSC).Methods:A retrospective study. A total of 29 CSC patients (31 eyes) with complete records who visited the Department of Ophthalmology in Peking University People's Hospital from August 1, 2021 to March 1, 2023 were included in this study. The patients were divided into complete absorption and incomplete absorption groups according to the status of SMF in the last visit. All the patients underwent ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) with a scanning range of 24 mm × 20 mm. The UWF SS-OCTA images were automatically analyzed in 9 regions (superotemporal, superior, superonasal, temporal, central, nasal, inferotemporal, inferior, and inferonasal). Alterations of choroidal vasculature in the nine subfields after SMF absorption were described, including choroidal thickness (CT), flow density of choriocapillaris layer, vessel density of large choroidal vessel layer, three-dimensional choroidal vascularity index (CVI), the mean choroidal vessel volume (mCVV), and the mean choroidal stroma volume (mCSV). The relevant factors affecting the complete absorption of SMF were additionally evaluated.Results:At baseline, CT ( Z=2.859, P=0.004), mCVV ( t=2.514, P=0.018), and mCSV ( Z=2.958, P=0.003) in the superotemporal region of the affected eyes in the incomplete absorption group were significantly higher than those in the complete absorption group. Compared with baseline, at the last visit, the proportion of asymmetric vortex veins in the complete absorption group was significantly decreased ( χ2=6.000, P=0.014), CVI in the superotemporal, superonasal, temporal, central, nasal, inferotemporal, and inferonasal regions ( t=-4.125, t=-3.247, Z=-3.213, t=-2.994, t=-3.417, t=-3.733, t=-3.795; P=0.001, 0.006, 0.001, 0.010, 0.005, 0.003, 0.002), the mCVV of 9 regions ( t=-2.959, t=-2.537, t=-2.235, t=-3.260, t=-3.022, t=-2.796, t=-2.747, Z=-2.107, t=-2.935; P=0.011, 0.025, 0.044, 0.006, 0.010, 0.015, 0.017, 0.035, 0.012) were significantly decreased. Compared to the complete absorption group, the choroidal blood flow changes in the non-complete absorption group were more limited, and CT in the upper region increased significantly at the last follow-up ( t=2.272, P=0.037). Multivariate logistic regression analysis revealed that baseline CT in the superotemporal region may be an independent risk factor affecting the complete absorption of SMF (odds ratio=0.981, 95% confidential interval 0.965-0.997, P=0.021). Conclusions:In the process of SMF absorption in CSC, significant reductions of choroidal blood flow were found in the large choroidal vessel layer, and there may be a locally compensatory increase in CT. In addition, baseline CT in superotemporal region is an independent risk factor affecting SMF absorption.

Central serous chorioretinopathy (CSC) is one of the representative pachychoroid spectrum disease. Although fundus fluorescein angiography and indocyanine green angiography can be used as the gold standard for the diagnosis of CSC, they are invasive examinations, which may bring certain risks in clinical application and cannot help us obtain quantitative parameters. Optical coherence tomography angiography (OCTA), as a non-invasive and quantitative examination, is an important imaging tool for understanding the pathogenesis, diagnosis and treatment of CSC. With the advancement of OCTA, the swept-source OCTA has a satisfying scanning depth, a wider scanning range and a higher resolution. The development of OCTA broadens the horizons of the pathogenesis of CSC, promotes the understanding of the pathophysiology of CSC, and sheds new light for its clinical diagnosis and treatment. Based on OCTA, the choroid and retina in eyes with CSC are presented with qualitative and quantitative changes in vascular system. OCTA-guided CSC treatment and the discovery of prognostic markers based on OCTA challenge the application of traditional imaging techniques in CSC. With the continuous improvement and progress of OCTA technology, traditional angiography combined with OCTA will bring great benefits to the diagnosis and treatment of CSC. This review summarizes the quantitative application of OCTA in the pathogenesis, diagnosis and treatment of CSC.

In China, the prevalence of overweight and obesity among adults is 34.3% and 16.4% respectively. Bariatric/metabolic surgery can effectively relieve morbid obesity by limiting nutrient absorption or regulating metabolism, consequently reducing obesity-related complications such as type 2 diabetes and hypertension and improving the quality of life for patients. Currently, the mainstream surgical methods are sleeve gastrectomy, Roux-en-Y gastric bypass, etc. Other new exploratory surgical methods, including combined laparoscopic sleeve gastrectomy, intragastric balloon, etc., are also undergoing continuous development. Here we reviewed the evolution of mainstream and emerging exploratory methods for bariatric/metabolic surgeries and discussed the merits and limitations of individual surgical methods, in aim to provide clinicians with more options for individualized treatment strategy for patients.

Objective: To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies. Methods: Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP, Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese bio-medical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are: (1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4) data from multiple reports but originated from one study, where we extract information from all reports; (5) guidelines, includes: national or academic guidelines/experts 'consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses). Results: Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and finally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing. Conclusions ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.

Objective:To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies.Methods:Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP, Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese biomedical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are: (1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4) data from multiple reports but originated from one study, where we extract information from all reports; (5) guidelines, includes: national or academic guidelines/experts 'consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses).Results:Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and finally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing.Conclusions:ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.

The advantages of 5G communication, including large bandwidth, low latency and wide connection, and rapid transmission, have proved to be vital in facilitating emergency medical rescue. On June 17th, 2019, an earthquake occurred in Channing, Yibin, Sichuan Province. Sichuan Provincial People’s Hospital initiated the Emergency Medical Rescue System for the rescue operation in the disastrous area. This was the first use of 5G emergency medical rescue worldwide. Remote consultations, injury assessments and helicopter transfers were carried out for the critical patients. Our rescue system have been effective and efficient in rapid responding, information transmission and the coordination of medical resources, which has led to the best possible medical decisions and treatments. However, there were challenges found in the application of this system: the stability of 5G signal, the optimization of the configuration of 5G ambulances, and the survival rate and self guarantee in the field. In conclusion, this practice of 5G emergency medical system provides a new paradigm and valuable experiences for the improvements in disaster rescue in China and worldwide.

BACKGROUND: Fibular fixation and tantalum rod implantation are two commonly used methods for the treatment of early osteonecrosis of the femoral head (ONFH), both of which can effectively delay or even reverse the progress of ONFH. However, further comparative evaluation on their mechanical properties and therapeutic efficacy is required.OBJECTIVE: To compare the clinical efficacy of fibular fixation and tantalum rod implantation on ONFH at early stage.METHODS: Fifty-eight patients (81 hips) suffered from ONFH with ARCO stage 1 and stage 2, and underwent fibular fixation (30 cases, 41 hips) or tantalum rod implantation (28 cases, 40 hips). Postoperatively, both groups were followed up for over 2 years. The Harris scores of the hip were compared between two groups before and after treatment. With femoral head collapse and the collapse distance > 4 mm as observation points, the survival rate of the femoral head was compared between two groups.RESULTS AND CONCLUSION: The postoperative Harris scores of the two groups were significantly improved than before (P < 0.05). With the appearance of femoral head collapse as the observation point, the Kaplan-Meier survival curve showed that the overall survival rate of the hip was 83% in the fibular fixation group and 65% in the tantalum rod implantation group. After examined by log-rank (Mantel-Cox), there was a significant difference in the survival rate of the hip at Stage IIC between two groups (P=0.0431). With > 4 mm collapse as the observation point, the Kaplan-Meier survival curve showed that overall survival rate of the hip was 95% in the fibular fixation group and 83% in the tantalum rod implantation group. After examined by log-rank (Mantel-Cox), there was a significant difference in the survival rate of the hip at Stage IIC between two groups (P=0.0418). To conclude, both fibular fixation and tantalum rods implantation applied to ONFH at early stage can effectively improve the hip function, and the survival rate of the hip at ARCO Stage IIC is better in patients undergoing fibular fixation than tantalum rod implantation.