Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Abstract Prevention and control of myopia requires comprehensive measures. Based on the system established earlier, the system is revised and upgraded. The original system emphasizes comprehensive measures and proposes to focus on both the symptoms and root causes. These measures are summarized into six aspects, three address the root cause measures including health education, glasses optics and visual environment, and three address symptoms measures including eye exercises, physical therapy and drugs. The paper is comprehensively supplemented and analyzes the primary and the secondary, and promotes physical therapy from treating the symptoms to treat both the symptoms and the root causes. These improvement measures will help promote the prevention and control of myopia in children and adolescents.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Background and Aims:Rupture is the most serious complication of abdominal aortic aneurysm,requiring rapid diagnosis,emergency surgery,and posing significant surgical challenges,with high mortality rates. Currently,there is very limited reporting on ruptured abdominal aortic aneurysm (rAAA) in our country,which presents numerous difficulties for the prevention and treatment of rAAA. This study collected the data of epidemiological characteristics,treatment outcomes,and prognosis of rAAA patients from multiple centers with a large sample size,analyzing the current status and trends of rAAA surgery in China over the past decade,aiming to provide reference for clinical practice.Methods:The clinical and follow-up data of 161 rAAA patients treated at five major vascular surgery centers (50 from Drum Tower Hospital Affiliated to the Medical School,Nanjing University;19 from the First Affiliated Hospital of Anhui Medical University;33 from the Second Affiliated Hospital of Nanchang University;31 from Qilu Hospital,Shandong University;and 28 from the First Affiliated Hospital of the University of Science and Technology of China) were retrospectively analyzed.Results:Among the 161 patients,124 (77.02％) were male and 37 (22.98％) were female,with an average age of 68.27 years. The median age at diagnosis was 70 years for males and 71 years for females. The overall mean aneurysm diameter was 7.11 cm,with males at 7.72 cm and females at 6.82 cm,showing a statistically significant difference (P<0.05). The main comorbidities were hypertension and coronary artery disease. Over 80％ of patients presented with abdominal pain as the initial symptom,while 15％ presented with low back pain,and 8 patients sought medical attention for dizziness or visual disturbances. Among the 161 patients,86 underwent open surgical repair (OSR),and 75 received endovascular aneurysm repair (EVAR). The proportion of EVAR has increased annually,reaching nearly 70％ in the past five years,and up to 90％ in patients aged over 70 years. All OSR procedures were performed under general anesthesia,while 20 EVAR cases used local anesthesia and 55 used general anesthesia. Compared to the OSR group,the EVAR group showed significant differences in operative time (231.77 min vs. 162.49 min),intraoperative blood transfusion volume (1578.56 mL vs. 843.87 mL),length of hospital stay (21.21 d vs. 15.34 d),ICU stay duration (8.28 d vs. 5.49 d),and hospitalization costs (108500 CNY vs. 132800 CNY) (all P<0.05). No significant differences were found between the EVAR and OSR groups in total complications or perioperative mortality rates (both P>0.05). The main causes of perioperative death included respiratory and circulatory failure,acute myocardial infarction,and severe infections. Postoperative follow-up was effectively conducted for 92 patients,with follow-up durations ranging from 10 to 142 months. Survival analysis revealed no significant difference in survival rate between the OSR and EVAR groups (P=0.3182).Conclusion:rAAA is a rare and high-risk disease,with certain clinical differences between male and female patients. The number of EVAR procedures has increased rapidly;however,EVAR has not shown a significant advantage over OSR in improving long-term survival rates.

Background and Aims:Rupture is the most serious complication of abdominal aortic aneurysm,requiring rapid diagnosis,emergency surgery,and posing significant surgical challenges,with high mortality rates. Currently,there is very limited reporting on ruptured abdominal aortic aneurysm (rAAA) in our country,which presents numerous difficulties for the prevention and treatment of rAAA. This study collected the data of epidemiological characteristics,treatment outcomes,and prognosis of rAAA patients from multiple centers with a large sample size,analyzing the current status and trends of rAAA surgery in China over the past decade,aiming to provide reference for clinical practice.Methods:The clinical and follow-up data of 161 rAAA patients treated at five major vascular surgery centers (50 from Drum Tower Hospital Affiliated to the Medical School,Nanjing University;19 from the First Affiliated Hospital of Anhui Medical University;33 from the Second Affiliated Hospital of Nanchang University;31 from Qilu Hospital,Shandong University;and 28 from the First Affiliated Hospital of the University of Science and Technology of China) were retrospectively analyzed.Results:Among the 161 patients,124 (77.02％) were male and 37 (22.98％) were female,with an average age of 68.27 years. The median age at diagnosis was 70 years for males and 71 years for females. The overall mean aneurysm diameter was 7.11 cm,with males at 7.72 cm and females at 6.82 cm,showing a statistically significant difference (P<0.05). The main comorbidities were hypertension and coronary artery disease. Over 80％ of patients presented with abdominal pain as the initial symptom,while 15％ presented with low back pain,and 8 patients sought medical attention for dizziness or visual disturbances. Among the 161 patients,86 underwent open surgical repair (OSR),and 75 received endovascular aneurysm repair (EVAR). The proportion of EVAR has increased annually,reaching nearly 70％ in the past five years,and up to 90％ in patients aged over 70 years. All OSR procedures were performed under general anesthesia,while 20 EVAR cases used local anesthesia and 55 used general anesthesia. Compared to the OSR group,the EVAR group showed significant differences in operative time (231.77 min vs. 162.49 min),intraoperative blood transfusion volume (1578.56 mL vs. 843.87 mL),length of hospital stay (21.21 d vs. 15.34 d),ICU stay duration (8.28 d vs. 5.49 d),and hospitalization costs (108500 CNY vs. 132800 CNY) (all P<0.05). No significant differences were found between the EVAR and OSR groups in total complications or perioperative mortality rates (both P>0.05). The main causes of perioperative death included respiratory and circulatory failure,acute myocardial infarction,and severe infections. Postoperative follow-up was effectively conducted for 92 patients,with follow-up durations ranging from 10 to 142 months. Survival analysis revealed no significant difference in survival rate between the OSR and EVAR groups (P=0.3182).Conclusion:rAAA is a rare and high-risk disease,with certain clinical differences between male and female patients. The number of EVAR procedures has increased rapidly;however,EVAR has not shown a significant advantage over OSR in improving long-term survival rates.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

Objective:To investigate the feasibility, efficacy and adverse reactions of programmed death-1(PD-1) inhibitors in patients with acquired immunodeficiency syndrome (AIDS) complicated with malignant tumor.Methods:From September 2020 to August 2021, patients with AIDS complicated with malignant tumor in Zhongnan Hospital of Wuhan University were enrolled. Data including basic information, laboratory test results, CD4 + T cell count, human immunodeficiency virus (HIV) viral load were collected. Patients were continuously administered intravenously PD-1 monoclonal antibody until disease progression or intolerant toxicity reaction occurred. Adverse reactions during treatment were recorded.And treatment outcomes were assessed once every 12 weeks after treatment. HIV viral load was measured after treatment once a week for four consecutive times, then once four weeks for two consecutive times, and then once every 12 weeks. Results:Ten patients were included in the study, including seven males and three females, three cases of Hodgkin′s lymphoma, two cases of cervical cancer and hepatocellular carcinoma respectively, one case of non-Hodgkin′s lymphoma, non-small cell lung cancer and anal cancer respectively. There were four patients with CD4 + T cell count of 100 to 200 cells/μL and two patients with CD4 + T cell count lower than 100 cells/μL. All patients had completed at least three cycles of treatment with PD-1 monoclonal antibody, HIV viral load remained lower than 20 copies /mL. Three cases achieved complete response and three cases achieved partial response. Adverse reactions were cutaneous capillary endothelial proliferation (CCEP) (seven cases), major bleeding (three cases), and hearing impairment (one case). Conclusions:PD-1 inhibitor has no adverse effect on the continuous suppression of HIV viral load and has an effect on tumor control, so it is a viable choice in AIDS patients complicated with tumor. However, due to its considerable adverse reactions, multidisciplinary cooperation is needed to reduce the risk of complications and deal with serious complications.

Objective:To investigate the long-term efficacy and safety of alternating double balloon occlusion combined with intra-aneurysm injection of human fibrin binder in the endovascular repair of ruptured abdominal aortic aneurysm (rAAA).Methods:The clinical data of 28 patients with rAAA admitted to Department of Vascular Surgery, the Fourth Affiliated Hospital of Guangxi Medical University from January 2015 to December 2019 were retrospectively analyzed. There were 23 males and 5 females, aged (62±5) years (range: 46 to 88 years).The maximum diameter of the tumors was (65.2±10.5) mm (range: 47.3 to 100.5 mm), all of which were subrenal rAAA. The intraoperative EVAR for abdominal aortic aneurysm was successfully performed under the emergency green channel procedure, and this surgery was assisted used the double balloon occlusion technique in aorta of inferior renal and superior renalcombined with intraoperative human fibrin binder injection technique. Observation indexes included: patients with preoperative preparation, operation time, hospitalization days, surgical treatment success rate and the incidence of postoperative complications, and aortic stent form during the follow-up period, the incidence of leakage, branch stents patency rate and infection rates.Results:The preoperative preparation time of 28 patients was (45.5±8.5) minutes (range:20 to 100 minutes). The operation time was (100.0±15.5) minutes (range:85 to 210 minutes), the ICU stay time was (7±2) days(range:1 to 17 days). The length of hospitalization was (13.5±2.5) days(range:5 to 43 days). The success rate of surgical treatment was 92.9% (26/28). Two patients died, 1 case died of postoperative multifocal lacunar cerebral infarction and massive gastrointestinal hemorrhage, and another elderly patient (84 years old) died of massive abdominal fluid due to preoperative abdominal aortic aneurysm rupture, postoperative complicated with significant abdominal compartment syndrome, and secondary multiple organ failure. Balloon occlusion of the upper renal aorta took (13±2)minutes (range:12 to 30 minutes). The intraoperative injection of fibrin adhesive was (14±2) ml(range:6 to 28 ml) in 22 cases. The incidence of major postoperative complications was 57.1% (16/28). Among the 26 patients who survived the surgery, 69.2% (18/26) completed the 3-year follow-up, and the follow-up time was (30±3) months(range:13 to 36 months). During the follow-up, the aortic stent was in good shape without obvious displacement. The incidence of leakage within 6 months after the operation was 10.7% (3/28), and there was no internal leakage in the patients who were followed up for 36 months after the operation. The patency rate of renal artery and iliac artery branch stents was 16/18. The incidence of stent infection was 7.7% (2/26), 1 case occurred at 1 month and another case at 6 months, respectively. All patients recovered after prolonged intensive anti-infection therapy.Conclusions:Under the standard emergency treatment process, the double balloon alternating occlusion technique combined with the intra-aneurysm injection of human fibrin adhesive technique can assist the successful completion of the endovascular repair of rAAA, effectively improve the success rate of treatment for patients, and reduce the incidence of postoperative leakage and serious complications. The mid-term and long-term results of EVAR for rAAA are good, safe and reliable.

Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.