BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Objective Based on the US Food and Drug Administration(FDA)adverse event Reporting System(FAERS),to explore the signal of adverse events of basiliximab in solid organ transplantation,and to provide reference for its clinical safety.Methods The adverse drug event(ADE)signals of basiliximab in solid organ transplantation from the first quarter of 2004 to the second quarter of 2024 were retrospectively analyzed in the FAERS database of the FDA.The reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method were used for signal mining.Results A total of 1,581 ADE reports related to the use of basiliximab were obtained,involving 27 system/organ classifications.A total of 460 ADE signals were identified.The top 5 PT signals in terms of report frequency were mainly elevated serum creatinine,fever,cytomegalovirus infection,decreased hemoglobin,and decreased lymphocyte count.The top 5 PT signals in terms of signal intensity were mainly cytomegalovirus infection,elevated serum creatinine,decreased lymphocyte count,increased neutrophil count,and thrombotic microangiopathy.New ADE signals identified included decreased lymphocyte count,thrombotic microangiopathy,eye organ diseases,Kaposi's sarcoma,elevated blood lactate dehydrogenase,elevated transaminases,and shock.Conclusion Data mining using FAERS database is helpful to find new ADE signals of basiliximab in solid organ transplantation.Clinicians should focus on new severe ADE signals such as coagulation function,ocular organ diseases,elevated transaminase,shock and so on.

Objective:To investigate the current status of application of stereotactic body radiation therapy (SBRT) in China, aiming to provide reference for promoting the development of this technology.Methods:From January to March 2024, a questionnaire was designed and distributed online, targeting member units of the Professional Committee of Stereotactic Radiosurgery Treatment, which covers 175 radiotherapy units in 30 provinces and regions nationwide. The survey focused on the current application of SBRT technology and its utilization in the treatment of early-stage non-small cell lung cancer (NSCLC). A statistical description of the survey results was presented.Results:Of 175 questionnaires distributed, a total of 130 valid responses were collected, with an effective response rate of 74.3%. A total of 81.5% (106/130) of the units had implemented SBRT technology, and 99.1% of the respondents believed it was necessary to further promote SBRT technology, yet the actual training rate was only 67.0%. SBRT equipment configuration: there were a total of 267 SBRT equipment, featuring a diverse range of types, with traditional linear accelerators as the mainstays, accounting for 76.0% ( n=203), followed by 12.0% ( n=32) for TOMO, 6.4% ( n=17) for Cyber knife, 3.7% ( n=10) for Gamma knife, and proton/heavy ion equipment at 1.5% ( n=4), respectively. The percentage of units with multi-leaf collimator leaf widths ≤0.5 cm was 93.4% (99/106). The application of SBRT: the first radiotherapy unit commenced SBRT in 2000, and this technology entered a period of rapid growth after 2015, sustaining a steady increase over the past decade; SBRT technology was mainly applied in the brain, lung, liver, bone, adrenal gland, and kidney, with application rates of 97.2%, 94.3%, 86.8%, 71.7%, 56.6%, and 27.4%, respectively, while the application rates for the pancreas, metastatic lymph nodes, and other parts were less than 5%. Current status of SBRT technology application in early-stage NSCLC: 90.6% (96/106) of units had implemented SBRT; pre-treatment multi-disciplinary diagnosis and treatment accounted for 77% (74/96); the proportion of application units for peripheral and central type lung cancer lesions both exceeded 57.3%, whereas the application rate for ultra-central type and lesions > 5 cm lung cancer was less than 30%; there was significant variability in the selection of reference guidelines, dose fractionation patterns, and the concept of central type among units. Conclusions:The development of SBRT technology in China is in a period of steady growth, but several issues such as low training rate and lack of standardization still exist. The survey results provide important reference for clinical training and promotion of SBRT technology in China.

Objective Based on the US Food and Drug Administration(FDA)adverse event Reporting System(FAERS),to explore the signal of adverse events of basiliximab in solid organ transplantation,and to provide reference for its clinical safety.Methods The adverse drug event(ADE)signals of basiliximab in solid organ transplantation from the first quarter of 2004 to the second quarter of 2024 were retrospectively analyzed in the FAERS database of the FDA.The reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method were used for signal mining.Results A total of 1,581 ADE reports related to the use of basiliximab were obtained,involving 27 system/organ classifications.A total of 460 ADE signals were identified.The top 5 PT signals in terms of report frequency were mainly elevated serum creatinine,fever,cytomegalovirus infection,decreased hemoglobin,and decreased lymphocyte count.The top 5 PT signals in terms of signal intensity were mainly cytomegalovirus infection,elevated serum creatinine,decreased lymphocyte count,increased neutrophil count,and thrombotic microangiopathy.New ADE signals identified included decreased lymphocyte count,thrombotic microangiopathy,eye organ diseases,Kaposi's sarcoma,elevated blood lactate dehydrogenase,elevated transaminases,and shock.Conclusion Data mining using FAERS database is helpful to find new ADE signals of basiliximab in solid organ transplantation.Clinicians should focus on new severe ADE signals such as coagulation function,ocular organ diseases,elevated transaminase,shock and so on.

Objective To investigate the effect of platelet lysate on mitochondrial function of astrocytes after spinal cord injury.Methods Astrocytoma cells SVGp12 were incubated with different concentrations of H2O2 (100 μmol/L,400 μmol/L,1000 μmol/L,2000 μmol/L),and the OD value was determined by CCK-8 assay. The H2O2 concentration with a cell inhibition rate of about 50％ was selected for follow-up experiments. The cells were incubated with different concentrations of platelet lysate (the volume ratios of platelet lysate to culture medium were 1∶10,1∶40,1∶80,1∶160 and 1∶320) for 24 hours,and the OD value was determined,thereby selecting the optimal concentration of platelet lysate based on the cell survival rate. SVGp12 cells were divided into the normal group (cultured normally without special treat-ment),the model group (incubated with 1000 μmol/L of H2O2 for 3 hours),and the treatment group (incubated with 1000 μmol/L of H2O2 for 3 hours and then treated with platelet lysate at a volume ratio of 1∶80). The mitochondrial function was evaluated by mitochondrial activity staining,mitochondrial membrane potential detection,and mitochondrial permeability transition pore detection. Results After incubating cells with 1000 μmol/L of H2O2 for 3 hours,the cell inhibition rate was 48％,and the OD value decreased significantly (P<0.01),confirming the successful establishment of a model of astrocytes with spinal cord injury. After treated with different concentrations of platelet lysate,the OD values and cell survival rate of the cells were higher than those in the model group (P<0.05). The concentration of platelet lysate (volume ratio of 1∶80) with cell viability of 20％ was selected for follow-up experiments. Platelet lysate could improve the morphology of injured astrocytes. The mitochondrial activity of the treatment group was significantly higher than that of the model group,and the mitochondrial activity of the model group was significantly lower than that of the normal group,with statistically significant differences (P<0.05). The mitochondrial membrane potential in the model group was lower than that in the normal group,and the mitochondrial membrane potential in the treatment group was higher than that in the model group,with statistically significant differences (P<0.01). The mitochondrial permeability in the model group was greater than that in the normal group,and the mitochondrial permeability in the treatment group was smaller than that in the model group,with statistically significant differences (P<0.01).Conclusion Platelet lysate can improve the survival rate of astrocytes after spinal cord injury,enhance the mitochondrial activity of cells,and improve the mitochondrial membrane potential and mitochondrial permeability transition pore opening.

Objective:To compare the efficacy of internal fixation with video thoracoscopy-assisted rib plating and open thoracotomy in the treatment of multiple rib fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 65 patients with multiple rib fracture who were admitted to Affiliated Bishan Hospital of Chongqing Medical University between May 2021 and May 2023, including 42 males and 23 females, aged 19-75 years [(51.6±7.0)years]. Of all, 33 patients were treated with internal fixation with video thoracoscopy-assisted rib plating (thoracoscopy group), while other 32 patients treated with internal fixation with open thoracotomy (thoracotomy group). Two groups were compared in terms of surgical incision length, intraoperative blood loss, surgical duration, duration of postoperative drainage tube placement, postoperative chest tube drainage, and length of hospital stay. Postoperative pain was assessed using the visual analogue scale (VAS) at 6, 12, 24, 48, and 72 hours postoperatively. Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were detected preoperatively, at 7 days, 6 months postoperatively and at the last follow-up. The excellent and good rate of fracture healing was evaluated at 6 months postoperatively and at the last follow-up. The incidence of postoperative complications was also assessed.Results:All the patients were followed up for 12-24 months [(15.2±2.2)months]. The surgical incision length, intraoperative blood loss, and surgical duration were (4.3±1.5)cm, (65.2±15.0)ml, and (68.8±13.1)minutes in the thoracoscopy group, shorter or less than (7.2±1.7)cm, (93.3±16.3)ml, and (93.7±15.9)minutes in the thoracotomy group ( P<0.01). The duration of drainage tube placement, postoperative chest tube drainage volume and length of hospital stay were (3.8±1.5)days, (357.3±38.6)ml and (12.3±1.7)days in the thoracoscopy group, shorter or less than (5.9±1.8)days, (424.9±45.4)ml, and (18.6±2.5)days in the thoracotomy group ( P<0.01). At 6, 12, 24, and 48 hours postoperatively, the VAS scores in the thoracoscopy group were (5.1±1.6)points, (4.7±1.5)points, (4.2±1.5)points, and (3.9±1.3)points, significantly lower than those in the thoracotomy group [(8.4±1.8)points, (7.3±1.5)points, (6.3±1.3)points, and (5.2±1.2)points] ( P<0.01). There was no statistically significant difference in the VAS scores between the two groups at 72 hours postoperatively ( P>0.05). There were no statistically significant differences in FVC, FEV1 and PEF between the two groups preoperatively, at 6 months postoperatively and at the last follow-up ( P>0.05). At 7 days postoperatively, FVC, FEV1 and PEF were (4.17±0.25)L, (2.24±0.24)L, and (5.53±0.50)L/s in the thoracoscopy group, significantly higher than those in the thoracotomy group [(4.01±0.23)L, (2.12±0.21)L, and (5.23±0.42)L/s] ( P<0.05). At 6 months postoperatively, the excellent and good rate was 94% (31/33) in the thoracoscopy group and 97% (31/32) in the thoracotomy group ( P>0.05). At the last follow-up, the excellent and good rate in both groups were 100% ( P>0.05). The incidence of complications was 15% (5/33) in the thoracoscopy group, lower than 41% (13/32) in the thoracotomy group ( P<0.05). Conclusion:Compared with internal fixation with open thoracotomy in the treatment of multiple rib fracture, the internal fixation with video thoracoscopy-assisted rib plating has the advantages of less surgical trauma, milder pain at the early stage after surgery, earlier postoperative recovery of pulmonary function and fewer complications.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.