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

OBJECTIVE: To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients. METHODS: Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores. RESULTS: The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05). CONCLUSION Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans ; Female ; Male ; Middle Aged ; Aged ; Fracture Fixation, Internal/instrumentation* ; Bone Wires ; Bone Plates ; Retrospective Studies ; Colles' Fracture/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Open Fracture Reduction/methods* ; Osteoporotic Fractures/surgery*

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged

Objective:To explore the clinical characteristics of patients with brucellosis complicated with epididymo-orchitis (Brucellar epididymo-orchitis, BEO), so as to provide reference for clinical diagnosis and treatment of BEO.Methods:General and clinical data of 293 male patients with acute brucellosis admitted to the Beidahuang Industry Group General Hospital from January 2023 to December 2024 were retrospectively collected. They were divided into a BEO group (30 cases) and a non-BEO group (263 cases) based on the presence or absence of epididymo-orchitis. Epidemic characteristics, clinical manifestations and laboratory examination results were compared and analyzed.Results:Among 293 male patients with acute brucellosis, the incidence of BEO was 10.24% (30/293). Their age was mainly concentrated in 45 - < 60 years old (53.33%, 16/30), and occupation was mostly farmers (63.33%, 19/30). There were no statistically significant differences in the distribution of age, occupation, exposure history and onset season between the BEO group and the non-BEO group ( P > 0.05). The distribution of abdominal pain and urinary frequency/urgency/pain symptoms was compared, and the differences were statistically significant ( P < 0.05). White blood cell count (WBC), neutrophil count (NEUT), and C-reactive protein (CRP) levels in the BEO group were higher than those in the non-BEO group ( P < 0.05), while the levels of cytokines interleukin (IL)-6 and interferon-γ (IFN-γ) were lower than those in the non-BEO group ( P < 0.05). After 6 - 8 weeks of hospitalization, the levels of WBC, NEUT, CRP, albumin, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, α-hydroxybutyrate dehydrogenase, lactate dehydrogenase, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, and IFN-γ in patients of the BEO group were significantly different from before treatment ( P < 0.05). Twenty-eight patients were cured, 1 patient underwent orchiectomy, and 1 patient experienced recurrence. Conclusions:Middle-aged male patients with brucellosis are more prone to BEO. Clinical manifestations and laboratory tests have certain diagnostic value for BEO. Suspected BEO patients should be diagnosed and treated as early as possible to reduce the occurrence of adverse prognosis.

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.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.