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

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

OBJECTIVES: To investigate the chain mediating role of family care and emotional management in the relationship between social support and anxiety among rural primary school students. METHODS: A questionnaire survey was conducted among students in grades 4 to 6 from four counties in Hunan Province. Data were collected using the Social Support Rating Scale, Family Care Index Scale, Emotional Intelligence Scale, and Generalized Anxiety Disorder -7. Logistic regression analysis was used to explore the influencing factors of anxiety symptoms. Mediation analysis was conducted to assess the chain mediating effects of family care and emotional management between social support and anxiety. RESULTS: A total of 4 141 questionnaires were distributed, with 3 874 valid responses (effective response rate: 93.55%). The prevalence rate of anxiety symptoms among these students was 9.32% (95%CI: 8.40%-10.23%). Significant differences were observed in the prevalence rates of anxiety symptoms among groups with different levels of social support, family functioning, and emotional management ability (P<0.05). The total indirect effect of social support on anxiety symptoms via family care and emotional management was significant (β=-0.137, 95%CI: -0.167 to -0.109), and the direct effect of social support on anxiety symptoms remained significant (P<0.05). Family care and emotional management served as significant chain mediators in the relationship between social support and anxiety symptoms (β=-0.025,95%CI:-0.032 to -0.018), accounting for 14.5% of the total effect. CONCLUSIONS Social support can directly affect anxiety symptoms among rural primary school students and can also indirectly influence anxiety symptoms through the chain mediating effects of family care and emotional management. These findings provide scientific evidence for the prevention of anxiety in primary school students from multiple perspectives.
Humans ; Female ; Male ; Social Support ; Anxiety/etiology* ; Child ; Students/psychology* ; Emotions ; Logistic Models

The glucagon receptor (GCGR) is a critical target for the treatment of metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity. Activation of GCGR enhances systemic insulin sensitivity through paracrine stimulation of insulin secretion, presenting a promising avenue for treatment. However, the discovery of effective GCGR agonists remains a challenging and resource-intensive process, often requiring time-consuming wet-lab experiments to synthesize and screen potential compounds. Recent advances in artificial intelligence technologies have demonstrated great potential in accelerating drug discovery by streamlining screening and efficiently predicting bioactivity. In the present work, we propose DeepGCGR, a two-layer deep learning model that leverages graph convolutional networks (GCN) integrated with a multiple attention mechanism to expedite the identification of GCGR agonists. In the first layer, the model predicts the bioactivity of various compounds against GCGR, efficiently filtering large chemical libraries to identify promising candidates. In the second layer, DeepGCGR classifies high bioactive compounds based on their functional effects on GCGR signaling, identifying those with potential agonistic or antagonistic effects. Moreover, DeepGCGR was specifically applied to identify novel GCGR-regulating compounds for the treatment of T2DM from natural products derived from traditional Chinese medicine (TCM). The proposed method will not only offer an effective strategy for discovering GCGR-targeting compounds with functional activation properties but also provide new insights into the development of T2DM therapeutics.
Deep Learning ; Drug Discovery/methods* ; Humans ; Diabetes Mellitus, Type 2/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To investigate the current status of early pain and agitation management in critically ill patients in Guizhou Province. METHODS: A retrospective study was performed using data collected from a quality control activity conducted between April and June 2021 in non-provincial public hospitals with general intensive care unit (ICU) in Guizhou Province. Hospital-level data included hospital name and grade, ICU staffing, and number of ICU beds. Patient-level data included characteristics of patients treated in the general ICU on the day of the survey (e.g., age, sex, primary diagnosis), as well as pain and agitation assessments and the types of analgesic and sedative medications administered within 24 hours of ICU admission. RESULTS: A total of 947 critically ill ICU patients from 145 hospitals were included, among which 104 were secondary-level hospitals and 41 were tertiary-level hospitals. Within 24 hours of ICU admission, 312 (32.9%) critically ill patients received pain assessments, and 277 (29.3%) received agitation assessments. Among the pain assessment tools, the critical care pain observation tool (CPOT) was used in 44.2% (138/312) of critically ill ICU patients, with a significantly higher usage rate in tertiary hospitals compared to secondary hospitals [52.3% (69/132) vs. 38.3% (69/180), P < 0.05]. The Richmond agitation-sedation scale (RASS) was used in 93.8% (260/277) of critically ill ICU patients for agitation assessment, with no significant difference between hospital levels. Among the 947 critically ill patients, 592 (62.5%) received intravenous analgesics within 24 hours, with remifentanil being the most commonly used [42.9% (254/592)]; 510 (53.9%) received intravenous sedatives, with midazolam being the most frequently used [60.8% (310/510)]. Mechanical ventilation data were available for 932 critically ill patients, of whom 579 (62.1%) received mechanical ventilation and 353 (37.9%) did not. Compared with non-ventilated patients, ventilated patients had significantly higher rates of analgesic and sedative use [analgesics: 77.9% (451/579) vs. 38.8% (137/353); sedatives: 71.8% (416/579) vs. 25.8% (91/353); both P < 0.05]. In terms of analgesic selection, ventilated patients were more likely to receive strong opioids than non-ventilated patients [85.8% (95/137) vs. 69.3% (387/451), P < 0.05]. For sedatives, ventilated patients preferred midazolam [66.6% (277/416)], whereas non-ventilated patients more often received dexmedetomidine [45.1 (41/91)]. Blood pressure within 24 hours of ICU admission were available for 822 critically ill patients, of whom 245 (29.8%) had hypotension and 577 (70.2%) did not. Compared with non-hypotensive patients, hypotensive patients had significantly higher rates of analgesic and sedative use [analgesics: 74.7% (183/245) vs. 59.8% (345/577); sedatives: 65.7% (161/245) vs. 51.3% (296/577); both P < 0.05], but there was no significant difference in the choice of analgesic or sedative agents between the two groups. CONCLUSIONS The proportion of critically ill ICU patients in Guizhou Province who received standardized pain and agitation assessments was relatively low. The most commonly used assessment tools were CPOT and RASS, while remifentanil and midazolam were the most frequently used analgesic and sedative agents, respectively. Secondary-level hospitals had a lower rate of using standardized pain assessment tools compared to tertiary-level hospitals. Mechanical ventilation and hypotension were associated with the use of analgesic and sedative medications.
Humans ; Critical Illness ; Intensive Care Units ; Analgesics/therapeutic use* ; Hypnotics and Sedatives/therapeutic use* ; Retrospective Studies ; China ; Pain Measurement ; Pain Management ; Female ; Male ; Critical Care ; Middle Aged

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects(VSD)in offspring.Methods A case-control study was conducted,recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants.A questionnaire survey collected data on maternal exposures,and blood samples were analyzed for genetic polymorphisms.Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD.Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake.Results The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD(P<0.05).The GC and CC genotypes at rs3768139,AG and GG at rs1050993,AT and TT at rs4659743,GG at rs3768142,and GT and TT at rs3820571 were associated with a decreased risk of VSD(P<0.05).The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD(P<0.05).Conclusions Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring.Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period,suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Objective:To compare the long-term prognosis between open versus closed reduction and internal fixation in the treatment of unstable pelvic fractures.Methods:The data of 402 consecutive patients with unstable pelvic fracture were retrospectively analyzed who had been treated at The First Medical Center and The Fourth Medical Center, PLA General Hospital, and Strategic Support Force Specialty Medical Center from March 2011 to March 2017. This cohort was divided into 2 groups according to the reduction methods. In the open group of 194 cases subjected to open reduction and internal fixation, there were 133 males and 61 females with a median age of 43.0 (30.7, 51.0) years, and 35 cases of type B and 159 cases of type C by the Tile classification. In the closed group of 208 cases subjected to closed reduction and internal fixation, there were 115 males and 93 females with a median age of 45.5 (32.0, 56.0) years, and 40 cases of type B and 168 cases of type C by the Tile classification. The 2 groups were compared in terms of 12-items Short Form Health Survey (SF-12) scores [physical component summary (PCS) and mental component summary (MCS)] at the last follow-up, time from injury to operation, frequency of intraoperative X-ray fluoroscopy, intraoperative and postoperative blood transfusion, operation time, and quality of postoperative fracture reduction.Results:There was no statistically significant difference between the 2 groups in the preoperative general data except for the gender, showing the 2 groups were comparable ( P>0.05). This cohort of 402 patients was followed up for 7.8(6.2, 8.8) years. At the last follow-up, the PCS [49.9 (45.4, 55.4) points] and MCS [53.1 (46.4, 57.6) points] in the closed group were significantly higher than those in the open group [48.2 (41.4, 52.7) and 46.5 (40.6, 53.6) points] ( P<0.05). The closed group incurred significantly shorter time from injury to operation [6 (5, 8) d] and operation time [180 (126, 260) min] than the open group [9 (6, 13) d and 240 (165, 334) min], significantly less intraoperative and postoperative blood transfusion [1.5 (0, 4.0) U] than the open group [5.0 (2.9, 8.0) U], significantly higher frequency of intraoperative X-ray fluoroscopy [104.5 (85.0, 132.0) times] than the open group [21.0 (18.0, 26.0) times], and a significantly higher excellent and good rate of postoperative fracture reduction (92.8%, 193/208) than the open group (86.6%, 168/194) (all P<0.05). Conclusion:In the treatment of patients with unstable pelvic fractures, compared with open reduction and internal fixation, closed reduction and internal fixation can not only significantly shorten the waiting time and operation time of patients, reduce the transfusion during operation, but also achieve better fracture reduction to ultimately improve the quality of life of patients.

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.