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

OBJECTIVES: In recent years, the incidence and detection rate of pancreatic cystic lesions (PCLs) have increased significantly. Endoscopic ultrasound (EUS) plays an indispensable role in the diagnosis and differential diagnosis of PCLs. However, evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration (EUS-FNA) and fine-needle biopsy (FNB) remains limited. This study aims to compare the diagnostic yield, adequacy of tissue acquisition, and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice. METHODS: A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021. The diagnostic yield, tissue acquisition adequacy, and incidence of adverse events were compared between the 2 groups. RESULTS: A total of 90 patients with PCLs were included (52 in the FNA group and 38 in the FNB group). The diagnostic yield was similar between the FNA and FNB groups (94.2% vs 94.7%, P>0.05). The adequacy of tissue acquisition was 71.2% in the FNA group and 81.6% in the FNB group (P>0.05). No statistically significant difference was observed in the incidence of adverse events between the 2 groups (P>0.05). CONCLUSIONS Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs, with excellent safety profiles. Both methods are safe and effective diagnostic tools for evaluating PCLs.
Humans ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects* ; Retrospective Studies ; Female ; Male ; Pancreatic Cyst/diagnostic imaging* ; Middle Aged ; Biopsy, Fine-Needle/adverse effects* ; Aged ; Pancreatic Neoplasms/diagnosis* ; Adult ; Endosonography/methods* ; Pancreas/pathology* ; Diagnosis, Differential

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

BACKGROUND:Restoring the normal level of reactive oxygen species and mitochondrial function of nucleus pulposus cells and inhibiting apoptosis of nucleus pulposus cells are key targets for delaying intervertebral disc degeneration.Prussian blue nanoparticles have peroxidase-like activity,which can effectively remove reactive oxygen species in the pathological microenvironment and protect nucleus pulposus cells from oxidative stress damage.OBJECTIVE:To investigate the biological functions and mechanisms of Prussian blue nanoparticles in delaying nucleus pulposus degeneration in rats.METHODS:Prussian blue nanoparticles were prepared by hydrothermal method,and their micromorphology and particle size were characterized.Prussian blue nanoparticles with different mass concentrations(20,40,60,80,and 100 μg/mL)were used to intervene in the caudal nucleus pulposus cells of passage 2 SD rats.Cell proliferation was detected by CCK-8 assay after 24 hours.60 μg/mL Prussian blue nanoparticles were used to intervene in the caudal nucleus pulposus cells of passage 2 SD rats.The viability of nucleus pulposus cells was observed by live-dead staining after 1 and 3 days.Passage 2 SD rat caudal vertebrae nucleus pulposus cells were obtained and observed for cell adhesion before being divided into three intervention groups.The control group did not receive any intervention.The lipopolysaccharide group was added with lipopolysaccharide.The lipopolysaccharide+Prussian blue nanoparticle group was added with lipopolysaccharide and 60 μg/mL Prussian blue nanoparticles.Reactive oxygen species,mitochondrial superoxide,and mitochondrial membrane potential were detected 24 hours after intervention.RT-qPCR detection and Alcian blue staining were performed 48 hours after intervention.RESULTS AND CONCLUSION:(1)Under transmission electron microscopy,Prussian blue nanoparticles were uniform nanocubes with an average particle size of 130 nm.(2)CCK-8 assay results showed that 20-60 μg/mL Prussian blue nanoparticles had no obvious cytotoxicity,and 60 μg/mL Prussian blue nanoparticles were selected for cell intervention in subsequent experiments.Live-dead staining results showed that 60 μg/mL Prussian blue nanoparticles had no effect on the viability of nucleus pulposus cells.(3)Compared with the control group,the levels of reactive oxygen species and mitochondrial superoxide in nucleus pulposus cells in the lipopolysaccharide group were increased(P＜0.01),the mitochondrial membrane potential was decreased(P＜0.01),the mRNA expressions of type Ⅱ collagen and aggrecan were decreased(P＜0.01),the mRNA expressions of matrix metalloproteinase 13 and thrombospondin integrin metallopeptidase 5 were increased(P＜0.01),and the positive area of Alcian blue staining was reduced(P＜0.01).Compared with the lipopolysaccharide group,the levels of reactive oxygen species and mitochondrial superoxide in nucleus pulposus cells in the lipopolysaccharide+Prussian blue nanoparticle group were decreased(P＜0.01),mitochondrial membrane potential increased(P＜0.01),mRNA expression of type Ⅱ collagen and aggrecan increased(P＜0.01),mRNA expression of matrix metalloproteinase 13 and thrombospondin integrin metallopeptidase 5 decreased(P＜0.01),and positive area of Alcian blue staining increased(P＜0.01).The results showed that Prussian blue nanoparticles delayed the degeneration of rat nucleus pulposus by reducing oxidative stress of nucleus pulposus cells,restoring mitochondrial function,and maintaining the balance of extracellular matrix synthesis and catabolism.

Objective:To analyze the epidemiological and clinical characteristics of leptospirosis in Wenzhou City, and to provide a scientific basis for formulating prevention and control strategies of leptospirosis in Wenzhou City.Methods:Information on leptospirosis case from 2019 to 2023 was collected from the China Information System for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the three-dimensional distribution and clinical manifestations of leptospirosis.Results:From 2019 to 2023, the annual average incidence rate of leptospirosis in Wenzhou City was 0.43/100 000, and the annual average mortality was 0.01/100 000. The incidence rate was the highest in 2021 (0.74/100 000), and there was a statistically significant difference in the incidence rate over the five years ( χ2 = 35.48, P < 0.001). Cases were reported in all regions in Wenzhou City except for Dongtou District and Longgang City, with Yongjia County had the highest number of cases (114 cases). The impact rate of streets/townships was 35.14% (65/185), among them Yongjia County had the highest impact rate of steets/townships (86.36%, 19/22). The onset season was from August to October (88.83%, 159/179), with a male to female ratio of 4.97 ∶ 1.00 (149/30). The age group of 61 - 70 years old was the most affected (39.66%, 71/179), and farmers were the main occupation (70.95%, 127/179). Twenty-six point eighty-two per cent (48/179) of the cases had a clear history of animal contact within one month before onset, and 68.16% (122/179) had a history of contact with contaminated water. The main clinical type was influenza-typhoid type (23.46%, 42/179), with the main clinical manifestations being fever (84.92%, 152/179), chills (55.87%, 100/179), and fatigue (62.57%, 112/179). Twelve point twenty-nine per cent 12.29% (22/179), 8.38% (15/179), and 22.91% (41/179) of cases showed conjunctival congestion, lymph node enlargement, and gastrocnemius muscle tenderness, respectively. Clinical outcomes showed that 73.74% (132/179) of the cases recovered or improved, and 3 cases died. Conclusions:From 2019 to 2023, the overall prevalence of leptospirosis in Wenzhou City is at a low level, but there are deaths that need to be taken seriously. In order to control the disease, continuous monitoring should be carried out, health education for relevant populations should be strengthened, and the risk of leptospirosis should be reduced.

BACKGROUND:Restoring the normal level of reactive oxygen species and mitochondrial function of nucleus pulposus cells and inhibiting apoptosis of nucleus pulposus cells are key targets for delaying intervertebral disc degeneration.Prussian blue nanoparticles have peroxidase-like activity,which can effectively remove reactive oxygen species in the pathological microenvironment and protect nucleus pulposus cells from oxidative stress damage.OBJECTIVE:To investigate the biological functions and mechanisms of Prussian blue nanoparticles in delaying nucleus pulposus degeneration in rats.METHODS:Prussian blue nanoparticles were prepared by hydrothermal method,and their micromorphology and particle size were characterized.Prussian blue nanoparticles with different mass concentrations(20,40,60,80,and 100 μg/mL)were used to intervene in the caudal nucleus pulposus cells of passage 2 SD rats.Cell proliferation was detected by CCK-8 assay after 24 hours.60 μg/mL Prussian blue nanoparticles were used to intervene in the caudal nucleus pulposus cells of passage 2 SD rats.The viability of nucleus pulposus cells was observed by live-dead staining after 1 and 3 days.Passage 2 SD rat caudal vertebrae nucleus pulposus cells were obtained and observed for cell adhesion before being divided into three intervention groups.The control group did not receive any intervention.The lipopolysaccharide group was added with lipopolysaccharide.The lipopolysaccharide+Prussian blue nanoparticle group was added with lipopolysaccharide and 60 μg/mL Prussian blue nanoparticles.Reactive oxygen species,mitochondrial superoxide,and mitochondrial membrane potential were detected 24 hours after intervention.RT-qPCR detection and Alcian blue staining were performed 48 hours after intervention.RESULTS AND CONCLUSION:(1)Under transmission electron microscopy,Prussian blue nanoparticles were uniform nanocubes with an average particle size of 130 nm.(2)CCK-8 assay results showed that 20-60 μg/mL Prussian blue nanoparticles had no obvious cytotoxicity,and 60 μg/mL Prussian blue nanoparticles were selected for cell intervention in subsequent experiments.Live-dead staining results showed that 60 μg/mL Prussian blue nanoparticles had no effect on the viability of nucleus pulposus cells.(3)Compared with the control group,the levels of reactive oxygen species and mitochondrial superoxide in nucleus pulposus cells in the lipopolysaccharide group were increased(P＜0.01),the mitochondrial membrane potential was decreased(P＜0.01),the mRNA expressions of type Ⅱ collagen and aggrecan were decreased(P＜0.01),the mRNA expressions of matrix metalloproteinase 13 and thrombospondin integrin metallopeptidase 5 were increased(P＜0.01),and the positive area of Alcian blue staining was reduced(P＜0.01).Compared with the lipopolysaccharide group,the levels of reactive oxygen species and mitochondrial superoxide in nucleus pulposus cells in the lipopolysaccharide+Prussian blue nanoparticle group were decreased(P＜0.01),mitochondrial membrane potential increased(P＜0.01),mRNA expression of type Ⅱ collagen and aggrecan increased(P＜0.01),mRNA expression of matrix metalloproteinase 13 and thrombospondin integrin metallopeptidase 5 decreased(P＜0.01),and positive area of Alcian blue staining increased(P＜0.01).The results showed that Prussian blue nanoparticles delayed the degeneration of rat nucleus pulposus by reducing oxidative stress of nucleus pulposus cells,restoring mitochondrial function,and maintaining the balance of extracellular matrix synthesis and catabolism.

Objective:To analyze the epidemiological and clinical characteristics of leptospirosis in Wenzhou City, and to provide a scientific basis for formulating prevention and control strategies of leptospirosis in Wenzhou City.Methods:Information on leptospirosis case from 2019 to 2023 was collected from the China Information System for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the three-dimensional distribution and clinical manifestations of leptospirosis.Results:From 2019 to 2023, the annual average incidence rate of leptospirosis in Wenzhou City was 0.43/100 000, and the annual average mortality was 0.01/100 000. The incidence rate was the highest in 2021 (0.74/100 000), and there was a statistically significant difference in the incidence rate over the five years ( χ2 = 35.48, P < 0.001). Cases were reported in all regions in Wenzhou City except for Dongtou District and Longgang City, with Yongjia County had the highest number of cases (114 cases). The impact rate of streets/townships was 35.14% (65/185), among them Yongjia County had the highest impact rate of steets/townships (86.36%, 19/22). The onset season was from August to October (88.83%, 159/179), with a male to female ratio of 4.97 ∶ 1.00 (149/30). The age group of 61 - 70 years old was the most affected (39.66%, 71/179), and farmers were the main occupation (70.95%, 127/179). Twenty-six point eighty-two per cent (48/179) of the cases had a clear history of animal contact within one month before onset, and 68.16% (122/179) had a history of contact with contaminated water. The main clinical type was influenza-typhoid type (23.46%, 42/179), with the main clinical manifestations being fever (84.92%, 152/179), chills (55.87%, 100/179), and fatigue (62.57%, 112/179). Twelve point twenty-nine per cent 12.29% (22/179), 8.38% (15/179), and 22.91% (41/179) of cases showed conjunctival congestion, lymph node enlargement, and gastrocnemius muscle tenderness, respectively. Clinical outcomes showed that 73.74% (132/179) of the cases recovered or improved, and 3 cases died. Conclusions:From 2019 to 2023, the overall prevalence of leptospirosis in Wenzhou City is at a low level, but there are deaths that need to be taken seriously. In order to control the disease, continuous monitoring should be carried out, health education for relevant populations should be strengthened, and the risk of leptospirosis should be reduced.

[Objective]To investigate the relationship between the non-fasting triglyceride and glucose(TyG)index and hyperglycemia in pregnancy during the third trimester in high altitudes.[Methods]This study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region,from January 2023 to April 2025.The non-fasting TyG index was calculated from non-fasting triglyceride(TG)and random plasma glucose(PG).Based on the tertiles of the non-fasting TyG index values,the individuals were split into three groups(corresponding to non-fasting TyG index of 8.89 and 9.21,respectively).The baseline clinical characteristics,lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups.Statistical analyses were performed using ANOVA,Kruskal-Wallis H test,Chi-square test,or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting.[Results]A total of 774 Tibetan singleton pregnant women were included,with a average age of 27.3±6.1 years,a pre-delivery body mass index(Pre-BMI)of(25.2±2.3)kg/m2,a proportion of 26.7%(207/774)primigravid women,the mean non-fasting TyG index was 9.1±0.4.Thirty pregnant women were diagnosed with hyperglycemia in pregnancy,with a detection rate of 3.9%(30/774).Statistically significant differences in serum total cholesterol(TC),TG,low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)levels were identified when comparing different non-fasting TyG groups(all P values<0.05).Subsequent trend test analysis indicated that the levels of TC,TG,LDL-C,and PG gradually increased with elevated the non-fasting TyG index(Ftrend TC=95.61,P<0.001;Ftrend TG=1 051.91,P<0.001;Ftrend LDL-C=97.20,P<0.001;Ftrend TG=195.20;P<0.001).After adjustment for maternal age,pre-delivery BMI,altitude,TC,LDL-C,and HDL-C,multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy(Model 1:OR=2.72,95%CI:1.13-6.53,P=0.026;Model 2:OR=2.56,95%CI:1.01-6.50,P=0.048;Model 3:OR=2.72,95%CI:1.06-6.97,P=0.037;Model 4:OR=4.02,95%CI:1.42-11.40,P=0.009)and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index,however,this association did not statistical significance(P trend>0.05).Curve fitting by restricted cubic splines(RCS)were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy,and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy(P for non-linear=0.515).[Conclusion]Non-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

The enterprise master patient index is an important tool for identifying the diagnosis and treatment records of the same patient in heterogeneous medical data from multiple sources. From June to December 2021, the National Children′s Cancer Monitoring Center screened and determined the enterprise master patient index index system and its recognition logic by literature analysis and expert consultation. Based on the National Children′s Cancer surveillance Platform (hereinafter referred to as the surveillance platform), a corresponding intelligent recognition algorithm system was developed. After multiple rounds of real data verification and adjustment, a enterprise master patient index suitable for multi-source heterogeneous medical data was constructed. From January 2022 to March 2024, the intelligent recognition algorithm system had completed the recognition of 2.46 million pediatric tumor case report cards, established 0.33 million primary indexes and their unique identification codes for malignant tumor patients, and improved the data management and application efficiency of the surveillance platform. The enterprise master patient index based on surveillance platforms had played an important role in the registration and follow-up of pediatric cancer cases and related medical research, which could provide references for the construction of master indexes on other medical big data platforms in China.