This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

Objective:To explore the factors that promote and hinder exercise adherence in long dialysis duration hemodialysis patients, and to provide a reference for improving their exercise levels.Methods:From March to May 2023, a qualitative research method using phenomenon approach was conducted and 15 patients with peritoneal dialysis for at least 10 years at the People′s Liberation Army Central Command Headquarters Hospital (Hankou Hospital) were selected for in-depth interviews using purposive sampling method. The data were analyzed using Colaizzi 7-step method and the main themes were extracted.Results:Among the 15 interviewers, there were 5 males and 10 females, aged 39-76 years old.Conclusions:The exercise level of long dialysis duration hemodialysis patients is influenced by multiple factors. Medical staff should correct their cognitive biases and change their behavioral attitudes, strengthen external supportive environments and reduce subjective normative pressures, gradually provide more objective support, thereby promoting the exercise training of long dialysis duration hemodialysis patients.

To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85％,12.88％,5.30％,3.79％,51.52％,and 6.06％,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9％(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVES: To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD). METHODS: A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier. RESULTS: DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%. CONCLUSIONS Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.
Child ; Humans ; Autism Spectrum Disorder/psychology* ; Diagnosis, Differential ; Machine Learning ; Social Behavior

Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a₂b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.
Humans ; Quality of Life ; Cross-Sectional Studies ; Cardiovascular Diseases/complications* ; Stress, Psychological