OBJECTIVE: To observe the effect of acupuncture on chondrocyte autophagy in rats of knee osteoarthritis (KOA) and explore its underlying mechanisms. METHODS: Forty male SPF-grade SD rats were randomized into a blank group, a model group, a suspension group, an acupuncture group, and a combined therapy group, 8 rats in each one. Except the blank group, KOA model was prepared by the injection with papain. The suspension exercise therapy (10 min each time, three times daily), acupuncture (at "Yanglingquan" [GB34], "Zusanli" [ST36], and "Dubi" [ST35] on the right side, 30 min each intervention, once daily) and the combined therapy (the suspension exercise therapy combined with acupuncture) were delivered in the suspension group, the acupuncture group and the combined therapy group, respectively. The intervention of each group was performed continuously for 6 days, and 4 consecutive weeks, at the interval of 1 day. Before and after intervention, Lequesne MG score was assessed in the rats. After intervention, HE staining was adopted to observe the cartilaginous tissue morphology of the right knee joints, and Mankin score was evaluated; the serum levels of interleukin (IL)-1β, IL-6, and tumor neurosis factor-α (TNF-α) were measured using ELISA; the real-time PCR was provided to determine the mRNA expression of collagen protein type Ⅱ(COL2), collagen protein type Ⅹ (COL10), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), and autophagy-regulated protein (Beclin-1) in the cartilaginous tissue of the right knee joint; Western blot was employed to detect the protein expression of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR) and Beclin-1 in the cartilaginous tissue of the right knee joint. RESULTS: Compared with the blank group, the rats in the model group showed the higher Lequesne MG score (P<0.01), thinner cartilage of the right knee, reduced chondrocytes and disordered arrangement, and higher Mankin score (P<0.01). Besides, in the model group, the serum levels of IL-1β, IL-6 and TNF-α were elevated (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 decreased (P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR increased (P<0.01) in the cartilaginous tissue of the right knee joint. Compared with the model group, in the suspension group, the acupuncture group and the combined therapy group, the Lequesne MG scores were reduced (P<0.01), the cartilage of the right knee was thickened, the arrangement of chondrocytes was improved, and the Mankin scores were lower (P<0.01). Besides, in these intervention groups, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05, P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. When compared with the suspension group and the acupuncture group, in the combined therapy group, the Lequesne MG score was reduced (P<0.01), and the Mankin score was reduced (P<0.05, P<0.01). Besides, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.05), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. CONCLUSION Acupuncture can promote cartilage regeneration of knee joint and autophagy in KOA rats, alleviate inflammation, so as to retard cartilage degeneration, which may be possibly associated with the PI3K/Akt/mTOR signaling pathway.
Animals ; Male ; Acupuncture Therapy ; Proto-Oncogene Proteins c-akt/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/physiopathology* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Signal Transduction ; Rats, Sprague-Dawley ; Chondrocytes/metabolism* ; Humans ; Autophagy ; Acupuncture Points

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

Background::Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods::About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.Results::At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion::Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Objective This study aimed to reveal critical genes regulating peri-implantitis during its development and construct a diagnostic model by using random forest(RF)and artificial neural network(ANN).Methods GSE-33774,GSE106090,and GSE57631 datasets were obtained from the GEO database.The GSE33774 and GSE106090 da-tasets were analyzed for differential expression and functional enrichment.The protein-protein interaction networks(PPI)and RF screened vital genes.A diagnostic model for peri-implantitis was established using ANN and validated on the GSE33774 and GSE57631 datasets.A transcription factor-gene interaction network and a transcription factor-micro-RNA(miRNA)regulatory network were also established.Results A total of 124 differentially expressed genes(DEGs)involved in the regulation of peri-implantitis were screened.Enrichment analysis showed that DEGs were mainly associated with immune receptor activity and cytokine receptor activity and were mainly involved in processes such as leukocyte and neutrophil migration.The PPI and RF screened six essential genes,namely,CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8.The receiver oper-ating characteristic curve(ROC)indicated that the ANN model had an excellent diagnostic performance.FOXC1,GA-TA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 may be a key miRNA.Con-clusion The diagnostic model of peri-implantitis constructed by RF and ANN has high confidence,and CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8 are potential diagnostic markers.FOXC1,GATA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 plays a vital role as a critical miRNA.

The paper-based microfluidic chip,also known as a paper chip,uses paper as the substrate on which the sample processing,biochemical reactions and assay processes are performed.Com-pared to other microfluidic chips,the paper chip has the advantages of widely availability of raw materials,lower cost,and easier disposal after use and ease of operation,making it more suitable for rapid on-site testing.This study systematically summarizes the production technology of paper chip and its research progress in animal pathogen detection,analyzes the existing problems of pa-per chip technology,and looks forward to the future research direction,so as to provide reference for the improvement of paper chip technology and its popularization and application.

Objective:To explore the factors associated with vascular luminal dilatational remodeling (VLDR) following balloon angioplasty for intracranial atherosclerotic stenosis (ICAS).Methods:A case-control study was conducted to analyze the data of symptomatic severe ICAS patients who received either paclitaxel-coated balloon angioplasty (PCBA) or plain balloon angioplasty (POBA) at our center from January 2019 to January 2022 and completed the six-month follow-up. The patients were divided into VLDR group and non-VLDR group according to whether VLDR occurred on follow-up digital subtraction angiography (DSA). The baseline data, preoperative and postoperative lesion characteristics (DSA), and perioperative related information were collected. The definition of VLDR was a decrease in luminal stenosis rate by more than 10% at the time of follow-up compared to the immediate postoperative period. Multivariate logistic regression was performed to analyze possible factors affecting VLDR such as balloon type, balloon length, and expansion time.Results:A total of 88 patients were included in this study, with 16 in the VLDR group and 72 in the non-VLDR group. The follow-up time for all included patients was 6.00 (5.00, 7.00) months. VLDR occurred in 18.2% (16/88) of cases, with a VLDR incidence of 30.4% (14/46) after PCBA and 4.8% (2/42) after POBA. Univariate logistic regression analysis revealed that treatment balloon type, balloon length, inflated time, immediate postoperative stenosis rate, follow-up time and Mori classification may affect the occurrence of VLDR. Multivariate logistic regression analysis showed that the use of paclitaxel-coated balloon (PCB) ( OR=9.82, 95% CI 1.99-48.49, P=0.005) and postoperative immediate stenosis rate ( OR=1.07, 95% CI 1.00-1.14, P=0.042) were independently associated with VLDR. Conclusion:The occurrence of VLDR following balloon angioplasty in ICAS was associated with the use of PCB and immediate postoperative stenosis rates, which will provide guidance for the clinical application of PCB.

Objective:To screen the incidence of proteinuria in rural areas of Shanxi province and construct a risk prediction model of proteinuria based on machine learning algorithm.Methods:It was a cross-sectional investigation study. The residents ≥30 years old in rural areas of Shanxi province from April to November 2019 were screened by multi-stage stratified sampling method, and data from questionnaire surveys, physical examinations, and laboratory examinations were collected. Urine albumin/creatinine ratio ≥30 mg/g was defined as proteinuria, and the incidence of proteinuria was calculated. Subjects were divided into proteinuria group and non-proteinuria group. The machine learning binary classification model of proteinuria and non-proteinuria was constructed based on the stackable integrated logistic regression algorithm (SE-LR), logistic regression, support vector machine, decision tree, random forest and extreme gradient lift algorithms, respectively. The area under the receiver operating characteristic curve, accuracy, recall, and F1 weights were used to evaluate the predictive efficiency of the comparison models. Finally, the importance of the predictive features of the model with the best overall performance was ranked.Results:There were 8 869 rural residents included in the study, aged (58.59±9.49) years old, with 3 872 males (43.66%) and 4 997 females (56.34%). The prevalence of proteinuria in rural areas of Shanxi province was 13.49% (1 196/8 869). Blood pressure, pulse, body mass index, waist circumference, proportion of obesity or overweight, proportion of hypertension, proportion of moderate to severe salt intake, glycosylated hemoglobin, uric pH value, urinary specific gravity, proportion of positive urinary occult blood, proportion of positive urinary glucose, proportion of positive urinary ketone body, proportion of urinary red blood cell count ≥5/μl, proportion of urinary white blood cell count ≥10/μl and urinary α1 microglobulin in the proteinuria group were all higher than those in the non-proteinuria group (all P<0.05). The proportions of lack of exercise and drinking history in the proteinuria group were lower than those in non-proteinuria group (both P<0.05). The overall performance of SE-LR model was the best, with the area under the curve (0.736, 95% CI 0.719-0.746) slightly lower than that of the logistic regression model (0.745, 95% CI 0.680-0.762), and the highest accuracy (0.844), recall rate (0.621) and F1 weighting value (0.801). In the SE-LR model, the orders of importance of the top 10 features were urinary α1- microglobulin, urinary occult blood, urinary sugar, uric acid basicity, smoking history,overweight or obesity, body mass index, total cholesterol, glycosylated hemoglobin and hypertension. Conclusions:The prevalence of proteinuria is high in rural areas of Shanxi province. The risk prediction model of proteinuria established by machine learning algorithm can predict the risk of proteinuria and identify its risk factors, which can provide a scientific basis for disease prevention, intervention, and treatment in the community and clinic to a certain extent.

OBJECTIVES: This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology. METHODS: Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis. RESULTS: A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets. CONCLUSIONS The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.
Humans ; Network Pharmacology ; Curcumin/therapeutic use* ; Molecular Docking Simulation ; Periodontitis/drug therapy* ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88-0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11-1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.
Adult ; Humans ; Cohort Studies ; Zinc ; Diet ; Hypertension/epidemiology* ; Eating ; China/epidemiology*

Objective:To investigate the effect of thrombus burden on the clinical outcome of endovascular recanalization in large vessel occlusive stroke.Methods:Patients with acute anterior circulation occlusion who underwent endovascular treatment within 24 hours after onset in Zhengzhou University People′s Hospital from January 2018 to December 2019 were retrospectively collected. According to the clot burden score (CBS) of DSA, total objectives were divided into CBS≥6 group (24 cases) and CBS<6 group (38 cases). Clinical data of the two groups were collected and the modified Rankin scale (mRS) was used to evaluate the clinical outcome at 90 days after surgery. Independent sample t-test, Wilcoxon rank sum test and χ 2 test were used to compare the clinical data between the two groups. Independent risk factors affecting the clinical outcome were analyzed by binary logistic regression. Results:There were no statistically significant differences in basic demographic data, stroke risk factors and other factors between the CBS≥6 group and CBS<6 group ( P>0.05).The proportion of using tirofiban after surgery in the CBS≥6 group (63.2%, 24/38) was lower than that in the CBS<6 group (87.5%, 21/24) (χ2=4.380, P=0.044). The discharge NIHSS score of the CBS≥6 group was [5.0 (3.3, 7.8) points] lower than CBS<6 group [8.5 (1.8, 14.5) points] ( Z=5.221, P=0.022). The proportion of postoperative mRS 0-2 was (91.7%, 22/24) in the CBS≥6 group higher than CBS<6 group(39.5%, 15/38) (χ2=20.486, P=0.001), there were no statistically significant differences between the two groups ( P<0.05). The results of binary logistics regression analysis showed the CBS groups (OR=0.042, 95%CI 0.007-0.244 , P=0.001) was an independent risk factor affecting good outcome. Subgroup analysis of whether tirofiban was used or not showed there was no statistically significant difference in clinical prognosis between the two groups ( P>0.05). Conclusions:The clinical outcome of CBS≥6 group is significantly better than that of CBS<6 group, and patients with small thrombus burden are more likely to get a good clinical outcome of 90 days.