Objective To investigate the analgesic effect of total saponins of Clematis(TSC)on trigeminal neuralgia(TN)rats by regulating the miR-26a-5p/Wnt5a signaling pathway.Methods The TN rat model was established through suborbital nerve constriction surgery.Fifty rats were divided into the TN group,the different doses of(50,200 mg/kg)TSC groups,the TSC+NC antagonist(200 mg/kg TSC+5 nmoL NC antagonist)group and the TSC+miR-26a-5p antagonist(200 mg/kg TSC+5 nmoL miR-26a-5p antagonist)group2025,with 10 mice per group.Another 10 rats were taken as the sham operation group,and only the infraorbital nerve of rats was exposed but not ligated.ELISA was used to detect the levels of tumor necrosis factor(TNF)-α and interleukin(IL)-6.HE staining was used to detect histopathological changes.Real-time fluorescence quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of miR-26a-5p and Wnt5a mRNA.Western blot assay was used to detect protein expressions of glial neurotrophic factor(GDNF),Wnt5a and brain-derived neurotrophic factor(BDNF)in trigeminal ganglion tissue.Dual luciferase reporter gene system was applied to validate the targeting relationship between miR-26a-5p and Wnt5a.Results Compared with the sham operation group,the expression levels of TNF-α,IL-6,Wnt5a protein and mRNA were obviously increased in the TN group,and the mechanical pain threshold,the expression levels of miR-26a-5p,GDNF and BDNF were obviously reduced(P＜0.05).Compared with the TN group,the expression of TNF-α,IL-6,Wnt5a protein and mRNA were greatly reduced in the 50 and 200 mg/kg TSC groups,and the mechanical pain threshold,the expression levels of miR-26a-5p,GDNF and BDNF were greatly increased.There were differences in different doses of TSC between the different groups(P＜0.05).Inhibition of miR-26a-5p reversed the protective effect of TSC on TN rats.Conclusion TSC exerts analgesic effects on TN rats by regulating the miR-26a-5p/Wnt5a signaling pathway.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To investigate the analgesic effect of total saponins of Clematis(TSC)on trigeminal neuralgia(TN)rats by regulating the miR-26a-5p/Wnt5a signaling pathway.Methods The TN rat model was established through suborbital nerve constriction surgery.Fifty rats were divided into the TN group,the different doses of(50,200 mg/kg)TSC groups,the TSC+NC antagonist(200 mg/kg TSC+5 nmoL NC antagonist)group and the TSC+miR-26a-5p antagonist(200 mg/kg TSC+5 nmoL miR-26a-5p antagonist)group2025,with 10 mice per group.Another 10 rats were taken as the sham operation group,and only the infraorbital nerve of rats was exposed but not ligated.ELISA was used to detect the levels of tumor necrosis factor(TNF)-α and interleukin(IL)-6.HE staining was used to detect histopathological changes.Real-time fluorescence quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of miR-26a-5p and Wnt5a mRNA.Western blot assay was used to detect protein expressions of glial neurotrophic factor(GDNF),Wnt5a and brain-derived neurotrophic factor(BDNF)in trigeminal ganglion tissue.Dual luciferase reporter gene system was applied to validate the targeting relationship between miR-26a-5p and Wnt5a.Results Compared with the sham operation group,the expression levels of TNF-α,IL-6,Wnt5a protein and mRNA were obviously increased in the TN group,and the mechanical pain threshold,the expression levels of miR-26a-5p,GDNF and BDNF were obviously reduced(P＜0.05).Compared with the TN group,the expression of TNF-α,IL-6,Wnt5a protein and mRNA were greatly reduced in the 50 and 200 mg/kg TSC groups,and the mechanical pain threshold,the expression levels of miR-26a-5p,GDNF and BDNF were greatly increased.There were differences in different doses of TSC between the different groups(P＜0.05).Inhibition of miR-26a-5p reversed the protective effect of TSC on TN rats.Conclusion TSC exerts analgesic effects on TN rats by regulating the miR-26a-5p/Wnt5a signaling pathway.

Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

With the advancement of China's healthcare reform,enhancing the capacity of primary healthcare services has become a pivotal task.Colorectal cancer,one of the most prevalent malignancies in China,highlights the critical importance of early screening and diagnosis to improve patient survival rates.This study,guided by the principles of Party building and Xi Jinping Thought on Socialism with Chinese Characteristics,examines the implementation and outcomes of a rural outreach program focused on colorectal cancer screening and diagnostic technologies.By promoting the dissemination of colorectal cancer screening initiatives,the paper aims to provide empirical evidence to support the deepening of primary-care services,foster high-quality ad-vancement of grassroots health services,and align with the national Healthy China Initiative,thereby more effectively safeguarding population health.

With the advancement of China's healthcare reform,enhancing the capacity of primary healthcare services has become a pivotal task.Colorectal cancer,one of the most prevalent malignancies in China,highlights the critical importance of early screening and diagnosis to improve patient survival rates.This study,guided by the principles of Party building and Xi Jinping Thought on Socialism with Chinese Characteristics,examines the implementation and outcomes of a rural outreach program focused on colorectal cancer screening and diagnostic technologies.By promoting the dissemination of colorectal cancer screening initiatives,the paper aims to provide empirical evidence to support the deepening of primary-care services,foster high-quality ad-vancement of grassroots health services,and align with the national Healthy China Initiative,thereby more effectively safeguarding population health.

Objective:To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality.Methods:This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone.Results:A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions:RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Background and objective Neoantigen reactive T cell(NRT)has the ability to inhibit the growth of tumors expressing specific neoantigens.However,due to the difficult immune infiltration and the inhibition of tumor micro en-vironment,the therapeutic effect of NRT in solid tumors is limited.In this study,we designed NRT cells(7×19 NRT)that can express both interleukin-7(IL-7)and chemokine C-C motif ligand 19(CCL19)in mouse lung cancer cells,and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells.Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma(LLC),prepared RNA vaccine,cultured NRT cells,constructed retroviral vectors encoding IL-7 and CCL19,transduced NRT cells and IL-7 and CCL19 were successfully ex-pressed,and 7×19 NRT was successfully obtained.The anti-tumor effect was evaluated in vivo and in vitro in mice.Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19,achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice.The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment.In addition,both 7×19 NRT treatment and conventional NRT treatment were safe.Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19,which is a safe and effective genetic modification of NRT.

ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets（QSQ）， an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected， and liver function indicators ［alanine aminotransferase （ALT）， aspartate amino-transferase （AST）， and alkaline phosphatase （ALP）］ of golden hamsters were detected. Hematoxylin-eosin （HE） staining was used to observe the degree of liver injury. In the experiments， a normal group， a model group， an atorvastatin calcium group， and low-， medium-， and high-dose QSQ groups （0.32， 0.64， 1.28 g·kg^-1 for mice， and 0.16， 0.32， 0.64 g·kg^-1 for golden hamsters） were set up. ResultCompared with the normal group， the acute hyperlipidemia model mice showed increased TC， TG， and LDL-C levels （P<0.01）， and the hyperlipidemia model mice showed increased TC and LDL-C levels （P<0.01）. Additionally， the hyperlipidemia model golden hamsters showed increased serum TC， TG， LDL-C， ALT， AST， and ALP levels （P<0.05， P<0.01）. HE staining indicated the presence of fat accumulation in the liver， accompanied by inflammatory reactions. Compared with the model group， QSQ of various doses could reduce TC， TG， and LDL-C levels in acute hyperlipidemia model mice （P<0.05， P<0.01）， and the high-dose QSQ could reduce TC and LDL-C levels （P<0.01） and increase HDL-C level （P<0.05） in hyperlipidemia model mice， as well as reduce TC， TG， and LDL-C levels in hyperlipidemia model golden hamsters （P<0.05， P<0.01）， especially in the first two weeks. In addition， atorvastatin calcium could further increase ALT， AST， and ALP levels （P<0.05， P<0.01） and aggravate liver function damage， while low-dose QSQ could reduce ALT， AST， and ALP （P<0.05）， and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.

To investigate the clinical manifestations and risk factors in patients with systemic lupus erythematosus (SLE) and cancers. From October 2010 to February 2019, 5 566 SLE patients hospitalized in the First Affiliated Hospital of Zhengzhou University were enrolled. A total of 69 cancer patients were identified, and the clinical characteristics and previous treatment were analyzed. Cervical carcinoma (21.74%, 15/69) and thyroid cancer (21.74%, 15/69) were the most common types of cancer. Most cancers were diagnosed in SLE patients with an age 40~50 years. The disease duration of SLE was from 60~120 months. SLE patients without cancers were usually diagnosed between 20~30 years with duration of symptoms less than 12 months. As to the previous treatment of SLE, the uses of glucocorticoid, cyclophosphamide, methotrexate and azathioprine were comparable between patients with cancers and without (P>0.05). However, the use of hydroxychloroquine was more frequent in SLE patients than in patients with cancers (P<0.01). Correlation analysis revealed significant correlation between disease course of SLE (OR=4.25, 95%CI 1.79~10.01,P<0.001), hydroxychloroquine (OR=0.26, 95%CI 0.12~0.59,P<0.001) and cancer risk. Long disease course may be a risk factor for SLE patients to develop cancer, whereas hydroxychloroquine could be a protective factor.