BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

College students shoulder the heavy responsibility of the times and are the key to improving the quality of the peo-ple.The strategic goal of"Healthy China"has put forward higher requirements for general education courses in universities.Immunity and Health is a general education course offered by Shandong University for the entire school.While optimizing teaching content in the classroom to achieve knowledge goals,it guides students to think about the emotional value behind knowledge,improve immune intel-ligence,and thus achieve the mission of cultivating talents for the construction of a"Healthy China".This article explores the develop-ment process of the teaching mode of"Immunity and Health",which has important practical significance for enhancing general educa-tion in universities and promoting the purpose of"advocating a healthy and civilized lifestyle,shaping self-discipline and healthy behavior"in China.

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Fibrosis ; Liver Diseases/drug therapy* ; Treatment Outcome ; Liver Cirrhosis/drug therapy*

Objective:To investigate the clinical effect of CAG stimulating regimen for refractory adult early T cell precursor acute lymphoblastic leukemia (ETP-ALL) complicated with fusarium infection and the clinical features as well as antifungal strategy of cutaneous fusarium infection.Methods:The diagnosis and treatment of 1 adult patient diagnosed as ETP-ALL complicated with cutaneous fusarium infection in the First Hospital of Jilin University in September 2020 were retrospectively analyzed, and related literatures were reviewed.Results:VICP chemotherapy regimen showed no effectiveness in this patient who was presented with persistent agranulocytosis complicated with cutaneous fusariosis infection. After amphotericin B therapy for infection, he achieved the stable disease and successfully underwent CAG stimulating regimen salvage treatment. The minimal residual disease turned into negative after consolidation chemotherapy based on the myeloid regimen. Finally this patient survived from haploid allogeneic hematopoietic stem cell transplantation after consolidation chemotherapy and fusarium was under the control by using posaconazole as secondary prevention therapy.Conclusions:CAG stimulating regimen can be recommended as reinduction therapy for relapsed/refractory ETP-ALL. Sequential therapy of amphotericin B followed by posaconazole can be a useful antifungal strategy for fusarium infection.

Objective:To construct a sensitive index system for nursing quality of patients with intracranial aneurysm rupture, so as to provide a basis for evaluating the nursing quality of patients with intracranial aneurysm rupture.Methods:Based on the "structure-process-outcome" quality structure model, a sensitive index system for nursing quality of patients with intracranial aneurysm rupture was preliminarily developed through literature analysis and semi-structured interviews. From December 2021 to March 2022, the Delphi method was used to conduct two rounds of consultation with 23 experts to establish a sensitive index system for nursing quality of patients with intracranial aneurysm rupture.Results:In the two rounds of consultation, the effective response rates of the questionnaires were all 100% (23/23), with expert authority coefficients of 0.78 and 0.75, and the Kendall's W of 0.170 and 0.101 respectively ( P<0.05). The final sensitive index system for nursing quality of patients with intracranial aneurysm rupture included 3 first-level indicators, 9 second-level indicators, and 39 third-level indicators. Conclusions:The sensitive index system for nursing quality of patients with intracranial aneurysm rupture is reliable and scientific, and can be used as a basis for evaluating the nursing quality of patients with intracranial aneurysm rupture.

Objective:To prospectively explore the treatment strategies for clinical difficulties in patients with hyperviremia HBeAg-positive chronic hepatitis B with incomplete response to first-line nucleos(t)ide analogues (NAs).Methods:Patients with hyperviremia HBeAg-positive chronic hepatitis B were treated with first-line NAs, including entecavir, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) for 48 weeks or more. Tenofovir amibufenamide (TMF) or TAF therapy was changed when HBV DNA remained positive and then divided into a TMF group and a TAF group. Clinical efficacy of treatment was evaluated at 24 and 48 weeks, including HBV DNA undetectable rates and virological and serological responses in both patient groups.Results:In the TMF group and the TAF groups, 30 and 26 cases completed 24-week follow-up, while 18 and 12 cases completed 48-week follow-up. There were no statistically significant differences in baseline HBV DNA, HBsAg, and HBeAg levels between the two groups before switching to TMF/TAF therapy ( P > 0.05). At 24 weeks of treatment, 19 (19/30, 63.33%) cases in the TMF group had HBV DNA negative conversion, while 14 (14/26, 53.85%) cases in the TAF group had HBV DNA negative conversion ( P > 0.05). Among the patients who completed 48 weeks of follow-up, 15 (15/18, 83.33%) cases in the TMF group and 7 (7/12, 58.33%) cases in the TAF group had negative HBV DNA tests ( P > 0.05). The changes in HBsAg and HBeAg levels between the two groups of patients at 24 and 48 weeks of treatment were not statistically significant compared to baseline ( P > 0.05). Conclusion:TMF is effective in treating patients with hyperviremia HBeAg-positive CHB with an incomplete response to first-line NAs treatment, but there is no significant difference compared to TAF.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Objective:To study the clinical efficacy of surgical resection combined with iodine-131 ( 131I) therapy in elderly patients with differentiated thyroid cancer and its influence on complications. Methods:Totally 82 elderly patients with differentiated thyroid cancer who were admitted to Chengde Central Hospital from March 2019 to March 2021 were selected and divided into observation group (41 cases) and control group (41 cases) according to the random number table. The control group underwent total thyroidectomy + neck lymph node dissection, and the observation group was treated with 131I after the operation on the basis of the control group. The indicators in the two groups were evaluated (postoperative observation time cutoff was 3 months), including perioperative indexes, postoperative complications, Karnofsky (KPS) score, serum levels of lymphocyte activating gene-3 (LAG-3) and recombinant human Dick-kopfx related protein-1 (DKK-1) before and after treatment, and the efficacy. Results:There was no significant difference between the two groups in the amount of intraoperative bleeding and operation time ( P > 0.05); the hospitalization time in the observation group [(6.72 ± 1.39) d] was shorter than that in the control group [(8.78 ± 1.43) d, P < 0.001]. The incidence of complications in the observation group (31.71%, 13/41) was lower than that in the control group (53.66%, 22/41, P = 0.045). After treatment, KPS scores in the two groups were higher than those before treatment ( P < 0.001); after treatment, KPS score in the observation group was higher than that in the control group ( P < 0.001). After treatment, the serum LAG-3 levels in the two groups were higher than those before treatment, while DKK-1 levels were lower than those before treatment ( P < 0.001); after treatment, the serum LAG-3 level in the observation group was higher than that in the control group, while the DKK-1 level was lower than that in the control group ( P < 0.001). The total effective rate of the observation group (95.12%, 39/41) was higher than that of the control group (80.49%, 33/41, P = 0.043). Conclusion:The clinical efficacy of surgical resection combined with 131I therapy in elderly patients with differentiated thyroid cancer is good, and it can reduce postoperative complications, up-regulate the expression of LAG-3 and down-regulate the expression of DKK-1.