Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

In recent years, the situation of climate change has intensified, posing a threat to public health. There is an urgent need to promote public health adaptation actions to climate change. In January 2025, the National Disease Control and Prevention Administration issued the "Guidelines for Public Health Adaptation Actions to Climate Change" (hereinafter referred to as the "Guidelines"). The Guidelines put forward 20 items of guidance on six categories of public health adaptation actions, including understanding basic concepts, comprehending important policies, learning core knowledge, paying attention to key populations, practicing a low-carbon lifestyle, and mastering protection skills. It elaborates on the key concepts and the latest policies that the public needs to understand, and also provides the behavioral concepts and protection skills that should be mastered to adapt to climate change. This article provides a systematic interpretation of the Guidelines, introducing the background, ideas, connotations, and applications of their compilation, with the aim of enhancing society′s cognitive understanding of the Guidelines.

The incidence rate of coronary atherosclerotic heart disease(commonly referred to as coronary heart disease)remains high in China.In clinical practice,drug therapy,percutaneous coronary intervention(PCI),and coronary artery bypass grafting(CABG)are commonly employed.For patients with multi-vessel coronary artery stenosis,minimally invasive interventional therapy is often the preferred option.However,for those with multi-vessel disease complicated by comorbidities,CABG is generally recommended.Despite its advantages,PCI carries risks such as vascular restenosis,thrombosis,and other adverse events.Consequently,hybrid coronary revascularization(HCR)has emerged as an alternative approach.This paper provides an overview of coronary heart disease and re-views the advantages,applications,and patient selection criteria for HCR.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

The incidence rate of coronary atherosclerotic heart disease(commonly referred to as coronary heart disease)remains high in China.In clinical practice,drug therapy,percutaneous coronary intervention(PCI),and coronary artery bypass grafting(CABG)are commonly employed.For patients with multi-vessel coronary artery stenosis,minimally invasive interventional therapy is often the preferred option.However,for those with multi-vessel disease complicated by comorbidities,CABG is generally recommended.Despite its advantages,PCI carries risks such as vascular restenosis,thrombosis,and other adverse events.Consequently,hybrid coronary revascularization(HCR)has emerged as an alternative approach.This paper provides an overview of coronary heart disease and re-views the advantages,applications,and patient selection criteria for HCR.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

In recent years, the situation of climate change has intensified, posing a threat to public health. There is an urgent need to promote public health adaptation actions to climate change. In January 2025, the National Disease Control and Prevention Administration issued the "Guidelines for Public Health Adaptation Actions to Climate Change" (hereinafter referred to as the "Guidelines"). The Guidelines put forward 20 items of guidance on six categories of public health adaptation actions, including understanding basic concepts, comprehending important policies, learning core knowledge, paying attention to key populations, practicing a low-carbon lifestyle, and mastering protection skills. It elaborates on the key concepts and the latest policies that the public needs to understand, and also provides the behavioral concepts and protection skills that should be mastered to adapt to climate change. This article provides a systematic interpretation of the Guidelines, introducing the background, ideas, connotations, and applications of their compilation, with the aim of enhancing society′s cognitive understanding of the Guidelines.

AIM:To investigate the improvement effect of blood flow-limited resistance training on renal fibro-sis in type 2 diabetes mellitus(T2DM)rats and its potential mechanism to attenuate renal fibrosis by inhibiting the trans-forming growth factor β1(TGF-β1)/Smad3 signaling pathway.METHODS:The T2DM model was prepared by combining a high-fat diet and streptozotocin(STZ),and after successful modeling,the rats were randomly divided into a T2DM con-trol group,a low-load resistance training group,a high-load resistance training group,a blood flow restriction group and a blood flow restriction combined with resistance training group for 8 weeks of exercise.The renal index,fasting blood glu-cose(FBG),serum creatinine(SCr),and blood urea nitrogen(BNU)were recorded in each group.The morphological changes of the kidneys were observed by hematoxylin and eosin(HE)and Masson's trichrome staining,and the collagen volume fraction was calculated.The mRNA expression levels of renal Klotho,TGF-β1,and α-smooth muscle actin(α-SMA)were detected by RT-qPCR.The protein expression levels of renal Klotho,TGF-β1,Smad3,phosphorylated Smad3(p-Smad3),α-SMA and connective tissue growth factor(CTGF)were detected using Western blot.RESULTS:Compared with the other groups,FBG,SCr,BNU,and renal collagen volume fraction were significantly decreased in the blood flow restriction combined with resistance training group of rats(P<0.05),Klotho expression was significantly in-creased(P<0.05),and the expression of TGF-β1,p-Smad3,CTGF and α-SMA was significantly decreased(P<0.05),and there was no significant change in the expression level of Smad3(P>0.05).CONCLUSION:Blood flow restriction combined with resistance training attenuates renal fibrosis in T2DM rats,the mechanism of which may be related to the up-regulation of Klotho expression,disruption of the TGF-β1/Smad3 signaling pathway,and inhibition of the deposition of epi-thelial-mesenchymal transformation.

Objective To evaluate the quality and authenticity of Ophiopogon japonicus in Shengmaiyin,establish ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)for the determination of three characteristic components(methylophiopogonanone A,liriopeside B and liriope muscari baily saponin C),and provide technical support for drug supervision.Methods Samples were analyzed on a Phenomenex Kinetex F5 C18 column(100 mm×3.0 mm,2.6 μm)in a gradient elution mode with 0.1％formic acid water and-0.1％formic acid acetonitrile as the mobile phase at a flow rate of 0.4 mL/min,the column temperature was 30 ℃,and the injection volume was 1 μL.Mass spectrometer detector,electro spray ion source of positive and negative ions,and multi-reaction monitoring mode were used.Results The linear ranges of methylophiopogonanone A,liriopeside B and liriope muscari baily saponin C were 0.016 7-1.666 0,0.039 7-15.872 0 and 0.022 5～8.988 0 ng(r＞0.999 9),respectively.The average recovery rates of these three components were 85.16％,86.95％and 95.07％,respectively,with RSSDs of 2.65％,1.45％and 1.14％(n=6).The content of methylophiopogonanone A in thirty-eight batches was quite different.Seven batches of liriopeside B or liriope muscari baily saponin C were detected.Conclusion The method is simple and sensitive,and suitable for determining of three characteristic components in Shengmaiyin,which provides references for the quality control of Ophiopogon japonicus in Shengmaiyin.

Objective:To explore the occurrence and clinical characteristics of thyroid dysfunction caused by sintilimab.Methods:The subjects were selected from malignant tumor patients who were treated with sintilimab during hospitalization in the Oncology Department in Heping Hospital Affiliated to Changzhi Medical College from July 1, 2021 to June 30, 2023. Electronic medical records of patients meeting the inclusion criteria were collected; the general conditions, sintilimab application, combined medication, and the thyroid function test results before and after sintilimab application were recorded. For patients with thyroid dysfunction, the causal analysis between sintilimab application and the dysfunction was conducted using Naranjo′s causality assessment scale. The clinical characteristics of sintilimab-related thyroid dysfunction were analyzed based on the medical records that had evaluation results of "certainly" or "probably".Results:A total of 145 patients were included in the analysis, and 24 (16.6%) had sintilimab-related thyroid dysfunction, with the causality assessment results "probably". Among the 24 patients, 14 were male and 10 were female, aged 37-87 years; 5 were treated with sintilimab monotherapy, 16 were with combination of chemotherapy drugs, and 3 were with combination of targeted drugs. All 24 patients had baseline thyroid function test results, of which 23 had normal thyroid function and 1 had subclinical hyperthyroidism. Twenty-four patients with thyroid dysfunction included 13 hypothyroidisms, 5 subclinical hypothyroidisms, 2 hyperthyroidisms, and 4 subclinical hyperthyroidisms; 11 occurred within 3 treatment cycles; the severity was grade 1 or 2, without obvious clinical symptoms, except that 4 hypothyroidism patients had mild fatigue. The 13 hypothyroidism patients were treated with levothyroxine sodium tablets (levothyroxine), 9 patients recovered or were improved, and 4 patients were with persistent but not worsening condition. Three of the 5 subclinical hypothyroidism patients were treated with levothyroxine, 2 patients recovered and 1 developed subclinical hyperthyroidism later; the remaining 2 patients were given intensive monitoring without medication intervention, and they developed hypothyroidism later, which recovered after treatment with levothyroxine. None of the 6 patients with hyperthyroidism or subclinical hyperthyroidism received any intervention. Of them, 1 patient with subclinical hyperthyroidism was self-healed and 5 patients developed hypothyroidism or subclinical hypothyroidism later. After giving levothyroxine, 3 patients recovered or were improved and 2 had persistent but not worsening condition.Conclusions:Thyroid dysfunction is the most common immune-related adverse events of sintilimab, mainly hypothyroidism. The clinical symptoms are not obvious, and the severity is mostly grade 1 or 2. When using sintilimab, the thyroid function of patients should be routinely monitored. When hypothyroidism occurs, timely supplementation of levothyroxine is recommended, and the prognosis is generally good.