OBJECTIVES: Patients with connective tissue diseases (CTD) have a high incidence of cardiac involvement, which often presents insidiously and can progress rapidly, making it one of the leading causes of death. Multiparametric cardiovascular magnetic resonance (CMR) provides a comprehensive quantitative evaluation of myocardial injury and is emerging as a valuable tool for detecting cardiac involvement in CTD. This study aims to investigate the correlations between CMR features and serological biomarkers in CTD patients, assess their potential clinical value, and further explore the impact of pre-CMR immunotherapy intensity on CMR-specific parameters, thereby evaluating the role of CMR in the early diagnosis of CTD-related cardiac involvement. METHODS: A retrospective analysis was conducted on 72 consecutive CTD patients who underwent CMR at Xiangya Hospital of Central South University between September 2019 and March 2024. Clinical data, serological markers, and CMR parameters were collected. Differences in CMR parameters were compared between CTD patients with positive and negative serological markers. Correlations between serological biomarkers and CMR parameters were analyzed, with subgroup analyses performed for different CTD subtypes. Logistic regression (univariate and multivariate) was applied to explore the effects of pre-CMR immunotherapy intensity on CMR parameters, and receiver operating characteristic (ROC) curve analysis was used to determine cutoff values. RESULTS: In differential analyses, CTD patients with elevated interleukin (IL)-1β and IL-6 levels exhibited significantly higher myocardial T₂ values compared with those with normal levels (P=0.014, P=0.012). Elevated IL-10 was associated with a higher prevalence of microvascular lesions on CMR (P=0.038). Correlation analysis revealed a significant positive association between high-sensitivity cardiac troponin T (hs-cTnT) and T₂ values (r=0.371, P=0.009). ROC analysis indicated that when the hs-cTnT threshold was 0.01 ng/mL, the sensitivity and specificity for predicting elevated left ventricular T₂ values were 85.71% and 61.11%, respectively [area under the curve (AUC)=0.767, P=0.001]. hs-cTnT and creatine kinase (CK) were also positively correlated with native T₁ values (r=0.371, P=0.009; r=0.364, P=0.032). Erythrocyte sedimentation rate (ESR) showed a positive correlation with the percentage of the late gadolinium enhancement (LGE) (r=0.236, P=0.047). Conversely, hs-cTnT correlated negatively with global radial strain (GRS) (r=-0.297, P=0.034), while CK correlated negatively with both GRS and global circumferential strain (GCS) (r=-0.292, P=0.022; r=-0.282, P=0.027). Among patients with elevated hs-cTnT, the cumulative glucocorticoid dose prior to CMR was negatively associated with elevated T₂ values (OR=0.997, P=0.018), and this correlation remained significant after adjusting for duration of steroid use (OR=0.997, P=0.044). ROC analysis showed that when the cumulative glucocorticoid dose did not exceed 613 mg/mL (prednisone equivalent), the sensitivity and specificity for predicting elevated T₂ values were 90.48% and 77.78%, respectively (AUC=0.862, P<0.001). CONCLUSIONS Several inflammatory biomarkers demonstrate correlations with specific CMR parameters, with hs-cTnT showing the strongest associations across multiple indices. Elevated hs-cTnT suggests a high likelihood of cardiac involvement in CTD patients. Furthermore, pre-CMR immunotherapy intensity significantly influences the specificity of T₂ mapping, indicating its importance in interpreting CMR results. These findings provide critical insights for clinicians in the early recognition, timely intervention, and disease evaluation. Future research should further explore the role of CMR in the assessment of CTD-related cardiac assessment of CTD-related cardiac involvement. Future studies should further explore the role of CMR in evaluating CTD cardiac manifestations and its integration with other clinical data to optimize patient management.
Humans ; Retrospective Studies ; Male ; Female ; Connective Tissue Diseases/blood* ; Middle Aged ; Adult ; Biomarkers/blood* ; Magnetic Resonance Imaging/methods* ; ROC Curve ; Interleukin-6/blood* ; Troponin T/blood*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

OBJECTIVE To observe the efficacy of Bioabsorbable steroid-eluting sinus stent implantation in endoscopic treatment of chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS In a self-controlled study,25 patients with CRSwNP who underwent nasal endoscopic surgery were randomly assigned to implant a Bioabsorbable steroid-eluting sinus stent into one side of the ethmoid sinus after nasal endoscopic surgery,leaving one side of the ethmoid sinus without stent implantation.Follow-up and endoscopic evaluation were performed before surgery,2 weeks,1 month,2 months,and 3 months after surgery.Main outcome measures:visual analogue scale(VAS)score,Lund-Kennedy endoscopic score,eosinophils(Eos)count in mucosal tissue,nasal discharge smear,postoperative intervention.RESULTS The Lund-Kennedy endoscopy score on the stent side was significantly lower than that on the control side at 1 and 3 months after surgery.There was no significant difference between the VAS scores of the stent side and the control side.One month after surgery,the Eos count of nasal mucosa pathology and Eos level of nasal secretions smear in patients with eosinophilic CRSwNP(eCRSwNP)and non-eosinophilic CRSwNP(neCRSwNP)on the stent side were significantly lower than those in the control side.However,there was no significant difference between eCRSwNP patients and neCRSwNP patients in the improvement degree of Eos count in nasal mucosa pathology and nasal secretions smear 1 month after stent operation.The ratio of requiring surgical intervention 1 month after surgery was lower in the neCRSwNP group than in the control group,while there was no significant difference between the two sides in the eCRSwNP group.The polypoid tissue score in neCRSwNP group were significantly lower than those in eCRSwNP group one month after surgery,the ratio of bilateral intervention in neCRSwNP group were lower than those in eCRSwNP group one month after surgery,with a significant difference on the stent side.CONCLUSION The application of Bioabsorbable steroid-eluting sinus stent in nasal endoscopy can improve the nasal endoscopy score,reduce the Eos inflammatory load,reduce surgical intervention,and thus improve the early postoperative outcome.Stent implantation can benefit both eCRSwNP patients and neCRSwNP patients.eCRSwNP patients with high inflammation burden may require more effective stents and release higher doses of corticosteroids to achieve higher benefits.

BACKGROUND:Traditional treatments for corneal alkali burns are limited,especially in controlling inflammation,preventing neovascularization,and inhibiting corneal scarring.Natural,synthetic,or composite materials provide a wide range of treatment options.However,the mechanism by which biomaterials promote corneal alkali burn repair has not yet been systematically understood. OBJECTIVE:To summarize the current research on biomaterials in promoting corneal alkali burn repair in and outside China,and review the mechanism and application of biomaterials in repairing corneal alkali burn. METHODS:The first author searched"cornea,alkali burn,amniotic membrane,hyaluronic acid,collagen,chitosan,polymer materials"as Chinese keywords and"amniotic membrane,hyaluronic acid,collagen,chitosan,polymer,cornea,alkali burn"as English keywords in PubMed,Web of Science,CNKI,and WanFang databases.According to inclusion and exclusion criteria,76 eligible articles were finally included for review. RESULTS AND CONCLUSION:(1)In the field of corneal alkali burn repair,biomaterials such as amniotic membrane,hyaluronic acid,collagen,chitosan,and degradable polymer materials have been widely studied and applied.Each of these biomaterials has its own characteristics,advantages,and disadvantages,and stands out in different aspects.(2)First and foremost,amniotic membranes are considered one of the most promising biomaterials due to their abundance of bioactive factors.They are biocompatible and can regulate the corneal inflammatory response.However,there are issues with donor shortages and susceptibility to infectious diseases.(3)Hyaluronic acid has good moisturizing properties and biocompatibility,and is able to improve the survival rate of corneal cells and increase corneal transparency.(4)The good biocompatibility and scaffold structure of collagen enable the promotion of corneal cell adhesion and proliferation,as well as the reconstruction of corneal tissue structure.(5)Chitosan is recognized for its good biocompatibility and degradability,making it suitable as a carrier for drug delivery and cell transplantation.(6)Degradable polymer materials have good controllability over degradation and can provide a good support and delivery platform for the repair of corneal alkali burns,but further research is needed on their stability and biocompatibility.(7)Overall,there is currently no single biomaterial that can completely address the repair problem of corneal alkali burns,and each biomaterial has its own specific application scenarios and limitations.(8)Future research directions should focus on further improving the properties and structure of biomaterials,exploring more effective combination applications,and deeply understanding the interaction mechanism between biomaterials and corneal tissue,in order to enhance the therapeutic effect of corneal alkali burns and the quality of life of patients.

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

Objectives:To investigate the expression of signal-induced proliferation-associated 1 (SIPA1) in colorectal cancer tissues and its relationship with patient prognosis. To explore the effects of SIPA1 on proliferation and migration abilities, as well as the possible molecular mechanisms.Methods:Using The Cancer Genome Atlas (TCGA) database to analyze the differential expression of SIPA1 and conduct survival analysis. Then, plotting receiver operating characteristic curve (ROC) and prognosis calibration curve analysis to assess the predictive capability and accuracy of SIPA1 for patient prognosis. Subsequently, verifying the expression levels of SIPA1 in tumor tissues and adjacent normal tissues using immunohistochemistry (IHC) and western blot (WB) assays(from March 1, 2023, to May 1, 2024, pathological specimens of five colorectal cancer patients were selected from the tissue bank of affiliated hospital of Nantong University. tissue microarrays were constructed using both cancerous tissues and adjacent normal tissues), and exploring the correlation between SIPA1 and clinical pathological parameters. Next, establishing SIPA1 stable knockdown cell lines in colorectal cancer cell lines DLD1 and HCT116, and assessing the biological behavior changes of tumor cells after SIPA1 knockdown through cell proliferation, invasion, and migration experiments. Validating the impact of SIPA1 on colorectal cancer cell proliferation in vivo through subcutaneous xenograft experiments in nude mice. Exploring the potential pro-tumor mechanisms of SIPA1 through pathway enrichment analysis, and confirming these using WB experiments. The proliferation, invasion and migration of tumor cells were detected after adding PI3K activator. Lastly, conducting correlation analysis between SIPA1 and immune checkpoint, as well as the association with immune cells in the tumor microenvironment. Results:Differential analysis showed that mRNA expression of SIPA1 in colorectal cancer tissues was significantly higher than that in adjacent normal tissues ( P＜0.05). Prognostic analysis indicated that patients with high expression of SIPA1 had poor overall survival ( P＜0.001), and the expression level of SIPA1was correlated with lymph node invasion ( P＜0.001) and N stage ( P＜0.05). ROC curve and prognosis calibration curve suggest that SIPA1 can effectively predict five-year survival rate of patients (AUC=0.7), and the predictive performance of the model is relatively accurate ( P＜0.001). WB experiments showed a significant increase in the expression level of SIPA1 protein in colorectal cancer specimens ( P＜0.001). Immunohistochemistry results indicated higher staining scores of SIPA1 in tumor tissues. In vitro experiments demonstrated that SIPA1 knockdown significantly inhibited the proliferation, invasion, and migration capabilities of colorectal cancer cells. In DLD1 and HCT116 cells, the SIPA1-knockdown group exhibited significantly lower absorbance compared to the control group (0.89±0.01 vs. 1.57±0.02 and 0.72±0.01 vs. 1.31±0.03, respectively, both P＜0.001). The SIPA1-knockdown group also demonstrated a reduced number of migrated cells relative to the control group (197.93±16.64 vs. 518.48±29.15 and 171.83±12.49 vs. 446.00±21.81, respectively, both P＜0.001). Furthermore, the cell wound-healing rate was significantly lower in the SIPA1-knockdown group than that in the control group [(0.32±0.01)% vs. (0.61±0.01)% and (0.28±0.01)% vs. (0.75±0.01)%, respectively, both P＜0.001]. In vivo animal experiments suggested that SIPA1 knockdown could inhibit tumor growth [(460.35±57.47) mm3 vs (1 177.55±208.24)mm3, (0.76±0.11)g vs (1.43±0.08)g, P＜0.05]. Pathway enrichment analysis revealed significant enrichment of the receptor tyrosine kinase signaling pathway, and SIPA1 knockdown could inhibit the activation of the phosphatidylinositide 3-kinases (PI3K)/protein kinase B (PKB)/glycogen synthase kinase-3β (GSK3β) signaling pathway. The PI3K activator reversed the inhibitory effect of SIPA1 silencing on tumor cell proliferation, invasion and migration. Correlation analysis indicated that high expression of SIPA1 was associated with immune checkpoints and various immunosuppressive cells (all P＜0.05). Conclusions:SIPA1 is highly expressed in colorectal cancer and associated with poor prognosis. SIPA1 may affect the proliferation and migration abilities of tumor cells by regulating the PI3K/AKT/GSK3β signaling pathway.

Objective:To investigate the curative effect and mechanism of hyperbaric oxygen therapy on nonalcoholic fatty liver disease in mice.Methods:Twenty-one 8-week-old male C57BL/6J mice were divided into three groups: control group (normal diet), model group (high-fat and high-cholesterol diet), and hyperbaric oxygen group (high-fat and high-cholesterol diet + hyperbaric oxygen therapy), with seven mice in each group. The changes in body weight, serum liver enzymes, and blood lipids were compared after treatment between the three groups. Hematoxylin-eosin staining, Oil Red O staining, Sirius red staining, and F4/80 immunohistochemical staining were used to observe the pathological changes in liver tissues. RT-qPCR and Western blot methods were used to detect the expression levels of oxidative stress and inflammatory factors. One-way analysis of variance was used for comparison among the groups.Results:Mice in the hyperbaric oxygen group had significantly improved liver histopathology. The serological levels of alanine aminotransferase, aspartate aminotransferase, and cholesterol were (77.50±13.59) U/L, (156.06±23.68) U/L, and (4.80±0.53) mmol/L, which were significantly lower than those in the model group [(109.43±16.88) U/L, (216.62±18.79) U/L, and (5.86±0.53) mmol/L, P<0.05], and accompanied by lower levels of lipid deposition, macrophage infiltration, and fibrosis. In addition, compared with the model group, the expression of antioxidant stress protein nuclear transcription factor erythroid 2-related factor 2 [(0.30±0.06) and (2.16±1.21), P<0.05] and heme oxygenase-1 [(0.48±0.19) and (1.01±0.18), P<0.05] in liver tissue showed an upward trend following hyperbaric oxygen treatment, which was also validated at the transcriptional level ( P<0.05). Simultaneously, compared with the model group, the mRNA expressions of tumor necrosis factor-α [(2.60±0.71) and (0.66±0.15), P<0.05], interleukin-1β [(2.41±1.01) and (0.78±0.23), P<0.05], and interleukin-6 [(3.61±2.17) and (0.94±0.25), P<0.05] in the liver tissue of mice in the hyperbaric oxygen group were decreased. The tumor necrosis factor-α protein level [(7.50±4.73) and (1.05±0.58), P<0.05] and interleukin-1β [(1.65±0.35) and (1.02±0.02), P<0.05] was reduced following hyperbaric oxygen treatment compared with those in the model group. Conclusion:Hyperbaric oxygen therapy can slow down the progression of nonalcoholic fatty liver disease by regulating the levels of oxidative stress and inflammation in the mice.

Objective To investigate the effects of preoperative anxiety on the intraoperative body temperature,recessive blood loss,and wound healing in elderly patients undergoing laparoscopic hysterectomy under general anesthesia.Methods A total of 118 elderly patients who underwent laparoscopic hysterectomy in Yancheng Third People's Hospital from January 2021 to December 2023 were selected as the research subjects,and they were divided into the normal group(69 cases with normal emotions)and the anxiety group(49 cases with anxiety emotions)according to the self-rating anxiety scale(SAS)score 1 day before operation.The core temperature at different time points and the incidence of intraoperative hypothermia were compared between the two groups.The intraoperative bleeding volume,incision drainage bleeding volume,recessive blood loss,incidence of adverse reactions,and wound healing were compared between the two groups.Results The core temperature 60 minutes after operation and at the end of operation in the anxiety group were significantly lower than those in the normal group(P<0.05).The incidence of intraoperative hypothermia in the anxiety group was significantly higher than that in the normal group(P<0.05).There was no statistically significant difference in the intraoperative bleeding volume or incision drainage bleeding volume between the two groups(P>0.05),while the recessive blood loss in the anxiety group was significantly higher than that in the normal group(P<0.05).The incidence of shivering in the anxiety group was significantly higher than that in the normal group(P<0.05);the incidence of poor wound healing in the anxiety group was significantly higher than that in the normal group(P<0.05).Conclusion For elderly patients who undergo laparoscopic hysterectomy for more than 60 minutes,the body temperature will significantly decrease,the incidence of intraoperative hypothermia and shivering is high,the recessive blood loss will significantly increase,which is prone to poor wound healing and is not conducive to the rapid recovery of patients after operation,if combined with anxiety before surgery.

Objective:To understand the potential characteristics of decision-making preparation in outpatient hypertensive patients based on latent profile analysis, to identify the influencing factors of different categories of decision-making preparation levels, and to explore the performance of different decision-making preparation types in facilitation of patients involvement in treatment decision-making.Methods:Through a cross-sectional study, 350 hypertensive patients attending outpatient clinics in five different types of healthcare institutions (general hospitals, specialised hospitals and community hospitals) in Tianjin during January to May 2024 who met the inclusion and exclusion criteria were selected by the convenience sampling method as study subjects. General Information Questionnaires, Preparation for Decision Making Scale, and Facilitation of Patient Involvement Scale were used for investigation.Results:Totally 350 valid questionnaires [178 males and 172 females aged 25-89(57.24 ± 13.39)years old] were collected. The decision-making preparation score of outpatient hypertensive patients was (64.19 ± 18.69). The latent profile analysis results showed that the decision-making preparation of outpatient hypertensive patients could be divided into three potential categories: decision-making information scarcity type accounted for 20.0%(70/350), decision-making balance negotiation type accounted for 39.7%(139/350), and decision-making preparation adequacy type accounted for 40.3%(141/350). The results of multiple Logistic regression analysis showed that age, medical insurance type, occupation, and children′s condition were the influencing factors for the potential categories of decision-making preparation in outpatient hypertensive patients (all P<0.05). Age [less than 35 years old: OR(95% CI)=0.127(0.020-0.796)], occupation [on the job: OR(95% CI)=2.010 (1.034-3.906)], were the influencing factors of decision-making balance negotiation group (all P<0.05). Medical insurance type [basic medical insurance for urban employees: OR(95% CI)=0.372(0.193-0.720)], occupation [on the job: OR(95% CI)=2.500(1.270-4.920)], children′s condition[junior and senior high school: OR(95% CI)=0.391(0.190-0.802)] were the influencing factors of decision-making preparation adequacy group (all P<0.05). Conclusions:The level of promoting patient participation among outpatients with hypertension is relatively high, and there are differences in the perceived degree of promoting patient participation among patients with different types of decision preparation.It is recommended that medical staff provide decision-making related information based on the characteristics of different decision-making preparation categories of patients, encourage patients to actively participate in decision-making, and construct targeted decision support plans.