[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

Objective:To investigate the changes of home blood pressure from weekdays to weekends and its influencing factors.Methods:This study was a national multicenter prospective registry study. Data came from the registry study on the “Action of controlling home blood pressure to target in ten thousand patients”. Hypertension patients receiving antihypertensive drugs in the above study were included, and the general clinical data of the enrolled patients were collected. Patients′ office and home blood pressure were measured at baseline, followed by home blood pressure measurements for 7 consecutive days, and blood pressure trends over a one-week period were analyzed. Multivariate linear stepwise regression was used to investigate the influencing factors of blood pressure change from weekdays to weekends, and subgroup analysis was conducted according to body mass index, alcohol consumption, fasting blood glucose ≥6.1 mmol/L or diabetes mellitus. Kappa consistency test was used to analyze the influence of removing weekend blood pressure data on home blood pressure monitoring results. Results:A total of 3 228 hypertensive patients aged (66.2±7.6) years were included, including 1 612 (49.9%) males. The weekly blood pressure changes of the study subjects showed a trend of gradually increasing during working days (Monday to Friday) and decreasing during weekends (Saturday to Sunday). The blood pressure on weekends was lower than that on weekdays, but the difference was not statistically significant ((128.2±13.7)/(79.7±8.7) mmHg vs. (128.3±12.9)/(79.8±8.3) mmHg, all P>0.05; 1 mmHg=0.133 kPa). The blood pressure on Sunday was significantly lower than that on Friday ((127.9±13.3)/(79.6±9.1) mmHg vs. (128.5±13.3)/(80.0±9.0) mmHg, all P<0.05). Subgroup analysis showed that hypertensive patients who were overweight and obese, drank alcohol, and had fasting blood glucose≥6.1 mmol/L or combined diabetes mellitus had a smaller decrease or increasing trend in home blood pressure from weekdays to weekends. Consistency test results showed that the mean blood pressure after removing the 2-day home blood pressure data on weekends was consistent with the mean blood pressure of one week ( Kappa=0.90). The mean blood pressure after removing only the blood pressure data of Sunday was slightly less consistent with the mean blood pressure of one week ( Kappa=0.88). Conclusions:The home blood pressure level of hypertensive patients receiving antihypertensive drugs showed a trend of gradually increasing during working days and decreasing at weekends. People with hypertension who were overweight and obese, drank alcohol, had high fasting blood sugar, or had combined diabetes mellitus, and their home blood pressure decreased less or increased from weekdays to weekends. The removal of 1-day Sunday blood pressure data but not 2-day weekend blood pressure data had impact on the one-week home blood pressure monitoring results.

Objective:To investigate the changes of home blood pressure from weekdays to weekends and its influencing factors.Methods:This study was a national multicenter prospective registry study. Data came from the registry study on the “Action of controlling home blood pressure to target in ten thousand patients”. Hypertension patients receiving antihypertensive drugs in the above study were included, and the general clinical data of the enrolled patients were collected. Patients′ office and home blood pressure were measured at baseline, followed by home blood pressure measurements for 7 consecutive days, and blood pressure trends over a one-week period were analyzed. Multivariate linear stepwise regression was used to investigate the influencing factors of blood pressure change from weekdays to weekends, and subgroup analysis was conducted according to body mass index, alcohol consumption, fasting blood glucose ≥6.1 mmol/L or diabetes mellitus. Kappa consistency test was used to analyze the influence of removing weekend blood pressure data on home blood pressure monitoring results. Results:A total of 3 228 hypertensive patients aged (66.2±7.6) years were included, including 1 612 (49.9%) males. The weekly blood pressure changes of the study subjects showed a trend of gradually increasing during working days (Monday to Friday) and decreasing during weekends (Saturday to Sunday). The blood pressure on weekends was lower than that on weekdays, but the difference was not statistically significant ((128.2±13.7)/(79.7±8.7) mmHg vs. (128.3±12.9)/(79.8±8.3) mmHg, all P>0.05; 1 mmHg=0.133 kPa). The blood pressure on Sunday was significantly lower than that on Friday ((127.9±13.3)/(79.6±9.1) mmHg vs. (128.5±13.3)/(80.0±9.0) mmHg, all P<0.05). Subgroup analysis showed that hypertensive patients who were overweight and obese, drank alcohol, and had fasting blood glucose≥6.1 mmol/L or combined diabetes mellitus had a smaller decrease or increasing trend in home blood pressure from weekdays to weekends. Consistency test results showed that the mean blood pressure after removing the 2-day home blood pressure data on weekends was consistent with the mean blood pressure of one week ( Kappa=0.90). The mean blood pressure after removing only the blood pressure data of Sunday was slightly less consistent with the mean blood pressure of one week ( Kappa=0.88). Conclusions:The home blood pressure level of hypertensive patients receiving antihypertensive drugs showed a trend of gradually increasing during working days and decreasing at weekends. People with hypertension who were overweight and obese, drank alcohol, had high fasting blood sugar, or had combined diabetes mellitus, and their home blood pressure decreased less or increased from weekdays to weekends. The removal of 1-day Sunday blood pressure data but not 2-day weekend blood pressure data had impact on the one-week home blood pressure monitoring results.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

Objective:To improve the aqueous solubility, biocompatibility, fluorescence, and sonosensitivity of curcumin, this study aims to transform curcumin into curcumin-derived carbon dots (Cur-CDs) to enhance the efficacy of sonodynamic therapy (SDT) of atherosclerosis (AS).Methods:Cur-CDs were synthesized via a hydrothermal method. The morphology was characterized by transmission electron microscopy, while Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were applied to analyze the chemical composition and surface functional groups. Optical properties were examined by UV-visible spectrophotometry and fluorescence spectroscopy. Cell proliferation and viability assay and a hemolysis experiment were performed to assess biocompatibility. The sonosensitivity of Cur-CDs was determined by the measurement of reactive oxygen species (ROS) produced by Cur-CDs.To verify the effect of Cur-CDs-mediated SDT on macrophage phenotype, the M1 and M2 macrophage marker genes were detected via real-time fluorescence quantitative polymerase chain reaction. The ability of Cur-CDs in plaque detection was assessed through in vivo fluorescence imaging and ex vivo aortic fluorescence imaging. Atherosclerotic plaque mice were divided into five groups: control group, curcumin group, Cur-CDs group, curcumin + low-intensity pulsed ultrasound (LIPUS) group, and Cur-CDs+ LPIUS group. Aortic Oil red O staining and blood lipid level measurements were conducted to evaluate the therapeutic efficacy of SDT on the plaques.Results:Cur-CDs exhibited a spherical morphology and a distinct lattice structure with the diameter of (1.87±0.35)nm. The aqueous solubility of Cur-CDs was about 10 5 times that of curcumin because of their abundant oxygen-containing hydrophilic functional groups.Cur-CDs at concentrations up to 500 mg/L had no significant impact on cell proliferation and viability, with a negligible hemolysis rate of <1%, indicating good biocompatibility of Cur-CDs. Cur-CDs exhibited a stable and excellent fluorescence with the maximum excitation and emission wavelengths of 420 nm and 530 nm, respectively. Cur-CDs had the potential to be used for plaque fluorescence imaging, with the fluorescence intensity at the plaque being significantly greater than that of curcumin( P<0.01). It was observed that Cur-CDs activated by LIPUS were capable of producing ROS, including 1O 2, ·OH, and ·O 2-, with the total amount of ROS exceeding that of curcumin( P<0.05). Cur-CDs-mediated SDT facilitated the transformation of macrophage phenotype from M1 to M2, with a more pronounced effect than that observed with curcumin-mediated SDT. Oil red O staining revealed the most significant reduction in plaque area and lipid content in the Cur-CDs+ LIPUS group, which was about three times greater than that in the curcumin+ LIPUS group, confirming the excellent efficacy of Cur-CDs-mediated SDT on plaques. Conclusions:The successfully prepared Cur-CDs exhibit superior aqueous solubility, biocompatibility, fluorescence, and sonosensitivity than curcumin, contributing to the significant improvement in sonodynamic efficacy on plaques.

Objective:To revaluate the systematic reviews/meta-analysis of the literature on acupuncture in the treatment of stroke spastic hemiplegia.Methods:CNKI, Wangfang, VIP, CBM, Cochrane Library, PubMed and Embase were searched for systematic reviews/meta-analyses of acupuncture in the treatment of stroke spastic hemiplegia from the establishment of the databases to July 27, 2022. AMSTAR 2 Scale, Prisma statement (2020) and GRADE system were used to evaluate the quality of the collected literature.Results:A total of 5 systematic reviews/meta-analyses were included, all of which were rated as very low by AMSTAR 2. The 5 studies involved a total of 22 outcome measures, and the GRADE rating results were intermediate evidence in 5, low evidence in 8, and very low evidence in 9.Conclusions:Acupuncture therapy has certain therapeutic effects on reducing the degree of limb spasms and improving limb motor function in patients. However, the methodological quality of the included literature is poor, and there is limited high-level evidence to support conclusions. More high-quality experimental research is still needed to provide strong evidence-based medicine evidence.

Cryptogenic organic pneumonia (COP) refers to organic pneumonia that has not been identified a clear cause by current medical methods. A small proportion of COP can exhibit severe and progressive characteristics, while severe COP can cause systemic inflammatory storms and can be secondary to hemophilia. This article reported a case of acute severe COP secondary to hemophilia. A 67-year-old male patient was admitted to the hospital due to cough, shortness of breath, and fever. At first, he was misdiagnosed as severe pneumonia, but failed to receive anti infection treatments. Sputum pathogenetic examination and Macrogene testing of alveolar lavage fluid were performed, and no etiology was found to explain the patient's condition. The condition was gradually worsened and hemophilia occurred to explain, suggesting that acute severe COP was relevant. After receiving hormone treatment, the condition gradually relieved and the absorption of lung lesions improved. Hemophilia secondary to COP is rare, and the specific mechanism needs further study.
Male ; Humans ; Aged ; Hemophilia A/complications* ; Pneumonia/diagnosis* ; Bronchoalveolar Lavage Fluid ; Cough ; Dyspnea/etiology*

Inflammatory bowel disease (IBD) is a disorder of immune and microbial dysregulation, induced by environmental factors in a genetically predisposed individual. Studies on IBD-associated genes have demonstrated that Paneth cells (PC) are central to the pathogenesis of IBD, especially in the development of Crohn′s disease (CD). The morphology, quantity and function of PC are easily affected by susceptible genes. In the intestine, PC participate in the formation of stem cell niche and secrete antimicrobial particles, which plays a vital role in regulating intestinal microbiota and maintaining intestinal mucosal homeostasis. Meanwhile, the proliferation and maturation of PC are also dependent on the symbiotic microbiota in the intestine. This review focuses on the interaction of susceptible genes, PC and intestinal microbiota, as well as their influence on the occurrence and development of IBD.

Venous thromboembolism is one of the serious and common complications of gynecological malignant tumors, and it is also the main cause of death of patients besides the tumor itself. Nursing staff plays an important role in the prevention of venous thrombosis. Step-by-step systematic nursing intervention can effectively reduce the occurrence of venous thrombosis. This article reviews the research progress of prevention and nursing of perioperative venous thromboembolism in patients with gynecological malignant tumors, aiming to provide help for the establishment and effective implementation of preventive nursing strategies for venous thromboembolism in patients with gynecological malignant tumors.