Objective To summarize the clinical features of infectious intracranial aneurysm (IIA) related to infective endocarditis (IE) and share our experiences in the diagnosis and treatment of IIA. Methods A retrospective analysis was conducted on the clinical data of 554 patients who underwent cardiac surgery for IE at the Department of Cardiac Surgery, Guangdong Provincial People's Hospital from September 2018 to August 2023. Patients with secondary IIA were included and reviewed. Based on the treatment strategies, patients were stratified into two groups: an antibiotic-only group and an endovascular treatment group. Results The cohort comprised 21 males and 10 females, with a median age of 33 years (IQR 26-53). Fifteen (48.4%) patients showed no significant neurological symptoms before IIA diagnosis. Seven patients received antibiotic therapy alone, while 24 underwent additional endovascular embolization, achieving technical success in 23 (95.8%) patients. The median interval between endovascular embolization and cardiac surgery was 2 days (IQR 0-6), with 9 patients undergoing concurrent procedures. In the antibiotic-only group, 3 (42.9%) patients suffered fatal IIA rupture. In contrast, only 1 (4.2%) death due to aneurysm rupture occurred in the endovascular treatment group. All surviving patients recovered well without new neurological deficits. Conclusion Routine neuroimaging screening for IIA is critical in IE patients. For those requiring cardiac surgery, endovascular embolization combined with antimicrobial therapy represents a reasonable strategy to mitigate rupture risks and improve outcomes.

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

OBJECTIVE: To explore clinical effect of reverse shoulder replacement in treating giant irreparable rotator cuff tear complicated with glenohumeral arthritis. METHODS: A retrospective analysis was performed on 18 patients (18 shoulders) with glenohumeral arthritis combined with large irreparable rotator cuff tear admitted from April 2020 to April 2022, including 10 males and 8 females, aged from 60 to 78 years old;7 patients on the left side, 11 patients on the right side;the course of disease ranged from 6 to 21 months;7 patients with grade 3 and 11 patients with grade 4 according to Goutallier grading;8 patients with grade 4b and 10 patients with grade 5 according to Hamada grading. Shoulder joint motion, visual analogue scale (VAS), University of California at Los Angeles (UCLA) score and Constant-Murley shoulder joint function score and complications were compared at the latest follow-up. RESULTS: Eighteen patients were followed up for 24 to 48 months. At the latest follow-up, shoulder joint flexion ranged from 120° to 145°, abduction ranged from 100° to 130°, and rotation ranged from 45° to 60°. VAS ranged from 1 to 3;Constant-Murley score ranged from 80 to 95;and UCLA scores ranged from 27 to 35, and 6 patients obtained excellent result, 11 good and 1 average. Dislocation of shoulder joint occurred in 1 patient at 3 months after operation, but no dislocation occurred after manual reduction. The incision surface infection occurred in 1 patient at 1 week after operation, and the incision healed after anti-infection and cleaning. The other patients did not have complications such as dislocation, infection, prosthesis loosening and peripheral fracture. CONCLUSION Reverse shoulder replacement for the treatment of huge irreparable rotator cuff injury combined with glenohumeral arthritis disease, the clinical effect is good, could significantly improve shoulder joint function and improve quality of life, but still need to strengthen the prevention and treatment of postoperative complications such as dislocation and infection.
Humans ; Male ; Female ; Middle Aged ; Rotator Cuff Injuries/physiopathology* ; Aged ; Retrospective Studies ; Arthroplasty, Replacement, Shoulder/methods* ; Range of Motion, Articular ; Shoulder Joint/physiopathology*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.

Objective To investigate the characteristics of immune exhaustion in sepsis and analyze its association with gut microbiota translocation.Methods A total of 130 mice were randomly divided into a cecal ligation and puncture(CLP)group(n=100)and a Sham group(n=30)Mouse model of sepsis was established with CLP procedure.Flow cytometry was used to analyze the proportions of peripheral blood CD4+T and CD8+T cells and programmed cell death protein 1(PD-1)positive T cell subsets in mice.Bacterial colonization in organs such as the heart,liver and kidneys was quantified by plating homogenates of the organs.Pathological changes in immune organs were observed with HE staining.The expression and localization of CD4?,CD8?,and PD-1?cells in immune organs were detected with immunohistochemical staining,and Image J software was employed for subsequent quantification of the number of the positive cells.Results HE staining demonstrated that immune organs exhibited varying degrees of pathological damages with disease progression.Compared with the Sham mice,the CLP mice exhibited significantly increased bacterial colonization in parenchymal organs and peripheral blood(P<0.05),notably in the liver,which showed the most severe infection.In the CLP group,the proportion of CD4+T lymphocytes in peripheral blood at days 1,3,and 5 postoperatively was decreased by 56%,70.57%,and 87.42%,respectively,when compared with the Sham group(P<0.001).The proportion of CD8+T lymphocytes was decreased by 48.33%relative to the Sham group only at day 5(P<0.001).In contrast,the proportion of CD4+T cell subsets expressing PD-1 was increased to 673.08,423.08,and 600 times that of the Sham group,respectively,at the same postoperative time points(P<0.001).Immunohistochemical results showed that,in the CLP group,the proportion of CD4+T cells in the thymus,spleen,and mesenteric lymph nodes was increased to 7.65,2.66,and 3.7 times that of the Sham group,respectively,at the early-stage peak(P<0.001),and then these proportions were decreased by 82.8%(P<0.001),41.9%(P<0.01),and 60.15%(P<0.001),respectively,at the late-stage trough when compared with the early-stage peak in the corresponding organs.The proportion of CD8+positive cells was increased in the early stage and then decreased insignificantly,while the proportion of PD-1+positive cells was increased continuously,and reached 6.24,13.9,and 20.96 times that of the Sham group at the peak in the thymus,spleen,and mesenteric lymph nodes respectively(P<0.001),with their expression regions showing a rough overlap with those of CD4+cells.Conclusion During sepsis,the inflammatory response can cause severe damage to immune organs and persistent exhaustion of CD4?T lymphocytes,leading to declined defenses against infection,which may be the main causes for exacerbated gut microbiota translocation and then systemic infection.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To compare the clinical outcomes of mitral valvuloplasty (MVP) and mitral valve replacement (MVR) for infective endocarditis, and to investigate the effect of MVP under different surgical risks. Methods A retrospective study was done on the patients with mitral infective endocarditis, who underwent surgical treatment in our department from January 2018 to March 2022. According to the procedures, the patients were divided into a MVP group and a MVR group. Propensity score matching method was applied with a ratio of 1:1 to eliminate the biases. The early and midterm outcomes were compared between the two groups after matching. According to the European System for Cardiac Operative Risk Evaluation Ⅱ(EuroSCORE-Ⅱ), the effect of MVP was compared between high and low risk patients. Results A total of 195 patients were collected. There were 141 patients in the MVP group (120 males, 85.1%) and 54 patients in the MVR group (41 males, 75.9%). The mean follow-up time was (34.0±16.1) months. Patients in the MVP group were younger [(42.7±14.6) years vs. (56.8±13.0) years, P<0.001] and had better preoperative conditions. The patients in the MVP group had a shorter ICU stay [3.0 (2.0, 5.0) d vs. 4.0 (3.0, 8.0) d, P=0.004], and lower incidences of low cardiac output syndrome (0.7% vs. 9.3%, P=0.007), in-hospital mortality (0.0% vs. 3.7%, P=0.023), and follow-up mortality (4.3% vs. 15.4%, P=0.007). However, after 1:1 propensity score matching, there were no statistical differences in the baseline data or postoperative and follow-up adverse events between the two groups (P>0.05). Also, there was no statistical difference in the mortality of high-risk patients between MVP and MVR group (P>0.05). There was no statistical difference in the reoperation or recurrent severe mitral regurgitation between high and low-risk patients in the MVP group (P>0.05). Conclusion MVP is feasible for treating mitral lesions caused by infective endocarditis with good early and midterm outcomes. For patients with severer preoperative conditions, if the leaflet damage is not severe, MVP may be a viable option, but validation with larger sample sizes is needed.

Objective:To investigate the genetic and clinical characteristics of 46,XX testicular disorders of sex development(DSD).Methods:We collected the clinical data on the patients with 46,XX testicular DSD diagnosed in the Center of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University from January 2017 to January 2023,and analyzed their genetic and clinical characteristics and the SRY gene chromosomal location for those with SRY-positive.Results:A total of 26 patients were included in this study,all with 46,XX and deletion of the AZFa,b and c regions,with a mean height of(168.3±5.9)cm,body weight of(64.0±7.5)kg,BMI of(22.66±2.79)kg/m2,left testis volume of(2.53±1.16)ml and right testis volume of(2.74 ±1.34)ml.The semen volume of the patients averaged 1.35(0.18-2.78)ml,FSH(36.85±18.01)IU/L,LH(19.71± 9.71)IU/L,and T(6.08±2.71)nmol/L.The SRY-negative patients had a higher incidence rate of development disorders in the re-productive system than the SRY-positive ones(5/6 vs 3/20,P=0.004),but no statistically significant differences were observed in the other parameters.The SRY gene was localized at the end of Xp in 13 of the 14SRY-positive cases,and at chromosome 15 in the other 1.Conclusion:46,XX testicular DSD has some similarity and heterogeneity in genetics and clinical characteristics.

Objective To observe the expression of NLRP3(NOD-like receptor protein 3)in diabetes nephropathy rats,and observe changes in expression of inflammatory and fibrosis factors after NLRP3 silencing and irbesartan(ARB)intervention,so as to explore the protective effect of irbesartan on diabetic nephropathy rats.Methods Male SD rats were randomly divided into 5 groups:Control group,Model group,Model+Blank group,Model+NLRP3 Sh group and Model+ARB group.The rats were killed 8 weeks and 12 weeks after the establishment of diabetes nephropathy model,and the kidney tissues were collected.Real-time PCR was used to detect the mRNA expression of NLRP3,Caspase-1,P65 and Vimentin.Western blot was used to detect the protein expression of NLRP3,P65,HSP47 and Vimentin.Immunofluorescence was used to observe the expression of NL-RP3,Caspase-1 and Vimentin.PAS,PASM and Masson staining were used to observe the pathological changes of kid-ney.Results Compared with Control group,the mRNA expressions of NLRP3,Caspase-1,P65 and Vimentin were increased(all P＜0.05),and the protein expressions of NLRP3,Caspase-1,P65,HSP47 and Vimentin were increased in Model group and Model+Blank group(all P＜0.05).Compared with Model group and Model+Blank group,the above indicators were decreased in Model+NLRP3 Sh group and Model+ARB group(all P＜0.05).And the differences of above indicators between Model group and Model+Blank group were statistically insignificant.The pathological staining results showed that NLRP3 silencing and ARB intervention inhibited the renal damage of diabetic rats,and relieved the glomerular hypertrophy,glomerular sclerosis,basement membrane expansion,and interstitial fi-brosis.Conclusion NLRP3 signaling pathway is activated in the kidney of diabetes nephropathy rats,and the expression of inflammatory and fibrosis factors is upregulated.Irbesartan can block NLRP3 signaling pathway and alleviate renal damage.Innate immune receptor NLRP3 may become a new therapeutic target for diabetes nephropathy.