BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

From the perspective of circular RNA forkhead box protein O3(circFOXO3) regulating glycolysis in osteoarthritis(OA) chondrocytes, this study investigated the mechanism by which Tougu Xiaotong Capsules(TGXTC) alleviated OA degeneration. In in vivo experiments, after randomized grouping and relevant interventions, morphological staining was used to observe structural changes in cartilage tissue. The mRNA level of circFOXO3 in cartilage tissue was detected by real-time quantitative PCR(RT-qPCR). Western blot analysis was used to detect changes in the expression of glucose transporter 1(GLUT1), hexokinase 2(HK2), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and matrix metalloproteinase 13(MMP13). In in vitro experiments, fluorescence in situ hybridization(FISH) was used to detect circFOXO3 expression in chondrocytes from each group. A lentiviral vector was used to construct circFOXO3-silenced(sh-circFOXO3) chondrocytes. RT-qPCR was used to analyze the changes in circFOXO3 levels after silencing, and Western blot was used to assess the regulatory effects of TGXTC on GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in interleukin-1β(IL-1β)-induced chondrocytes under sh-circFOXO3 conditions. Masson staining and alcian blue staining results showed that the cartilage layer structure in the TGXTC and positive drug groups was improved compared with that in the model group. The mRNA level of circFOXO3 was significantly upregulated in both the TGXTC and positive drug groups, while the expression of the above-mentioned proteins was significantly reduced. FISH results showed that TGXTC upregulated the fluorescence intensity of circFOXO3 in IL-1β-induced chondrocytes. In the circFOXO3 silencing experiment, compared with the IL-1β group, circFOXO3 levels in the IL-1β + sh-circFOXO3 group were significantly decreased. Compared with the IL-1β + TGXTC group, circFOXO3 levels were significantly reduced in the IL-1β + sh-circFOXO3 + TGXTC group. Western blot results indicated that the elevated levels of GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in chondrocytes of the IL-1β group were significantly inhibited by TGXTC intervention. However, this regulatory effect was attenuated after circFOXO3 silencing. In conclusion, TGXTC alleviate glycolytic metabolism disorder in OA chondrocytes and delay OA degeneration by regulating circFOXO3.
Chondrocytes/metabolism* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; RNA, Circular/metabolism* ; Osteoarthritis/genetics* ; Glycolysis/drug effects* ; Humans ; Forkhead Box Protein O3/metabolism* ; Male ; Capsules ; Matrix Metalloproteinase 13/genetics*

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.
Humans ; Hypospadias/surgery* ; Male ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Child, Preschool ; Child ; Postoperative Complications/etiology* ; Urethra/surgery* ; Plastic Surgery Procedures/methods* ; Surgical Flaps ; Penis/surgery* ; Treatment Outcome ; Infant

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term "immunosuppression" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.
Ferroptosis/immunology* ; Humans ; Immune Tolerance/immunology* ; Animals ; Immunosuppression Therapy ; Iron/metabolism* ; Neoplasms/immunology*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.

Objective:To investigate the diagnostic value of serum homocysteine(Hcy),soluble stromelysin 2(sST2)and cystatin C(CysC)for chronic heart failure(CHF).Methods:A total of 86 CHF patients admitted in our hospital were se-lected as CHF group,and 86 healthy individuals who underwent physical examination simultaneously were selected as healthy control group.Serum levels of Hcy,sST2 and CysC,plasma level of N terminal pro brain natriuretic peptide(NT-proBNP)and cardiac function indexes[left atrial diameter(LAD),left ventricular end diastolic diameter(LVEDd),left ventricular ejection fraction(LVEF)]were measured between two groups.Pearson correlation analysis was used to analyze the correlation among serum Hcy,sST2,CysC,plasma NT-proBNP and cardiac function indexes.Receiver operating characteristic curve(ROC)was drawn to evaluate the diagnostic value of serum Hcy,sST2 and CysC and their combined detection for CHF.Results:Compared with healthy control group,there were significant rise in scrum levels of Hcy,sST2 and CysC,plasma NT-proBNP level,LAD and LVEDd,and significant reduction in LVEF in CHF group,P=0.001 all.Pearson correlation analysis indicated that serum Hcy,sST2 and CysC levels were significant positively correlated with plas-ma NT-proBNP level,LAD and LVEDd(r=0.385～0.511,P＜0.05 or＜0.01),and significant inversely correlated with LVEF(r=-0.424～-0.402,P＜0.05 all).AUC of single detection of serum Hcy,sST2 and CysC diagnosing CHF was 0.624,0.720 and 0.870 respectively,and AUC of their combination was 0.865,which was significantly higher than any single detection,P＜0.05 or＜0.01.Conclusion:Serum levels of Hcy,sST2 and CysC abnormally increase in CHF patients,which can be used as auxiliary diagnostic indexes for CHF.The triple combined detection is of great signifi-cance for the diagnosis of CHF.