BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

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

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals ; Rats ; Network Pharmacology ; Tandem Mass Spectrometry ; Male ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid ; Blood Glucose/drug effects* ; Rats, Sprague-Dawley ; Hypoglycemic Agents/administration & dosage* ; Poria/chemistry* ; Diabetes Mellitus, Experimental/metabolism* ; NF-kappa B/genetics* ; Gastrointestinal Microbiome/drug effects* ; Humans

The choice of biopsy method is critical in diagnosing prostate cancer (PCa). This retrospective cohort study compared systematic biopsy (SB) or cognitive fusion-targeted biopsy combined with SB (CB) in detecting PCa and clinically significant prostate cancer (csPCa). Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center (Shanghai, China) between January 2019 and December 2023 were analyzed. Propensity score matching (PSM) was used to balance baseline characteristics, and detection rates were compared before and after PSM. Subgroup analyses based on prostate-specific antigen (PSA) levels and Prostate Imaging-Reporting and Data System (PI-RADS) scores were performed. Primary and secondary outcomes were the detection rates of PCa and csPCa, respectively. Of 2572 men, 1778 were included in the PSM analysis. Before PSM, CB had higher detection rates for both PCa (62.9% vs 52.4%, odds ratio [OR]: 1.54, P < 0.001) and csPCa (54.9% vs 43.3%, OR: 1.60, P < 0.001) compared to SB. After PSM, CB remained superior in detecting PCa (63.1% vs 47.9%, OR: 1.86, P < 0.001) and csPCa (55.0% vs 38.2%, OR: 1.98, P < 0.001). In patients with PSA 4-12 ng ml -1 (>4 ng ml -1 and ≤12 ng ml -1 , which is also applicable to the following text), CB detected more PCa (59.8% vs 40.7%, OR: 2.17, P < 0.001) and csPCa (48.1% vs 27.7%, OR: 2.42, P < 0.001). CB also showed superior csPCa detection in those with PI-RADS 3 lesions (32.1% vs 18.0%, OR: 2.15, P = 0.038). Overall, CB significantly improves PCa and csPCa detection, especially in patients with PSA 4-12 ng ml -1 or PI-RADS 3 lesions.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Propensity Score ; Retrospective Studies ; Middle Aged ; Aged ; Image-Guided Biopsy/methods* ; Prostate-Specific Antigen/blood* ; Prostate/diagnostic imaging*

OBJECTIVE: To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells. METHODS: K562 cells were treated with ginsenoside-Rg5 and imatinib. Cell survival was detected by CCK-8 assay, and IC₅₀ were calculated separately for each drug. Based on the value of IC₅₀ of ginsenoside-Rg5 and imatinib, an appropriate concentration gradient was selected for the combination. The synergistic effect of the two drug was analyzed using the online software synergy finder. The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy. RESULTS: Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dosedependent manner(r =-0.991， r =-0.942). The synergy score ZIP >10 was measured by Synergy Finder online software, indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells. The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96% and 8.13%, respectively, while the rate increased to 21.35% with the combination of two drugs, the apoptosis rate in the combination group was higher than that in the single-drug group ( P <0.05). The proportion of K562 cells in the G₀/G₁ phase was significantly increased with the combined treatment of two drugs( P <0.05). The protein expression levels of p-PI3K, p-AKT, p-mTOR in K562 cells treated with the combination were significantly decreased, with noticeable downregulation of BCL-2 and upregulation of BAX, leading to a decreased Bcl-2/BAX ratio, while no significant changes were observed in the non-phosphorylated forms of PI3K, AKT, and mTOR proteins. CONCLUSION The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.
Humans ; Ginsenosides/pharmacology* ; Imatinib Mesylate ; K562 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction/drug effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Drug Synergism ; Apoptosis/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Proliferation/drug effects*

The incidence of knee osteoarthritis(KOA)is in-creasing year by year,seriously affecting patients'health.Mes-enchymal stem cells are multipotent cells with multiple differen-tiation functions.The extracellular vesicles released by these cells can carry various"cargo"to corresponding cells and tis-sues,exerting biological functions.They have shown great clini-cal potential in the treatment of KOA.This study reviews the therapeutic effects and mechanisms of extracellular vesicles se-creted by mesenchymal stem cells from different tissues such as bone marrow,adipose tissue,and synovium in KOA.It is found that miRNA is an important biological component in exerting therapeutic effects.The study also discusses the research pro-gress of engineered extracellular vesicles in KOA,pointing out the current challenges in clinical application,such as standard-ized acquisition of extracellular vesicles and difficulties in targe-ted action,aiming to provide a certain reference for the basic re-search and clinical application of extracellular vesicle therapy for KOA.

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.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

OBJECTIVE: To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift. METHODS: From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared. RESULTS: A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05). CONCLUSION Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans ; Male ; Female ; Adult ; Anterior Cruciate Ligament Reconstruction/methods* ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Retrospective Studies ; Anterior Cruciate Ligament/surgery* ; Range of Motion, Articular