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

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.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.

Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Along with the change in lifestyle and diet, diabetes mellitus with hyperlipidemia has been a major risk and death factor for cardiovascular disease with the increasing incidence of diabetes mellitus with hyperlipidemia year by year. In order to promote and make full use of unique characteristics and advantages of TCM, the guidance writing group adopted the pattern of combination with disease and syndrome to make a standardized approach to diagnosis and treatment based on emphasis on diagnosis and treatment. Guidelines for the Diagnosis and Treatment of Diabetes Mellitus with Hyperlipidemia Combined with Disease and Syndrome (hereinafter referred to as " the Guideline") was published in the World Chinese Medicine in August, 2021. Based on the pattern of combination with disease and syndrome, the Guideline highlights the significant characteristics, such as: precise diagnosis and treatment by combined with disease and syndrome, updating criteria, rehabilitation diet therapy and exercise and following the principles which include but not limited to evidence-based medicine. According to the evidence of evidence-based medicine and expert consensus, the Guideline gives recommendations for diagnosis, treatment and rehabilitation of diabetes mellitus with hyperlipidemia. In the article, the main contents and characteristics of the new guideline were interpreted in order to provide concise and practical guidance for clinicians and promote the clinical popularization and application of the Guideline.