To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction （GDFMD） in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome， thereby providing evidence-based medical evidence for the treatment of Wilson's disease （WD）-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1， 2023， to October 1， 2024. Participants were divided into a control group and an observation group， with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate （DMPS）. On this basis， the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days， for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses， respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement （LSM）， liver serological markers ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， type Ⅳ collagen （C-Ⅳ）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢNP）， and hyaluronic acid （HA）］， fibrosis index based on 4 factors （FIB-4）， AST to platelet ratio index （APRI）， unified Wilson's disease rating scale part Ⅱ （UWDRS-Ⅱ）， traditional Chinese medicine （TCM） syndrome score， 24-hour urinary copper， and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment， LSM levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses， and the improvement of LSM levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the levels of HA， LN， PⅢNP， and C-Ⅳ decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses， and the levels of HA， LN， and PⅢNP were more obvious （P<0.05）. After four treatment courses in the observation group， the levels of HA， LN， PⅢNP， and C-Ⅳ were improved more significantly （P<0.05）. Compared with those before treatment， ALT and AST levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with the control group after treatment， there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses， and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， APRI score and FIB-4 index level decreased in both groups after two and four treatment courses （P<0.05）. Compared with those in control group after treatment， there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses， and the APRI score in the observation group was more obvious after four treatment courses （P<0.05）， with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment， the levels of TCM syndrome scores decreased in both groups after two and four treatment courses （P<0.05）. Compared with that of the control group after treatment， there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses， and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously， and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses （P<0.05）. Compared with those of the control group after treatment， there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses， and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious （P<0.05）. Compared with those before treatment， the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses （P<0.05）. Compared with those in the control group after treatment， the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses （P<0.01）. After two treatment courses， the 24-h urine copper level in the observation group showed a gradual decreasing trend， although it was higher than that before treatment. After four treatment courses， the control group had an improvement rate of 91.43%， an effective rate of 34.29%， and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%， an effective rate of 71.43%， and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group （P<0.05）. Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy， and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety， which is worthy of clinical popularization and application.

ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction （GDFMD） in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome， thereby providing evidence-based medical evidence for the treatment of Wilson's disease （WD）-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1， 2023， to October 1， 2024. Participants were divided into a control group and an observation group， with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate （DMPS）. On this basis， the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days， for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses， respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement （LSM）， liver serological markers ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， type Ⅳ collagen （C-Ⅳ）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢNP）， and hyaluronic acid （HA）］， fibrosis index based on 4 factors （FIB-4）， AST to platelet ratio index （APRI）， unified Wilson's disease rating scale part Ⅱ （UWDRS-Ⅱ）， traditional Chinese medicine （TCM） syndrome score， 24-hour urinary copper， and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment， LSM levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses， and the improvement of LSM levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the levels of HA， LN， PⅢNP， and C-Ⅳ decreased in both groups after two and four treatment courses （P<0.05）. Compared with those after treatment， there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses， and the levels of HA， LN， and PⅢNP were more obvious （P<0.05）. After four treatment courses in the observation group， the levels of HA， LN， PⅢNP， and C-Ⅳ were improved more significantly （P<0.05）. Compared with those before treatment， ALT and AST levels decreased in both groups after two and four treatment courses （P<0.05）. Compared with the control group after treatment， there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses， and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， APRI score and FIB-4 index level decreased in both groups after two and four treatment courses （P<0.05）. Compared with those in control group after treatment， there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses， and the APRI score in the observation group was more obvious after four treatment courses （P<0.05）， with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment， the levels of TCM syndrome scores decreased in both groups after two and four treatment courses （P<0.05）. Compared with that of the control group after treatment， there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses， and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses （P<0.05）. Compared with those before treatment， the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously， and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses （P<0.05）. Compared with those of the control group after treatment， there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses， and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious （P<0.05）. Compared with those before treatment， the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses （P<0.05）. Compared with those in the control group after treatment， the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses （P<0.01）. After two treatment courses， the 24-h urine copper level in the observation group showed a gradual decreasing trend， although it was higher than that before treatment. After four treatment courses， the control group had an improvement rate of 91.43%， an effective rate of 34.29%， and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%， an effective rate of 71.43%， and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group （P<0.05）. Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy， and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety， which is worthy of clinical popularization and application.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective: To analyze the association between intraoperative blood transfusion and adverse perinatal outcomes(a composite of maternal death, hepatic encephalopathy, etc) in patients with acute fatty liver of pregnancy (AFLP), identify independent risk factors for these outcomes, and develop and validate a risk prediction model for early identification of high-risk patients. Methods: Clinical data of 56 AFLP patients admitted to our hospital from January 2008 to January 2025 were retrospectively analyzed. The chi-square test was used to compare the incidence of adverse perinatal outcomes between the transfusion group and the non-transfusion group. Univariate and multivariate Firth-penalized logistic regression analyses were performed to identify independent predictors of adverse outcomes. Based on the identified independent risk factors, a combined prediction model was developed. Internal validation was performed using the Bootstrap method (1 000 resamplings) to assess the model′s generalizability. Model performance was evaluated using receiver operating characteristic(ROC) curves and calibration curves. Finally, a nomogram for predicting adverse perinatal outcomes in AFLP was constructed. Results: Overall, 57.1%(32/56) of the patients received blood product transfusion during the termination of pregnancy. Multivariate Firth-penalized logistic regression analysis showed that, given the limited sample size, intraoperative blood transfusion had no independent statistical effect on adverse outcomes (OR=0.812, 95%CI:0.133-3.698, P=0.797). Mediation analysis also revealed no significant indirect effect. The independent risk factors were decreased preoperative fibrinogen (OR=14.062, 95%CI:2.389-126.656, P=0.003), pregnancy with infection (OR= 4.536, 95%CI:1.143-22.107, P=0.031), and cesarean section (OR=8.691, 95%CI:1.321-90.081, P=0.023). The combined prediction model achieved an AUC of 0.881 (95% CI:0.793-0.969, P<0.001), indicating good discrimination. At the optimal cut-off value, the sensitivity was 65.6%, specificity 95.8%, positive predictive value 95.5%, and negative predictive value 67.6%. Internal validation by the Bootstrap method showed that the predictive model had good discrimination and no obvious overfitting. The calibration curve demonstrated that the model′s predicted risk was consistent with the actual observed risk. Based on this, an AFLP perinatal adverse outcome nomogram model was constructed. Conclusion: Under the limited sample size of this study, no independent statistical effect of intraoperative blood product infusion on adverse perinatal outcomes in AFLP patients was detected. A multivariate Firth-penalized logistic regression model incorporating decreased preoperative fibrinogen, pregnancy with infection, and cesarean delivery demonstrated good discrimination and calibration. The derived nomogram may serve as an exploratory tool for early risk stratification and proactive intervention.

Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the changes in blood betatrophin in overweight and obese children，and analyze the relationship with glucose and lipid metabolism.Methods:A total of 177 children，including overweight-obese children and healthy controls，who visited the pediatric endocrinology clinic of Tianjin First Central Hospital from July 1，2021 to May 31，2023 were selected as study subjects. They were divided into an overweight-obese group（104 cases）and a normal control group（73 cases）. Data from both groups were collected and analyzed to explore the relationship between betatrophin and parameters such as body mass index（BMI）and glycolipid metabolism-related indicators.Results:The age［10.5（8.0，12.0）years vs 8.0（6.0，12.0）years］，fasting insulin［19.99（11.47，31.60）μIU/ml vs 7.27（5.02，10.99）μIU/ml］，triglyceride［0.95（0.74，1.31）mmol/L vs 0.75（0.62，0.92）mmol/L］，total cholesterol［（3.88 ± 0.72）mmol/L vs（3.60 ± 0.66）mmol/L］，low-density lipoprotein cholesterol［（2.37 ± 0.63）mmol/L vs（2.06 ± 0.62）mmol/L］，uric acid［353.20（287.40，434.12）μmol/L vs 278.60（218.00，313.80）μmol/L］，Betatrophin［22.54（17.08，27.53）mIU/L vs 19.30（15.78，23.33）mIU/L］，and fatty liver［31 cases（29.8%）vs 1 case（1.4%）］in overweight-obese group children were all higher than those in the normal control group children，and the differences were statistically significant（all P<0.01）.After adjusting for confounding factors such as age and BMI，partial correlation analysis revealed a positive correlation between betatrophin and triglycerides（ P<0.05）. Receiver operating characteristic（ROC）curve analysis indicated that a betatrophin level of 22 mIU/L had predictive value for hypertriglyceridemia，with an area under the curve（AUC）of 0.705（95% CI：0.566-0.843），showing statistical significance（ P=0.014）. Conclusion:Betatrophin may be associated with weight gain in children，mainly involved in the triglyceride metabolism.

Objective : To investigate the association between single nucleotide polymorphism(SNP) of PROS1 gene and recurrent spontaneous abortion(RSA) in Baotou Han population. Methods : 158 RSA patients and 158 control subjects were selected as the study subjects, and the activities of protein S, protein C and antithrombin-Ⅲ were measured. The rs13062355, rs6441600 and rs12634349 loci of PROS1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Non-conditional Logistic regression was used to analyze the correlation between three SNPs of PROS1 gene and the risk of RSA. Results : The protein S and antithrombin-Ⅲ activities of RSA patients decreased significantly(P<0.05). PROS1 SNP rs13062355 was associated with the risk of RSA under the dominant model: compared with genotype TT, patients with CT+CC genotypes had a reduced risk of RSA(OR=0.398, 95%CI: 0.249-0.638); SNP rs6441600 and rs12634349 were not associated with the risk of RSA(P>0.05). In the haplotypes constructed by PROS1 rs13062355, rs6441600 and rs12634349, Haplotype C-C-C was statistically different between the two groups(P<0.05). The third-order interaction model rs13062355-rs6441600-rs12634349 was associated with the risk of RSA. Conclusion PROS1 SNP rs13062355 may be associated with the risk of RSA in Han women in Baotou area. Haplotype C-C-C of PROS1 rs13062355, rs6441600 and rs12634349 reduces the risk of RSA. The third-order model rs13062355-rs6441600-rs12634349 interaction has a synergistic effect on the occurrence of RSA.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.