ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

Dental mesenchymal stem cells (DMSCs) are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability. The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques. These methods can influence the cellular microenvironment, activate disparate signaling pathways, and induce different biological effects. "Epigenetic regulation" refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences, such as histone methylation. Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages. The most important sites of histone methylation in tooth organization were found to be H3K4, H3K9, and H3K27. Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites, generating distinct chromatin structures associated with specific downstream transcriptional states. Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications. A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation. Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4, H3K9, and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments. This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.
Mesenchymal Stem Cells/physiology* ; Humans ; Osteogenesis/genetics* ; Histones/metabolism* ; Cell Differentiation/physiology* ; Methylation ; Odontogenesis/genetics* ; Epigenesis, Genetic

ObjectiveTo observe the efficacy of Huoxue Jiedu Formulas （活血解毒方药， HJF） as an adjunctive treatement for patients with binding of stasis and toxin syndrome during the vulnerable period after acute myocardial infarction （AMI） percutaneous coronary intervention （PCI） surgery， and to explore its potential mechanism from the perspective of serum neutrophil extracellular traps （NETs）. MethodsA total of 129 patients with binding of stasis and toxin syndrome within 6 months after PCI for AMI were enrolled and divided into a treatment group （65 cases） and a control group （64 cases） based on patients' willingness to take Chinese herbal medicine. The control group received standard western medical therapy alone， while the treatment group additionally received HJF， one dose daily. Both groups were treated for four weeks. Before and after treatment， TCM syndrome scores were assessed. Seattle angina questionnaire （SAQ） was used to record angina stability and frequency scores， while the short form-36 health survey （SF-36） was employed to assess quality of life across eight dimensions， including physical functioning， role-physical， bodily pain， general health， vitality， social functioning， role-emotional， and mental health. The Pittsburgh sleep quality index （PSQI） was used to evaluate sleep quality， and the patient health questionnaire-15 （PHQ-15） was used to assess psychosomatic symptoms； Duke activity status index （DASI） was used to measure daily physical activity. Serum levels of neutrophil extracellular traps （NET） markers including myeloperoxidase-DNA （MPO-DNA）， neutrophil elastase-DNA （NE-DNA）， and citrullinated histone H3 （CitH3） were measured in 20 patients from the treatment group. ResultsAfter treatment， TCM syndrome score， PSQI score and PHQ-15 score in both groups significantly decreased， while DASI score， angina stability and frequency scores， and all eight dimensions of the SF-36 scale significantly increased （P＜0.05）. Compared to the control group， the treatment group had significantly lower TCM syndrome scores and significantly higher DASI， angina stability and frequency scores （P＜0.05）， as well as higher scores in the SF-36 dimensions of physical functioning， role-physical， social functioning， bodily pain， and vitality （P＜0.05）. After treatment， serum levels of MPO-DNA， CitH3， and NE-DNA in the treatment group were significantly reduced （P＜0.05）. ConclusionHJF combined with conventional therapy can significantly improve angina symptoms， TCM syndrome scores， and psychosomatic conditions in patients with binding of stasis and toxin syndrome during the vulnerable period after AMI. It also enhances quality of life， sleep quality， and daily physical activity. The underlying mechanism may be associated with the inhibition of serum NETs level.

Invasive pulmonary aspergillosis is the most common type of pulmonary aspergillosis. This paper reported a patient with pulmonary aspergillosis secondary to obstructive pulmonary disease and other underlying diseases. The clinical manifestations included wheezing, cough, fever and wheezing rale in the lungs. Diagnosis was ultimately confirmed through pathogens targeted next generation sequencing and pathological examination of respiratory coughs. Following comprehensive treatment that included antifungal therapy, the patient was cured and discharged with a good prognosis.

Objective:To investigate the effect of long-term oral aspirin on the changes in the aneurysm sac and persistent type Ⅱ endoleak after endovascular aortic repair (EVAR) of infrarenal abdominal aortic aneurysms based on propensity score-matched analysis.Methods:A retrospective cohort study was used to analyze the clinical data of 133 patients with infrarenal abdominal aortic aneurysms treated with EVAR from January 2019 to December 2021 in the Department of Vascular Surgery, Nanjing Drum Tower Hospital. There were 113 males and 20 females, aged (74.8±7.2) years (range: 59 to 95 years). Patients were divided into the group receiving aspirin ( n=80) and the group not taking aspirin ( n=53) based on whether they took aspirin regularly for a long time after surgery. The two groups were matched in a 1∶1 ratio using propensity score matching and the caliper value was 0.05. Cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in primary endpoint events (enlargement of the aneurysm sac, occurrence of persistent type Ⅱ endoleak) and secondary endpoint events (adverse cardiovascular events and clinically relevant bleeding events) between the two groups. Results:The follow-up time was (38.4±11.8) months (range: 30 to 58 months). Among the 133 patients, a total of 25 cases (18.8%) suffered enlargement of the aneurysm sac, including 20 cases in the group receiving aspirin and 5 cases in the group not taking aspirin; 35 cases (26.3%) suffered persistent type Ⅱ endoleak, including 26 cases in the group receiving aspirin and 9 cases in the group not taking aspirin. Adverse cardiovascular events occurred in 11 cases (8.3%) and clinically relevant bleeding events were reported in 5 cases (3.8%). A matched cohort was established after propensity score matching, resulting in 32 cases per group. The survival analysis found that the rate of aneurysm sac enlargement was significantly higher in the group receiving aspirin than that in the group not taking aspirin (Log-rank test: P=0.010), and the incidence of persistent type Ⅱ endoleak was significantly higher than that in the group not taking aspirin (Log-rank test: P=0.019). The incidence of adverse cardiovascular events and clinically relevant bleeding events were not significantly different in two groups (Log-rank test: P=0.061, P=0.286). Conclusions:The risk of aneurysm sac expansion and persistent type Ⅱ endoleak were significantly higher in patients taking long-term aspirin after EVAR than in the group not taking asprin. Therefore, high-risk abdominal aortic aneurysm patients who are prone to aneurysm sac expansion should be evaluated in advance so that the risks and benefits of surgery can be comprehensively evaluated and treatment strategies can be optimized.

Objective:To investigate the correlation between pre- and post-treatment changing trends in peripheral blood inflammatory markers and efficacy and their predictive value for prognosis in non-small cell lung cancer (NSCLC) patients treated with the first-line immunotherapy plus chemotherapy.Methods:The clinical data of NSCLC patients admitted to the Department of Radiation and Chemotherapy for Lung Oncology, Zhongnan Hospital of Wuhan University from October 2018 to May 2023 were retrospectively analyzed. The χ2 test was used to analyze the correlation between the changing trend of peripheral blood inflammatory markers and the efficacy of immunotherapy plus chemotherapy. The influencing factors of objective response rate (ORR) were assessed using binary logistic regression analysis. Kaplan-Meier survival curve and Cox proportional hazards model were used to analyze the prognostic value of the changing trend of peripheral blood inflammation markers on patients' prognosis. Results:A total of 102 NSCLC patients treated with first-line immunotherapy plus chemotherapy were included. The proportion of patients with bone metastases was higher in the lymphocyte to monocyte ratio (LMR) decreased group ( n=50) than that in the increased group ( n=52) ( χ2=4.28, P=0.039), whereas the pathological type of patients in the platelet to lymphocyte ratio (PLR) decreased group ( n=51) was more common in squamous carcinoma compared to patients in the increased group ( n=51) ( χ2=18.99, P<0.001), and a higher proportion of patients in the prognostic nutritional index (PNI) decreased group ( n=46) was female than that in the increased group ( n=56) ( χ2=4.29, P=0.038), with statistically significant differences. The 2-cycle objective response rate (ORR) of patients in the LMR increased and decreased groups was 63.5% (33/52) and 44.0% (22/50) ( χ2=3.89, P=0.049), the 2-cycle ORR of patients in the neutrophil to lymphocyte ratio (NLR) increased ( n=24) and decreased ( n=78) groups was 29.2% (7/24) and 61.5% (48/78) ( χ2=7.74, P=0.005), and the 2-cycle ORR for patients in the systemic immune inflammatory index (SII) increased group ( n=27) and decreased group ( n=75) was 33.3% (9/27) and 61.3% (46/75) ( χ2=6.26, P=0.012), with statistically significant differences. Multivariate analysis showed that the changing trend of inflammatory markers in peripheral blood were not related to ORR. The Kaplan-Meier survival curve indicated that patients in the group with SII decreased had longer median progression-free survival (PFS) (not reached vs. 7.1 months, χ2=9.35, P=0.002) and median overall survival (OS) (not reached vs. 16.6 months, χ2=11.08, P<0.001) than those in the SII increased group, and patients in the NLR decreased group had longer median OS (not reached vs. 22.2 months, χ2=4.56, P=0.033) than that in the NLR increased group. Univariate analysis suggested that both brain and bone metastasis ( HR=4.04, 95% CI: 1.23-13.35, P=0.022), increased SII ( HR=2.83, 95% CI: 1.41-5.66, P=0.003) were found to be significant factors affecting the PFS of NSCLC patients, both brain and bone metastasis ( HR=3.47, 95% CI: 1.05-11.45, P=0.041), increased NLR ( HR=2.17, 95% CI: 1.05-4.51, P=0.037) and increased SII ( HR=3.12, 95% CI: 1.54-6.30, P=0.002) were found to be significant factors affecting the OS of NSCLC patients. Multivariate analysis demonstrated that both brain and bone metastasis ( HR=4.32, 95% CI: 1.30-14.40, P=0.017) and increased SII ( HR=2.89, 95% CI: 1.44-5.81, P=0.003) were independent risk factors for PFS in NSCLC patients, both brain and bone metastasis ( HR=3.76, 95% CI: 1.13-12.50, P=0.031) and increased SII ( HR=3.47, 95% CI: 1.28-9.41, P=0.014) remained independent risk factors for OS in patients with NSCLC. Conclusion:The changing trend of peripheral blood inflammatory markers of NSCLC patients cannot independently predict the efficacy of 2-cycle immunotherapy plus chemotherapy. Both brain and bone metastasis, as well as the changing trend of SII can be used as important indicators to predict PFS and OS in advanced NSCLC patients treated with first-line immunotherapy plus chemotherapy. The simultaneous occurrence of brain and bone metastasis and SII increased suggest poor prognosis of NSCLC patients.

Invasive pulmonary aspergillosis is the most common type of pulmonary aspergillosis. This paper reported a patient with pulmonary aspergillosis secondary to obstructive pulmonary disease and other underlying diseases. The clinical manifestations included wheezing, cough, fever and wheezing rale in the lungs. Diagnosis was ultimately confirmed through pathogens targeted next generation sequencing and pathological examination of respiratory coughs. Following comprehensive treatment that included antifungal therapy, the patient was cured and discharged with a good prognosis.

Objective:To investigate the effect of long-term oral aspirin on the changes in the aneurysm sac and persistent type Ⅱ endoleak after endovascular aortic repair (EVAR) of infrarenal abdominal aortic aneurysms based on propensity score-matched analysis.Methods:A retrospective cohort study was used to analyze the clinical data of 133 patients with infrarenal abdominal aortic aneurysms treated with EVAR from January 2019 to December 2021 in the Department of Vascular Surgery, Nanjing Drum Tower Hospital. There were 113 males and 20 females, aged (74.8±7.2) years (range: 59 to 95 years). Patients were divided into the group receiving aspirin ( n=80) and the group not taking aspirin ( n=53) based on whether they took aspirin regularly for a long time after surgery. The two groups were matched in a 1∶1 ratio using propensity score matching and the caliper value was 0.05. Cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in primary endpoint events (enlargement of the aneurysm sac, occurrence of persistent type Ⅱ endoleak) and secondary endpoint events (adverse cardiovascular events and clinically relevant bleeding events) between the two groups. Results:The follow-up time was (38.4±11.8) months (range: 30 to 58 months). Among the 133 patients, a total of 25 cases (18.8%) suffered enlargement of the aneurysm sac, including 20 cases in the group receiving aspirin and 5 cases in the group not taking aspirin; 35 cases (26.3%) suffered persistent type Ⅱ endoleak, including 26 cases in the group receiving aspirin and 9 cases in the group not taking aspirin. Adverse cardiovascular events occurred in 11 cases (8.3%) and clinically relevant bleeding events were reported in 5 cases (3.8%). A matched cohort was established after propensity score matching, resulting in 32 cases per group. The survival analysis found that the rate of aneurysm sac enlargement was significantly higher in the group receiving aspirin than that in the group not taking aspirin (Log-rank test: P=0.010), and the incidence of persistent type Ⅱ endoleak was significantly higher than that in the group not taking aspirin (Log-rank test: P=0.019). The incidence of adverse cardiovascular events and clinically relevant bleeding events were not significantly different in two groups (Log-rank test: P=0.061, P=0.286). Conclusions:The risk of aneurysm sac expansion and persistent type Ⅱ endoleak were significantly higher in patients taking long-term aspirin after EVAR than in the group not taking asprin. Therefore, high-risk abdominal aortic aneurysm patients who are prone to aneurysm sac expansion should be evaluated in advance so that the risks and benefits of surgery can be comprehensively evaluated and treatment strategies can be optimized.

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.

Objective:To compare the postoperative recurrence rates between Thulium laser en bloc resection of bladder tumor (ERBT) and traditional transurethral resection of bladder tumor (TURBT) in treating patients with non-muscle invasive bladder cancer (NMIBC).Methods:A retrospective analysis was conducted on the clinical data of 1 439 patients with NMIBC who underwent either Thulium laser ERBT or TURBT in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between January 2010 and March 2024. Among them, 201 patients received Thulium laser ERBT, while 1 238 patients underwent TURBT. Propensity score matching (PSM) was employed in a 1∶1 ratio to eliminate selection bias due to non-random assignment, ensuring the comparability of clinical baseline data such as gender, age, pathological diagnosis, T stage, tumor grade, tumor size, and tumor number between the two groups. Kaplan-Meier method was used to generate recurrence-free survival curves for the matched groups, and the log-rank test was conducted to compare differences between the groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting postoperative recurrence.Results:After PSM matching, 193 patients were included in each group. There were no statistically significant differences between the two groups in terms of gender ( P=0.317), age ( P=0.207), pathological type ( P=0.756), T stage ( P=0.402), tumor grade ( P=0.965), tumor size ( P=0.821), or number of tumors ( P=0.421). The median follow-up time was 16.2(8.0, 33.9) months. Excluding patients with non-urothelial tumors such as adenocarcinoma and squamous cell carcinoma, there were 180 cases in the Thulium laser ERBT group and 184 cases in the TURBT group. Survival analysis showed that the postoperative recurrence rate of urothelial carcinoma patients in the Thulium laser ERBT group was lower than that in the TURBT group [20.0%(36/180) vs. 38.6%(71/184), P<0.001]. Stratified survival analysis indicated that in patients with tumor diameters ≤30 mm [22.3%(29/130) vs. 33.6%(45/134), P=0.017] or >30 mm [14.0%(7/50) vs. 52.0%(26/50), P=0.002], the Thulium laser ERBT group had lower postoperative recurrence rate compared to the TURBT group.Among patients with single tumor, the recurrence rate in the Thulium laser ERBT group was lower than in the TURBT group[10.5%(11/105) vs. 31.5%(35/111), P<0.001]. However, among patients with multiple tumors, there was no statistically significant difference in recurrence rates between the Thulium laser ERBT group and the TURBT group [35.7%(25/70) vs. 47.9%(34/71), P=0.061]. Univariate and multivariate Cox regression analyses indicated that Thulium laser ERBT treatment was an independent protective factor against postoperative recurrence in NMIBC patients ( HR=0.44, 95% CI 0.30-0.66, P<0.001). Patients with adenocarcinoma ( HR=5.85, 95% CI 2.07-16.51, P<0.001), squamous cell carcinoma ( HR=2.98, 95% CI 1.04-8.55, P=0.042), or other types of tumors ( HR=2.98, 95% CI 1.14-7.75, P=0.026) had higher risks of recurrence. High-grade tumor patients faced increased risks of postoperative recurrence ( HR=1.84, 95% CI 1.21-2.79, P=0.004). Additionally, tumors >30 mm had increased risks of postoperative recurrence compared to those ≤30 mm ( HR=2.00, 95% CI1.31-3.05, P=0.001). Patients with single tumor had significantly reduced risks of postoperative recurrence compared to those with multiple tumors ( HR=0.50, 95% CI 0.34-0.73, P<0.001). Conclusions:Regardless of tumor diameter (≤30 mm or >30 mm), Thulium laser ERBT significantly reduces the postoperative recurrence rate in patients with urothelial carcinoma compared to TURBT, with the advantage being more pronounced in patients with single bladder tumor. Additionally, patients with high-grade tumors, tumor diameters >30 mm, or multiple bladder tumors have higher risk of postoperative recurrence.