Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus(T2DM) patients with different disease durations. Methods A total of 288 patients with impaired pancreatic function who were treated from June 2019 to June 2020 were selected. They were divided into three groups,short duration group (≤10 years group,n=95),medium duration group (10～20 years group,n=96) and long duration group (≥20 years group,n=97). Three groups of patients were treated with Dapagliflozin in addition to the regular insulin therapy for 6 months. Clinical efficacy,blood glucose indices,pancreatic β-cell function and complications during the treatment period were compared among the three groups. Results After treatment,there was a significant decrease in the values of three groups including WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,BMI,FIns and HOMA-IR(P<0.05). Meanwhile,HDL-C,C-P,HOMA-β and HOMA-IS values showed a significant increase(P<0.05). After treatment,WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,FIns and HOMA-IR increased in turn(P<0.05),while HDL-C,C-P,HOMA-β and HOMA-IS decreased in turn in ≤10 years group,10～20 years group,≥20 years group(P<0.05). The BMI of 10～20 years group was lower than that of ≤10 years group and ≥20 years group (P<0.05),while the BMI of ≥20 years group was higher than that of ≤10 years group (P<0.05). Conclusions In overweight/obese T2DM patients with different DM durations,Dapagliflozin combined with insulin treatment shows a significant advantage in lowering blood glucose indices and improving pancreatic β-cell function,especially for patients with a shorter disease duration.

BACKGROUND:In addition to apoptosis,recent studies have discovered novel forms of programmed cell death in periprosthetic osteolysis,which is involved in regulating local chronic inflammation and the outcome of osteoblast and osteoclast under pathological conditions.This has an important value for the treatment and prognosis of periprosthetic osteolysis. OBJECTIVE:To provide new ideas and strategies for the prevention and treatment of periprosthetic osteolysis by summarizing studies on the novel forms of programmed cell death. METHODS:The first author used the computer to search the articles published from 2005 to 2022.Chinese search terms"wear particles,periprosthetic osteolysis,programmed cell death,apoptosis,autophagy,pyroptosis,necrotizing apoptosis,iron death"were used to search the databases of CNKI,WanFang and VIP.English search terms"osteolysis,wear debris,wear particles,peri*prosthetic osteolysis,PPOL,aseptic loosening,autophagy,regulated cell death,programmed cell death,apoptosis,pyroptosis,autophagic cell death,autophagy,necroptosis,ferroptosis"were used for search in PubMed and Web of Science databases.A total of 68 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:(1)Inadequate or excessive activation of autophagy can cause cell death,inhibit bone formation,and promote bone resorption,leading to bone metabolism disorders and osteolysis.(2)Recent studies have paid close attention to pyroptosis in periprosthetic osteolysis,where the Nod-like receptor,pyrin containing 3 inflammasome plays an important role in local inflammation.Inhibiting pyroptosis can effectively alleviate osteolysis.(3)In vitro studies have shown that necroptosis can inhibit the formation and function of osteoblasts and osteoclasts,affecting the process of osteolysis and destruction.(4)Ferroptosis is the newest form of programmed cell death,which is regulated by complex signaling pathways and mechanisms,but is not yet fully understood.(5)Autophagy,pyroptosis,necroptosis,and ferroptosis play important roles in the development of periprosthetic osteolysis,and their associated signaling pathways and genes require further investigation.

Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus(T2DM) patients with different disease durations. Methods A total of 288 patients with impaired pancreatic function who were treated from June 2019 to June 2020 were selected. They were divided into three groups,short duration group (≤10 years group,n=95),medium duration group (10～20 years group,n=96) and long duration group (≥20 years group,n=97). Three groups of patients were treated with Dapagliflozin in addition to the regular insulin therapy for 6 months. Clinical efficacy,blood glucose indices,pancreatic β-cell function and complications during the treatment period were compared among the three groups. Results After treatment,there was a significant decrease in the values of three groups including WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,BMI,FIns and HOMA-IR(P<0.05). Meanwhile,HDL-C,C-P,HOMA-β and HOMA-IS values showed a significant increase(P<0.05). After treatment,WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,FIns and HOMA-IR increased in turn(P<0.05),while HDL-C,C-P,HOMA-β and HOMA-IS decreased in turn in ≤10 years group,10～20 years group,≥20 years group(P<0.05). The BMI of 10～20 years group was lower than that of ≤10 years group and ≥20 years group (P<0.05),while the BMI of ≥20 years group was higher than that of ≤10 years group (P<0.05). Conclusions In overweight/obese T2DM patients with different DM durations,Dapagliflozin combined with insulin treatment shows a significant advantage in lowering blood glucose indices and improving pancreatic β-cell function,especially for patients with a shorter disease duration.

Objective     To investigate the perioperative clinical effects and follow-up results of minimally invasive coronary artery bypass grafting (MICS CABG) versus conventional coronary artery bypass grafting (CABG) in thoracotomy. Methods     The patients who received off-pump CABG in Beijing Anzhen Hospital from January 2017 to October 2021 were collected. Among them, the patients receiving MICS CABG performed by the same surgeon were divided into a minimally invasive group, and the patients receiving median thoracotomy were into a conventional group. By propensity score matching, preoperative data were balanced. Perioperative and postoperative follow-up data of the two groups were compared. Results     A total of 890 patients were collected. There were 211 males and 28 females, aged 60.54±9.40 years in the minimally invasive group, and 487 males and 164 females, aged 62.31±8.64 years in the conventional group. After propensity score matching, there were 239 patients in each group. Compared with the conventional group, patients in the minimally invasive group had longer operation time, shorter drainage duration, less drainage volume on the first postoperative day, shorter postoperative hospital stay, and lower rate of positive inotropenic drugs use, while there was no statistical difference in the mean number of bypass grafts, ICU stay, ventilator-assisted time, blood transfusion rate or perioperative complications (P>0.05). During the median follow-up of 2.25 years, there was no statistical difference in major adverse cardiovascular and cerebrovascular events, including all-cause death, stroke or revascularization between the two groups (P>0.05). Conclusion    Reasonable clinical strategies can ensure perioperative and mid-term surgical outcomes of MICS CABG not inferior to conventional CABG. In addition, MICS CABG has the advantages in terms of postoperative hospital stay, postoperative drainage volume, and rate of positive inotropic drugs use.

Objective:The perioperative and early follow-up data of the simultaneous hybrid CAS+ OPCABG and sequential CAS+ OPCABG were compared to evaluate the safety and efficacy of the simultaneous CAS+ OPCABG.Methods:A total of 26 patients with coronary heart disease complicated with carotid artery stenosis received CAS plus OPCABG hybrid surgery in our hospital from January 2020 to July 2021, among which 12 patients received simultaneous CAS+ OPCABG and 14 patients received staged sequential CAS+ OPCABG.The perioperative and postoperative follow-up data of 3 months were compared and analyzed.Results:There were no significant differences in the operation time, drainage on the first day after surgery, ventilator assisted time and ICU time between the two groups.The amount of intraoperative blood loss in the simultaneous group was more than that in the staged group, but no secondary thoracotomy occurred in both groups. The number of days in hospital after operation was significantly less in the simultaneous group. There was 1 case of perioperative cerebral infarction and 1 case of myocardial infarction in the staged group, but there was no statistical difference between the two groups. There was no new cerebral infarction in the two groups, carotid artery ultrasound stent was unobstructed, and there was no statistical difference in cardiac function grading and left ventricular ejection fraction 3 months after operation.Conclusion:Simultaneous CAS+ OPCABG surgery is safe and feasible, it is recommended as the first choice especially for patients with severe myocardial ischemiaor severe left main artery disease caused.How to reduce the risk of bleeding and alleviat carotid sinus reflex are major issues that need to be concerned.

Objective     To compare the mid- and long-term efficacy of minimally invasive coronary artery bypass grafting (MICS) versus conventional coronary artery bypass grafting (CABG). Methods     This study analyzed 679 patients with coronary heart disease treated in the Minimally Invasive Heart Center of Beijing Anzhen Hospital from 2015 to 2019, including 532 males and 147 females with an average age of 61.16 years. A total of 281 patients underwent MICS (a MICS group) and 398 patients underwent conventional CABG (a CABG group). The clinical data of the patients in the two groups were analyzed. Results    The average operation time was longer (P<0.001), the total hospital stay was shorter (P<0.001), and the amount of drainage 24 h after the operation was less (P=0.029) in the MICS group. There was no statistical difference in the incidence of perioperative complications between the two groups. The median follow-up time was 2.68 years. The follow-up results showed that the total incidence of cumulative main adverse cardiovascular and cerebrovascular events in the CABG group was higher at 2 years (6.2% vs. 3.8%) and 4 years (9.3% vs. 7.6%), but the difference was not statistically significant (P>0.05). There was no statistical difference in 2- or 4-year all-cause death between the two groups (3.5% vs. 2.8%, 5.6% vs. 2.8%, P>0.05). At the same time, there was no statistical difference in the incidence of myocardial infarction, stroke or revascularization between the two groups (P>0.05). Conclusion    Compared with conventional CABG, MICS can achieve satisfactory mid- and long-term outcomes.

Objective    To study the learning curve of minimal invasive coronary artery bypass grafting (MICS CABG) and the influence on the perioperative clinical effects by analyzing operation time. Methods    From March 2012 to November 2020, 212 patients underwent MICS CABG by the same surgeon. Among them, 59 patients (52 males and average age of 62.89±8.27 years) with single vessel bypass grafting were as a single-vessel group and 153 patients (138 males, average age of 59.80±9.22 years) with multi-vessel bypass grafting were as a multi-vessel group. Two sets of operation time-operation sequence scatter plots were made and learning curve was analyzed by cumulative summation (CUSUM) and regression method of operation time. The surgical data of each group before and after the inflection point of the learning curve were compared with the main clinical outcome events within 30 days after surgery. Results    There was no death, perioperative myocardial infarction and stroke in 212 MICS CABG patients and no transfer to cardiopulmonary bypass or redo thoracotomy. The learning curve conformed to the cubic fitting formula. In the single- vessel group, CUSUM (x operation number)=–1.93+93.45×x–2.33×x2+0.01×x3, P=0.000, R2=0.986, the tipping point was 27 patients. In the multi-vessel group, CUSUM (x)=y=2.87+1.15×x–1.29× x2+3.463×x3, P=0.000, R2=0.993, and the tipping point was 59 patients. The two sets of case data were compared before and after the learning curve and there was no statistical difference in main clinical outcomes within 30 days (mortality, acute myocardial infarction, stroke, perioperative blood transfusion rate), ventilator tube, and intensive care unit retention. Conclusion    The learning curve of MICS CABG conforms to the cubic formula, and the process transitions from single to multiple vessels bypass. To enter the mature stage of the learning phase, a certain number of patients need to be done. Reasonable surgical procedures and quality control measures can ensure the safety during the learning phase.

Objective    To investigate the safety and effectiveness of minimally invasive coronary artery bypass grafting (MICABG) through comparing the perioperative clinical effects of conventional surgery and MICABG. Methods    A total of 543 patients in the single medical group of Beijing Anzhen Hospital who underwent beating coronary artery bypass grafting from January 2017 to September 2020 were collected, including 161 patients receiving MICABG (a minimally invasive group, 143 males and 18 females, aged 60.08±9.21 years), 382 patients receiving median thoracotomy (a conventional group, 284 males and 98 females, aged 61.68±8.81 years). The propensity score was used to match 143 patients in each of the two groups, and the perioperative data of the two groups were summarized and analyzed. Results    There was no death, perioperative myocardial infarction or stroke in the minimally invasive group. Compared with the conventional group, the minimally invasive group had longer operation time (296.36±89.4 min vs. 217.80±50.63 min, P=0.000), less number of bypass grafts (2.86±1.03 vs. 3.17±0.78, P=0.005), shorter postoperative hospital stay (6.29±1.46 d vs. 6.78±2.61 d, P=0.031), less drainage on postoperative day 1 (339.57±180.63 mL vs. 441.92±262.63 mL, P=0.001) and lower usage rate of inotropic drugs (9.09% vs. 26.57%, P=0.001). There was no statistical difference between the two groups in postoperative ICU stay ventilator assistance time, blood transfusion rate, secondary thoracotomy rate, or use of mechanical equipment. Conclusion    Reasonable clinical strategies can ensure the satisfactory overall safety of MICABG. In addition, it has the advantages of shorter postoperative hospital stay, less bleeding and smaller dosage of inotropic drugs.