Objective To investigate the role of CCCTC-binding factor(CTCF)in the development of oxaliplatin(OXA)-induced gastric cancer drug-tolerant cells(DTCs)and to preliminarily elucidate its underlying mechanisms.Methods The DTCs model of gastric cancer was established by treating MGC803 cells with OXA.Overexpression and knockdown of CTCF in MGC803 cells were performed to observe their effects on the formation of DTCs in gastric cancer.Additionally,Bcl2-like protein 1(BCL2L1)was knocked down in CTCF-overexpressing cells,and its impact on DTCs formation was evaluated.Flow cytometry was used to analyze the effects of varying CTCF/BCL2L1 expression levels on the apoptosis of gastric cancer cells under OXA treatment.Immunohistochemistry(IHC)was employed to detect the expression levels of CTCF/BCL2L1 in gastric cancer tissues,and the therapeutic outcomes of neoadjuvant chemotherapy in patients with different CTCF/BCL2L1 expression levels were assessed.Results Gastric cancer DTCs can be obtained following a regimen of continuous treatment of MGC803 cells with a specific concentration of oxaliplatin(OXA,1.5 μmol/L)for 5 days,followed by an additional 5-day culture period post-treatment cessation.The upregulation of CTCF has been shown to facilitate the formation of DTCs in gastric cancer,whereas its downregulation inhibits this process(P<0.05).In MGC803 gastric cancer cells,the expression level of BCL2L1 is positively correlated with that of CTCF.Knockdown of BCL2L1 in MGC803 cells overexpressing CTCF can reverse the pro-DTC formation effect of CTCF(P<0.05).Overexpression of CTCF confers resistance to OXA-induced apoptosis in gastric cancer cells,and this anti-apoptotic effect can be reversed by BCL2L1 knockdown in MGC803 cells overexpressing CTCF(P<0.05).In the tumor tissues of the majority of gastric cancer patients,the expression levels of BCL2L1 are positively correlated with those of CTCF,and the efficacy of neoadjuvant chemotherapy is notably reduced in patients with high expression of the CTCF/BCL2L1 axis compared to those with low expression(P<0.05).Conclusion CTCF promotes the formation of OXA-related gas-tric cancer DTCs by upregulating BCL2L1 expression and inhibiting apoptosis,making the CTCF/BCL2L1 axis a potential therapeutic target for DTCs in gastric cancer.

Objective To investigate the role of CCCTC-binding factor(CTCF)in the development of oxaliplatin(OXA)-induced gastric cancer drug-tolerant cells(DTCs)and to preliminarily elucidate its underlying mechanisms.Methods The DTCs model of gastric cancer was established by treating MGC803 cells with OXA.Overexpression and knockdown of CTCF in MGC803 cells were performed to observe their effects on the formation of DTCs in gastric cancer.Additionally,Bcl2-like protein 1(BCL2L1)was knocked down in CTCF-overexpressing cells,and its impact on DTCs formation was evaluated.Flow cytometry was used to analyze the effects of varying CTCF/BCL2L1 expression levels on the apoptosis of gastric cancer cells under OXA treatment.Immunohistochemistry(IHC)was employed to detect the expression levels of CTCF/BCL2L1 in gastric cancer tissues,and the therapeutic outcomes of neoadjuvant chemotherapy in patients with different CTCF/BCL2L1 expression levels were assessed.Results Gastric cancer DTCs can be obtained following a regimen of continuous treatment of MGC803 cells with a specific concentration of oxaliplatin(OXA,1.5 μmol/L)for 5 days,followed by an additional 5-day culture period post-treatment cessation.The upregulation of CTCF has been shown to facilitate the formation of DTCs in gastric cancer,whereas its downregulation inhibits this process(P<0.05).In MGC803 gastric cancer cells,the expression level of BCL2L1 is positively correlated with that of CTCF.Knockdown of BCL2L1 in MGC803 cells overexpressing CTCF can reverse the pro-DTC formation effect of CTCF(P<0.05).Overexpression of CTCF confers resistance to OXA-induced apoptosis in gastric cancer cells,and this anti-apoptotic effect can be reversed by BCL2L1 knockdown in MGC803 cells overexpressing CTCF(P<0.05).In the tumor tissues of the majority of gastric cancer patients,the expression levels of BCL2L1 are positively correlated with those of CTCF,and the efficacy of neoadjuvant chemotherapy is notably reduced in patients with high expression of the CTCF/BCL2L1 axis compared to those with low expression(P<0.05).Conclusion CTCF promotes the formation of OXA-related gas-tric cancer DTCs by upregulating BCL2L1 expression and inhibiting apoptosis,making the CTCF/BCL2L1 axis a potential therapeutic target for DTCs in gastric cancer.

Objective:To investigate the impact of magnolol(MG)on liver injury in rats with severe acute pancreatitis(SAP)through receptor interacting protein kinase(RIPK)1/RIPK3/mixed lineage kinase domain-like protein(MLKL)signaling pathway and its mechanism.Methods:The SAP rat model was induced by sodium taurocholate.The rats were randomly grouped into sham operation group(Sham group),model group(SAP group),MG group,RIPK1 inhibitor Necrostatin-1 group(Nec-1 group),and magnolol+RIPK1 inhibitor Necrostatin-1 group(MG+Nec-1 group).The pathological tissue morphology of pancreas and liver were observed by HE staining;the apoptosis rate of hepatocyte was observed by TUNEL staining;an automated biochemical analyzer was used to deter-mine serum ALT,AST and AMY contents;ELISA kits were used to detect the contents of TNF-α,IL-1β and IL-6;Western blot was used to detect the protein expression levels of p-RIPK1,RIPK1,p-RIPK3,RIPK3,p-MLKL and MLKL.Results:Compared with Sham group,pancreatic and hepatic cells in SAP group had edema and hemorrhage,and inflammatory cells increased,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6,and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously increased(P<0.05).Compared with SAP group,pancreatic and liver injury in MG group and Nec-1 group were obviously reduced,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6 and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously decreased(P<0.05),the MG and Nec-1 groups showed no significant differences in any measured indices(P>0.05);the effect on SAP in MG+Nec-1 group was better than that in MG group and Nec-1 group.Conclu-sion:MG can alleviate liver injury in SAP rats by inhibiting RIPK1/RIPK3/MLKL signaling pathway.

Objective:To investigate the impact of magnolol(MG)on liver injury in rats with severe acute pancreatitis(SAP)through receptor interacting protein kinase(RIPK)1/RIPK3/mixed lineage kinase domain-like protein(MLKL)signaling pathway and its mechanism.Methods:The SAP rat model was induced by sodium taurocholate.The rats were randomly grouped into sham operation group(Sham group),model group(SAP group),MG group,RIPK1 inhibitor Necrostatin-1 group(Nec-1 group),and magnolol+RIPK1 inhibitor Necrostatin-1 group(MG+Nec-1 group).The pathological tissue morphology of pancreas and liver were observed by HE staining;the apoptosis rate of hepatocyte was observed by TUNEL staining;an automated biochemical analyzer was used to deter-mine serum ALT,AST and AMY contents;ELISA kits were used to detect the contents of TNF-α,IL-1β and IL-6;Western blot was used to detect the protein expression levels of p-RIPK1,RIPK1,p-RIPK3,RIPK3,p-MLKL and MLKL.Results:Compared with Sham group,pancreatic and hepatic cells in SAP group had edema and hemorrhage,and inflammatory cells increased,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6,and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously increased(P<0.05).Compared with SAP group,pancreatic and liver injury in MG group and Nec-1 group were obviously reduced,the expression levels of serum ALT,AST,AMY,TNF-α,IL-1β,IL-6 and p-RIPK1/RIPK1,p-RIPK3/RIPK3,p-MLKL/MLKL ratio in liver tissue were obviously decreased(P<0.05),the MG and Nec-1 groups showed no significant differences in any measured indices(P>0.05);the effect on SAP in MG+Nec-1 group was better than that in MG group and Nec-1 group.Conclu-sion:MG can alleviate liver injury in SAP rats by inhibiting RIPK1/RIPK3/MLKL signaling pathway.

Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixed-effects model. Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed. Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

Objective:To investigate the application value of mixed reality (MR) technology in reconstruction of soft tissue defect of extremities with free anterolateral thigh flap(ALTF).Methods:From December 2019 to November 2021, a retrospective analysis was performed on 10 patients who had undergone ALTF reconstruction of soft tissue defects in extremities in Department of Orthopaedics, the First People's Hospital of Yunnan Province. Four patients had the defects in hand and 6 patients in foot and ankle. For the 6 patients in emergency surgery, the time from injury to admission was 4.0-15.0 hours, with an average of 7.3 hours. Four patients with soft tissue defects caused by chronic infection and ulcers were given debridement, and the soft tissue defects were reconstructed by flap transfer at the second stage. The defect area were from 8.0 cm×5.0 cm to 22.0 cm×8.0 cm. Preoperatively, 3D bone-vessel-flap model was established based on the lower extremity CTA scans. Intraoperatively, MR technology was used to project the 3D model on the flap donor site to observe the virtual profile of vessel shape in real time, to locate the perforator and the course of the perforator, and observe the consistency between the virtual image and the actual anatomy of the perforator. The appearance, texture and colour of the flap were recorded at the last follow-up. Hand function was evaluated by the total activity movement (TAM), and foot and ankle function was evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS).Results:The position location and course of perforator vessels were reconstructed successfully in all patients before surgery. The MR technology was used to locate the perforator, and the course of the virtual perforator was consistent with the actual anatomy, and the matching reached 100%. The length of vascular pedicle measured before surgery was at 11.02 cm±1.37 cm. And that measured during surgery was at 11.21 cm±1.23 cm ( P=0.748, t=-0.326). The difference was not statistically significant ( P>0.05). The flap area was at 9.0 cm×6.0 cm to 23.0 cm×9.0 cm. The donor site was sutured directly in one stage. All patients were entered postoperative followed-up for 1 to 24 months, with an average of 13.5 months. All the flaps survived after surgery. The flap with good appearance, colour and texture, and only one linear scar was left in the donor site. According to the TAM of the hand function, 3 cases were excellent and 1 was fair. Foot and ankle function were evaluated according to the AOFAS, 5 cases were in excellent and 1 was good. Conclusion:MR technology applied to the surgery of ALTF can locate the course of the flap vessels in real time, guide the operation, improve the operation efficiency and reduce the risk in surgery.

Objective To construct YOLOv5x deep learning network model based on SPECT whole body bone scanning,and to observe its value for diagnosing benign and malignant bone lesions.Methods Totally 699 patient who underwent SPECT bone scanning were enrolled,with a total of 5 182 bone lesions,including 3 105 malignant and 2 077 benign lesions.Then 1 121 bone images were divided into training set(n=897),validation set(n=112)or test set(n=112)at the ratio of 8∶1∶1.After augmentation on training set and validation set,the data were inputted to YOLOv5x deep learning network for training to obtain a recognition model.The sensitivity,specificity and accuracy of this model for diagnosing benign and malignant bone lesions were analyzed,and the consistency between its diagnosis results and gold standards was evaluated based on test set.Results The sensitivity,specificity and accuracy of bone scanning YOLOv5x deep learning network model for identifying malignant bone lesions was 95.75％,87.87％and 91.60％,respectively,and for identifying benign bone lesions was 91.62％,94.38％and 93.14％,respectively.The area under the curve(AUC)of this model for identifying bone lesions on bone scanning images was 0.98,for malignant and benign bone lesions was 0.97 and 0.98,respectively.The consistency between the diagnosis results of this model for malignant and benign bone lesions and the gold standards were both good(Kappa=0.83,0.86,both P＜0.05).Conclusion YOLOv5x deep learning network model based on SPECT whole body bone scanning was helpful for diagnosing benign and malignant bone lesions.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.