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 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 compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

Volume loss caused by aging process, diseases, trauma and surgical treatments, could lead to facial depressions, profoundly affecting appearance. Injectable fillers could help to correct this type of disfigurements and are preferred by plastic surgeons and patients due to their quality of minimal invasiveness and better delicateness. Among these fillers, collagen stimulators such as poly-L-lactic acid(PLLA) and polycaprolactone(PCL) are biodegradable synthetic polymers that can stimulate collagen formation and thus gradually restore tissue volume. These polymers have been used worldwide to treat facial aging changes and human immunodeficiency virus-associated facial fat lipoatrophy, demonstrating ideal results in volume enhancement and facial rejuvenation. The progress and clinical applications of compound injectables based on biodegradable collagen stimulators are summarized.

Volume loss caused by aging process, diseases, trauma and surgical treatments, could lead to facial depressions, profoundly affecting appearance. Injectable fillers could help to correct this type of disfigurements and are preferred by plastic surgeons and patients due to their quality of minimal invasiveness and better delicateness. Among these fillers, collagen stimulators such as poly-L-lactic acid(PLLA) and polycaprolactone(PCL) are biodegradable synthetic polymers that can stimulate collagen formation and thus gradually restore tissue volume. These polymers have been used worldwide to treat facial aging changes and human immunodeficiency virus-associated facial fat lipoatrophy, demonstrating ideal results in volume enhancement and facial rejuvenation. The progress and clinical applications of compound injectables based on biodegradable collagen stimulators are summarized.

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.

Objective:Numerous studies have shown that neuroplasticity plays an important role in the pathogenesis of depression. This study aimed to investigate the relationship between the brain derived neurotrophic factor (BDNF) (Val66Met, rs6265) genotype and gray matter volume (GMV) in the first episode and treatment-naive patients with major depressive disorder (MDD) and healthy subjects.Methods:This study included 41 first episode and treatment-naive MDD patients (MDD group) and 44 sex and age matched healthy controls (HC group). All participants were arranged to take magnetic resonance imaging (MRI) scan. Meanwhile, BDNF rs6265 polymorphism was detected. Voxel-based morphometry (VBM) method was then performed to test the impact of the diagnosis (MDD vs. HC) and BDNF genotype (Met allele vs. Val/Val homozygous) on GMV. Results:There was no statistically significant difference on BDNF rs 6265 sites alleles frequency and genotype between MDD and HC groups (MDD χ 2=0.004, P>0.05; HC χ2=0.048, P>0.05). Gray matter volume in the left precuneus ( F=3.702, P<0.001), right middle temporal gyrus ( F=4.020, P<0.001) and cerebellum vermis_4_5 ( F=3.836, P<0.001) was larger in MDD patients than in the control group. BDNF genotype had effects on left fusiform gyrus ( F=-4.152, P<0.001). BDNF genotype-diagnosis interaction was found to be associated with left anterior cingulate cortex ( F=-4.775, P<0.001) and right anterior cingulate ( F=-3.795, P<0.001). For participants with Val/Val homozygous, compared to HC group, the volume of left anterior cingulate was reduced in MDD patients ( F=-3.729, P<0.001). For participants with the Met allele, compared to healthy controls, MDD patients showed significantly increased GMV in the left middle frontal gyrus ( F=4.317, P<0.001), right inferior occipital gyrus ( F=4.744, P<0.001), right supramarginal gyrus ( F=3.838, P<0.001), and left median cingulate gyrus( F=4.041, P<0.001). Separately in MDD patients and the control group, the GMV did not differ between the Val/Val homozygous group and the Met allele group. Conclusion:BDNF rs6265 alleles could be related to brain structural abnormalities in MDD patients, and could further explain the pathological mechanism of MDD.

Objective:Numerous studies have shown that neuroplasticity plays an important role in the pathogenesis of depression. This study aimed to investigate the relationship between the brain derived neurotrophic factor (BDNF) (Val66Met, rs6265) genotype and gray matter volume (GMV) in the first episode and treatment-naive patients with major depressive disorder (MDD) and healthy subjects.Methods:This study included 41 first episode and treatment-naive MDD patients (MDD group) and 44 sex and age matched healthy controls (HC group). All participants were arranged to take magnetic resonance imaging (MRI) scan. Meanwhile, BDNF rs6265 polymorphism was detected. Voxel-based morphometry (VBM) method was then performed to test the impact of the diagnosis (MDD vs. HC) and BDNF genotype (Met allele vs. Val/Val homozygous) on GMV. Results:There was no statistically significant difference on BDNF rs 6265 sites alleles frequency and genotype between MDD and HC groups (MDD χ 2=0.004, P>0.05; HC χ2=0.048, P>0.05). Gray matter volume in the left precuneus ( F=3.702, P<0.001), right middle temporal gyrus ( F=4.020, P<0.001) and cerebellum vermis_4_5 ( F=3.836, P<0.001) was larger in MDD patients than in the control group. BDNF genotype had effects on left fusiform gyrus ( F=-4.152, P<0.001). BDNF genotype-diagnosis interaction was found to be associated with left anterior cingulate cortex ( F=-4.775, P<0.001) and right anterior cingulate ( F=-3.795, P<0.001). For participants with Val/Val homozygous, compared to HC group, the volume of left anterior cingulate was reduced in MDD patients ( F=-3.729, P<0.001). For participants with the Met allele, compared to healthy controls, MDD patients showed significantly increased GMV in the left middle frontal gyrus ( F=4.317, P<0.001), right inferior occipital gyrus ( F=4.744, P<0.001), right supramarginal gyrus ( F=3.838, P<0.001), and left median cingulate gyrus( F=4.041, P<0.001). Separately in MDD patients and the control group, the GMV did not differ between the Val/Val homozygous group and the Met allele group. Conclusion:BDNF rs6265 alleles could be related to brain structural abnormalities in MDD patients, and could further explain the pathological mechanism of MDD.