Objective To investigate the role of sphingosine kinase-1(SPHK1)in regulating migration and invasion of gastric cancer(GC)cells.Methods TIMER2.0,GEPIA and HPA databases were used to investigate SPHK1 expression in GC,and its association with prognosis of the patients was analyzed using Kaplan-Meier Plotter database.In 40 clinical GC and adjacent tissue samples,SPHK1 and MKI67 expressions were detected with immunohistochemistry,Western blotting,and RT-qPCR.Gene enrichment pathway analysis was conducted to explore the biological functions of SPHK1.In HGC-27 and MGC-803 cells,the effects of lentivirus-mediated SPHK1 knockdown or overexpression on cell migration and invasion and expressions of key proteins in the nuclear factor-κB(NF-κB)signaling were evaluated using cell scratch test,Transwell assays and Western blotting.The changes in tumorigenic capacity of the transfected GC cells were evaluated in nude mice.Results SPHK1 was highly expressed in GC tissues in negative correlation with overall survival,overall survival after progression,and relapse-free survival of the patients(all P<0.001).In clinical GC samples,SPHK1 and MKI67 expressions showed a positive correlation(P=0.00049)and were both significantly up-regulated(P<0.001).Gene enrichment pathway analysis suggested the involvement of SPHK1 in cell adhesion,migration,angiogenesis and the NF-κB pathway(P<0.05).In the cell experiment,SPHK1 knockdown significantly decreased while SPHK1 overexpression enhanced migration and invasion abilities of the GC cells.SPHK1 positively regulated the expressions of phosphorylated P65(P-P65),VEGFA and IL-17,and blocking the NF-κB pathway by PDTC significantly lowered migration and invasion ability of the cells.In nude mice,the GC cells with SPHK1 knockdown resulted in significantly reduced tumor size and mass,while the SPHK1-overexpressing cells showed enhanced tumorigenicity.Conclusion SPHK1 regulates migration and invasion of GC cells via the NF-κB signaling pathway and may serve as a potential diagnostic marker for GC progression.

Objective To investigate the effects and mechanisms of five-element music on the social behavior of the children of mothers with fear stress during pregnancy and provide a basis for the early prevention and treatment of clinical fetogenic affective disorders.Methods Forty-five pregnant mice were randomly divided into three groups:a control group,model group,and five-element music group.The model and five-element music group models were established using the bystander electric shock method.Additionally,the five-element music group was exposed to Palace Tune five-element music daily from 17:00 to 19:00 during pregnancy.On the 19th day of pregnancy,ELISA was employed to assess the levels of adrenocorticotropin(ACTH)and cortisol(CORT)in the serum of pregnant mice in each group for modeling evaluation.The offspring were subsequently grouped with their mother and underwent an 8-week-old three-box social experiment to observe their social behavior.We used the immunofluorescence double-labeling method to detect glutamatergic neuron activity in the medial prefrontal cortex(mPFC)of the offspring.High-performance liquid chromatography was employed to measure the total glutamate(Glu)content in the mPFC,while Gorky staining was used to observe changes in the dendritic spines of mPFC neurons in the offspring.Results Compared to those in the blank group,pregnant mice in the model group exhibited a significant increase in the levels of ACTH and CORT in their serum,and there was a significant decrease in the social interaction time and social novelty preference index of their offspring.There was also a significant decrease in glutamate neuron activity,glutamate content,and neuronal dendritic spine density.In contrast,compared with those in the model group,pregnant mice in the five-element music group demonstrated a reduction in the levels of ACTH and CORT in the serum,and there were improvements in the social behavior,glutamate neuron activity,glutamate content,and condition of neuronal dendritic spines in the offspring.Conclusions Intervention with five-element music effectively ameliorated the offspring's social behavior disorder result ing from prenatal fear stress;the mechanism was potentially linked to enhanced glutamate neuron activity in the mPFC region.

Objective To investigate the role of sphingosine kinase-1(SPHK1)in regulating migration and invasion of gastric cancer(GC)cells.Methods TIMER2.0,GEPIA and HPA databases were used to investigate SPHK1 expression in GC,and its association with prognosis of the patients was analyzed using Kaplan-Meier Plotter database.In 40 clinical GC and adjacent tissue samples,SPHK1 and MKI67 expressions were detected with immunohistochemistry,Western blotting,and RT-qPCR.Gene enrichment pathway analysis was conducted to explore the biological functions of SPHK1.In HGC-27 and MGC-803 cells,the effects of lentivirus-mediated SPHK1 knockdown or overexpression on cell migration and invasion and expressions of key proteins in the nuclear factor-κB(NF-κB)signaling were evaluated using cell scratch test,Transwell assays and Western blotting.The changes in tumorigenic capacity of the transfected GC cells were evaluated in nude mice.Results SPHK1 was highly expressed in GC tissues in negative correlation with overall survival,overall survival after progression,and relapse-free survival of the patients(all P<0.001).In clinical GC samples,SPHK1 and MKI67 expressions showed a positive correlation(P=0.00049)and were both significantly up-regulated(P<0.001).Gene enrichment pathway analysis suggested the involvement of SPHK1 in cell adhesion,migration,angiogenesis and the NF-κB pathway(P<0.05).In the cell experiment,SPHK1 knockdown significantly decreased while SPHK1 overexpression enhanced migration and invasion abilities of the GC cells.SPHK1 positively regulated the expressions of phosphorylated P65(P-P65),VEGFA and IL-17,and blocking the NF-κB pathway by PDTC significantly lowered migration and invasion ability of the cells.In nude mice,the GC cells with SPHK1 knockdown resulted in significantly reduced tumor size and mass,while the SPHK1-overexpressing cells showed enhanced tumorigenicity.Conclusion SPHK1 regulates migration and invasion of GC cells via the NF-κB signaling pathway and may serve as a potential diagnostic marker for GC progression.

Objective To investigate the effect of continuous intraoperative insulin infusion on my-ocardial blood perfusion after cardiac surgery under cardiopulmonary bypass(CPB).Methods Forty-eight patients,21 males and 27 females,aged 55-80 years,BMI 18-28 kg/m2,ASA physical status Ⅱ-Ⅳ,who underwent elective cardiac surgery with CPB were selected and randomly divided into two groups:the insulin group(group I,n = 25)and the control group(group C,n = 23).The same anesthesia protocol was implemented in both groups.After induction of anesthesia,group Ⅰ received intravenously infusion of in-sulin 30 mU·kg-1·h-1,glucose 0.12 g·kg-1·h-1,and potassium chloride 0.06 mmol·kg-1·h-1,and group C received saline 10 ml/h,all of which were infused until the end of surgery.The targeted blood glucose range for both groups was set at 6.1-11.1 mmol/L.Transesophageal echocardiography(TEE)was performed 10 minutes after induction of general anesthesia(T2)and before the end of surgery(T6)to ex-amine the coronary sinus(CS)flow spectrum and diameter,pulmonary venous flow spectrum,and calculate CS net antegrade flow velocity time integral(VTI).Femoral mean arterial pressure(MAP),central venous pressure(CVP),stroke volume(SV),cardiac index(CI)and peripheral vascular resistance index(SVRI)were recorded at T2,2 minutes before CPB(T3),the end of CPB(T5),and T6.The concentra-tions of blood glucose and lactate 5 minutes before anesthesia induction(T1),T3,30 minutes after CPB(T4),T5,T6,6 hours after surgery(T7),12 hours after surgery(T8),and 24 hours after surgery(T9)were recorded.The levels of high-sensitivity C-reactive protein(hs-CRP),high-sensitivity troponin I(hs-TnI),and creatine kinase isoenzyme(CK-MB)were recorded 1 day preoperatively,1 and 2 days post-operatively.Results Compared with group C,in group I,CS net antegrade flow VTI and blood flow per minute were significantly increased(P<0.05),and pulmonary venous peak atrial reversal wave velocity(ARp)was significantly reduced at T6(P<0.05),SV and CI were significantly increased and SVRI was significantly decreased at T5 and T6(P<0.05),lactate concentration was significantly decreased at T7 and T8(P<0.05),hs-CRP and CKMB were significantly decreased 1 and 2 days postoperatively(P<0.05),hs-TnI was significantly reduced 2 days postoperatively(P<0.05).Conclusion Continuous insulin admin-istration during cardiac surgery with CPB while maintaining blood glucose at 6.1-11.1 mmol/L can enhance myocardial blood perfusion,mitigate postoperative inflammatory response,and reduce myocardial injury.

Objective:To explore the relationship between calcitonin receptor (CALCR) expression and clinicopathologic features and prognosis of gastric cancer patients.Methods:A retrospective analysis was performed to collect 108 samples of gastric cancer patients treated in Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College from January 2014 to November 2017. Immunohistochemistry (IHC) was used to analyze the differential expression of calcitonin receptors in gastric cancer and adjacent tissues, and the relationship and significance between their expression and clinical pathological parameters were analyzed K-M and ROC curves were used to assess the K-M and ROC curves were used to evaluate the effect of CALCR expression on patients' postoperative survival and to predict the 5-year postoperative survival rate. The comparison of inter group rates in count data was performed using χ2 test, and the Kaplan Meier method was used to estimate overall survival and progression free survival. The comparison of survival differences was performed using the Log-rank method test. Results:CALCR was mainly expressed in the cytoplasm and its expression in gastric cancer tissues(62.04%(67/108)) was higher than that in paracancerous tissues (13.89% (15/108)), and the differences were statistically significant ( χ2=53.16, P<0.001). The tissue infiltration depth (91.04% (61/67)), lymph node metastasis (73.1% (49/67)), and peripheral blood CA19-9 (32.8% (22/67)) in gastric cancer patients with high expression of CALCR were higher than those in the low expression group of CALCR (63.41% (26/41), 53.7% (22/41), 12.2% (5/41)), and the differences were statistically significant ( χ2 values were 12.40, 4.28, and 4.78; P values were <0.001, 0.038, and 0.016). The results of K-M curve and Log-rank test showed that among gastric cancer patients, the postoperative 5-year survival rate of patients with high expression of CALCR was lower than that of patients with low expression (11.9% (8/67) and 43.9% (18/41), Log-rank χ2=29.92, P<0.001). The results of the ROC curve showed that the area under the curve was 0.772, sensitivity was 87.8%, specificity was 53.7%, indicating that CALCR is of high value in predicting the 5-year survival rate of gastric cancer patients after surgery. Conclusion:CALCR is highly expressed in gastric cancer tissue and is associated with the pathological characteristics of patients. High expression of CALCR suggests poor prognosis, indicating that it has the potential to become an important indicator for evaluating the survival prognosis of gastric cancer patients.

Objective:To investigate the influencing factors of reflux esophagitis after sleeve gastrectomy and its plus procedures.Methods:The retrospective case-control study was conducted. The clinical data of 130 patients who underwent sleeve gastrectomy and its plus procedures (jejunal bypass, duodenal-jejunal bypass) for the treatment of metabolic diseases in the First Affiliated Hospital of Nanjing Medical University from May 2010 to August 2021 were collected. There were 34 males and 96 females, aged (32±8)years, with the body mass index (BMI) as (38±7)kg/m 2. Observation indicators: (1) incidence of reflux esophagitis before and after surgery; (2) clinical manifestations of reflux esophagitis and treatment; (3) influencing factors of reflux esopha-gitis after surgery; (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. In univariate analysis, the median value of clinical variable was used for grouping and the chi-square test was used for subsequent analysis. Multivariate analysis was conducted using Logistic stepwise regression model. Results:(1) Incidence of reflux esophagitis before and after surgery. Of 130 patients, there were 5 cases with Los Angeles classification grade A reflux esopha-gitis before the surgery, and there were 35 cases with reflux esophagitis after surgery, including 26 cases as Los Angeles classification grade A esophagitis, 8 cases as Los Angeles classification grade B esophagitis and 1 case as Los Angeles classification grade C esophagitis. There was a significant difference in the incidence of reflux esophagitis for patients before and after surgery ( P<0.05). (2) Clinical manifestations of reflux esophagitis and treatment. The 5 patients with preoperative reflux esophagitis described with no obvious heartburn and acid regurgitation and did not receive treat-ment. For the 35 patients with postoperative reflux esophagitis, 22 cases described with heartburn and acid regurgitation, and 13 cases described without any symptoms. Of the 35 patients, 10 were treated with continuous oral proton pump inhibitors, 2 were treated with intermittent oral proton pump inhibitors, 10 were relieved by dietary adjustment, and 13 were not treated. For the 95 patients without postoperative reflux esophagitis, 5 cases described with heartburn and acid regurgitation, requiring continuous oral proton pump inhibitor treatment. The remaining 90 cases described no heartburn and acid regurgitation and did not receive treatment. (3) Influencing factors of reflux esophagitis after surgery. Results of multivariate analysis showed that the preoperative reflux diagnostic questionnaire scoring >0 and the occurrence of postoperative heartburn and acid regurgi-tation were independent risk factors of postoperative reflux esophagitis ( odds ratio=7.84, 47.16, 95% confidence interval as 2.04?30.20, 11.58?192.11, P<0.05). (4) Follow-up. All 130 patients were followed up for 17(range, 12?60)month after surgery. The BMI, percentage of total weight loss, diabetes remission rate, fasting blood glucose and glycosylated hemoglobin of the 130 patients at postoperative 12 month were (25±4)kg/m 2, 31%±8%, 84.6%(22/26), (5.6±1.2)mmol/L and 5.9%±1.3%. Conclusions:The sleeve gastrectomy and its plus procedures increase the risk of postoperative reflux esophagitis. Preoperative reflux diagnostic questionnaire scoring>0 and the occurrence of postoperative heartburn and acid regurgitation are independent risk factors of postoperative reflux esophagitis. Dietary adjustment and proton pump inhibitor therapy can alleviate symptoms of reflux esophagitis, but cannot cure reflux esophagitis.

Objective:To compare the 1-year effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy with Roux-en-Y duodenal bypass (SG+RYDJB) on weight loss, remission of diabetes, and postoperative complications in patients with obesity and type 2 diabetes.Methods:A single-center retrospective cohort study was conducted at the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2020. Sixty-four patients with type 2 diabetes and body mass index (BMI) of 27.5-40.0 kg/m 2 were included in this study and divided into the RYGB group ( n=34) and the SG+RYDJB group ( n=30). In both procedures, the biliopancreatic branch was measured 100 cm distal to the Treitz ligament, and the food branch was measured 100 cm distal to the gastric or duodenojejunal anastomosis. Patients were followed up by telephone or WeChat, a free messaging and calling app at 1, 3, 6, and 12 months postoperatively to determine their weight loss and remission of diabetes. The primary outcomes were the weight loss and reduction in blood glucose concentrations at 1 year after surgery and postoperative complications. Other postoperative changes, including body weight, BMI, percentage of total weight loss (%TWL), percentage of excess weight loss (%EWL), glycated hemoglobin A1c (HbA1c), and fasting blood glucose at 1 year after surgery were also assessed. Results:There were no significant differences in baseline data between the two groups (all P>0.05). No conversion to open surgery or death occurred in either group. Operation time was longer in the SG+RYDJB than the RYGB group (137.8±22.1 minutes vs. 80.0±24.9 minutes, t=9.779, P<0.001) and the incidence of perioperative complications was higher in the SG+RYDJB than the RYGB group (20% [6/30] vs. 2.9% [1/34], χ 2=4.761, P=0.029). However, the postoperative hospital stay was similar between the two groups [3.0 (3.0, 4.3) days vs. 3.0 (4.0, 6.0) days, U=641.500, P=0.071]. Perioperative complications comprised small gastric pouch anastomotic leakage in one patient in the RYGB group and leakage (three patients) and bleeding (two patients with gastrointestinal bleeding and one with trocar site bleeding) in the SG+RYDJB group. Long-term complications were as follows. The incidence of anemia was significantly higher in the RYGB than the SG+RYDJB group (26.5% [9/34] vs. 3.3% [1/30], χ 2=6.472, P=0.011). However, there were no significant differences in incidences of postoperative reflux, dumping syndrome, alopecia, diarrhea, constipation or foul-smelling flatus between the two groups (all P>0.05). Compared with 1 year before surgery, the body weights and fasting plasma glucose concentrations of patients in the SG+RYDJB and RYGB group (72.4±10.6 kg vs. 98.5±14.2 kg, respectively; 68.2±10.0 kg vs. 91.9±14.8 kg, respectively), BMI (25.2±2.9 kg/m 2 vs. 34.3±4.2 kg/m 2, respectively; 24.3±2.4 kg/m 2 vs. 32.7±3.7 kg/m 2, respectively) (5.5±1.6 vs. 10.6±3.3, respectively; 5.8±2.1 vs. 9.0±3.4, respectively); HbA1c (5.7±0.8 vs. 9.7±1.2, respectively; 9.1±1.9 vs. 5.9±0.9, respectively) were significantly lower at 1 year after surgery (all P<0.05). However, the % TWL (26.5%±6.0% vs. 25.6%±4.4%, t=0.663, P=0.510) and % EWL (109.1%±38.2% vs. 109.4%±40.3%, t=-0.026, P=0.026), rate of complete remission of diabetes at 1 year (80.0% [24/30] vs. 82.4% [28/34], χ 2=0.058, P=0.810] did not differ significantly between the two groups (all P>0.05). Conclusions:Although SG+RYDJB surgery compared with RYGB is more difficult to perform, it can achieve similar weight loss and remission of diabetes and is associated with a lower incidence of anemia because of the preservation of the pylorus.

Objective:To compare the 1-year effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy with Roux-en-Y duodenal bypass (SG+RYDJB) on weight loss, remission of diabetes, and postoperative complications in patients with obesity and type 2 diabetes.Methods:A single-center retrospective cohort study was conducted at the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2020. Sixty-four patients with type 2 diabetes and body mass index (BMI) of 27.5-40.0 kg/m 2 were included in this study and divided into the RYGB group ( n=34) and the SG+RYDJB group ( n=30). In both procedures, the biliopancreatic branch was measured 100 cm distal to the Treitz ligament, and the food branch was measured 100 cm distal to the gastric or duodenojejunal anastomosis. Patients were followed up by telephone or WeChat, a free messaging and calling app at 1, 3, 6, and 12 months postoperatively to determine their weight loss and remission of diabetes. The primary outcomes were the weight loss and reduction in blood glucose concentrations at 1 year after surgery and postoperative complications. Other postoperative changes, including body weight, BMI, percentage of total weight loss (%TWL), percentage of excess weight loss (%EWL), glycated hemoglobin A1c (HbA1c), and fasting blood glucose at 1 year after surgery were also assessed. Results:There were no significant differences in baseline data between the two groups (all P>0.05). No conversion to open surgery or death occurred in either group. Operation time was longer in the SG+RYDJB than the RYGB group (137.8±22.1 minutes vs. 80.0±24.9 minutes, t=9.779, P<0.001) and the incidence of perioperative complications was higher in the SG+RYDJB than the RYGB group (20% [6/30] vs. 2.9% [1/34], χ 2=4.761, P=0.029). However, the postoperative hospital stay was similar between the two groups [3.0 (3.0, 4.3) days vs. 3.0 (4.0, 6.0) days, U=641.500, P=0.071]. Perioperative complications comprised small gastric pouch anastomotic leakage in one patient in the RYGB group and leakage (three patients) and bleeding (two patients with gastrointestinal bleeding and one with trocar site bleeding) in the SG+RYDJB group. Long-term complications were as follows. The incidence of anemia was significantly higher in the RYGB than the SG+RYDJB group (26.5% [9/34] vs. 3.3% [1/30], χ 2=6.472, P=0.011). However, there were no significant differences in incidences of postoperative reflux, dumping syndrome, alopecia, diarrhea, constipation or foul-smelling flatus between the two groups (all P>0.05). Compared with 1 year before surgery, the body weights and fasting plasma glucose concentrations of patients in the SG+RYDJB and RYGB group (72.4±10.6 kg vs. 98.5±14.2 kg, respectively; 68.2±10.0 kg vs. 91.9±14.8 kg, respectively), BMI (25.2±2.9 kg/m 2 vs. 34.3±4.2 kg/m 2, respectively; 24.3±2.4 kg/m 2 vs. 32.7±3.7 kg/m 2, respectively) (5.5±1.6 vs. 10.6±3.3, respectively; 5.8±2.1 vs. 9.0±3.4, respectively); HbA1c (5.7±0.8 vs. 9.7±1.2, respectively; 9.1±1.9 vs. 5.9±0.9, respectively) were significantly lower at 1 year after surgery (all P<0.05). However, the % TWL (26.5%±6.0% vs. 25.6%±4.4%, t=0.663, P=0.510) and % EWL (109.1%±38.2% vs. 109.4%±40.3%, t=-0.026, P=0.026), rate of complete remission of diabetes at 1 year (80.0% [24/30] vs. 82.4% [28/34], χ 2=0.058, P=0.810] did not differ significantly between the two groups (all P>0.05). Conclusions:Although SG+RYDJB surgery compared with RYGB is more difficult to perform, it can achieve similar weight loss and remission of diabetes and is associated with a lower incidence of anemia because of the preservation of the pylorus.

Objective:To explore the influence of flipped classroom combined with case-based learning (CBL) teaching mode on teaching effect of X-ray cephalometric analysis in orthodontic experimental class.Methods:In the study, 70 undergraduates majoring in stomatology were selected as research objects and randomized into teaching reform group and traditional group in average. Flipped classroom combined with CBL teaching mode was adopted in teaching reform group, while traditional group adopted traditional teaching mode. Questionnaire was used to investigate the students' evaluation on the two teaching modes, and the accuracy of the measurement of X-ray cephalometrics of the two groups was compared and analyzed respectively. GraphPad Prism 7.03 software was used to perform t test and chi-square test. Results:Teaching reform group believed that this kind of teaching mode could improve the ability of self-study, communication coordination ability, independent problem solving ability, and logic and language expression ability, deepen the understanding of the project connotation, and apply the X-ray cephalometrics to the actual clinical case analysis and diagnosis. Compared with the traditional group, there were significant differences ( P<0.05). In the accuracy evaluation of measurement values, the absolute values of 70% measurement items in teaching reform group were higher than those in the traditional group, but the difference was not statistically significant ( P>0.05). Only in bone type Ⅲ malocclusion, the absolute values of Y-axis angle and FMA were lower than those of the traditional group, and the difference was statistically significant ( P<0.05). Conclusion:Flipped classroom combined with CBL teaching mode can help students improve self-study ability, communication cooperation ability and the ability of solving problem independently and clinical application. However, the accuracy evaluation of measurement values in teaching reform group were lower than that of the traditional group, indicating that this teaching method in the experimental teaching of X-ray cephalometric analysis needs to be further improved.

Objective To analyze the changing antibiotic resistance profile of the Klebsiella pneumoniae strains isolated from blood cultures during the last 9 years in our hospital for rational use of antibiotics. Methods Antibiotic resistance of the K. pneumoniae strains isolated from blood cultures from 2009 to 2017 was retrospectively analyzed. Medical records of the corresponding inpatients were reviewed and analyzed. Results A total of 6 917 bacterial strains were isolated from blood cultures between 2009 and 2017, of which 311 strains (4.5％) were Klebsiella pneumoniae. Complete antimicrobial susceptibility data were available for 298 of the 311 strains. The K. pneumoniae strains isolated from blood cultures showed increasing resistance rate to the antimicrobial agents in the nine-year period. The resistance rates to piperacillin-tazobactam, cefotetan, amikacin, carbapenem antibiotics increased from 0 to 48.6％. The prevalence of CRKP increased from 0 in 2009 to 48.7％ in 2017. The inpatients with K. pneumoniae isolate from blood cultures were mainly found in general surgery, cardio-thoracic surgery department, emergency room, and pediatrics surgery department. Significant difference was found between CRKP-associated inpatients and non-CRKPassociated inpatients in the time to detection of K. pneumoniae, exposure to antimicrobial agents, invasive procedure, length of hospital stay, and prognosis (P＜0.001). Conclusions The antibiotic resistance profile of the K. pneumoniae strains isolated from blood cultures showed a rising tendency during the period from 2009 to 2017. Clinical microbiology laboratory should pay more attention to strengthening antibiotic resistance surveillance. Clinicians should reduce the use of invasive procedures and use appropriate antimicrobial agents to prevent the emergence of antibiotic-resistant strains.