OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

Objective To observe the value of ultrasound combined with hematologic tests for diagnosing acute complicated appendicitis.Methods Data of 225 patients with acute appendicitis confirmed by surgery and postoperative pathology were retrospectively analyzed.The patients were divided into acute complicated appendicitis group(complicated group,n=33)and acute uncomplicated appendicitis group(uncomplicated group,n=192)based on operational and post operation pathological findings.Clinical data,hematologic test results and ultrasound findings before operation were compared between groups.Multivariate logistic regression was used to construct a combination model for diagnosing acute complicated appendicitis.Receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the diagnostic value of predictive factor alone and their combination for diagnosing acute complicated appendicitis,which were then compared with DeLong test.Results Compared with uncomplicated group,patients in complicated group were older,with higher proportion of fever and vomiting,higher level of C reactive protein(CRP)and of neutrophil-to-lymphocyte ratio(NLR),larger external diameters of appendix,also higher proportion of appendiceal intracavitary fecalith and periappendiceal abscess(all P＜0.05).Multivariate logistic regression analysis showed that elevated serum CRP and NLR,increased external diameter of appendix and periappendiceal abscess were all predictive factors of acute complicated appendicitis(all P＜0.05).The diagnostic efficiency of logistic regression model constructed based on the above factors(AUC=0.854)was higher than that of each single predictive factor alone(Z=2.548-4.527,all P＜0.05).Conclusion Ultrasound combined with hematologic tests had high value for diagnosing acute complicated appendicitis.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

Objective:To explore the clinical predicting value of serum intestinal fatty acid-binding protein (I-FABP) in the development of esophageal varices (EV) in patients with chronic hepatitis B cirrhosis.Method:We used case-control study. A retrospective analysis was performed on the clinical data of 169 patients with hepatitis B cirrhosis who were admitted to the Affiliated Hospital of Yanbian University from September 2020 to October 2023. EV diagnosis and grades were based on gastroscopy. Enzyme-linked immunosorbent assay was used to measure the serum level of I-FABP on admission. Spearman correlation analysis was used to investigate the correlation among variables. Contributing factors of EV were evaluated using univariate and multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of I-FABP for EV presence.Results:The gastroscopy showed 59 patients without EV. The median of I-FABP in the EV Group was significantly higher than that in the no-EV Group [2.01 (1.39, 2.89) μg/L vs 0.96 (0.77, 1.91) μg/L], and the difference was statistically significant ( Z=5.585, P<0.001). I-FABP showed significant positive correlations between model for end-stage liver disease sore and Von Willebrand Factor Antigen/thrombocyte Ratio ( r=0.523, 0.328, both P<0.001). Multiple logistic regression analysis identified I-FABP as the independent factor contributing to the presence of EV ( OR=1.73, P=0.045). The area under the curve of I-FABP predicting EV was 0.76. The cut-off was 1.46 μg/L. Conclusion:I-FABP is a potential marker for the formation of EV in patients with hepatitis B cirrhosis, and its increased concentration is related to reduced hepatic reserve and portal hypertension.

Objective To observe the value of ultrasound combined with hematologic tests for diagnosing acute complicated appendicitis.Methods Data of 225 patients with acute appendicitis confirmed by surgery and postoperative pathology were retrospectively analyzed.The patients were divided into acute complicated appendicitis group(complicated group,n=33)and acute uncomplicated appendicitis group(uncomplicated group,n=192)based on operational and post operation pathological findings.Clinical data,hematologic test results and ultrasound findings before operation were compared between groups.Multivariate logistic regression was used to construct a combination model for diagnosing acute complicated appendicitis.Receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the diagnostic value of predictive factor alone and their combination for diagnosing acute complicated appendicitis,which were then compared with DeLong test.Results Compared with uncomplicated group,patients in complicated group were older,with higher proportion of fever and vomiting,higher level of C reactive protein(CRP)and of neutrophil-to-lymphocyte ratio(NLR),larger external diameters of appendix,also higher proportion of appendiceal intracavitary fecalith and periappendiceal abscess(all P＜0.05).Multivariate logistic regression analysis showed that elevated serum CRP and NLR,increased external diameter of appendix and periappendiceal abscess were all predictive factors of acute complicated appendicitis(all P＜0.05).The diagnostic efficiency of logistic regression model constructed based on the above factors(AUC=0.854)was higher than that of each single predictive factor alone(Z=2.548-4.527,all P＜0.05).Conclusion Ultrasound combined with hematologic tests had high value for diagnosing acute complicated appendicitis.

Objective:To explore the clinical predicting value of serum intestinal fatty acid-binding protein (I-FABP) in the development of esophageal varices (EV) in patients with chronic hepatitis B cirrhosis.Method:We used case-control study. A retrospective analysis was performed on the clinical data of 169 patients with hepatitis B cirrhosis who were admitted to the Affiliated Hospital of Yanbian University from September 2020 to October 2023. EV diagnosis and grades were based on gastroscopy. Enzyme-linked immunosorbent assay was used to measure the serum level of I-FABP on admission. Spearman correlation analysis was used to investigate the correlation among variables. Contributing factors of EV were evaluated using univariate and multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of I-FABP for EV presence.Results:The gastroscopy showed 59 patients without EV. The median of I-FABP in the EV Group was significantly higher than that in the no-EV Group [2.01 (1.39, 2.89) μg/L vs 0.96 (0.77, 1.91) μg/L], and the difference was statistically significant ( Z=5.585, P<0.001). I-FABP showed significant positive correlations between model for end-stage liver disease sore and Von Willebrand Factor Antigen/thrombocyte Ratio ( r=0.523, 0.328, both P<0.001). Multiple logistic regression analysis identified I-FABP as the independent factor contributing to the presence of EV ( OR=1.73, P=0.045). The area under the curve of I-FABP predicting EV was 0.76. The cut-off was 1.46 μg/L. Conclusion:I-FABP is a potential marker for the formation of EV in patients with hepatitis B cirrhosis, and its increased concentration is related to reduced hepatic reserve and portal hypertension.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

Objective:To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts.Methods:C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry.Results:On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion:High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

Objective To investigate the value of intestinal fatty acid binding protein(I-FABP)in predicting the development and progression of acute-on-chronic liver failure(ACLF).Methods A retrospective analysis was performed for the clinical data of 168 patients with decompensated liver cirrhosis who were admitted to The Affiliated Hospital of Yanbian University from September 2020 to March 2023.The conditions of the patients with ACLF on admission were observed,and the patients were followed up for 6 months to identify new-onset ACLF cases.ELISA was used to measure the serum level of I-FABP on admission.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups,and the Kruskal-Wallis H rank sum test was used for comparison between multiple groups;the chi-square test was used for comparison of categorical data between groups;the Jonckheere-Terpstra test was used for trend analysis.The Spearman correlation analysis was used to investigate the correlation between two variables,and the multivariate Cox regression analysis was used to investigate the influencing factors for new-onset ACLF during follow-up.The Kaplan-Meier curve was used to analyze the onset of ACLF in different groups,and the log-rank test was used for the analysis of such differences.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to investigate the performance of I-FABP in predicting the development and progression of ACLF.Results Among the 168 patients enrolled in this study,there were 43 patients with ACLF and 125 patients without ACLF,among whom 19 developed ACLF during follow-up.The patients with ACLF on admission had a significantly higher level of I-FABP than those without ACLF(Z=4.359,P<0.001).The patients with new-onset ACLF had a significantly higher level of I-FABP than those without new-onset ACLF(Z=3.414,P<0.001).The level of I-FABP increased with the increase in ACLF severity grade(H=17.385,P<0.001,Ptrend<0.001).The multivariate Cox regression analysis showed that I-FABP was independently associated with new-onset ACLF during follow-up(hazard ratio=2.138,95%confidence interval[CI]:1.297-3.525,P=0.003),and the tertile of I-FABP showed a good discriminatory ability(χ2=12.16,P<0.001).The ROC curve showed that I-FABP had a good performance in predicting the development and progression of ACLF,with an area under the ROC curve of 0.854(95%CI:0.791-0.903)and 0.747(95%CI:0.661-0.820),respectively,and an optimal cut-off value of 2.07 μg/L and 1.86 μg/L,respectively.Conclusion I-FABP can be used as a biomarker to predict the development and progression of ACLF,and it may help to identify high-risk patients and improve clinical management.

Objective:To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts.Methods:C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry.Results:On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion:High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.