OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

OBJECTIVE To explore the clinical efficacy of dapagliflozin for stable coronary heart disease combined with heart failure （HF）. METHODS A prospective study method was employed. A total of 158 patients with stable coronary heart disease and HF admitted to our hospital from January 1， 2023， to January 1， 2024， were enrolled. Using a random number table method， they were divided into dapagliflozin group （n＝76） and conventional treatment group （n＝82）. All patients received conventional treatment， including diuretic， aspirin， losartan， metoprolol and statins. Patients in the dapagliflozin group were additionally administered Dapagliflozin tablets at a dose of 10 mg once daily on top of the conventional treatment. The treatment duration was six months. The changes in left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， fasting blood glucose， N-terminal pro-brain natriuretic peptide （NT-proBNP）， the number of angina attacks， the duration of angina attacks， and lipoprotein-associated phospholipase A2 before and after treatment were compared between the two groups. The occurrence of adverse reactions such as renal dysfunction， liver dysfunction， urinary system infections， new-onset dialysis， hypotension and hypoglycemia was evaluated in the two groups during treatment. RESULTS During the study， 16 patients were lost to follow-up. Ultimately， 70 patients in the dapagliflozin group and 72 patients in the conventional treatment group completed the study. Before treatment， there were no statistically significant differences in the aforementioned indicators between the two groups （P＞0.05）. Compared with before treatment， after treatment， both groups showed significant shortening in LVESD and LVEDD， significant increases in LVEF， significant reductions in NT-proBNP and lipoprotein-associated phospholipase A2 levels， and significant reductions in the number of angina attacks and the duration of angina attacks （P＜0.05）； the improvements in the dapagliflozin group were more significant than those in the conventional treatment group （P＜0.05）. There was no statistically significant difference between the two groups in fasting blood glucose levels and the incidence of the aforementioned adverse reactions （P＞0.05）. CONCLUSIONS Adding dapagliflozin to conventional treatment can shorten LVESD and LVEDD， increase LVEF levels， reduce NT-proBNP and lipoprotein-associated phospholipase A2 levels， and decrease the number and duration of angina attacks in patients with stable coronary heart disease combined with HF， thereby improving their cardiac function， and demonstrates good safety.

Objective To investigate the effects of five-element music on depressive behaviors and intestinal flora in offspring of fear-stress rats during pregnancy.Methods Thirty-six 0.5-day pregnant Wistar rats were divided randomly into a control group,fear-stress group,and five-element music group,and the subsequent litters continued the maternal grouping.Pregnant rats in the fear-stress and five-element music groups were modeled on days 1～19 of gestation using the bystander electric method,while the five-element music group was also exposed to Feather Tune five-element music intervention.The fear behavior and serum glucocorticoid(GC)levels in pregnant rats were assessed on day 20 of pregnancy by open field test and enzyme-linked immunosorbent assay,respectively,to evaluate the effectiveness of the model.Depression in 3-week-old offspring was evaluated by open field,tail suspension,and sucrose preference tests.Norepinephrine(NE),dopamine(DA),and 5-hydroxytryptamine(5-HT)levels in the hippocampus of the offspring were measured by high-performance liquid chromatography.Changes in the intestinal flora of the offspring were analyzed by 16S rRNA sequencing.Expression levels of the proximal colonic proteins claudin1,occludin,and ZO1 in the offspring were measured by Western blot assay.Results Pregnant rats in the fear-stress group stayed longer in the area around the open field(P＜0.05),had fewer entries into the central area(P＜0.001),and had higher serum GC levels compared with those in the blank group(P＜0.001).In contrast,five-element music exposure reversed these behavioral changes(P＜0.05)and serum GC levels(P＜0.001)in the fear-stress group.Offspring in the fear-stress group exhibited decreased open-field crossing frequency(P＜0.01),reduced sucrose preference index,and longer immobility time in the tail suspension test(P＜0.05),compared with those in the blank group,together with significantly decreased NE,DA,and 5-HT levels in the hippocampus(P＜0.05).Rats in the fear-stress group showed decreased diversity of the intestinal flora(P＜0.01)and significant alterations in flora structure,including higher abundance of Proteobacteria,Enterobacteriaceae,Enterococcus,and Escherichia(P＜0.05),and lower abundance of Spirochaetes,Spirochaetaceae,Lachnospiraceae,Ruminococcaceae,Treponema,Prevotella,Coprococcus,Allobaculum,Ruminococcus,and Dorea(P＜0.05).The proximal colonic proteins Claudin1,Occludin,and ZO1 were significantly downregulated(P＜0.05).The open-field crossing frequency,sucrose preference index,and duration of tail suspension immobilization were improved in the five-element music group compared with those in the fear-stress group(P＜0.05),while DA and 5-HT levels were significantly restored in the hippocampus(P＜0.05),species diversity of the intestinal flora increased(P＜0.01)and changes in the abundance of the flora were reversed,and the proximal colonic proteins Occludin and ZO1 expression were significantly upregulated(P＜0.05).Conclusions Five-element music intervention during pregnancy can ameliorate fear-stress-induced depression behaviors and intestinal flora disorders in the offspring.

Objective To investigate the effects of five-element music on depressive behaviors and intestinal flora in offspring of fear-stress rats during pregnancy.Methods Thirty-six 0.5-day pregnant Wistar rats were divided randomly into a control group,fear-stress group,and five-element music group,and the subsequent litters continued the maternal grouping.Pregnant rats in the fear-stress and five-element music groups were modeled on days 1～19 of gestation using the bystander electric method,while the five-element music group was also exposed to Feather Tune five-element music intervention.The fear behavior and serum glucocorticoid(GC)levels in pregnant rats were assessed on day 20 of pregnancy by open field test and enzyme-linked immunosorbent assay,respectively,to evaluate the effectiveness of the model.Depression in 3-week-old offspring was evaluated by open field,tail suspension,and sucrose preference tests.Norepinephrine(NE),dopamine(DA),and 5-hydroxytryptamine(5-HT)levels in the hippocampus of the offspring were measured by high-performance liquid chromatography.Changes in the intestinal flora of the offspring were analyzed by 16S rRNA sequencing.Expression levels of the proximal colonic proteins claudin1,occludin,and ZO1 in the offspring were measured by Western blot assay.Results Pregnant rats in the fear-stress group stayed longer in the area around the open field(P＜0.05),had fewer entries into the central area(P＜0.001),and had higher serum GC levels compared with those in the blank group(P＜0.001).In contrast,five-element music exposure reversed these behavioral changes(P＜0.05)and serum GC levels(P＜0.001)in the fear-stress group.Offspring in the fear-stress group exhibited decreased open-field crossing frequency(P＜0.01),reduced sucrose preference index,and longer immobility time in the tail suspension test(P＜0.05),compared with those in the blank group,together with significantly decreased NE,DA,and 5-HT levels in the hippocampus(P＜0.05).Rats in the fear-stress group showed decreased diversity of the intestinal flora(P＜0.01)and significant alterations in flora structure,including higher abundance of Proteobacteria,Enterobacteriaceae,Enterococcus,and Escherichia(P＜0.05),and lower abundance of Spirochaetes,Spirochaetaceae,Lachnospiraceae,Ruminococcaceae,Treponema,Prevotella,Coprococcus,Allobaculum,Ruminococcus,and Dorea(P＜0.05).The proximal colonic proteins Claudin1,Occludin,and ZO1 were significantly downregulated(P＜0.05).The open-field crossing frequency,sucrose preference index,and duration of tail suspension immobilization were improved in the five-element music group compared with those in the fear-stress group(P＜0.05),while DA and 5-HT levels were significantly restored in the hippocampus(P＜0.05),species diversity of the intestinal flora increased(P＜0.01)and changes in the abundance of the flora were reversed,and the proximal colonic proteins Occludin and ZO1 expression were significantly upregulated(P＜0.05).Conclusions Five-element music intervention during pregnancy can ameliorate fear-stress-induced depression behaviors and intestinal flora disorders in the offspring.

Objective:To introduce the clinical application of "page-turning" superior pancreatic lymph node dissection in laparoscopic D2 radical gastrectomy for gastric cancer.Methods:Patients who were confirmed to have adenocarcinoma by preoperative gastroscopy and pathological biopsy, with tumor staging evaluated by imaging as cT1~4aN0~3M0, without neoadjuvant therapy, and without absolute surgical contraindications, underwent laparoscopic radical gastrectomy for gastric cancer with "page-turning" superior pancreatic lymph node dissection. The "page-turning" superior pancreatic lymph node dissection was performed in four steps: (1) Expose the posterior gastric mesentery and dissect No.11p lymph nodes; (2) Expose the left gastric mesentery and dissect No.7, No.8a and No.9 lymph nodes; (3) Expose the right gastric mesentery and dissect No.5 lymph nodes; (4) Expose the left edge of the portal vein and dissect No.12a lymph nodes.Results:From April 2018 to October 2024, 112 patients with gastric cancer underwent laparoscopic D2 radical gastrectomy with "page-turning" superior pancreatic lymph node dissection, including 21 cases in the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 78 cases in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, and 13 cases in the Department of Gastrointestinal Surgery, Jilin Provincial People's Hospital. The TNM staging of all patients was as follows: 31 cases in stage Ⅰ, 24 cases in stage Ⅱ, and 57 cases in stage Ⅲ; 62 cases of differentiated adenocarcinoma and 50 cases of undifferentiated adenocarcinoma; the median length of tumors was 3.8 cm. All patients successfully completed the operation without conversion to open surgery, no intraoperative massive hemorrhage or postoperative death. The median total number of lymph nodes dissected in all patients was 32, and the median number of positive lymph nodes was 4.5. The overall postoperative complication rate was 5.4% (6/112), all of which were Clavien-Dindo grade Ⅱ, including pulmonary infection, pleural effusion, and incisional infection, all cured by symptomatic treatment. The median follow-up was 41.8 (2-78) months, with 7 cases lost to follow-up. During the follow-up period, 27 cases (25.7%) had tumor recurrence and 16 cases (15.2%) died.Conclusions:The "page-turning" superior pancreatic lymph node dissection technique is safe and feasible in laparoscopic radical gastrectomy for gastric cancer.

Objective This study examines serum lipid metabolism characteristics in colorectal cancer patients and its diagnostic potential.Methods Serum samples from 57 colorectal cancer patients and 54 healthy controls underwent lipidomic analysis using ultra-high performance liquid chromatography-time-of-flight mass spec-trometry,combined with principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Differential lipids were identified based on criteria of P<0.05,VIP>1,and fold change<0.67 or>1.5.These lipids were further evaluated using receiver operating characteristic(ROC)analysis to identify biomarkers with strong diagnostic value.Results Five classes and 66 differential lipids were identified,with phos-phatidylcholine(PC)and triglyceride(TG)comprising 59.09%.KEGG pathway enrichment indicated involvement in glycerophospholipid and glycerol ester metabolism pathways.ROC analysis identified Sphinganine,MG(19∶0),LysoPC(18∶2),PA(42∶6),PC(36∶5),PC(36∶4),PC(38∶6),and PC(40∶8)as having areas under the curve greater than 0.85.Conclusion The lipid metabolic profile of colorectal cancer(CRC)patients can be systematically analyzed through the efficient enrichment of lipid metabolites in serum using the UPLC-Q/TOF-MS technique,in conjunction with a modified Bligh-Dyer method.The identification of eight specific lipids including Sphinganine,MG(19∶0),LysoPC(18∶2),PA(42∶6),PC(36∶5),PC(36∶4),PC(38∶6),and PC(40∶8)offer novel insights and parameters for differentiating between healthy individuals and those diagnosed with colorec-tal cancer.

Objective:To investigate the molecular mechanisms by which HMGB1 in lung cancer cells affects the function of lung cancer cells themselves and immune cells through the NF-κB pathway.Methods:Western blot detected HMGB1 expressions in Lewis lung cancer(LLC)cells,Raw264.7 cells,and mouse spleen cells,while tumor cell lysates(TCL)with low HMGB1 was pre-pared by inhibiting HMGB1 expression in lung cancer cells with glycyrrhetinic acid(GA);the effects of endogenous HMGB1 inhibi-tion or TCL with low HMGB1 on apoptosis and proliferation of lung cancer cells were detected by flow cytometry and CCK-8;TCL with normal HMGB1 or TCL with low HMGB1 was prepared by freeze-thawing;Raw264.7 cells and mouse splenocytes were treated with them for 48 h.Apoptosis and CD69 expression were detected by flow cytometry,and secretion of cytokines IL-2,IL-4,IL-6,TNF-α and TNF-β were detected by ELISA;Western blot detected lung cancer cells or immune cells.Western blot was performed to detect the protein expression of key signaling molecules of the NF-κB signaling pathway in lung cancer cells or immune cells.Results:HMGB1 was expressed in LLC cells,Raw264.7 cells,and mouse spleen cells,among which LLC cells had the highest expression of HMGB1,and 30 μg/ml GA had the best inhibitory effect on HMGB1 expression in LLC cells.Endogenous HMGB1 in LLC cells could promote cell proliferation.Exogenous HMGB1 in TCL induced apoptosis in lung cancer cells and inhibited immune cell activation and prolifera-tion.Inhibition of endogenous HMGB1 in lung cancer cells leaded to activation of the apoptosis-inducing factor CASP9 in the NF-κB signaling pathway,which was inhibited in lung cancer cells or immune cells after the action of TCL with low HMGB1.Conclusion:Tumor cell HMGB1 has a dual role in lung carcinogenesis,promoting the proliferation of lung cancer cells while suppressing the func-tion of immune cells,which in turn causes lung carcinogenesis,a process associated with the activation of the NF-κB signaling path-way in different cells.

Objective:To discuss the feasibility and safety of stage I anastomosis and T-tube fistulation in laparoscopic local resection of duodenal tumors.Methods:A descriptive case series study was used to retrospectively analyze the clinical diagnosis and treatment data of 14 patients with duodenal tumors who successfully underwent laparoscopic local resection of duodenal tumors + phase I anastomosis + T-tube ostomy in the Guangdong Provincial Hospital of Chinese Medicine and the First Affiliated Hospital of Guangzhou University of Chinese Medicine from October 2021 to March 2024. The resection and reconstruction steps of laparoscopic local resection of duodenal tumor + phase I anastomosis + T-tube ostomy are as follows: (1) after the safe margin is clear, the duodenal tumor is completely removed in full thickness, and the specimen bag is taken out and sent to frozen section to determine the nature of the tumor and the negative margin; (2) Perforate the anterior duodenal wall below the tumor plane, place a 16# T tube, and fix it with laparoscopic purse string suture. The abdominal wall is led out through the duodenum, and the duodenal T tube fistulation is performed; (3) The duodenum was continuously sutured in a full-thickness transverse shape, and the seromuscular layer was strengthened to form a phase I anastomosis. The nutritional improvement of patients after operation was mainly observed, and the intraoperative situation and postoperative complications were recorded.Results:No conversion to laparotomy, postoperative emergency reoperation, intraoperative and postoperative complications occurred in 14 patients with duodenal tumors who completed laparoscopic local resection of duodenal tumors + phase I anastomosis + T-tube ostomy. The operation time was (225.43 ± 56.54) min, and the intraoperative blood loss was (72.14 ± 74.65) ml. The patient recovered well after operation, and no severe postoperative abdominal bleeding occurred. Postoperative gastrointestinal angiography showed that the anastomotic stoma was unobstructed, and there were no stenosis, anastomotic leakage and other related complications. There was no significant difference in serum albumin [(37.09 ± 3.53) g/L vs. (37.52 ± 4) g/L] and hemoglobin [(100.79 ± 31.93) g/L vs. (103.07 ± 19.6) g/L] between before and 1 week after operation ( P > 0.05). Conclusion:Laparoscopic local resection of duodenal tumor + phase I anastomosis + T-tube fistulation can be used as one of the safe and feasible improved methods for local resection of duodenal tumor to effectively reduce the occurrence of related complications.

Objective:To investigate the efficacy and safety of a self-controlled chain ring combined with tissue clip traction-assisted technique for endoscopic submucosal dissection (ESD) of early colorectal tumors.Methods:Data of patients with early colorectal tumors in technically challenging locations who underwent ESD at the Digestive Endoscopy Center of Jiangsu Province Hospital of Chinese Medicine from January 2021 to April 2024 were enrolled in the retrospective cohort study. According to the treatment methods, they were divided into the traction-assisted ESD group (a self-controlled chain ring combined with tissue clip traction-assisted) and the traditional ESD group (without traction). Clinical endoscopic data, treatment conditions, and complications were compared between the two groups.Results:A total of 61 patients were enrolled, including 29 patients in the traction-assisted ESD group and 32 patients in the traditional ESD group. There were no significant differences in age, gender, tumor size, shape, location, pit pattern, pathological type, depth of invasion, one-time complete resection, or curative resection between the two groups ( P>0.05). The traction-assisted group demonstrated significantly shorter dissection times (37.55±20.44 min VS 60.78±29.34 min, t=-3.552, P<0.001) and lower complication rates [3.4% (1/29) VS 25.0% (8/32), χ2=4.035, P=0.045]. Complications in the traction-assisted ESD group included 1 muscularis propria superficial injury (no perforation/uncontrollable bleeding), versus 6 muscularis injuries and 2 micro-perforations in controls. Conclusion:The combined traction technique improves dissection efficiency and reduces procedural risks for challenging colorectal ESD.

Objective:To investigate the value of the water pressure method (WPM) for endoscopic submucosal dissection (ESD) of difficult early gastrointestinal cancer.Methods:Clinical data of 7 patients with difficult early gastrointestinal cancer who underwent WPM-ESD at Digestive Endoscopy Center of Jiangsu Province Hospital of Chinese Medicine from April 2023 to April 2024 were retrospectively collected. Operation time, complete resection rate and complications were recorded.Results:WPM-ESD was successfully completed in all 7 cases. According to the lesion location and factors for difficulty, there were 2 cases of early esophageal cancer (1 case with remarkable external compression, and the other with remarkable hyperkeratosis), 1 case of early gastric cancer (a large lesion located at the greater curvature), 1 case of early descending duodenal cancer (severe submucosal fibrosis due to a history of two sessions of biopsies), 2 cases of early colon cancer (1 case with severe submucosal adipose deposition, and the other with deep submucosal invasion ), and 1 case of early rectal cancer (close to the dentate line). Operation time ranged from 15-85 min. Only 1 case required supplemental rubber-band traction. Complete resection was achieved in all 7 cases. Two patients developed fever postoperatively; no perforation, bleeding or other complications were observed.Conclusion:WPM demonstrates feasibility and efficacy for ESD in difficult early gastrointestinal cancer.