ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

Objective:To analyze the relationship between serum neutrophil elastase (NE) level and assisted pregnancy outcome in infertility patients with polycystic ovary syndrome (PCOS).Methods:A total of 137 infertility patients with PCOS who planned to undergo in vitro fertilization-embryo transfer (IVF-ET) treatment in Xianyang Central Hospital from January 2020 to January 2023 were prospectively selected. Serum NE level was measured before IVF-ET transplantation, and the pregnancy-assisted outcome of infertility patients with PCOS were analyzed. The relationship between serum NE level and assisted pregnancy outcome in PCOS infertility patients was analyzed.Results:The proportion of age ≥ 35 years old and serum NE levels in the failure group were higher than those in the success group: 50.00% (41/82) vs. 30.91%(17/55), (73.64 ± 6.74) mg/L vs. (60.71 ± 5.99) mg/L, while serum anti-Mullerian hormone (AMH) level were lower than those in the success group: (3.61 ± 1.17) μg/L vs. (4.89 ± 1.25) μg/L. The thickness of the endometrium was thicker than that in the success group: (10.63 ± 1.78) mm vs. (7.88 ± 1.28) mm, with statistically significant differences ( P<0.05). Multivariate Logistic regression analysis showed that thick endometrial thickness, high serum NE level and low serum AMH level were associated with assisted pregnancy failure in PCOS infertility patients ( P<0.05). A receiver operating characteristic (ROC) curve was drawn, and the results showed that the AUC of endometrial thickness, serum NE and AMH levels for predicting IVF-ET assisted pregnancy failure in PCOS infertility patients was greater than 0.7, which had certain predictive value. Serum NE had the best predictive effect, and when serum NE was 66.60 mg/L, ideal sensitivity and specificity of 85.40% and 87.30% could be obtained. Conclusions:The level of NE is related to the outcome of assisted pregnancy in PCOS infertility patients, and an increase in serum NE level can increase the risk of assisted pregnancy failure in PCOS infertility patients.

Objective To investigate the impact of high-frequency repetitive transcranial magnetic stimula-tion(rTMS)combined with biofeedback-assisted dry swallowing training on treating dysphagia following a stroke.Methods A total of 152 patients with dysphagia after stroke,admitted to the hospital from January 2022 to January 2024,were randomly divided into four groups using a random number table,with 38 cases in each group.The biofeedback group received biofeedback-assisted dry swallowing training,the magnetic stimulation group received high-frequency rTMS on the unaffected side,the combined group received both biofeedback-assisted dry swallowing training and high-frequency rTMS on the unaffected side,and the placebo group received conventional swallowing training and sham rTMS.All interventions lasted for 4 weeks.Clinical efficacy was recorded,and pre-and post-treatment assessments of the upper esophageal sphincter(UES)opening time,opening degree,and pharyngeal contraction duration were performed using multifunctional esophageal manometry.Additionally,swallowing func-tion,nutritional status,neurological function,and quality of life were compared.Results The clinical efficacy of the combined group was higher than that of the biofeedback and magnetic stimulation groups.Post-treatment UES opening time,opening degree,and pharyngeal contraction duration were(205.33±29.01)ms,(1.14±0.34)cm,and(559.19±63.48)ms,respectively,which were significantly better than those in the other 3 groups(P<0.05).The swallowing function scores of the combined group were(6.04±0.83)and(20.03±3.26)points,and significant improvements were observed in swallowing function,nutritional status,neurological function,and quality of life(P<0.05).Conclusion High-frequency rTMS combined with biofeedback-based dry swallowing training signifi-cantly improves the efficacy in the treatment of dysphagia after stroke.

Objective:To analyze the relationship between serum neutrophil elastase (NE) level and assisted pregnancy outcome in infertility patients with polycystic ovary syndrome (PCOS).Methods:A total of 137 infertility patients with PCOS who planned to undergo in vitro fertilization-embryo transfer (IVF-ET) treatment in Xianyang Central Hospital from January 2020 to January 2023 were prospectively selected. Serum NE level was measured before IVF-ET transplantation, and the pregnancy-assisted outcome of infertility patients with PCOS were analyzed. The relationship between serum NE level and assisted pregnancy outcome in PCOS infertility patients was analyzed.Results:The proportion of age ≥ 35 years old and serum NE levels in the failure group were higher than those in the success group: 50.00% (41/82) vs. 30.91%(17/55), (73.64 ± 6.74) mg/L vs. (60.71 ± 5.99) mg/L, while serum anti-Mullerian hormone (AMH) level were lower than those in the success group: (3.61 ± 1.17) μg/L vs. (4.89 ± 1.25) μg/L. The thickness of the endometrium was thicker than that in the success group: (10.63 ± 1.78) mm vs. (7.88 ± 1.28) mm, with statistically significant differences ( P<0.05). Multivariate Logistic regression analysis showed that thick endometrial thickness, high serum NE level and low serum AMH level were associated with assisted pregnancy failure in PCOS infertility patients ( P<0.05). A receiver operating characteristic (ROC) curve was drawn, and the results showed that the AUC of endometrial thickness, serum NE and AMH levels for predicting IVF-ET assisted pregnancy failure in PCOS infertility patients was greater than 0.7, which had certain predictive value. Serum NE had the best predictive effect, and when serum NE was 66.60 mg/L, ideal sensitivity and specificity of 85.40% and 87.30% could be obtained. Conclusions:The level of NE is related to the outcome of assisted pregnancy in PCOS infertility patients, and an increase in serum NE level can increase the risk of assisted pregnancy failure in PCOS infertility patients.

Objective To investigate the impact of high-frequency repetitive transcranial magnetic stimula-tion(rTMS)combined with biofeedback-assisted dry swallowing training on treating dysphagia following a stroke.Methods A total of 152 patients with dysphagia after stroke,admitted to the hospital from January 2022 to January 2024,were randomly divided into four groups using a random number table,with 38 cases in each group.The biofeedback group received biofeedback-assisted dry swallowing training,the magnetic stimulation group received high-frequency rTMS on the unaffected side,the combined group received both biofeedback-assisted dry swallowing training and high-frequency rTMS on the unaffected side,and the placebo group received conventional swallowing training and sham rTMS.All interventions lasted for 4 weeks.Clinical efficacy was recorded,and pre-and post-treatment assessments of the upper esophageal sphincter(UES)opening time,opening degree,and pharyngeal contraction duration were performed using multifunctional esophageal manometry.Additionally,swallowing func-tion,nutritional status,neurological function,and quality of life were compared.Results The clinical efficacy of the combined group was higher than that of the biofeedback and magnetic stimulation groups.Post-treatment UES opening time,opening degree,and pharyngeal contraction duration were(205.33±29.01)ms,(1.14±0.34)cm,and(559.19±63.48)ms,respectively,which were significantly better than those in the other 3 groups(P<0.05).The swallowing function scores of the combined group were(6.04±0.83)and(20.03±3.26)points,and significant improvements were observed in swallowing function,nutritional status,neurological function,and quality of life(P<0.05).Conclusion High-frequency rTMS combined with biofeedback-based dry swallowing training signifi-cantly improves the efficacy in the treatment of dysphagia after stroke.

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective:In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups.Results:There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant ( t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ2=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences ( Z=0.406, P=0.685). Conclusions:Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Objective:In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups.Results:There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant ( t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ2=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences ( Z=0.406, P=0.685). Conclusions:Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Objective To investigate the effect of evolocumab combined with levocarnitine after emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods A total of 120 STEMI patients were selected and randomly divided into treatment group (60 cases) and control group (60 cases). The control group was given STEMI basic treatment plus levocarnitine, and the treatment group was given evolocumab on the basis of the control group. The therapeutic effectiveness, coronary artery microcirculation [B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF)], coronary arteriole status[Thrombolysis in Myocardial Infarction (TIMI) risk score, preprotein converting enzyme subtilysin 9 (PCSK9) and low density lipoprotein cholesterol (LDL-C)] and incidence of adverse reactions were compared between the two groups before and after treatment. Results After treatment, the total effective rate of treatment group was significantly higher than that of control group (P < 0.05). After treatment, BNP level in two groups was significantly lower than before treatment, and the level in the treatment group was significantly lower than that in the control group (P < 0.05); LVEF in the two groups was significantly higher than before treatment, and the treatment group was significantly higher than the control group (P < 0.05). After treatment, the TIMI risk score of the two groups was significantly decreased, and the treatment group was significantly lower than the control group (P < 0.05). The levels of PSCK9 and LDL-C in the two groups were significantly lower than before treatment, and the treatment group was significantly lower than the control group (P < 0.05). After treatment, there was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Evolocumab combined with levocarnitine can improve cardiac function and coronary microcirculation in STEMI patients after emergency PCI, and has high safety.

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.