Background and purpose:Accurately locating pulmonary nodules is the key to the success of thoracoscopic surgery.This study aimed to investigate the strategy and evaluate the feasibility,safety,and clinical value of thoracoscopic surgical treatment for pulmonary nodules located beneath the interlobar pleura and close to the pulmonary hilum.Methods:The patients who underwent pulmonary nodule surgery at Liaocheng Tumor Hospital from May 2023 to November 2024 were enrolled,and the patients who did not meet the inclusion criteria were excluded.This study was approved by the Ethics Committee of Liaocheng Tumor Hospital(EC-20240112-1020)and informed consent was obtained from the patients.The research was designed as a prospective single-arm study.The patients were treated with wedge resection,which was performed following CT-guided localization,where the location needle was inserted through the interlobar pleura.The feasibility of the procedure was evaluated by analyzing the success rate of preoperative localization and perioperative complications.Results:A total of 28 patients who met the inclusion criteria were included in this study.There were 5 male and 23 female patients with an average age of(56.0±8.5)years(range 38-69 years).In all,28 patients with 28 nodules underwent thoracoscopic wedge resection,and the preoperative CT-guided localization was successfully performed in all patients,without urgent complications.The mean operation time of thoracoscopic surgery was(15.6±4.0)min,intraoperative bleeding was(20.9±14.3)mL,and postoperative drainage was(214.3±62.2)mL.No cases of postoperative air leaks or conversion to thoracotomy were observed.The average length of hospital stay was(5.4±0.9)days.The postoperative histological diagnosis revealed 3 benign lesions(pulmonary fibrosis in 2 cases,atypical adenomatous hyperplasia in 1 case)and 25 malignant lesions(adenocarcinoma in situ in 5 cases,minimally invasive adenocarcinoma in 16 cases,and invasive adenocarcinoma in 4 cases).Conclusion:Thoracoscopic wedge resection following CT-guided nodule localization through the interlobar pleura is a feasible approach for nodules located beneath the interlobar pleura and close to the pulmonary hilum.The method ensures precise tumor localization,adequate margin,and minimal loss of normal lung tissue,with a low incidence of postoperative complication,which has important guiding significance for the surgical treatment of pulmonary nodules in such special locations.

Objective:To analyze the value of diffusion tensor imaging (DTI) combined with magnetic resonance spectroscopy (MRS) in the clinical grading and prognosis assessment of brain glioma.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with brain glioma admitted to Yan'an People's Hospital from January 2010 to December 2023. The cohort included 40 males and 32 females, with ages ranging from 25 to 76 years and an average age of (40.3 ± 6.8) years. All patients underwent routine magnetic resonance imaging plain scans, contrast-enhanced ultrasound examination, DTI, and MRS prior to surgery. Measurements were conducted for fractional anisotropy (FA), N-acetyl aspartate (NAA), choline compounds (Cho), and creatinine (Cr). Additionally, the ratios of NAA/Cho, Cho/Cr, and NAA/Cr were calculated. The imaging characteristics of brain glioma were analyzed, and the clinical utility of these indicators for grading and prognosis assessment of brain glioma was evaluated.Results:DTI results of the 72 included patients revealed disruption of the white matter fiber tracts surrounding the tumors. MRS of the 72 included patients showed either approximately normal values or indicated elevated Cho and Cr levels, along with decreased NAA levels. Diffuse mild to moderate enhancement was observed in 35 patients (48.61%), presenting with a patchy pattern that suggested a higher tumor grade. When comparing low-grade gliomas (LGG) and high-grade gliomas (HGG) to the corresponding healthy tissue, significant differences were observed in FA value in the peritumoral edema region [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.62 ± 0.08) × 10 -3 mm2/s for LGG, and (0.17 ± 0.05) × 10 -3 mm2/s vs. (0.62 ± 0.09) × 10 -3 mm2/s for HGG] , NAA/Cho ratio [(0.36 ± 0.11) vs. (1.41 ± 0.33) for LGG, and (0.19 ± 0.06) vs. (1.42 ± 0.35) for HGG], Cho/Cr ratio [(2.39 ± 0.51) vs. (1.12 ± 0.26) for LGG, and (3.81 ± 0.94) vs. (1.12 ± 0.28) for HGG], and NAA/Cr ratio [(0.75 ± 0.24) vs. (1.52 ± 0.31) for LGG, and (0.38 ± 0.12) vs. (1.52 ± 0.29) for HGG]. All observed differences were statistically significant ( tLGG = 26.56, 19.09, 14.03, 12.42; tHGG = 27.64, 21.90, 17.34, 22.97, all P < 0.05). There were statistically significant differences in FA [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.17 ± 0.05) × 10 -3 mm2/s], NAA/Cho [(0.36 ± 0.11) vs. (0.19 ± 0.06)], Cho/Cr [(2.39 ± 0.51) vs. (3.81 ± 0.94)], and NAA/Cr [(0.75 ± 0.24) vs. (0.38 ± 0.12)] between LGG and HGG ( t = 2.26, 7.85, 8.17, 7.95, all P < 0.05). Follow-up conducted 6 months to 3 years postoperatively revealed that the Cho/Cr ratio in the death group was significantly higher than that in the survival group [2.172 (1.662, 2.863) vs. 2.729 (2.431, 3.689), U = 2.17, P < 0.05]. However, there were no statistically significant differences in FA, NAA/Cho, and NAA/Cr values between survival and death groups ( P > 0.05). Conclusions:Combined DTI and MRS can reveal specific imaging characteristics of brain gliomas, providing valuable information for clinical grading of brain gliomas. Furthermore, the Cho/Cr ratio is associated with prognosis and may serve as a potential imaging biomarker for predicting the outcome of brain gliomas.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

AIM:This study investigated the role of solute carrier family 7 member 11(SLC7A11)in sul-fasalazine(SAS)-induced ferroptosis in acute myeloid leukemia(AML)cells,focusing on the inhibitory effect of nuclear factor E2-related factor 2(NRF2)nuclear translocation-mediated activation of SLC7A11 on ferroptosis and its underlying mechanisms.METHODS:SAS-induced proliferation in AML cell lines,Kasumi-1 and THP-1,was assessed using the MTS assay.Cell death inhibitors were employed to determine the mode of cell death.Lipid reactive oxygen species(ROS)levels were measured by flow cytometry;Fe2+,malonodialdehyde(MDA),glutathione(GSH)levels,and glutathione per-oxidase 4(GPX4)activity were assessed using micromethods.Quantitative PCR(qPCR)was performed to evaluate changes in SLC7A11 mRNA during SAS-induced ferroptosis,while Western blot measured SLC7A11 and GPX4 protein levels.Moreover,Western blot assessed NRF2 nuclear translocation post-SAS treatment.The NRF2 inhibitor ML385 was used to validate these effects.SLC7A11 mRNA and protein levels were then measured following combined SAS and ML385 treatment via qPCR and Western blot.Cell viability and ferroptosis-related indices were evaluated under the same treatment conditions.Furthermore,a shRNA vector targeting SLC7A11 was constructed to assess changes in cell viability and ferroptosis markers after SLC7A11 knockdown with SAS.GPX4 protein levels were examined following SLC7A11 knockdown.RESULTS:SAS significantly inhibited the proliferation of Kasumi-1 and THP-1 cells at 200 μmol/L and 300 μmol/L,respectively(P<0.05).Only ferroptosis inhibitors(Fer-1 and DFO)significantly reversed SAS-induced cy-totoxicity(P<0.01).SAS increased lipid ROS,Fe2+,and MDA levels(P<0.01),while reducing GSH and GPX4 activity(P<0.01).The mRNA and protein expressions of SLC7A11 increased during SAS-induced ferroptosis(P<0.01),where-as GPX4 protein decreased significantly(P<0.01).SAS significantly increased the nuclear-to-cytoplasmic NRF2 ratio(P<0.01),which decreased upon co-treatment with ML385(P<0.05).Following SAS and ML385 co-treatment,both SLC7A11 mRNA and protein levels were downregulated(P<0.01).This combination treatment further reduced AML cell viability(P<0.01),an effect reversed by Fer-1 and DFO(P<0.01).Compared with SAS alone,the combination of SAS and ML385 significantly increased lipid ROS,Fe2+,and MDA while reducing GSH levels and GPX4 activity(P<0.01).SLC7A11 knockdown was successfully achieved.Compared with the NC shRNA group,SLC7A11 knockdown cells showed significantly decreased viability after SAS treatment,which was reversed by Fer-1 and DFO(P<0.01).Lipid ROS,Fe2+,and MDA content were significantly increased(P<0.01),and GSH and GPX4 were substantially decreased(P<0.05).Moreover,GPX4 protein expression was considerably reduced after SLC7A11 knockdown(P<0.01).CONCLUSION:SAS induces ferroptosis in AML cells.It promotes the nuclear translocation of NRF2 protein,which activates SLC7A11 ex-pression.Inhibition of NRF2 or downregulation of SLC7A11 sensitizes AML cells to SAS-induced ferroptosis.

Background and purpose:Accurately locating pulmonary nodules is the key to the success of thoracoscopic surgery.This study aimed to investigate the strategy and evaluate the feasibility,safety,and clinical value of thoracoscopic surgical treatment for pulmonary nodules located beneath the interlobar pleura and close to the pulmonary hilum.Methods:The patients who underwent pulmonary nodule surgery at Liaocheng Tumor Hospital from May 2023 to November 2024 were enrolled,and the patients who did not meet the inclusion criteria were excluded.This study was approved by the Ethics Committee of Liaocheng Tumor Hospital(EC-20240112-1020)and informed consent was obtained from the patients.The research was designed as a prospective single-arm study.The patients were treated with wedge resection,which was performed following CT-guided localization,where the location needle was inserted through the interlobar pleura.The feasibility of the procedure was evaluated by analyzing the success rate of preoperative localization and perioperative complications.Results:A total of 28 patients who met the inclusion criteria were included in this study.There were 5 male and 23 female patients with an average age of(56.0±8.5)years(range 38-69 years).In all,28 patients with 28 nodules underwent thoracoscopic wedge resection,and the preoperative CT-guided localization was successfully performed in all patients,without urgent complications.The mean operation time of thoracoscopic surgery was(15.6±4.0)min,intraoperative bleeding was(20.9±14.3)mL,and postoperative drainage was(214.3±62.2)mL.No cases of postoperative air leaks or conversion to thoracotomy were observed.The average length of hospital stay was(5.4±0.9)days.The postoperative histological diagnosis revealed 3 benign lesions(pulmonary fibrosis in 2 cases,atypical adenomatous hyperplasia in 1 case)and 25 malignant lesions(adenocarcinoma in situ in 5 cases,minimally invasive adenocarcinoma in 16 cases,and invasive adenocarcinoma in 4 cases).Conclusion:Thoracoscopic wedge resection following CT-guided nodule localization through the interlobar pleura is a feasible approach for nodules located beneath the interlobar pleura and close to the pulmonary hilum.The method ensures precise tumor localization,adequate margin,and minimal loss of normal lung tissue,with a low incidence of postoperative complication,which has important guiding significance for the surgical treatment of pulmonary nodules in such special locations.

Objective:To investigate the risk factors of hypoparathyroidism (HPT) and hypocalcemia in patients undergoing total thyroidectomy (TT), and to explore the changes of parathyroid hormone and blood calcium after TT.Methods:The clinical data of 101 patients undergoing TT from November 2018 to September 2022 in the First Hospital of Hebei Medical University were retrospectively analyzed. The basic clinical data were recorded. The blood calcium and parathyroid hormone levels were measured before surgery and 1 d, 1 week after surgery. The occurrence of postoperative hypocalcemia was recorded. According to postoperative parathyroid hormone level, the patients were divided into control group (normal parathyroid function) and HPT group (reduced parathyroid hormone level). The patients with postoperative hypocalcemia symptoms were classified as the hypocalcemia symptoms group, and the patients without postoperative hypocalcemia symptoms were classified as the non-hypocalcemia symptoms group. Multivariate Logistic regression was used to analyze the independent risk factors of HPT and hypocalcemia in TT patients.Results:The postoperative parathyroid hormone level decreased in 41 cases (HPT group) and normal in 60 cases (control group). There were 24 patients with postoperative hypocalcemia symptoms (hypocalcemia symptoms group) and 77 patients without postoperative hypocalcemia symptoms (non-hypocalcemia symptoms group). The rate of using bipolar electric coagulation forceps in HPT group was significantly lower than that in control group: 31.71% (13/41) vs. 76.67% (46/60), while the rate of central lymph node dissection was significantly higher than that in control group: 82.93% (34/41) vs. 60.00% (36/60), and there were statistical differences ( P<0.01 and <0.05). Multivariate Logistic regression analysis result showed that TT combined with unilateral or bilateral central lymph node dissection was an independent risk factor for HPT in TT patients ( OR = 1.706 and 1.501, 95% CI 1.019 to 2.856 and 1.052 to 2.140, P<0.05). The preoperative serum calcium, postoperative serum calcium and postoperative parathyroid hormone in hypocalcemia symptoms group were significantly lower than those in hypocalcemia symptoms group: (2.32 ± 0.11) mmol/L vs. (2.37 ± 0.11) mmol/L, (2.16 ± 0.21) mmol/L vs. (2.25 ± 0.18) mmol/L and 3.00 (1.00, 5.45) ng/L vs. 19.90 (8.50, 33.80) ng/L, and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that postoperative parathyroid hormone was an independent risk factor of hypocalcemia symptoms in TT patients ( OR = 0.927, 95% CI 0.883 to 0.974, P<0.01). In patients with HPT, the blood calcium at 1 week after surgery was significantly lower than that at 1 d after surgery: (2.07 ± 0.19) mmol/L vs. (2.17 ± 0.25) mmol/L, and there was statistical difference ( t = 2.05, P<0.05); the parathyroid hormone at 1 week after surgery was significantly higher than that at 1 d after surgery: 8.30 (3.55, 19.55) ng/L vs. 3.60 (1.00, 6.85) ng/L, and there was statistical difference ( Z = - 3.78, P<0.01). Conclusions:When performing TT, standardizing the surgical techniques, reducing unnecessary central lymph node dissection, and using bipolar electric coagulation forceps as much as possible can help to reduce the occurrence of postoperative HPT. The levels of postoperative parathyroid hormone and blood calcium should be promptly detected, the change of both should be given attention, and do a good job in preventing and treating hypocalcemia.

Objective To construct a nomogram prediction model for predicting hemoglobin A1c(HbA1c)failure in type 2 diabetes mellitus(T2DM)patients.Methods A total of 936 inpatients with T2DM admitted to the Department of Endocrinology of the Affiliated Hospital of Shandong Second Medical University from January 2021 to January 2022 were selected as the research objects and divided into the non-standard group(HbA1c≥7%,n=801)and the standard group(HbA1c<7%,n=135).Univariate analysis was used to screen the related factors of HbA1c failure.Logistic regression multivariate model was used to analyze the influencing factors of HbA1c failure in T2DM patients.The R language was used to construct a nomogram,and the area under the receiver operating characteristic(ROC)curve(AUC)was used to evaluate the predictive ability of the model.The C-index and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Results There were statistically significant differences in triglyceride(TG),low-density lipoprotein cholesterol,direct bilirubin,urinary albumin/creatinine ratio(UACR),self-monitoring of blood glucose(SMBG),meat and vegetable pairing,hot pot,whole grain and animal viscera consumption between the two groups(P<0.05).Logistic regression analysis showed that TG(OR 1.699,95%CI 1.298～2.222),UACR(OR 1.003,95%CI 1.001～1.005),SMGB(OR 0.480,95%CI 0.313～0.735),more meat and less vegetables(OR 1.432,95%CI 1.062～1.931)were the influencing factors of HbA1c failure.The AUC of the nomogram prediction model based on the influencing factors was 0.711,with C-index 0.710(95%CI 0.663～0.758)and good calibration(χ2=11.185,P=0.191).Conclusions The nomogram prediction model for HbA1c failure in T2DM patients established based on TG,UACR,SMGB,meat and vegetarian mix has good discrimination and calibration,which can provide certain reference value for warning of poor blood glucose control.

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Objective To construct a nomogram prediction model for predicting hemoglobin A1c(HbA1c)failure in type 2 diabetes mellitus(T2DM)patients.Methods A total of 936 inpatients with T2DM admitted to the Department of Endocrinology of the Affiliated Hospital of Shandong Second Medical University from January 2021 to January 2022 were selected as the research objects and divided into the non-standard group(HbA1c≥7%,n=801)and the standard group(HbA1c<7%,n=135).Univariate analysis was used to screen the related factors of HbA1c failure.Logistic regression multivariate model was used to analyze the influencing factors of HbA1c failure in T2DM patients.The R language was used to construct a nomogram,and the area under the receiver operating characteristic(ROC)curve(AUC)was used to evaluate the predictive ability of the model.The C-index and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Results There were statistically significant differences in triglyceride(TG),low-density lipoprotein cholesterol,direct bilirubin,urinary albumin/creatinine ratio(UACR),self-monitoring of blood glucose(SMBG),meat and vegetable pairing,hot pot,whole grain and animal viscera consumption between the two groups(P<0.05).Logistic regression analysis showed that TG(OR 1.699,95%CI 1.298～2.222),UACR(OR 1.003,95%CI 1.001～1.005),SMGB(OR 0.480,95%CI 0.313～0.735),more meat and less vegetables(OR 1.432,95%CI 1.062～1.931)were the influencing factors of HbA1c failure.The AUC of the nomogram prediction model based on the influencing factors was 0.711,with C-index 0.710(95%CI 0.663～0.758)and good calibration(χ2=11.185,P=0.191).Conclusions The nomogram prediction model for HbA1c failure in T2DM patients established based on TG,UACR,SMGB,meat and vegetarian mix has good discrimination and calibration,which can provide certain reference value for warning of poor blood glucose control.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.