OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Objective:To investigate the relationship between Ig class switch recombination(CSR)and mismatch repair(MMR)protein,microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(MALT lymphoma).Methods:Forty cases of MALT lymphoma archived in the Department of Pathology,Jiading District Central Hospital,Shanghai University of Medicine & Health Sciences were selected as the observation group,and twenty cases of benign lymphoid tissue hyperplasia were as the control group.The expressions of IgG,IgM,IgD,and IgA in both groups were detected by immunohistochemical double staining,and MMR proteins including MLH1,MSH2,MSH6,and PMS2 in both groups were detected by immunohistochemistry.Multiplex fluorescence PCR capillary electrophoresis was used to detect microsatellite phenotype in tumor and adjacent tissues of the experimental group.Results:In the observation group,the proportions of single Ig heavy chain expression(mode Ⅰ),negative expression(mode Ⅱ),and multiple expression(mode Ⅲ)were 65％(26/40),27.5％(11/40),and 7.5％(3/40),respectively,while in the control group were 0(0/20),5％(1/20),and 95％(19/20).The proportion of Ig heavy chain expression mode Ⅰ+Ⅱ in the observation group was 92.5％,which was significantly higher than 5％in the control group(P＜0.0 1).In the observation group,partial deletion of MMR protein was observed in 3 cases(7.5％),including 2 cases of MSH6 deletion and 1 case of both MSH6 and PMS2 deletion.In the control group,there was 1 case(5％)with PMS2 deletion.There was no significant difference in the deletion rate of MMR protein between the two groups(P＞0.05).A total of 5 cases of microsatellite instability(MSI)were detected in the observation group,including 1 case of low-frequency MSI(MSI-L),4 cases of high-frequency MSI(MSI-H),and 2 cases of MSI-H with MSH6 deletion.When the loss expression of MSI-H or MMR protein was counted as a positive result,the MSI-H rate detected by PCR capillary electrophoresis was 10％(4/40),which was slightly higher than the MMR protein deletion rate detected by immunohistochemistry(7.5％,3/40),but there was no statistically significant difference between the two groups(P＞0.05).The MMR protein deletion rates among the Ig heavy chain protein expression mode Ⅰ,mode Ⅱ,and mode Ⅲ groups were 0(0/26),18.2％(2/11),and 33.3％(1/3),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).The MMR protein deletion rates among the MSS,MSI-L,and MSI-H groups were 2.9％(1/35),0(0/1),and 50％(2/4),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).MMR protein deficiency was positively correlated with Ig heavy chain expression pattern and MSI(r=0.41,P＜0.05;r=0.48,P＜0.05),but Ig heavy chain expression pattern was not correlated with MSI(r=0.02,P＞0.05).Conclusion:Ig heavy chain CSR detection is helpful for the differential diagnosis of MALT lymphoma.Low frequency MMR protein deletion and MSI-H phenotype exist in MALT lymphoma,which may be of certain value for the study of its occurrence,development and clinical treatment.

Objective:To investigate the treatment and prognosis of esophageal cancer patients with pulmonary resection history.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 58 esophageal cancer patients with pulmonary resection history who were admitted to Chest Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Jiangxi Provincial People's Hospital from May 2019 to April 2024 were collected. There were 52 males and 6 females, aged (69±3)years. Observation indicators: (1) surgical and postopera-tive conditions; (2) postoperative pathological examination results; (3) follow-up; (4) stratified analysis. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parametric rank sum test. The Kaplan-Meier method was used to plot survival curve and calculate survival rate, and the Log-rank test was used for survival analysis. Results:(1) Surgical and postoperative conditions. Of the 58 esophageal cancer patients, 49 patients underwent transthoracic approach (26 cases of ipsilateral approach and 23 cases of contralateral approach of pulmonary resection history), and 9 patients underwent mediastinoscopic-laparoscopic approach. There were 57 cases with R 0 resection and 1 case with R 2 resection because of tumor invading carina. The total operation time of 58 patients was (246±27)minutes, and the volume of intraoperative blood loss was (114±29)mL. There was no unplanned reoperation or perioperative death for all patients. The duration of postoperative hospital stay of 58 patients was (10.4±4.6)days, and time for intensive care unit stay was (1.4±0.5)days, and no patient readmitted to intensive care unit due to changes in conditions. The postoperative total incidence of complications of 58 patients was 41.4%(24/58). The Clavien-Dindo grading of complications for all patients was 1-2 grade. (2) Postoperative pathological examination results. Results of postoperative pathological examination showed there were 51 cases of squamous cell carcinoma, 6 cases of adenocarcinoma, and 1 case of melanoma. Number of lymph node dissected of 58 patients was 27±6. The ratio of patient with positive lymph node was 37.9%(22/58). One patient may experience more than 1 region of positive lymph node metastasis. Results of postoperative pathological staging showed 5 cases of ⅠA stage, 2 cases of ⅠB stage, 13 cases of ⅡA stage, 15 cases of ⅡB stage, 4 cases of ⅢA stage, 16 cases of ⅢB stage, and 3 cases of ⅣA stage. Thirteen of the 58 patients underwent neoadjuvant therapy, with the pathological staging as 6 cases of Ⅰ stage, 4 cases of Ⅱ stage, 3 cases of ⅢB stage after therapy. Results of postoperative tumor regression grade for the 13 patients with neoadjuvant therapy showed 4 cases of grad 0, 3 cases of grade 1, 6 cases of grade 2. (3) Follow-up. All 58 patients were followed for 24 (4, 50)months, and no patient died within 90 days after surgery. During the follow-up period, 19 patients experienced tumor recurrence and metastasis and 17 patients died. Twenty-one patients underwent postoperative adjuvant therapy, including 7 cases with chemoradiotherapy, 7 cases with chemotherapy, 3 cases with chemotherapy and immunotherapy, 2 cases with immuno-therapy, 2 cases with radiotherapy. The postoperative 1-, 2-year overall survival rates of the 58 patients were 91.3%, 78.7%, respectively, of whom undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery with postoperative 1-, 2-year overall survival rates as 89.2%, 83.1% and 85.7%, 53.6%, respectively. The postoperative 1-, 2-year esophageal cancer specific survival rates for patients undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery were 94.4%, 87.9% and 85.7%, 71.4%, respectively. There was no significant difference in postoperative 1-, 2-year overall survival rates and postoperative 1-, 2-year esophageal cancer specific survival rates between patients undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery ( P>0.05). (4) Stratified analysis. Of the 49 patients underwent transthoracic approach for esophageal cancer, there were significant differences in surgical method, surgical type, time of chest surgery, cases with upper mediastinal lymph node dissection, and duration of postoperative hospital stay between patients with pulmonary resection history as ipsilateral approach and contralateral approach ( χ2=11.74, 11.68, t=-2.25, χ2=8.45, t=-2.17, P<0.05), and there was no significant difference in total operation time, volume of intraoperative blood loss, the number of lymph node dissected, post-operative total complications, and postoperative pathological TNM staging ( P>0.05). For patients with pulmonary resection history as ipsilateral approach and contralateral approach, the postopera-tive 1-, 2-year esophageal cancer specific survival rates were 95.5%, 95.5% and 81.4%, 71.1%, showing a significant difference between them ( χ2=5.63, P<0.05). Conclusions:The transthoracic approach and mediastinoscopic-laparoscopic approach are safe and feasible for esophageal cancer patients with pulmonary resection history. Compared with patients with pulmonary resection history as contralateral approach, patients with pulmonary resection history as ipsilateral approach have a higher ratio of McKeown surgery, minimally invasive surgery and upper mediastinal lymph node dissection, shorter time of chest surgery and duration of postoperative hospital stay, better esophageal cancer specific survival rate. And there is no increase in perioperative risk.

Aim To explore the effects of Kui Jie Kang(KJK)on modulating the farnesoid X receptor(FXR)pathway in the gut microbiota and bile acid metabolism in mice with ulcerative colitis(UC).Methods Mice were subjected to DSS-induced UC and randomly as-signed to the control(CON),model(MOD),and two KJK-dosed groups(KJK.H at 12.8 g·kg-1,KJK.L at 3.2 g·kg-1).Mouse body weight was recorded,and disease activity index(DAI)was scored.The his-topathological changes in colonic tissue were observed via HE staining,and the number of goblet cells and mucosal layer repair were assessed using PAS and Al-cian blue staining.Bile acid content in feces was measured using LC-MS/MS,gut microbiota composition was analyzed by 16S rRNA gene sequencing,and the expression of FXR target genes and related proteins was detected by RT-qPCR and Western blot.Results KJK significantly ameliorated colonic shortening,de-creased disease activity index in UC mice,reduced his-topathological scores,increased the number of goblet cells and mucus secretion,altered the levels of primary and secondary bile acids,and increased the relative a-bundance of beneficial bacteria such as Lactobacillus.Additionally,it significantly upregulated the expression of FXR and FGF15 mRNA and protein in colonic tissue and downregulated the expression of hepatic CYP7A1 mRNA,and the correlation analysis in this study clearly revealed a significant correlation between bile acid me-tabolism disorders and gut microbiota imbalance in UC.Conclusion KJK activates the intestinal FXR-FGF15-CYP7A1 pathway,thereby regulating bile acid metabolism and restoring gut microbiota balance,which may be key to its improvement of UC.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Objective:To investigate the effect of curcumin on blood glucose levels in pregnant women at high risk of Gestational Diabetes Mellitus(GDM).Methods:One hundred and twenty-four pregnant women with high-risk factors for GDM were included in a cross-sectional study according to the inclusion and exclusion criteria.After undergoing an Oral Glucose Tolerance Test,participants were divided into the GDM group(n=61)and the non-GDM group(n=63).Subsequently,a randomized controlled trial was performed to compare Fasting Plasma Glucose(FPG)levels between the control group(n=8)and the intervention group(n=8).Results:The cross-sectional study revealed that the GDM group had significantly higher rates of pre-pregnancy BMI ≥ 24 kg/m2,early pregnancy HbA1c≥5.7％,impaired fasting glucose or glucose tolerance,and lack of exercise compared to the non-GDM group(P＜0.05).FPG levels in the GDM group were significantly higher than those in the non-GDM group at all stages of pregnancy.Multivariable linear regression analysis showed that the impact of high-risk factors on FPG gradually diminished as pregnancy progressed.In the randomized controlled experiment,all cases in the control group developed GDM;one case in the curcumin intervention group did not,whose intervention time was the earliest and longest.Pearson correlation analysis indicated a positive correlation between the duration of curcumin intervention and changes in FPG values,although the correlation was not statistically significant(P＞0.05).By the descriptive statistical analysis,within-group comparisons showed no significant differences in the median and percentiles of FPG values between the control group in late pregnancy and early pregnancy.However,the median and percentiles of FPG values were significantly lower post-intervention compared to curcumin pre-intervention.Between-group comparisons revealed that the mean FPG in the curcumin intervention group decreased significantly more than in the control group.These results suggested that curcumin might have a potential impact on FPG.No significant differences were observed in neonatal outcomes between the curcumin intervention and control groups.Conclusions:Pregnant women with high risk factors for GDM should be paid enough attention in clinical practice.All these results have demonstrated that curcumin has a positive regulatory effect on FPG in patients with GDM,which may provide a new adjunctive method for the treatment of GDM.

Objective:To investigate the treatment and prognosis of esophageal cancer patients with pulmonary resection history.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 58 esophageal cancer patients with pulmonary resection history who were admitted to Chest Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Jiangxi Provincial People's Hospital from May 2019 to April 2024 were collected. There were 52 males and 6 females, aged (69±3)years. Observation indicators: (1) surgical and postopera-tive conditions; (2) postoperative pathological examination results; (3) follow-up; (4) stratified analysis. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parametric rank sum test. The Kaplan-Meier method was used to plot survival curve and calculate survival rate, and the Log-rank test was used for survival analysis. Results:(1) Surgical and postoperative conditions. Of the 58 esophageal cancer patients, 49 patients underwent transthoracic approach (26 cases of ipsilateral approach and 23 cases of contralateral approach of pulmonary resection history), and 9 patients underwent mediastinoscopic-laparoscopic approach. There were 57 cases with R 0 resection and 1 case with R 2 resection because of tumor invading carina. The total operation time of 58 patients was (246±27)minutes, and the volume of intraoperative blood loss was (114±29)mL. There was no unplanned reoperation or perioperative death for all patients. The duration of postoperative hospital stay of 58 patients was (10.4±4.6)days, and time for intensive care unit stay was (1.4±0.5)days, and no patient readmitted to intensive care unit due to changes in conditions. The postoperative total incidence of complications of 58 patients was 41.4%(24/58). The Clavien-Dindo grading of complications for all patients was 1-2 grade. (2) Postoperative pathological examination results. Results of postoperative pathological examination showed there were 51 cases of squamous cell carcinoma, 6 cases of adenocarcinoma, and 1 case of melanoma. Number of lymph node dissected of 58 patients was 27±6. The ratio of patient with positive lymph node was 37.9%(22/58). One patient may experience more than 1 region of positive lymph node metastasis. Results of postoperative pathological staging showed 5 cases of ⅠA stage, 2 cases of ⅠB stage, 13 cases of ⅡA stage, 15 cases of ⅡB stage, 4 cases of ⅢA stage, 16 cases of ⅢB stage, and 3 cases of ⅣA stage. Thirteen of the 58 patients underwent neoadjuvant therapy, with the pathological staging as 6 cases of Ⅰ stage, 4 cases of Ⅱ stage, 3 cases of ⅢB stage after therapy. Results of postoperative tumor regression grade for the 13 patients with neoadjuvant therapy showed 4 cases of grad 0, 3 cases of grade 1, 6 cases of grade 2. (3) Follow-up. All 58 patients were followed for 24 (4, 50)months, and no patient died within 90 days after surgery. During the follow-up period, 19 patients experienced tumor recurrence and metastasis and 17 patients died. Twenty-one patients underwent postoperative adjuvant therapy, including 7 cases with chemoradiotherapy, 7 cases with chemotherapy, 3 cases with chemotherapy and immunotherapy, 2 cases with immuno-therapy, 2 cases with radiotherapy. The postoperative 1-, 2-year overall survival rates of the 58 patients were 91.3%, 78.7%, respectively, of whom undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery with postoperative 1-, 2-year overall survival rates as 89.2%, 83.1% and 85.7%, 53.6%, respectively. The postoperative 1-, 2-year esophageal cancer specific survival rates for patients undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery were 94.4%, 87.9% and 85.7%, 71.4%, respectively. There was no significant difference in postoperative 1-, 2-year overall survival rates and postoperative 1-, 2-year esophageal cancer specific survival rates between patients undergoing McKeown surgery and mediastinoscopic-laparoscopic surgery ( P>0.05). (4) Stratified analysis. Of the 49 patients underwent transthoracic approach for esophageal cancer, there were significant differences in surgical method, surgical type, time of chest surgery, cases with upper mediastinal lymph node dissection, and duration of postoperative hospital stay between patients with pulmonary resection history as ipsilateral approach and contralateral approach ( χ2=11.74, 11.68, t=-2.25, χ2=8.45, t=-2.17, P<0.05), and there was no significant difference in total operation time, volume of intraoperative blood loss, the number of lymph node dissected, post-operative total complications, and postoperative pathological TNM staging ( P>0.05). For patients with pulmonary resection history as ipsilateral approach and contralateral approach, the postopera-tive 1-, 2-year esophageal cancer specific survival rates were 95.5%, 95.5% and 81.4%, 71.1%, showing a significant difference between them ( χ2=5.63, P<0.05). Conclusions:The transthoracic approach and mediastinoscopic-laparoscopic approach are safe and feasible for esophageal cancer patients with pulmonary resection history. Compared with patients with pulmonary resection history as contralateral approach, patients with pulmonary resection history as ipsilateral approach have a higher ratio of McKeown surgery, minimally invasive surgery and upper mediastinal lymph node dissection, shorter time of chest surgery and duration of postoperative hospital stay, better esophageal cancer specific survival rate. And there is no increase in perioperative risk.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.

As the first defense of respiratory system,airway epi-thelial cells(AECs)play an important role in separating the re-spiratory internal and external environment.They are essential for the natural immune function.Small airway lesions are an im-portant early pathology of chronic obstructive pulmonary disease(COPD),when AECs are exposed to harmful particles or gases for a long time,the epithelial barrier is damaged,and the signa-ling pathways which involved in differentiation,repair,and in-flammatory are disordered,resulting in epithelial cell cycle stag-nation and accelerated aging.A number of studies have sugges-ted that AECs of COPD patients express high levels of aging markers,suggesting that senescence of AECs is closely related to COPD.This review discusses the potential mechanisms of AECs senescence in COPD,the impact of AECs senescence on the de-velopment and severity of the disease,and highlights potential targets for modulating cellular senescence in airway epithelium as a therapeutic approach in COPD.