1.Chaihu and Longgu Mulitang Regulates ERK/CREB Signaling Pathway to Ameliorate Hippocampal Nerve Injury in Mouse Model of Depression
Shiyu JI ; Li WANG ; Zhuo ZHANG ; Yingzhe GAO ; Zefeng ZHANG ; Siyu CHEN ; Guangjing XIE ; Ping WANG ; Panpan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):1-9
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.
2.Closed reduction with a self-developed T-frame plus robotic navigation to treat supracondylar humeral fractures of Gartland type Ⅲ in children
Chi TANG ; Zhe BAI ; Ninan QI ; Sitong YUE ; Ye LI ; Zefeng GAO ; Chenglin NIU ; Zhongli ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(11):985-990
Objective:To study the efficacy of closed reduction with a self-developed T-frame plus robotic navigation in the treatment of supracondylar humeral fractures of Gartland type Ⅲ in children.Methods:A retrospective study was conducted to analyze the data of 67 children with supracondylar fracture of Gartland type Ⅲ who had undergone surgery at The Fifth Hospital of Harbin from January 2023 to March 2024. There were 35 males and 32 females with an age of (5.6±1.2) years. The children were divided into 2 groups according to different surgical methods. The control group (33 cases) was treated by closed reduction and internal fixation with percutaneous K-wire and the study group (34 cases) by closed reduction with a self-developed T-frame plus robotic navigation for internal fixation with percutaneous K-wire. The operation time, anatomical reduction, intraoperative fluoroscopy frequency, intraoperative needle adjustment, Flynn score at the last follow-up and complications were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All children were followed up for (6.3±2.5) months after surgery. There were no significant differences in operation time, Flynn score at the last follow-up or incidence of complications between the study and the control groups ( P>0.05). The rate of anatomical reduction in the study group (97.1%, 33/34) was significantly higher than that in the control group (54.5%, 18/33), and the intraoperative fluoroscopy frequency [(11.6±2.5) times] and needle adjustment (5.6±1.2) times in the study group were significantly lower than those in the control group [(37.2±2.1) times and (28.7±3.9) times] ( P<0.05). Conclusions:In the treatment of supracondylar humeral fractures of Gartland type Ⅲ in children, our self-developed T-frame can play a good role in fracture reduction and temporary fixation, avoiding iatrogenic secondary injuries caused by freguent reduction and adjustment of needle threading in the course of robotic navigation.
3.Efficacy and safety analysis of venetoclax combined with hypomethylating agents for the treatment of higher-risk myelodysplastic syndromes in the real world
Qingyan GAO ; Bing LI ; Shiqiang QU ; Lijuan PAN ; Meng JIAO ; Jinying ZHAO ; Zefeng XU ; Zhijian XIAO ; Tiejun QIN
Chinese Journal of Hematology 2024;45(2):156-162
Objective:To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) .Methods:From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis.Results:①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five na?ve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions:There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.
4.Clinical characteristics and prognosis of patients with myelodysplastic syndrome with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50%
Yanping ZENG ; Bing LI ; Tiejun QIN ; Zefeng XU ; Shiqian QU ; Lijuan PAN ; Qingyan GAO ; Meng JIAO ; Junying WU ; Huijun WANG ; Chengwen LI ; Yujiao JA ; Qi SUN ; Zhijian XIAO
Chinese Journal of Hematology 2024;45(7):651-659
Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.
5.Risk factors for leukemia transformation in patients with myelodysplastic syndromes
Songyang ZHAO ; Zefeng XU ; Tiejun QIN ; Shiqiang QU ; Chengwen LI ; Yujiao JIA ; Lijuan PAN ; Bing LI ; Qingyan GAO ; Meng JIAO ; Huijun HUANG ; Zhijian XIAO
Chinese Journal of Hematology 2022;43(10):818-825
Objective:To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) .Methods:From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done.Results:The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age ( P<0.001) , bone marrow blast percentage ( P<0.001) , bone marrow fibrosis ( P=0.046) , WHO classification ( P<0.001) , IPSS-R ( P<0.001) and IPSS-R karyotype group ( P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference ( P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation ( P=0.034) , DNMT3A mutation ( P=0.026) , NRAS mutation ( P=0.027) and NPM1 mutation ( P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups ( HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation ( HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation ( HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion:Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.
6.Research advances in imaging evaluation of extramural vascular invasion of rectal cancer
Wei GAO ; Aishi LIU ; Zefeng WANG ; Jianjun REN ; Lei ZHAO ; Fen'e HAO
Chinese Journal of Digestive Surgery 2021;20(3):355-358
Extramural vascular invasion of rectal cancer is an important factor affecting the prognosis of patients with rectal cancer. Accurate diagnosis of extramural vascular invasion before surgery can guide the formulation of treatment plans, thereby improving prognosis and long-term survival of patients. Magnectic resonance imaging examination and computed tomography examination are the main examination methods for preoperative evaluation of rectal cancer. The authors review the role of imaging examinations in the evaluation of extramural vascular invasion of rectal cancer.
7.Clinical value of outpatient screening in department of general surgery during the COVID-19 outbreak
Gang LI ; Peng ZHANG ; Zefeng XIA ; Zheng WANG ; Jinbo GAO ; Yueping LONG ; Kailin CAI ; Guobin WANG ; Kaixiong TAO
Chinese Journal of Digestive Surgery 2020;19(4):356-359
Objective:To investigate the clinical value of outpatient screening in department of general surgery during the Corona Virus Disease 2019 (COVID-19) outbreak.Methods:The retrospective and descriptive study was conducted. The clinical data of 57 patients who visited surgery clinic and emergency department of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology between February 1st and 26th in 2020 were collected. There were 30 males and 27 females, aged (53±16)years, with a range from 17 to 87 years. All the 57 patients were measured score of outpatient screening in department of general surgery. The score ≥3 indicated high risk and the score < 3 indicated low risk. Observation indicators: (1) clinical data of patients; (2) score of outpatient screening for COVID-19 of patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were described as M (IQR), and comparison between groups was analyzed by the rank sum test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Clinical data of patients: of the 57 patients, there were 12 males and 14 females of the 26 confirmed or suspected cases, versus 18 males and 13 females of the 31 non-infection cases, showing no significant difference between the two groups ( χ2=0.805, P>0.05). The 26 confirmed or suspected cases of COVID-19 had an age of (57±16)years, and 31 non-infection cases had an age of (50±16) years, with no significant difference between the two groups ( t=-1.646, P>0.05). (2) Score of outpatient screening for COVID-19 of patients: the score of outpatient screening for COVID-19 of the 26 confirmed or suspected cases was 3.0(4.0), versus 1.0(1.0) of the 31 non-infection cases, showing a significant difference between the two groups ( Z=-3.695, P<0.05). There were 17 and 9 of the 26 confirmed or suspected cases with high risks and low risks, respectively, versus 3 and 28 of the 31 non-infection cases, with a significant difference between the two groups ( χ2=19.266, P<0.05). Conclusion:During the COVID-19 outbreak, outpatient screening in department of general surgery can effectively screen out high-risk patients.
8.Effect of hydroxycamptothecin-based transcather arterial chemoembolization combined with hepatectomy for liver cancer
Yubao SONG ; Zefeng GAO ; Zhifeng YAN ; Yushan ZHAO
Chinese Journal of General Surgery 2019;34(2):118-121
Objective To evaluate transcather arterial chemoembolization (TACE) with hydroxycamptothecin combined with hepatectomy in treatment of primary liver cancer.Methods 64 primary liver cancer cases admitted and treated in Shanxi Provincial Cancer Hospital were divided into two groups with 32 cases in each.The control group were treated by surgery only and in the study group patients received TACE and hepatectomy.Results 0.5-year and 1-year recurrence rate in the study group were respectively 9.38% and 28.13%,significantly lower than those in the control group.There was no significant difference in the 2-year recurrence rate between the two groups.0.5-year,1-year and 2-year survival rate in the study group were respectively 93.75%,84.38% and 65.63%,significantly better than those in the control group.The AST and ALT were respectively (86 ±42)U/L,(96 ±55)U/L which were lower than those in the control group.The ALB and TBiL were respectively (32 ± 10) g/L and (24 ± 9) μmol/L,which were not significantly different with the control group.Conlunsion Hydroxycamptothecinbased TACE combined with hepatectomy is better than hepatectomy only for the treatment of primary liver cancer.
9.The expression and significance of S100A8 in Oral Squamous Cell Carcinoma
Zefeng QU ; Hong MA ; Xiaofeng DUAN ; Rui LIU ; Qiong GAO
Journal of Practical Stomatology 2018;34(1):127-128
The expression of calcium binding protein S100A8 in 30 controls of normal oral tissue and 35 cases of OSCC was detected by immunohistochemical staining and Western blot respectively. The positive expression of S100A8 protein in OSCC and the controls was 68. 5% and 36. 7% respectively(P < 0. 05). S100A8 may play a role in the development of OSCC.
10. Comparison of clinical value of total gastrectomy and proximal gastrectomy in the treatment of gastric fundus carcinoma
Hairong XIN ; Yubao SONG ; Longyue WANG ; Zefeng GAO
Chinese Journal of Primary Medicine and Pharmacy 2018;25(9):1130-1133
Objective:
To compare the clinical value of total gastrectomy and proximal gastrectomy in the treatment of gastric fundus carcinoma.
Methods:
80 patients with gastric fundus cancer were divided into observation group and control group according to the random number method.The observation group was treated with total gastrectomy, and the control group was treated by proximal gastrectomy.The operation-related conditions, such as operation time, intraoperative bleeding and postoperative anal exhaust time of the two groups were compared.After surgery R0 resection rate and 2-year survival rate were analyzed.
Results:
The operative time in the observation group was (86.3±1.9)min, which was shorter than (102.3±2.6)min in the control group (

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