OBJECTIVE To investigate the mechanism of Qushi huoxue decoction in improving metabolic-associated fatty liver disease （MAFLD） based on the AMP-activated protein kinase/mammalian target of rapamycin/UNC-51-like kinase 1 （AMPK/mTOR/ULK1） autophagy signaling pathway.METHODS Male C57BL/6J mice were randomly divided into normal group， model group， and low-， medium-， and high-dose Qushi huoxue decoction groups [4.10， 8.20， 16.40 mg/（g·d）]， with 10 mice in each group. Except for the normal group， mice in the other groups were fed a high-fat diet for 12 weeks to establish the MAFLD model. Starting 24 hours after modeling， mice in each group were administered the drug solution or normal saline once daily for 6 consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， alanine transaminase （ALT）， aspartate transferase （AST）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected according to the kit instructions. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe pathological changes in mouse liver tissue. Western blot and immunofluorescence staining were used to detect the expression and positive protein expression related to the AMPK/mTOR/ULK1 autophagy signaling pathway.RESULTS Compared with the normal group， the serum levels of TC， TG， ALT， AST， and LDL-C in the model group were significantly increased， while the HDL-C level was significantly decreased （ P ＜0.01）. HE staining showed obvious steatosis in hepatocytes of the model group， and oil red O staining showed a large amount of lipid droplet accumulation in liver tissue. Western blot and immunofluorescence staining results showed that the expression levels of p-mTOR/mTOR and p62 proteins， as well as the relative fluorescence intensities of p-mTOR and p62 proteins in liver tissue of the model group， were significantly increased/enhanced （ P ＜0.01）， while the expression levels of p-AMPK/AMPK， ULK1， and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） proteins， as well as the relative fluorescence intensities of p-AMPK and LC3 proteins， were significantly decreased/weakened （ P ＜0.01）. After intervention with Qushi huoxue decoction， the above pathological changes and abnormal indicators in liver tissue of mice in the low-， medium-， and high-dose groups were significantly reversed， with most indicators showing statistically significant differences （ P ＜0.05 or P ＜0.01）.CONCLUSIONS Qushi huoxue decoction can significantly improve liver pathology， blood lipid levels， and liver function in MAFLD model mice； this improvement may be achieved through the activation of the AMPK/mTOR/ULK1 autophagy signaling pathway.

Objective To investigate the effects of Huayu Xiaopi Decoction on the proliferation and migration of AGS cells;To explore its mechanism in treating precancerous lesions of gastric cancer.Methods AGS cells were divided into blank group,inhibitor group and Huayu Xiaopi Decoction high-,medium-and low-dosage groups.The blank group was cultured with 15%control serum,the inhibitor group was cultured with 10 μmol/L HIF-1α inhibitor,and the Huayu Xiaopi Decoction high-,medium-and low-dosage groups were cultured with 12%,6%and 3%drug containing serum,respectively.CCK-8 method was used to detect cell survival rate,cell migration ability was detected by scratch test,immunofluorescence was used to detect the expressions of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase(MMP)-2 and MMP-9 in AGS cells,the expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 mRNA and HIF-1α,COX-2,VEGF,VEGFR2 proteins in AGS cells were detected by RT-PCR and Western blot.Results Compared with the blank group,the cell survival rate and migration rate were significantly decreased in the inhibitor group and each dosage of Huayu Xiaopi Decoction groups(P<0.05),the expressions of PCNA,MMP-2 and MMP-9 significantly decreased in the inhibitor group and Huayu Xiaopi Decoction high-and medium-dosage groups(P<0.05),the mRNA expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 and the protein expression of HIF-1α,COX-2,VEGF,VEGFR2 were significantly decreased(P<0.05).Conclusion Huayu Xiaopi Decoction can inhibit the proliferation and migration of AGS cells,and its mechanism is related to the regulation of the expression of key molecules in HIF-1α/VEGF signaling pathway.

Objective To investigate the effects of Huayu Xiaopi Decoction on the proliferation and migration of AGS cells;To explore its mechanism in treating precancerous lesions of gastric cancer.Methods AGS cells were divided into blank group,inhibitor group and Huayu Xiaopi Decoction high-,medium-and low-dosage groups.The blank group was cultured with 15%control serum,the inhibitor group was cultured with 10 μmol/L HIF-1α inhibitor,and the Huayu Xiaopi Decoction high-,medium-and low-dosage groups were cultured with 12%,6%and 3%drug containing serum,respectively.CCK-8 method was used to detect cell survival rate,cell migration ability was detected by scratch test,immunofluorescence was used to detect the expressions of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase(MMP)-2 and MMP-9 in AGS cells,the expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 mRNA and HIF-1α,COX-2,VEGF,VEGFR2 proteins in AGS cells were detected by RT-PCR and Western blot.Results Compared with the blank group,the cell survival rate and migration rate were significantly decreased in the inhibitor group and each dosage of Huayu Xiaopi Decoction groups(P<0.05),the expressions of PCNA,MMP-2 and MMP-9 significantly decreased in the inhibitor group and Huayu Xiaopi Decoction high-and medium-dosage groups(P<0.05),the mRNA expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 and the protein expression of HIF-1α,COX-2,VEGF,VEGFR2 were significantly decreased(P<0.05).Conclusion Huayu Xiaopi Decoction can inhibit the proliferation and migration of AGS cells,and its mechanism is related to the regulation of the expression of key molecules in HIF-1α/VEGF signaling pathway.

Objective:To construct a prediction model for postoperative poor in-hospital prognosis in patients with traumatic brain injury (TBI) and evaluate its predictive performance.Methods:A retrospective case control study was conducted to analyze the clinical data of 1 120 TBI patients admitted to Changde Hospital Affiliated to Xiangya Medical College of Central South University from May 2019 to December 2024. The patients were divided into the training set ( n=784) and verification set ( n=336) at a ratio of 7∶3. Based on the Glasgow outcome scale-extended (GOS-E) at discharge, the training set was stratified into favorable prognosis group ( n=335, GOS-E 5-8 points) and poor prognosis group ( n=449, GOS-E 1-4 points). The two groups in the training set were compared in terms of general baseline indicators, TBI-related clinical indicators, and admission laboratory blood test results. Univariate analysis and Lasso regression analysis were employed to screen risk factors associated with postoperative poor in-hospital prognosis in TBI patients. Multivariate Logistic regression analysis was used to determine independent risk factors and construct a regression equation. The regression equation was presented using R language to create a visual nomogram for predicting postoperative poor in-hospital prognosis in TBI patients. In both the training set and verification set, the predictive performance of the model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC), plotting calibration curves, and performing decision curve analysis (DCA). Results:The results of the univariate analysis indicated that the age, Charlson complication index (CCI), time from trauma to admission, time from trauma to operation, cause of injury, abbreviated injury scale (AIS) (head and neck), injury severity score (ISS), admission Glasgow coma scale (GCS), admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, decompressive craniotomy, intraoperative blood loss, intraoperative blood transfusion, traumatic cerebral infarction, postoperative delayed bleeding, epilepsy seizures, as well as the following admission tested results including red blood cell count, white blood cell count, platelet count, neutrophil percentage, percentage of lymphocytes, albumin, total bilirubin, urea nitrogen, thrombin time (TT), prothrombin time (PT), international standardized ratio (INR), glutamic aminotransferase, alanine aminotransferase, creatinine, and blood glucose were statistically different between the two groups in the training set ( P<0.05). Lasso regression analysis suggested 14 risk factors of age, CCI, cause of injury, head and neck AIS, ISS, admission GCS, admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraoperative blood loss, admission platelet count, admission albumin, admission blood glucose for postoperative poor in-hospital prognosis. The results of the multivariate Logistic regression analysis showed that age ( OR=1.02, 95% CI 1.00, 1.03, P<0.01), CCI ( OR=1.46, 95% CI 1.02, 2.09, P<0.05), head and neck AIS ( OR=1.43, 95% CI 1.11, 1.85, P<0.01), ISS ( OR=2.16, 95% CI 1.39, 3.35, P<0.01), admission GCS ( OR=1.59, 95% CI 1.19, 2.13, P<0.01), intracerebral hematoma ( OR=4.41, 95% CI 2.15, 9.44, P<0.01), intraoperative blood loss ( OR=1.05, 95% CI 1.00, 1.09, P<0.05), admission platelet count ( OR=0.98, 95% CI 0.97, 0.99, P<0.01), admission blood glucose ( OR=1.08, 95% CI 1.02, 1.15, P<0.05) could be the main risk factors to construct a prediction model for postoperative poor in-hospital prognosis in TBI patients. Meanwhile, a regression equation was constructed: Logit[ P/(1- P)]=-2.4+ 0.02×"age"+0.38×"CCI"+0.36×"head and neck AIS"+0.77×"ISS"+0.47×"admission GCS"+1.48×"intracerebral hematoma"+0.05×intraoperative blood loss-0.02×admission platelet count+0.08×admission blood glucose. In the training set, the predictive model for poor postoperative in-hospital prognosis in TBI patients achieved an AUC of 0.87 (95% CI 0.84, 0.89), with a Youden′s index of 0.57, sensitivity of 73.70%, and specificity of 83.00%. In the verification set, the model showed an AUC of 0.80 (95% CI 0.76, 0.85), with a Youden′s index of 0.63, sensitivity of 65.20%, and specificity of 77.90%. In the training set, the Brier score for the calibration curve was 0.14 (95% CI 0.13, 0.16). In the verification set, the Brier score for the calibration curve was 0.18 (95% CI 0.15, 0.20). The DCA diagram indicated that the nomogram prediction model provided high clinical net benefit for predicting postoperative poor in-hospital prognosis in TBI patients. Conclusion:The prediction model for postoperative poor in-hospital prognosis in TBI patients, constructed based on age, CCI, head and neck AIS, ISS, admission GCS, intracerebral hematoma, intraoperative blood loss, admission platelet count, and admission blood glucose, exhibits good predictive performance.

Objective:To construct a prediction model for postoperative poor in-hospital prognosis in patients with traumatic brain injury (TBI) and evaluate its predictive performance.Methods:A retrospective case control study was conducted to analyze the clinical data of 1 120 TBI patients admitted to Changde Hospital Affiliated to Xiangya Medical College of Central South University from May 2019 to December 2024. The patients were divided into the training set ( n=784) and verification set ( n=336) at a ratio of 7∶3. Based on the Glasgow outcome scale-extended (GOS-E) at discharge, the training set was stratified into favorable prognosis group ( n=335, GOS-E 5-8 points) and poor prognosis group ( n=449, GOS-E 1-4 points). The two groups in the training set were compared in terms of general baseline indicators, TBI-related clinical indicators, and admission laboratory blood test results. Univariate analysis and Lasso regression analysis were employed to screen risk factors associated with postoperative poor in-hospital prognosis in TBI patients. Multivariate Logistic regression analysis was used to determine independent risk factors and construct a regression equation. The regression equation was presented using R language to create a visual nomogram for predicting postoperative poor in-hospital prognosis in TBI patients. In both the training set and verification set, the predictive performance of the model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC), plotting calibration curves, and performing decision curve analysis (DCA). Results:The results of the univariate analysis indicated that the age, Charlson complication index (CCI), time from trauma to admission, time from trauma to operation, cause of injury, abbreviated injury scale (AIS) (head and neck), injury severity score (ISS), admission Glasgow coma scale (GCS), admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, decompressive craniotomy, intraoperative blood loss, intraoperative blood transfusion, traumatic cerebral infarction, postoperative delayed bleeding, epilepsy seizures, as well as the following admission tested results including red blood cell count, white blood cell count, platelet count, neutrophil percentage, percentage of lymphocytes, albumin, total bilirubin, urea nitrogen, thrombin time (TT), prothrombin time (PT), international standardized ratio (INR), glutamic aminotransferase, alanine aminotransferase, creatinine, and blood glucose were statistically different between the two groups in the training set ( P<0.05). Lasso regression analysis suggested 14 risk factors of age, CCI, cause of injury, head and neck AIS, ISS, admission GCS, admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraoperative blood loss, admission platelet count, admission albumin, admission blood glucose for postoperative poor in-hospital prognosis. The results of the multivariate Logistic regression analysis showed that age ( OR=1.02, 95% CI 1.00, 1.03, P<0.01), CCI ( OR=1.46, 95% CI 1.02, 2.09, P<0.05), head and neck AIS ( OR=1.43, 95% CI 1.11, 1.85, P<0.01), ISS ( OR=2.16, 95% CI 1.39, 3.35, P<0.01), admission GCS ( OR=1.59, 95% CI 1.19, 2.13, P<0.01), intracerebral hematoma ( OR=4.41, 95% CI 2.15, 9.44, P<0.01), intraoperative blood loss ( OR=1.05, 95% CI 1.00, 1.09, P<0.05), admission platelet count ( OR=0.98, 95% CI 0.97, 0.99, P<0.01), admission blood glucose ( OR=1.08, 95% CI 1.02, 1.15, P<0.05) could be the main risk factors to construct a prediction model for postoperative poor in-hospital prognosis in TBI patients. Meanwhile, a regression equation was constructed: Logit[ P/(1- P)]=-2.4+ 0.02×"age"+0.38×"CCI"+0.36×"head and neck AIS"+0.77×"ISS"+0.47×"admission GCS"+1.48×"intracerebral hematoma"+0.05×intraoperative blood loss-0.02×admission platelet count+0.08×admission blood glucose. In the training set, the predictive model for poor postoperative in-hospital prognosis in TBI patients achieved an AUC of 0.87 (95% CI 0.84, 0.89), with a Youden′s index of 0.57, sensitivity of 73.70%, and specificity of 83.00%. In the verification set, the model showed an AUC of 0.80 (95% CI 0.76, 0.85), with a Youden′s index of 0.63, sensitivity of 65.20%, and specificity of 77.90%. In the training set, the Brier score for the calibration curve was 0.14 (95% CI 0.13, 0.16). In the verification set, the Brier score for the calibration curve was 0.18 (95% CI 0.15, 0.20). The DCA diagram indicated that the nomogram prediction model provided high clinical net benefit for predicting postoperative poor in-hospital prognosis in TBI patients. Conclusion:The prediction model for postoperative poor in-hospital prognosis in TBI patients, constructed based on age, CCI, head and neck AIS, ISS, admission GCS, intracerebral hematoma, intraoperative blood loss, admission platelet count, and admission blood glucose, exhibits good predictive performance.

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

The various mechanisms of kyphosis of the spine and the differential diagnosis of related diseases to guide the selection of appropriate surgical timing, correct spinal osteotomy and reasonable surgical methods. The 24 patients with kyphosis from January 2016 to January 2018 were diagnosed. All patients underwent kyphosis orthopedics, mainly spinal wedge osteotomy, to obtain orbital purpose by wedge osteotomy. The indexes of the spine form, activity, and pain were observed after operation. Of the 24 patients with kyphosis, 5 patients were treated conservatively, and the symptoms of kyphosis were effectively relieved. 19 patients underwent kyphosis orthopedic surgery, and the anterior spine and posterior closed osteotomy. The patients recovered well after surgery and were followed up regularly. The treatment of high anterior spine and posterior closed osteotomy in patients with kyphosis has accurate surgery effect. There are no complications such as pain and internal fixation during the regular follow-up.

Objective To observe the clinical effect of alprostadil combined with Yiqi Huoxue Huatan Tongluo Decoction in treating arteriosclerosis obliterans.Methods 60 cases of lower extremity arteriosclerosis occlusion disease outpatient and hospitalized patients were randomly divided into treatment group and control group according to the random number table method, each group were 30, the oral administration of enteric coated aspirin experimental group is set to control group intravenous injection of alprostadil treatment for 4 weeks, the treatment group was treated with Huatan Tongluo Decoction on the basis of the control group.The clinical symptoms, blood vessel function (ABI),low density lipoprotein-cholesterol (LDL-C), total cholesterol( TC) were observed in the two groups of patients, and blood rheology indexes included whole blood viscosity, fibrinogen, liver and kidney function and adverse reactions.ResuIts Total effective rate of the treatment group was 93.33% than control group 73.33% (P<0.05), the treatment group of ankle brachial index ( ABI) was better than the control group, the treatment group TC, LDL-C, high shear whole blood viscosity, low shear whole blood viscosity, fibrinogen protein improve were better than those of the control group (P<0.05).ConcIusion Disease curative effect is better than pure alprostadil in the treatment of occlusion Huoxue Huatan Tongluo Decoction combined with alprostadil in the treatment of lower limb arteriosclerosis.

Objective To investigate the clinicopathological factors related with the lymph node ratio (LNR) in colorectal cancer patients.Methods The clinical and pathological data of 177 colorectal cancer patients who were treated by surgery in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from January 2011 to December 2013 were collected.The association between LNR and clinicopathological factors were evaluated by single factor analysis nsingx x2 test.Results Gender,age,tumor location,tumor size,gross type,depth of infiltration,infiltration extent around bowel wall and preoperative serum CA199 concentration were not related with LNR (P ＞0.05),but tumor histological type,tumor differentiation,preoperative serum CEA,CA125 concentration were related with LNR (P =0.001,0.004,0.004,0.025).Conclusions Tumor histological type,tumor differentiation,preoperative serum CEA,CA125 may be the important factors related with LNR in colorectal cancer.

Objective To detect the expression level of miRNA-575 by pancreatic cancer stem cells.Methods Pancreatic cancer cell lines were cultured with serum-free medium.The cancer stem cells were obtained and their characteristics were observed with an invasion assay,a xenograft experiment,and flow cytometry analysis.Moreover,qRT-PCR was used to detect the expression of miR-575.Results A small subpopulation of cells in both ASPC-1 and PANC-1 cells survived and formed spheres in the absence of serum.The mean number of migrated cells of PANC-1 and ASPC-1 spheres was (147.3±18.6) cells and (113.2±12.9) cells.Therefore,the spheres have higher invasive ability compared with those of parental cells.As few as 5 × 105 cells in PANC-1 and ASPC-1 spheres could initiate a xenograft tumor in NOD/SCID mice,which suggested the tumorigenicity of the spheres was 100 times those of parental cell lines.The percentages of CD24+CD44+ in spheres were 0.38％-0.43％ and 4.91％-5.21％,which showed increased expression compared with ASPC-1 and PANC-1 cell lines (P＜0.05).The expression of miR-575 in spheres was 3.71 and 3.83 times its expression in cell lines ASPC-1 and PANC-1 respectively (P＜0.05).Conclusions Pancreatic cancer cell spheres may be a source for collecting cancer stem cells in a serum-free medium culture,and MiR 575 may play an important role in regulating the biological characteristics of pancreatic cancer stem cells.