Nonalcoholic fatty liver disease(NAFLD)is currently a chronic liver disease with the highest prevalence rate in the world,with complex pathogeneses and limited clinical treatment methods.Over the past 20 years,the discovery of active components for NAFLD treatment from traditional Chinese medicine and compound prescriptions of the components that can exert a multi-target effect has been one of the research hotspots.Based on the chemical components of traditional Chinese medicine,this article elaborates on the active components with a promising future in the treatment of NAFLD,including flavonoids,phenols,terpenoids,alkaloids,and saponins,as well as the compound prescriptions of active components with a synergistic effect,in order to provide new ideas for the strategies of pharmacotherapy for NAFLD.

Objectives:To investigate the survival and tumor recurrence after en bloc spondylectomy of spinal tumor and analyze the risk factors of postoperative tumor recurrence.Methods:This is a retrospective case series study. Data of 101 patients undergoing en bloc spondylectomy of spinal tumors in the Musculoskeletal Tumor Center, Peking University People′s Hospital from December 2006 to June 2022 were analyzed. There were 58 males and 43 females, aged (38.2±15.8) years (range: 10 to 79 years) at the time of surgery; the follow-up time was(44.0±36.0) months (range: 12 to 171 months).Among them, there were 25 relapsed patients, with 7 females and 18 males; aged (34.8±16.3) years (range: 12 to 66 years) at the time of surgery. The types of tumors included 5 giant cell tumors of bone, 6 osteosarcomas, 1 chordoma, 5 chondrosarcomas, 1 undifferentiated sarcoma, 1 fibrosarcoma, 2 Ewing sarcomas, 3 metastases and 1 malignant giant cell tumor of bone. Survival analysis of overall and relapsed patients were performed using the Kaplan-Meier curves. A segmented regression model was used to fit the sequence of recurrence rate changes over time since admission and identify change points for further analysis on risk factors. Univariate and multivariate Logistic regression analysis were performed to assess risk factors associated with recurrence rate; results from multivariate regression analysis were presented using a forest plot.Results:The tumor recurrence rate after en bloc spondylectomy was 24.8% (25/101).The overall median recurrence-free survival after en bloc spondylectomy was 161 months (95% CI: 92 months to NA).The median recurrence-free survival of recurrent patients was 13 months (95% CI: 12 to 27 months).Regarding the classification based on tumor malignancy, and relapse-free survival of metastatic tumors was significantly shorter ( P=0.007); and among the surgical margin groups, relapse-free survival of R0 group was significantly better than the R1 and R2 groups ( P<0.01). According to the segmented regression model, the tumor recurrence rate for en bloc spondylectomy showed a significant downward trend over time, with relatively higher recurrence rates before 2009 and a relatively stable trend after 2014. The results of univariate analysis showed that surgical margin and time of admission were the influencing factors of patient recurrence. The results of multivariate analysis showed that the R1 resection( OR=13.453,95% CI:2.897 to 97.941, P=0.002) and R2 resection( OR=11.379,95% CI:2.658 to 79.429, P=0.003) were independent influencing factor affecting patient recurrence. Conclusions:The overall tumor recurrence rate after en bloc spondylectomy was high. The surgical margin of tumor resection is an independent risk factor affecting tumor recurrence. Specifically, R2 and R1 resections significantly increase the risk of tumor recurrence.

AIM:To explore the therapeutic effect of teprenone(geranylgeranylacetone,GGA)on lipopolysac-charide(LPS)-induced cardiac dysfunction and its mechanism.METHODS:(1)Eight-week-old male C57BL/6 wild-type mice and carboxyl terminus of heat shock protein 70(HSP70)-interacting protein(CHIP)gene knockout mice were randomly divided into control group,LPS group,LPS+GGA group and GGA group,with 8 mice in each group.The model was established by intraperitoneal injection of LPS(25 mg/kg),and 1 h after LPS stimulation,mice were given intraperito-neal injection of GGA(100 mg/kg).The technique of high-resolution ultrasonography system was used to evaluate the car-diac function of mice.The serum of mice from each group were collected to detect the levels of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH).HE staining was performed to observe histological changes of cardiac tissues.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in cardiac tissues.West-ern blot was used to detect the protein levels of HSP70,CHIP,karyopherin-α 2(KPNA2),myeloperoxidase(MPO),vas-cular cell adhesion molecule(VCAM),intercellular cell adhesion molecule(ICAM),and nuclear factor-κB(NF-κB)in cardiac tissues.(2)In vitro cell inflammation model was established using mouse myocardial cells HL-1 stimulated with LPS.ELISA was used to detect the levels of TNF-α and IL-6 in cell supernatants.Western blot was used to detect the pro-tein expression levels of HSP70,CHIP,and KPNA2 in myocardial cells.Immunofluorescence staining was performed to observe the content of nuclear NF-κB.RESULTS:(1)GGA effectively improved cardiac function of LPS-stimulated mice,significantly increased ejection fraction and left ventricular fractional shortening(P<0.01),reduced serum levels of CK-MB and LDH(P<0.01),and alleviated myocardial injury.(2)GGA significantly reduced the release of TNF-α and IL-6 caused by LPS(P<0.01),as well as nuclear translocation of NF-κB,decreased the levels of KPNA2,MPO,VCAM and ICAM in cardiac tissues,and increased the levels of HSP70 in cardiac tissues and cells(P<0.01).(3)In CHIP knockout myocardial cells and mice,GGA failed to inhibit LPS-induced inflammatory response and lost its effect on im-proving cardiac function.CONCLUSION:The protective effect of GGA against LPS-caused cardiac dysfunction of mice is related to increasing expression of HSP70 and promoting CHIP activation,which inhibits the translocation of NF-κB into nucleus and suppresses inflammatory factor release.CHIP knockout abolishes the effects of GGA on reducing LPS-induced inflammatory response and myocardial injury.

Objectives:To investigate the survival and tumor recurrence after en bloc spondylectomy of spinal tumor and analyze the risk factors of postoperative tumor recurrence.Methods:This is a retrospective case series study. Data of 101 patients undergoing en bloc spondylectomy of spinal tumors in the Musculoskeletal Tumor Center, Peking University People′s Hospital from December 2006 to June 2022 were analyzed. There were 58 males and 43 females, aged (38.2±15.8) years (range: 10 to 79 years) at the time of surgery; the follow-up time was(44.0±36.0) months (range: 12 to 171 months).Among them, there were 25 relapsed patients, with 7 females and 18 males; aged (34.8±16.3) years (range: 12 to 66 years) at the time of surgery. The types of tumors included 5 giant cell tumors of bone, 6 osteosarcomas, 1 chordoma, 5 chondrosarcomas, 1 undifferentiated sarcoma, 1 fibrosarcoma, 2 Ewing sarcomas, 3 metastases and 1 malignant giant cell tumor of bone. Survival analysis of overall and relapsed patients were performed using the Kaplan-Meier curves. A segmented regression model was used to fit the sequence of recurrence rate changes over time since admission and identify change points for further analysis on risk factors. Univariate and multivariate Logistic regression analysis were performed to assess risk factors associated with recurrence rate; results from multivariate regression analysis were presented using a forest plot.Results:The tumor recurrence rate after en bloc spondylectomy was 24.8% (25/101).The overall median recurrence-free survival after en bloc spondylectomy was 161 months (95% CI: 92 months to NA).The median recurrence-free survival of recurrent patients was 13 months (95% CI: 12 to 27 months).Regarding the classification based on tumor malignancy, and relapse-free survival of metastatic tumors was significantly shorter ( P=0.007); and among the surgical margin groups, relapse-free survival of R0 group was significantly better than the R1 and R2 groups ( P<0.01). According to the segmented regression model, the tumor recurrence rate for en bloc spondylectomy showed a significant downward trend over time, with relatively higher recurrence rates before 2009 and a relatively stable trend after 2014. The results of univariate analysis showed that surgical margin and time of admission were the influencing factors of patient recurrence. The results of multivariate analysis showed that the R1 resection( OR=13.453,95% CI:2.897 to 97.941, P=0.002) and R2 resection( OR=11.379,95% CI:2.658 to 79.429, P=0.003) were independent influencing factor affecting patient recurrence. Conclusions:The overall tumor recurrence rate after en bloc spondylectomy was high. The surgical margin of tumor resection is an independent risk factor affecting tumor recurrence. Specifically, R2 and R1 resections significantly increase the risk of tumor recurrence.

Objective:To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion.Methods:This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning.Results:Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion:In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

Objective:To assess the clinical outcome of patients with spinal tumors who received en bloc resection in our center and to provide theoretical basis for developing novel surgical technique in en bloc resection for spinal tumor.Methods:We retrospectively reviewed the clinical and follow-up data of 113 patients who received en bloc resection for spinal tumors in Musculoskeletal Tumor Center, Peking University People's Hospital from Jan. 2007 to Dec. 2021. There were 68 males and 45 females with an average age of 38.7±16.7 (10-79) years. Primary malignant spinal tumors, primary aggressive spinal tumors and solitary metastatic spinal tumors were diagnosed in 55, 27 and 31 patients, respectively. The surgeries were planned according to the surgical classification for en bloc resection for spinal tumors proposed by Boriani et al, which classified the en bloc resection for spinal tumor into 7 types. The general condition (gender, age, histological diagnosis, location of the lesion, number of involved vertebrae, pre-operative neurological function), surgical procedure (type of surgery, stage of surgery, reconstruction method for anterior structure, duration of surgery, intra-operative haemorrhage, surgical margin), peri- and post-operative complication (intra- and peri-operative complication, post-operative neurological function), and survival [overall survival (OS), recurrence-free survival (RFS) and implant survival (IS)] of patients were retrospectively analyzed.Results:All surgeries accomplished uneventfully except one intra-operative death owing to the haemorrhagic shock caused by injury of major blood vessel. Mean duration of surgery and volume of intra-operative haemorrhage was 517.6±267.4 min and 3802.7±3039.4 ml, respectively. R0 resection was achieved in 48 patients. Three patients died in peri-operative period. Intra- and peri-operative complications were identified in 44 patients (38.9%). 109 patients were followed up with a mean time of 39.4±35.2 months. 27 patients died during follow-up period. The average post-operative overall survival (OS) was 115.4[95% CI (97.9, 133.0)]months and the 5-year OS rate was 64.1%[95% CI (52.3%, 75.9%)]. In patients with primary malignant spinal tumors, the OS of patients with R2 resection was significantly poorer than that of patients with R0/R1 resection ( P=0.024); in patients with metastatic tumors, no difference of OS was observed in patients with different surgical margins ( P=0.612). There were 29 recurrences, and the mean RFS was 105.8 [95% CI (87.5, 124.1)] months. In patients with primary malignant and aggressive spinal tumors, the RFS of patients underwent R2 resection was significantly lower than that of patients underwent R0/R1 resection ( P=0.008, P=0.027); in patients with metastatic spinal tumors, no significant difference of RFS was found in patients with different surgical margin (P=0.707). Conclusion:Although en bloc resection for spinal tumors indicates high morbidity, it significantly improves the OS of patients with primary malignant spinal tumors and the local control of primary malignant and aggressive spinal tumors.

Humans ; Diabetic Nephropathies/pathology* ; Kidney/pathology* ; Biopsy ; Diabetes Mellitus, Type 2/pathology* ; Retrospective Studies ; Glomerular Filtration Rate ; Disease Progression

ObjectiveTo investigate the mechanism of Zuogui Jiangtang Qinggan prescription （ZJQP） in improving glucose and lipid metabolism in loss of skeletalmuscle-specific insulin-like growth factor-1 receptor function （MKR） mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD）. MethodNAFLD was induced by high-fat diet feeding for 8 weeks in MKR mice， which were randomly divided into model group， metformin group （0.067 g·kg^-1）， and ZJQP high and low-dose groups（14.8， 7.4 g·kg^-1）. Ten FVB mice of the same age were used as the normal group. After 8 weeks of drug treatment， the oral glucose tolerance test （OGTT） was performed， the serum was taken to detect triacylglycerol （TG） and total cholesterol （TC）， and the wet weight of the mouse liver was weighed. Haematoxylin-eosin （HE） staining and oil red O staining were performed to assess histopathology of liver. The mRNA expression and protein expression of Fork head box protein O1 （FoxO1）， phosphoenolpyruvate carboxykinase （PEPCK）， glucose-6-phosphatase （G6Pase）， and apolipoprotein C3 （ApoC-Ⅲ） in liver tissues were detected by real-time fluorescent quantitative PCR （Real-time PCR） and Western blot， respectively. ResultAs compared with the normal group， the levels of fasting blood glucose， liver index， serum TG， TC， and OGTT of mice in the model group increased significantly （P<0.01）. As compared with model group， the fasting blood glucose and liver index of the mice in the metformin group and the ZJQP group decreased significantly （P<0.01）， the serum levels of TG and TC in the high-dose ZJQP group decreased significantly （P<0.05，P<0.01）， and the OGTT of mice in the metformin group and the high-dose ZJQP group improved （P<0.05）. In histopathology， as compared with the normal group， mice in the model group showed decreased lipid droplets and vacuoles in hepatocytes， and their volumes became larger. Compared with the model group， the ZJQP group and metformin group showed that the lipid droplets in liver tissues were reduced， the vacuoles in liver cells were reduced， and the volume was smaller. At the molecular level， as compared with the normal group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in liver tissues of mice in the model group were significantly up-regulated （P<0.01）. As compared with the model group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in the ZJQP group was significantly decreased （P<0.01）. ConclusionZJQP can improve the glucose and lipid metabolism of T2DM with NAFLD and repair the pathological damage of liver， which may be through regulating the expression of FoxO1， PEPCK， G6Pase， ApoC-Ⅲ-related proteins in liver tissues to achieve the effects of regulating lipid， lowering glucose， and delaying hepatic steatosis.

En bloc resection of spine tumor is the essential treatment method for primary malignant spine tumor,primary aggressive spine tumor and solitary spine metastasis.It can achieve good local control and improve the prognosis.However,given the complex anatomic structure and major adjacent tissue and organ of the spine,en bloc resection of spine tumor remains the research hotspot in surgical treatment of spine tumor.On the basis of adequate surgical classification and surgical strategy,experienced surgical team for spine tumor can achieve good surgical margin while decreasing the morbidity of the en bloc resection of spine tumor.However,the details of surgical classification and surgical strategy require further study.

Objective:To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA).Methods:The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged ( M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Results:The elderly (age≥60 years) ( OR=2.428, 95% CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) ( OR=1.089, 95% CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) ( OR=1.122, 95% CI: 1.078 to 1.168), total bilirubin (every rise of 1 μmol/L) ( OR=2.629, 95% CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95% CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion:The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.