Type 1 diabetes mellitus and non-alcoholic fatty liver disease: a two-sample Mendelian randomization study.

Background: NAFLD (Nonalcoholic fatty liver disease) is becoming an increasingly common cause of chronic liver disease. Metabolic dysfunction, overweight/obesity, and diabetes are thought to be closely associated with increased NAFLD risk. However, few studies have focused on the mechanisms of NAFLD occurrence in T1DM. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between T1DM and NAFLD with/without complications, such as coma, renal complications, ketoacidosis, neurological complications, and ophthalmic complications. Multiple Mendelian randomization methods, such as the inverse variance weighted (IVW) method, weighted median method, and MR-Egger test were performed to evaluate the causal association of T1DM and NAFLD using genome-wide association study summary data from different consortia, such as Finngen and UK biobank. Results: We selected 37 SNPs strongly associated with NAFLD/LFC (at a significance level of p < 5 × 10-8) as instrumental variables from the Finnish database based on the T1DM phenotype (8,967 cases and 308,373 controls). We also selected 14/16 SNPs based on with or without complications. The results suggest that the genetic susceptibility of T1DM does not increase the risk of NAFLD (OR=1.005 [0.99, 1.02], IVW p=0.516, MR Egger p=0.344, Weighted median p=0.959, Weighted mode p=0.791), regardless of whether complications are present. A slight causal effect of T1DM without complications on LFC was observed (OR=1.025 [1.00, 1.03], MR Egger p=0.045). However, none of the causal relationships were significant in the IVW (p=0.317), Weighted median (p=0.076), and Weighted mode (p=0.163) methods. Conclusion: Our study did not find conclusive evidence for a causal association between T1DM and NAFLD, although clinical observations indicate increasing abnormal transaminase prevalence and NAFLD progression in T1DM patients.

Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients.

Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.

Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice.

Metabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in MAFLD progression. Male mice with liver Pck1 deficiency fed a normal diet displayed hepatic lipid disorder and liver injury, whereas fibrosis and inflammation were aggravated in mice fed a high-fat diet with drinking water containing fructose and glucose (HFCD-HF/G). Forced expression of hepatic PCK1 by adeno-associated virus ameliorated MAFLD in male mice. PCK1 deficiency stimulated lipogenic gene expression and lipid synthesis. Moreover, loss of hepatic PCK1 activated the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increasing secretion of platelet-derived growth factor-AA (PDGF-AA), and promoting hepatic stellate cell activation. Treatment with RhoA and AKT inhibitors or gene silencing of RhoA or AKT1 alleviated MAFLD progression in vivo. Hepatic PCK1 deficiency may be important in hepatic steatosis and fibrosis development through paracrine secretion of PDGF-AA in male mice, highlighting a potential therapeutic strategy for MAFLD.

Features of gastric cancer by anatomic subsite in northern China: A multi-center Health Science Report database study.

BACKGROUND: The features of gastric cancer based on the anatomic site remain unknown in northern China patients. AIM: To analyze gastric cancer features and associated trends based on the anatomical site in northern China patients. METHODS: This cross-sectional study used incident gastric cancer case data from 10 Peking University-affiliated hospitals (2014 to 2018). The clinical and prevailing local features were analyzed. RESULTS: A total of 10709 patients were enrolled, including antral (42.97%), cardia (34.30%), and stomach body (18.41%) gastric cancer cases. Cancer in the cardia had the highest male:female ratio, proportion of elderly patients, and patients with complications, including hypertension, diabetes, cerebrovascular, and coronary diseases (P < 0.001). gastric cancer involving the antrum showed the lowest proportion of patients from rural areas and accounted for the highest hospitalization rate and cost (each P < 0.001). The proportion of patients with cancer involving the cardia increased with an increase in the number of gastroesophageal reflux disease cases during the same period (P < 0.001). Multivariate analysis revealed that tumor location in the cardia increased the risk of in-hospital mortality (P = 0.046). Anatomical subsite was not linked to postoperative complications. CONCLUSION: The features of gastric cancer based on the anatomical site differ between northern China and other regions, both globally and within the country. Social factors may account for these differences and should affect policy-making and clinical practice.

A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10-15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10-3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10-16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Effect of reproductive health education on self efficacy and intention of condom use among college freshmen / 中国学校卫生

Objective@#To analyze the influence of reproductive health education in middle school on self efficacy and intention of condom use among college freshmen, so as to provide evidence for fertility protection related intervention and policy making.@*Methods@#A questionnaire survey was conducted among college freshmen in Beijing by hierarchical cluster sampling method. A total of 3 001 students were surveyed. The difference was compared by using χ 2 test and ANOVA. Multivariate linear and Logistic regression model was used to analyze the influencing factors associated with condom use self efficacy and condom use intention.@* Results@#The overall rate that reproductive health education received before college among freshmen in Beijing was 65.11%. The college freshmen from urban areas reported more adequate reproductive health education (71.11%) than those from non urban areas before college (59.36%)( P <0.05). The total scores of UNGASS (4.22±0.90 vs 4.05±0.98), condom use self efficacy (24.64±5.34 vs 23.09±4.93) and the intention of condom use (82.44% vs 70.88%) of college freshmen received reproductive health education in middle school were higher than those of college students without pre college reproductive health education( P <0.01). Multiple linear regression analysis showed that the score of condom use self efficacy of college students received pre college reproductive health education was higher than those without pre college reproductive health education( β =1.21, 95% CI =0.79-1.63, P <0.01). Multivariate Logistic regression analysis showed that reproductive health, the intention of condom use of college freshmen who received pre college reproductive health education was higher than that of college freshmen without reproductive health education( OR =1.63, 95% CI =1.33-2.01, P <0.01).@*Conclusion@#Reproductive health education in middle school can improve college freshmen s self efficacy and intention of condom use, contribute to the implementation of safe sex, and is of great significance to the protection of college students fertility.

Features of colorectal cancer in China stratified by anatomic sites: A hospital-based study conducted in university-affiliated hospitals from 2014 to 2018.

OBJECTIVE: The clinical and biological characteristics of colorectal cancer have been found to differ depending on the anatomic site of the cancer. However, for Chinese patients, there is limited information on the proportion of cases at each site and the related features. In this study, we explored the location, distribution and other features of colorectal cancers at each anatomic site in Chinese patients. METHODS: We conducted a hospital-based study using hospitalization summary reports from 10 Peking University-affiliated hospitals from 2014 to 2018; the reports covered a total of 2,097,347 hospitalizations. Incident cases were chosen as the study population, and their epidemiological features were further analyzed. RESULTS: A total of 20,739 colorectal cancer patients were identified. Rectum was the most common location (48.3%) of the cancer, whereas the proportions of patients with distal and proximal colon cancer were 24.5% and 18.6%, respectively. Patients with rectal cancer were predominantly male and were the youngest for all anatomical sites (each P<0.001). The highest proportion of emergency admissions, the longest hospital stays and the highest hospitalization costs were found in patients with proximal colon cancer (each P<0.001). The proximal colon cancer subgroup included the highest proportions of patients with medical histories of cholecystectomy, cholecystolithiasis and/or gallbladder polyps and appendectomy (P=0.009, P<0.001 and P<0.001, respectively). The distal colon cancer subgroup included the highest proportions of patients with medical histories of diabetes and hypertension (P<0.001, respectively). CONCLUSIONS: The patterns of colorectal cancer observed in this study differ from those reported for Western patients and show a significantly higher proportion of patients with rectal cancer. Different epidemiological features were also found based on anatomic sites. Further studies based on tumor location should be conducted to facilitate more accurate screening and treatment.

Cervical cytology screening facilitated by an artificial intelligence microscope: A preliminary study.

BACKGROUND: Cervical cytology screening is usually laborious with a heavy workload and poor diagnostic consistency. The authors have developed an artificial intelligence (AI) microscope that can provide onsite diagnostic assistance for cervical cytology screening in real time. METHODS: A total of 2167 cervical cytology slides were selected from a cohort of 10,601 cases from Shenzhen Maternity and Child Healthcare Hospital, and the training data set consisted of 42,073 abnormal cervical epithelial cells. The recognition results of an AI technique were presented in a microscope eyepiece by an augmented reality technique. Potentially abnormal cells were highlighted with binary classification results in a 10× field of view (FOV) and with multiclassification results according to the Bethesda system in 20× and 40× FOVs. In addition, 486 slides were selected for the reader study to evaluate the performance of the AI microscope. RESULTS: In the reader study, which compared manual reading with AI assistance, the sensitivities for the detection of low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions were significantly improved from 0.837 to 0.923 (P < .001) and from 0.830 to 0.917 (P < .01), respectively; the κ score for atypical squamous cells of undetermined significance (ASCUS) was improved from 0.581 to 0.637; the averaged pairwise κ of consistency for multiclassification was improved from 0.649 to 0.706; the averaged pairwise κ of consistency for binary classification was improved from 0.720 to 0.798; and the averaged pairwise κ of ASCUS was improved from 0.557 to 0.639. CONCLUSIONS: The results of this study show that an AI microscope can provide real-time assistance for cervical cytology screening and improve the efficiency and accuracy of cervical cytology diagnosis.

Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation.

Although cancer cells are frequently faced with a nutrient- and oxygen-poor microenvironment, elevated hexosamine-biosynthesis pathway (HBP) activity and protein O-GlcNAcylation (a nutrient sensor) contribute to rapid growth of tumor and are emerging hallmarks of cancer. Inhibiting O-GlcNAcylation could be a promising anticancer strategy. The gluconeogenic enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) is downregulated in hepatocellular carcinoma (HCC). However, little is known about the potential role of PCK1 in enhanced HBP activity and HCC carcinogenesis under glucose-limited conditions. In this study, PCK1 knockout markedly enhanced the global O-GlcNAcylation levels under low-glucose conditions. Mechanistically, metabolic reprogramming in PCK1-loss hepatoma cells led to oxaloacetate accumulation and increased de novo uridine triphosphate synthesis contributing to uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis. Meanwhile, deletion of PCK1 also resulted in AMPK-GFAT1 axis inactivation, promoting UDP-GlcNAc synthesis for elevated O-GlcNAcylation. Notably, lower expression of PCK1 promoted CHK2 threonine 378 O-GlcNAcylation, counteracting its stability and dimer formation, increasing CHK2-dependent Rb phosphorylation and HCC cell proliferation. Moreover, aminooxyacetic acid hemihydrochloride and 6-diazo-5-oxo-L-norleucine blocked HBP-mediated O-GlcNAcylation and suppressed tumor progression in liver-specific Pck1-knockout mice. We reveal a link between PCK1 depletion and hyper-O-GlcNAcylation that underlies HCC oncogenesis and suggest therapeutic targets for HCC that act by inhibiting O-GlcNAcylation.

Transcriptomic changes associated with PCK1 overexpression in hepatocellular carcinoma cells detected by RNA-seq.

Phosphoenolpyruvate carboxykinase 1 (PCK1), a step limiting enzyme of gluconeogenesis, is downregulated in hepatocellular carcinoma (HCC). Overexpression of PCK1 has been shown to suppress hepatoma cell growth, but the underlying mechanism remains unclear. We used recombinant adenovirus overexpressing PCK1 or GFP in Huh7 cells, and the differentially expressed genes (DEGs) were identified by RNA-Seq. 180 were upregulated by PCK1 overexpression, whereas 316 were downregulated. Pathway analysis illustrated that PCK1 was closely correlated with Wnt signaling pathway and TGF-beta signaling pathway. Hence, Wnt signaling pathway and its downstream component, FZD2, FZD6, FZD7 and ß-catenin were confirmed by qRT-PCR and Western blot. In vivo we also observed that PCK1 had restrained tumor growth as a result of decreasing expression of ß-catenin. Whole-transcriptomic profile analysis discovered that overexpression of PCK1 downregulates several oncogenic signaling pathways in HCC, providing potential therapeutic targets for improving HCC therapy.

PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis.

BACKGROUND: Altered glucose metabolism endows tumor cells with metabolic flexibility for biosynthesis requirements. Phosphoenolpyruvate carboxykinase 1 (PCK1), a key enzyme in the gluconeogenesis pathway, is downregulated in hepatocellular carcinoma (HCC) and predicts poor prognosis. Overexpression of PCK1 has been shown to suppress liver tumor growth, but the underlying mechanism remains unclear. METHODS: mRNA and protein expression patterns of PCK1, AMPK, pAMPK, and the CDK/Rb/E2F pathway were determined using qRT-PCR and western blotting. Cell proliferation ability and cell cycle were assessed by MTS assay and flow cytometric analysis. The effect of PCK1 on tumor growth was examined in xenograft implantation models. RESULTS: Both gain and loss-of-function experiments demonstrated that PCK1 deficiency promotes hepatoma cell proliferation through inactivation of AMPK, suppression of p27Kip1 expression, and stimulation of the CDK/Rb/E2F pathway, thereby accelerating cell cycle transition from the G1 to S phase under glucose-starved conditions. Overexpression of PCK1 reduced cellular ATP levels and enhanced AMPK phosphorylation and p27Kip1 expression but decreased Rb phosphorylation, leading to cell cycle arrest at G1. AMPK knockdown significantly reversed G1-phase arrest and growth inhibition of PCK1-expressing SK-Hep1 cells. In addition, the AMPK activator metformin remarkably suppressed the growth of PCK1-knockout PLC/PRF/5 cells and inhibited tumor growth in an orthotropic HCC mouse model. CONCLUSION: This study revealed that PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis and supports a potential therapeutic and protective effect of metformin on HCC.

PCK1 Downregulation Promotes TXNRD1 Expression and Hepatoma Cell Growth via the Nrf2/Keap1 Pathway.

Gluconeogenesis, generates glucose from small carbohydrate substrates, and drives the metabolic flux in parallel but opposite to glycolysis. The cytoplasmic isoform of phosphoenolpyruvate carboxykinase (PCK1 or PEPCK-C), a rate-limiting enzyme in gluconeogenesis, initiates the gluconeogenesis process and is reportedly dysregulated in multiple types of cancer. Gluconeogenesis mainly occurs in the liver during fasting, and previous studies have demonstrated that PCK1 acts as a tumor suppressor in hepatocellular carcinoma (HCC); however, the role of PCK1 in cancer progression remains incompletely understood. In the current study, we found that PCK1 expression was decreased in HCC as compared to adjacent normal liver tissues, and low PCK1 expression correlated with poor patient prognosis. Furthermore, overexpression of PCK1 suppressed reactive oxygen species (ROS) production and nuclear translocation of Nrf2 in hepatoma cells. In addition, thioredoxin reductase 1 (TXNRD1), an antioxidant enzyme regulated by the Nrf2/Keap1 pathway, was downregulated upon overexpression of PCK1 in HCC cell lines. Furthermore, we verified this axis using nude mouse xenograft model. Finally, we found that auranofin, a TXNRD1 inhibitor, enhanced the sensitivity of PCK1-knockout hepatoma cells to sorafenib-induced apoptosis. Taken together, our findings suggest that PCK1 deficiency promotes hepatoma cell proliferation via the induction of oxidative stress and the activation of transcription factor Nrf2, and that targeting the TXNRD1 antioxidant pathway sensitizes PCK1-knockout hepatoma cells to sorafenib treatment in vitro.

Applying manofluorography in the evaluation of dysphagia after brainstem injury / 中华物理医学与康复杂志

Objective To evaluate the swallowing function of patients with dysphagia after brainstem injury using manofluorography (MFG),analyzing the abnormal biomechanical and kinematic parameters as well as any correlation between changes in the pharynx and the upper esophageal sphincter (UES) measured manometrically and changes in the kinematics of the hyoid bone.Methods Thirteen patients with dysphagia after brainstem injury (the patient group) and 13 healthy participants (the control group) underwent manofluorography.Kinematics and biomechanical changes during swallowing were compared between the two groups and the correlations between the observations were analyzed.Results The patient group showed significantly lower maximum pressure and rate of pressure change at the base of the tongue and in the hypopharynx,as well as less hyoid anterior displacement,smaller and briefer UES opening,but significantly higher minimum pressure at UES relaxation.The duration of tongue root elevation and hypopharynx pressure was also shorter than in the control group,on average.There was a negative correlation between hyoid anterior displacement and the minimum pressure on UES relaxation in the control group,and a positive correlation between hyoid anterior displacement and the maximum pressure at the base of the tongue and in the hypopharynx in the patient group.Conclusions The concurrent use of manometry and video-fluorography for evaluating dysphagia can be an objective and effective diagnostic tool for the comprehensive evaluation of swallowing function.

Assessing pharyngeal function for brainstem stroke survivors with dysphagia using videofluoroscopy digital analysis / 中华物理医学与康复杂志

Objective To evaluate the effect of the modified balloon dilatation intervention on the pharyngeal constriction function of the brainstem stroke survivors with dysphagia using videofluoroscopy-based digital analysis.Methods Thirty brainstem stroke survivors with pharyngeal dysphagia were recruited and randomly divided into a treatment group and a control group,with 15 in each.The treatment group was treated with the modified balloon dilatation in addition to the routine treatment of 30min,respectively,once a daily,3 days a week,whiled a control group was treated with routine treatment of 30min twice a day,3 days a week.Before and after the treatment,the rate and duration of pharyngeal constriction were measured in both groups.Results After the treatment,the rate of pharyngeal constriction in the treatment group was (0.20 ± 0.030),(0.14 ± 0.05) and (0.15 ± 0.04) when swallowing thin liquid,thick liquid and pasty food,significantly better than before the treatment.The duration of the pharyngeal constriction was (990.34 ±96.14),(1010.47 ± 133.64) and (1180.10 ± 121.27) ms,respectively,also significantly better than before the treatment.In the control group,significant differences were also observed in the rate and duration of pharyngeal constriction before and after the treatment.Conclusions Digital analysis based on videofluoroscopy can be used to quantify swallowing function effectively,and the rate and duration of pharyngeal constriction can be used to evaluate the pharyngeal function before and after treatment.

The effect of transcranial magnetic stimulation on the motor-evoked potentials of the suprahyoid muscles / 中华物理医学与康复杂志

Objective To explore the effect of theta-burst stimulation (TBS) of the motor cortex on the suprahyoid muscles and the mechanism through which the bilateral motor cortex regulates the suprahyoid muscles.Methods Continuous TBS (cTBS) was applied to the left motor cortex followed by intermittent TBS (iTBS) applied to the right motor cortex of 24 healthy subjects.The motor-evoked potentials (MEPs) of the suprahyoid muscles on both sides were recorded before the stimulation and after 15 and 30 minutes.The MEP amplitudes of the left and right suprahyoid muscles were analyzed using repeated measures analysis of variance.Results Before stimulation, the average MEP amplitudes of the left and right suprahyoid muscles were (375.29 ± 176.09) μV and (368.17 ± 149.02) μV respectively, significantly lower than the values after the stimulation.Conclusion iTBS can distinctly enhance the excitability of the right motor cortex controlling the suprahyoid muscles and reverse the inhibition caused by cTBS applied to the left motor cortex.Clarifying the effect of TBS on the excitability of the bilateral motor cortex is important for the rehabilitation of dysphagic stroke survivors.

The influence of bolus volume on oropharygeal swallowing in healthy subjects / 中华物理医学与康复杂志

Objective To observe the effects of bolus volume on pharyngeal and upper esophageal sphincter pressures and durations in healthy volunteers by using high-resolution manometry (HRM).Methods Twentyfour health subjects were recruited and asked to swallow three volumes of bolus (3 ml,5 ml and 10 ml) in the neutral head position.Pressure and duration measurements were acquired by utilizing a high-resolution solid-state manometer,with an emphasis on the hypopharynx and upper esophageal sphincter (UES).Variables including UES residual pressure,UES relaxation duration,maximum hypopharygeal pressure and hypopharyngeal pressure duration were analyzed across bolus volumes and consistencies by using three-way repeated measures analysis of variance (ANOVA) to investigate influence of bolus volume.Results UES residual pressure [-1.71 mmHg(3 ml thick liquid)vs.-4.68 mmHg(10 ml thick liquid)],UES relaxation duration[590.45 ms(3 ml thick liquid) vs.702.49 ms (10 ml thick liquid)],maximum hypopharygeal pressure [169.91 mmHg (3 ml thick liquid) vs.204.42 mmHg (10 ml thick liquid)] and hypopharyngeal pressure duration(P ＜0.05) varied significantly across bolus volumes when swallowing water or thick liquid.The UES relaxation duration,UES residual pressure and maximum hypopharyngeal pressure had a direct positive relationship with bolus volume.There was significant differences with regard to UES relaxation duration [685.75 ms(3 ml paste)vs.772.27 ms (10 ml paste)] but not to UES residual pressure (P ＞ 0.05) and maximum hypopharyngeal pressure (P ＞ 0.05) across bolus volume when swallowing paste.Conclusions Difference in hypopharyngeal pressure and duration,UES residual pressure and duration were detected across varying bolus volumes.Consideration of these variables is paramount in understanding normal and pathological swallowing.

Effect of preventive medication on the structure and blood flow of the femoral head with steroid-induced osteonecrosis / 中国组织工程研究

BACKGROUND: At present, the researches on steroid-induced avascular necrosis of the femoral head are mostly concentrated on the treatment of formed necrosis. And there are fewer reports on how to prevent the ostoenecrosis of the femoral head in the course of steroid therapy.OBJECTIVE: To observe the effect of preventive medication on femoral head structure and blood flow in steroid-induced osteonecrosis.DESIGN: Randomized controlled experiment.SETTING: Department of Pharmacology, Department of Anatomy, Medical College of Shaoguan University; Department of Nuclear Medicine, Guangdong Province Yuebei People's Hospital.MATERIALS: Thirty adult New Zealand rabbits of either sex, whose body mass was (2.5±0.5) kg.METHODS: The experiment was carried out in the Central Laboratory,Medical College of Shaoguan University, the Department of Electron Microscope, the Northern Campus of Guangzhou, Sun Yat-sen University, and the Department of Nuclear Medicine, Guangdong Province Yuebei People's Hospital from April to July 2005. ①Thirty rabbits were divided randomly into 3 groups with 10 rabbits in each group: control group with intramuscular injection of 1 mL/kg normal saline twice a week and meanwhile, intragastric administration of normal saline(10 mL/d), steroid group with intramuscular injection of dexamethasone sodium phosphate(1 mL/kg) twice a week and meanwhile, intragastric administration of normal saline(10 mL/d),treatment group with intramuscular injection of dexamethasone sodium phosphate(1 mL/kg) twice a week and meanwhile, intragastric administration ofXuesaitong(25 mg/kg), Zhibituo(350 mg/kg) and alendronate(5 mg/kg)daily for 8 weeks. ②After 1 week of drug withdrawal, the blood flow of femoral head was measured in all the rabbits with radioactive microsphere technique, and the histological changes were observed under light microscope and electron microscope.MAIN OUTCOME MEASURES: ①Blood flow of the femoral head in each group.②Histological and morphological changes, and ultrastructure of the femoral head cartilage in each group.RESULTS: ①The blood flow in the treatment group was more than that in the steroid group[(0.261±0.042), (0.197±0.053) mL/(min·g), q=6.10,P ＜ 0.01]. Compared with the control group[(0.243±0.039) mL/(min ·g)],the difference was not significant. ②The number of empty bone lacunae in the treatment group was fewer significantly than that in the steroid group [(15.22±5.49), (24.78±7.87) pieces, q=6.35, P ＜ 0.01]. However, there was no difference between the treatment group and control gruop [(10.38±3.78)pieces].③In the treatment group, the bone cells were normal, the endoplasmic reticula were abundant and the cellular nuclei were of normal shape.In the steroid group, the bone cells contracted in volume, the pyknosis occurred, the chromatin gathered to the edge and the bone lacuna enlarged.CONCLUSION: While using steroid hormone for long, using Xuesaitong,Zhibituo and alendronate may elevate the blood flow of femoral head, improve the tissue structure of bone and prevent or lighten steroid-induced necrosis of femoral head.