Objective To explore the effects of gossypol acetate on the morphological features and the gene expression in the femoral head of Sprague-Dawley rat in vivo after treated with dexamethasone .Methods Dexamethasone(Dex) was injected into the abdominal cavity of SD rats at an dose of 10 mg/kg ,twice a week ,and feed gossypol acetate 5 mg · kg -1 · d-1 .The controls re-ceived saline 2 mL injection .The treatment lasted for 12 and 20 weeks .The slices of the femoral head were made for HE and immu-nohistochemical study .The total mRNA was extracted for RT-PCR assessment .Results The cancellous bone trabecular became sparse ,trabecular bone area ratio decreased ,bone marrow fat tissue increased .These changes were fitted for pathological character of bone necrosis .The gossypol acetate could not affect the pathological changes .The proportion of the positive stained osteoblasts increased ,adipocytes decreased .PPARγ,C/EBPα,11β-HSD1 expression enhanced ,Runx2 down regulated in the treatment groups and GAA group .Conclusion Dex can induce evident pathological changes conform to the characters of femoral head necrosis .They may have closed correlation between 11β-HSD1 and the gene expression .But GAA could not affected the pathological changes and abnormality of the gene expression .

Neural stem cells were labeled with superparamagnetic iron oxide (SPIO) and tracked by MRI in vitro and in vivo after implantation. Rat neural stem cells were labeled with SPIO combined with PLL by the means of receptor-mediated endocytosis. Prussian blue staining and electron microscopy were conducted to identify the iron particles in these neural stem cells. SPIO-labeled cells were tracked by 4.7T MRI in vivo and in vitro after implantation. The subjects were divided into 5 groups, including 5 x 10(5) labeled cells cultured for one day after labeling, 5 x 10(5) same phase unlabeled cells, cell culture medium with 25 mug Fe/mL SPIO, cell culture medium without SPIO and distilled water. MRI scanning sequences included T(1)WI, T(2)WI and T(2)*WI. R(2) and R(2)* of labeled cells were calculated. The results showed: (1) Neural stem cells could be labeled with SPIO and labeling efficiency was 100%. Prussian blue staining showed numerous blue-stained iron particles in the cytoplasm; (2) The average percentage change of signal intensity of labeled cells on T(1)WI in 4.7T MRI was 24.06%, T2WI 50.66% and T(2)*WI 53.70% respectively; (3) T2 of labeled cells and unlabeled cells in 4.7T MRI was 516 ms and 77 ms respectively, R(2) was 1.94 s(-1) and 12.98 s(-1) respectively, and T(2)* was 109 ms and 22.9 ms, R(2)* was 9.17 s(-1) and 43.67 s(-1) respectively; (4) Remarkable low signal area on T(2)WI and T(2)*WI could exist for nearly 7 weeks and then disappeared gradually in the left brain transplanted with labeled cells, however no signal change in the right brain implanted with unlabeled cells. It was concluded that neural stem cells could be labeled effectively with SPIO. R2 and R(2)* of labeled cells were increased obviously. MRI can be used to track labeled cells in vitro and in vivo.

Objective To evaluate effects of camptothecin on the autophagy of HaCaT cells.Methods Some cultured HaCaT cells were divided into several groups to be treated with camptothecin at concentrations of 5,10,25,50,100 and 200 nmol/L,and 0.1％ dimethyl sulfoxide (DMSO) (control group),respectively.Cell counting kit-8 (CCK-8) assay was conducted to estimate the proliferative activity of HaCaT cells after 24-and 48-hour treatment,flow cytometry to evaluate cell apoptosis after 24-hour treatment,and Western blot analysis to measure the expression of autophagy-related proteins microtubuleassociated protein 1 light chain 3 (LC3) and p62.Some HaCaT cells were divided into 2 groups to be treated with 10 nmol/L camptothecin and 0.1％ DMSO for 24 hours,respectively.Then,indirect immunofluorescence assay (IFA) was performed to determine the LC3 expression.Results Camptothecin at low concentrations of 5 and 10 nmol/L had no significant effects on the proliferation and apoptosis of HaCaT cells.Compared with the control group,the cellular proliferative rates were significantly inhibited by (31.23 ± 1.00)％,(54.21 ± 8.10)％ and (66.75 ± 10.70)％ in the 50-,100-and 200-nmol/L camptothecin groups after 24-hour treatment respectively,and by (25.81 ± 5.99)％,(44.35 ± 5.32)％,(65.81 ± 8.28)％ and (73.23 ± 9.59)％ in the 25-,50-,100-and 200-nmol/L camptothecin groups after 48-hour treatment respectively (all P ＜ 0.001).After 24-hour treatment,the apoptosis rates were significantly higher in the 50-,100-and 200-nnol/L camptothecin groups (14.46％ ± 2.38％,19.15％ ± 1.59％,29.88％ ± 1.37％,respectively) than in the control group (3.80％ ± 0.13％,all P ＜ 0.001).After 24-hour treatment with 5 and 10 nmol/L camptothecin,the protein expression of LC3 Ⅱ was significantly up-regulated,while p62 protein expression was significantly down-regulated:IFA showed that the percentage of autophagosome-positive cells was significantly higher in the 10-nmol/L camptothecin group than in the control group after 24-hour treatment (36.67％ ± 4.55％ vs.6.23％ ± 0.92％,t =6.546,P =0.003).Conclusions Camptothecin at low concentrations of 5 and 10 nmol/L can induce autophagy of HaCaT cells,but has no obvious effects on cell proliferation and apoptosis.Camptothecin at concentrations of 50,100 and 200 nmol/L can inhibit cell proliferation,promote cell apoptosis,and decrease autophagy levels.

Studies have shown that a variety of diseases such as cardiovascular disease, renal disease and cancer are closely related to trimethylamine oxide (TMAO). Clinically, abnormal elevation of TMAO has been used as an evaluation index of atherosclerosis (AS) prior to imaging. In this study, we investigated the effects of lipid metabolism disorders as well as pharmacological interventions on urinary TMAO using a hyperlipidemic golden gopher model. The study used 48 Syrian golden hamster modeled with a high-fat diet for 2 weeks, and then ezetimibe, simvastatin, ezetimibe and simvastatin groups were administered for 4 consecutive weeks, as well as the clinical trial drug, IMM-H007, for pharmacological intervention. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: SCXK (Beijing) 2021-0011). Urine from rats was analyzed for 2D band selective heteronuclear single quantum coherence (2D bs-HSQC) at week 2 and 4 after drug administration. The results indicated that, in comparison to the control group, the high-fat diet significantly elevated urinary TMAO levels in the model group of hamsters after both 2 and 4 weeks of treatment (P < 0.05). Urinary TMAO levels were significantly reduced (P < 0.05) in the model group after 2 or 4 weeks of intervention with ezetimibe, simvastatin, combination therapy, and IMM-H007, showing a marked decrease even after 2 weeks of treatment. The detection of TMAO could precede the measurement of serum biochemical indicators, facilitating earlier efficacy assessment. This study evaluated the modulatory effects of clinical drugs and clinical trial drugs on TMAO, which provides useful information for clinical drug use and drug research. It also provides a means of TMAO detection based on 2D NMR technology, which is helpful for the clinical application of TMAO detection index.

OBJECTIVETo investigate the effect of chronic endurance exercise on microcirculatory reserve capacity of biceps brachii in Chinese rowers and provide a certain basis for the date standard foundation of monitoring of functional status and the foundation of database of reserve capacity of blood of Chinese rowers.

METHODSEmpty stomach in the morning, 77 rowers from different groups and 24 common health people were noninvasive tested by using PeriFlux System 5000, the test indexes include the microcirculatory reserve capacity and other related indexes of biceps brachii. The test sites of all athletes were the same space in biceps brachii of the right side of body, there was no space differences of all athletes . All athletes were tested in the relatively stable functional status, common people were healthy. The test value included basic values and heating values, put the before and after heating of microcirculatory blood perfusion (MBP) as the microcirculatory reserve capacity.

RESULTSHeavyweight female (198. 97 ± 98. 81) > heavyweight male (183. 45 ± 64. 31) > lightweight male (151. 01 ± 65. 96) > lightweight female(140.53 ± 43.22) > common male people(127.21 ± 56.38) > common female people(103.54 ± 33.41), the microcirculatory reserve capacity of each group athletes were higher than common people, except the comparison between lightweight female and common male people, and there was no significant difference among the different group athletes.

CONCLUSIONChronic endurance exercise can improve the microcirculatory reserve capacity of rowers, especially the heavyweight rowers; the normal value of microcirculatory reserve capacity of heavy weight rowers should be more than 160, and lightweight rowers should be more than 120. There was no significant difference among different sex athletes, if the value of microcirculatory reserve capacity is significant lower than normal, it shows that athletes are in the state of fatigue.

Arm ; Athletes ; Female ; Humans ; Male ; Microcirculation ; Muscle, Skeletal ; blood supply ; Sports

Objective To investigate the efficacy and side effects of the molecular targeted drug sunitinib in the treatment of metastatic renal cell carcinoma(mRCC). Methods Fifteen patients with histopathological confirmed mRCC,including 10 males and 5 females,were enrolled in the study.The median age was 56(range from 37 to 73 years).Fourteen cases of clear-cell RCC and 1 papillary RCC were diagnosed.Thirteen patients had prior nephrectomy,and 6 patients were treated with cytokines previously.All of the patients were given sunitinib at a dosage of either 50 mg daily(4 weeks on/2 weeks off)or 37.5 mg daily continuously.Objective response rate(ORR),progressive-free survival(PFS)and overall survival(OS)were evaluated,and adverse events were also observed. Results The median follow-up was 13 months(2-24 months).According to RECIST,partial response could be evaluated in 8 patients and stable was found in another 5 patients.Only 2 patients were confirmed disease progression.The ORR was 53% with the disease control rate of 87%,However,the median PFS and OS were not yet available due to the short-term follow-up.During the treatment,the most common adverse events experienced by patients were hand-foot syndrome 11/15(73%),changes in hair color 10/15(67%),mucositis 9/15(60%),alopecie 9/15(60%),diarrhea 8/15(53%)and neutropenia 8/15 (53%). All of adverse events were manageable and reversible. Conclusions Sunitinib as a single agent in the treatment for Chinese mRCC patient is efficient and the side effects are reversible. Further long-term follow-up and expanded samples should be expected to confirm the efficacy and safety of sunitinib.

AIM:To investigate the expression of transmembrane protein 16A(TMEM16A) in Fischer rat thy-roid follicular epithelial ( FRT) cells and its electrophysiologic properties .METHODS: The eukaryotic expression vector of pUB6/V5-TMEM16A was constructed and transfected into FRT cells by liposome-mediated transfection .In order to ob-tain the high efficiency of gene transfection and expression , the quantity and ratio of lipid/DNA complexes were optimized . The FRT cells stably expressing TMEM16A were gained by the selection with blasticidin and confirmed by the techniques of RT-PCR and immunofluorescence .The expression and location of TMEM 16A in the FRT cells were observed under an in-verted fluorescence microscope .TMEM16A protein was associated with calcium-dependent chloride current , as measured with halide-sensitive fluorescent protein and patch-clamp technique .RESULTS: The results of double digestion and se-quencing indicated that TMEM16A was cloned into pUB6/V5.The results of RT-PCR and immunofluorescence confirmed that TMEM16A was expressed in the FRT cells after transfection with TMEM16A.The classical calcium-activated chloride channel currents were recorded in the FRT cells stably expressing TMEM 16A by the technique of patch-clamp and halide-sensitive fluorescent protein YFP-H148Q/I152L.CONCLUSION:The protein expression of TMEM16A in the FRT cells was observed.TMEM16A is the molecular identity of calcium-activated chloride channels .

Objective To investigate altered microstructural integrity in acute carbon monoxide(CO)intoxication by diffusion tensor imaging (DTI).Methods A total of 25 CO intoxication patients (5.0±1.44 post-intoxication)and 37 healthy volunteers matched with age, sex and educational level were involved and underwent DTI.The fractional anisotropy (FA)and apparent diffusion confficient (ADC) of total 26 regions of bilateral cerebellum,substantia nigra,hippocampus,white matter of frontal lobe,head of caudate nucleus,pallidum,thalamus, anterior limb of internal capsule,posterior limb of internal capsule,white matter of occipital lobe,white matter of parietal lobe,and genu of corpus callosum,splenium of corpus callosum were measured.Compared the patients against control for FA and ADC by paired t-test.Results FA of patients with CO intoxication decreased in bilateral pallidum,anterior limb of internal capsule,substantia nigra,right cerebellum,left below frontal white matter,right frontal white matter and genu of corpus callosum (P <0.05).ADC decreased in right substantia nigra,and left pallidum (P <0.05).ADC increased in right frontal white matter and bilateral occipital lobe white matter (P<0.05).Conclusion There is loss of microstructural integrity in acute CO intoxication,perhaps representing the underlying mechanism of delayed encephalopathy after carbon monoxide poisoning.

OBJECTIVETo analysis the outcomes and the technique of surgical operation of osteoporotic ankle fracture in the elderly.

METHODSOne hundred and twenty-eight patients with osteoporotic ankle fracture were treated by surgical operation from January 2003 to December 2008, included 26 males and 102 females, with an average age of 69 years old ranging from 50 to 82 years. According to Lange-Hanson classification, there were 113 cases of supinatio-extorsion, 18 of pronate-extorsion, 5 of supinatio-adduction, 2 of pronate-abduction. The methods of fixation, the complications, and the AOFAS scores after operation were recorded.

RESULTSAll the 128 patients were followed up from 6 months to 6 years (averaged in 36 months). Delayed wound healing occurred in 11 cases (8.6%). There was no deep infection, nonunion of the fracture, and revision. The average AOFAS scores after operation was 83.6 +/- 6.3 (the mean pain scores were 33.5 +/- 5.6, the mean function scores were 40.2 +/- 7.4, the mean alignment scores were 10).

CONCLUSIONSurgical treatment should be the first choice in osteoporotic ankle fracture in most cases. Improved procedures can make the results better.

Aged ; Aged, 80 and over ; Ankle Injuries ; surgery ; Female ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Retrospective Studies

Objective To evaluate the clinical value of left bundle branch pacing(LBBP)in HF pa-tients requiring cardiac resynchronization therapy(CRT).Methods A total of 128 HF patients who met the indicatons for CRT Class Ⅰ and Ⅱ and admitted in Department of Cardiology of Northern Jiangsu People's Hospital from January 2018 to January 2023 were consecutively recrui-ted,and 32 patients of them having left bundle branch electrode implantation due to failure of cor-onary sinus electrode implantation were assigned into the LBBP group,and the rest 96 patients getting conventional biventricular pacing(BVP)into the BVP group.The pacing parameters and other indicators were observed in the two groups at the time of implantation.Follow-up visits were made to the Special Clinic of"Arrhythmia and Cardiac Pacemaker"in Northern Jiangsu People's Hospital at 1,3,6,and 12 months after surgery,and then,the visits were conducted every 3 to 4 months thereafter.Clinical evaluation,12-lead electrocardiography,echocardiography,detections for programmable controller and pacemaker function and other tests were completed at each follow-up.Readmission or death events due to HF were recorded.Results Compared with the preoperative results,both groups obtained shorter QRS duration,better NYHA class,smaller LVEDD and increased LVEF at the last follow-up(P＜0.05).At the time point,shorter QRS du-ration,better NYHA class and higher LVEF were observed in the LBBP group than the BVP group(P＜0.05).There were no significant differences in pacing parameters between the two groups at the time of implantation and the last follow-up(P＞0.05).No statistical difference was found in readmission rate between the LBBP group and the BVP group(18.75％vs 16.67％,P＞0.05).Conclusion LBBP is safe and effective,and can improve the cardiac function of HF pa-tients.LBBP may provide a new option for patients who have failed traditional CRT.