Objective To explore the effect of a herbalcompound Gehua Jiejue Dizhi Decoction (GJDD) on the liver fat deposition and the expression of PXR, and the mRNA and protein expression of its target genes CYP3A11 and CYP3A25in the liver tissues of mouse models of alcoholic fatty liver.Methods Twenty-nine healthy male C57BL/6J mice were randomly divided into control group (n=5), model group (n=8), high dose GJDD group (n=8)and low dose GJDD group (n=8).The mouse model of alcoholic fatty liver was prepared according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) method.Then, the mice were treated with the high dose and low dose GJDD for 9 days.Serum glutamic-pyruvic transaminase (AST) and aspartate aminotransferase (AST) were detected by enzyme-linked immunosorbent assay (ELISA).Liver fat deposition was detected by oil red O staining.Real-time RT-PCR and immunohistochemistry were performed to examine the expressions of PXR, CYP3A11 and CYP3A25.Results Compared with the model group, the liver fat deposition in the intervention groups was significantly reduced in a dose-dependent manner, with a significant increase of the expression of PXR and CYP3A25 (P < 0.01).The serum ALT level was significantly reduced in the model group (P < 0.01), while the transcriptional levels of CYP3A11 mRNA in the groups were similar (P ≥ 0.05).Conclusions Gehua Jiejue Dizhi Decoction has obvious therapeutic effect on the AFLD in mice, which may be related to the activation of PXR and its target genes CYP3A25.

Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

OBJECTIVETo observe the efficacy of He-wei Jie-gu (Chinese characters) decoction on femoral intertrochanteric fractures after internal fixation in elderly.

METHODSFrom January 2010 to January 2012, 90 elderly patients with osteoporotic intertrochanteric fracture were randomly divided into two groups. The patients in experimental group were treated with open reduction and internal fixation, He-wei Jie-gu decoction and Caltrate D in oral, including 18 males and 27 females with an average age of (77.8±11.3) years old ranging from 65 to 89 years old;the time from injured to operation was 2 to 9 days with an average of (6.6±2.1) days; according to Evans-Jensen classification, 17 cases were in type I, 8 in type II, 15 in type III, 3 in type IV, 2 in type V. Meanwhile, the patients in control group were treated with open reduction and internal fixation, Caltrate D in oral, including 16 males and 29 females with an average age of (81.2±9.6) years old ranging from 67 to 91 years old; the time from injury to operation was 2 to 10 days with an average of (6.8±2.6) days; according to Evans-Jensen classification, 15 cases were in type I, 10 in type II, 14 in type III, 4 in type W, 2 in type V. The VAS score, hip BMD value before and after treatment, fracture healing and the Harris function score after operation were recorded and compared.

RESULTSAll patients were followed up from 3 to 9 months with an average of (5.6±2.8) months. Compared with the control group, the VAS score of the experimental group had an obviously reduction (F=98.138, P<0.01) after treatment; the hip BMD value at 3 months after treatment in the experimental group was higher than that of the control group (P<0.05); the fracture healing rate of the experimental group was higher than that of the control group (P<0.05); Harris score in 3 months of follow-up in the experimental group was higher than that of the control group (t=2.542, P<0.05); all the differences between two groups were statistically significant (P<0.05).

CONCLUSIONHe-wei Jie-gu decoction can reduce postoperative pain and increase bone mineral density after internal fixation of femoral intertrochanteric fracture in elderly, promote the fracture healing and functional recovery in the hip joint.

Aged ; Aged, 80 and over ; Bone Density ; Combined Modality Therapy ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Femur ; injuries ; surgery ; Fracture Fixation, Internal ; Hip Fractures ; surgery ; Humans ; Male ; Osteoporotic Fractures ; drug therapy ; physiopathology ; surgery ; Pain, Postoperative ; drug therapy ; physiopathology

Objective To understand the present condition of preclinical dental undergraduate in-terns' AIDS-related knowledge. Methods The questionnaire was designed referring to domestic and foreign relevant questionnaires. The cluster sampling method was used to conduct the questionnaire survey among the undergraduates who started their clinical internship in July 2016 in three domestic colleges, using SPSS 14.0 statistical software to analyze it. Results In this survey, 144 questionnaires were distributed, and 144 ones were filled out and sent back. The survey results suggested that 97.22％ (140) of interns held a posi-tive attitude towards aiding HIV-infected patients despite that 96.53％ (139) of interns knew that dental medical staff was considered to be highly susceptible with HIV. In spite of the fact that most interns knew AIDS-related knowledge and protection measures, 40.28％ (58) of interns were not clear about incubation period of AIDS, and the average awareness of children's AIDS and methods to disinfect HIV-infected dental instruments was less than half in the interns. Meanwhile it was found that 86.81％ (125) of interns didn't perform well in terms of complying with the principles of confidentiality in AIDS prevention and treatment. Conclusion Dental clinical interns' attitudes towards AIDS-infected patients should be praised. Further-more, they should accept education about infection control to have a deeper understanding about AIDS-related clinical manifestations and legal knowledge in order to reduce the probability of nosocomial infec-tion of AIDS.

OBJECTIVETo observe the effect of nourishing Yin, strengthening Qi and activating blood decoction on Fas/FasL in salivary glands of NOD mice with Sjogren's syndrome and their mRNA expression.

METHODThirty-two NOD mice were randomly divided into the model group, the traditional Chinese medicine group (TCM group, orally given 0.4 mL nourishing Yin, strengthening Qi and activating blood decoction as per 100 g x kg(-1) everyday), the hydroxychloroquine group (given 0.4 mL hydroxychloroquine as per 60 mg x kg(-1) everyday), the traditional Chinese medicine and western medicine group (TCM WM group, given nourishing Yin, Strengthening Qi and activating blood decoction 50 g x kg(-1) and hydroxychloroquine 60 mg x kg(-1), 0.4 mL everyday), with eight mice in each group. Eight Balb/C mice were selected as the normal control group (normal group). All of mice were killed after eight weeks, and their submaxillary glands were dissected. The expression levels of Fas/FasL were examined by immunohistochemical method, and the FasL mRNA was detected by RT-PCR.

RESULTThe expression levels of Fas/FasL in salivary glands of the model group were higher than that of other groups (P < 0.05). The expression level of FasL of the normal group was much lower than that in the hydroxychloroquine group (P < 0.05). The relative expression level of Fas mRNA in salivary glands of the model group was higher than that in other groups, but the control group was notably lower than other groups (P < 0.05). The expression level of FasL mRNA in salivary glands of the model group was higher than that in TCM and TCM WM groups (P < 0.05). But the expression level in TCM WM group was notably lower than the hydroxychloroquine group (P < 0.05).

CONCLUSIONThe nourishing Yin, strengthening Qi and activating blood decoction could down-regulate the expression level of Fas/FasL in salivary glands of NOD mice with Sjogren's syndrome and their mRNA expression, and had a better efficacy after being combined with hydroxychloroquine. The nourishing Yin, strengthening Qi and activating blood decoction might treat the Sjogren's Syndrome by reducing apoptosis which is regulated by Fas/FasL

Animals ; Fas Ligand Protein ; genetics ; Female ; Gene Expression Regulation ; Medicine, Chinese Traditional ; methods ; Mice ; Mice, Inbred NOD ; Qi ; RNA, Messenger ; genetics ; metabolism ; Salivary Glands ; metabolism ; Sjogren's Syndrome ; blood ; genetics ; therapy ; Yin-Yang ; fas Receptor ; genetics

Objective To explore the clinical features, surgical techniques and treatment efficacy of blood blis?ter-like aneurysms (BBA) of the internal carotid artery (ICA). Method We retrospectively reviewed 45 BBAs of the ICA treated surgically at our department between Jan. 2006 and Jan. 2016. The data was analyzed. Results Direct clipping of BBA was performed in 38 patients, clipping over wrapping in 3 patients and trapping of ICA in 4 patients. Intraoperative rupture occurred in 12 patients (27%). Postoperative cerebral infarction developed in 10 cases (22%). Seven patients died (16%). During the follow-up time of 47 months (range, 6~126 months), Good results were achieved in 34 patients (76%) with a modified Rankin Scale (mRS) 0~2 and 4 patients were in mRS 3~5. Follow-up angiography revealed a re?currence of BBA in one patient, which was retreated with endovascular coiling. No rebleeding was found in all fol?lowed-up patients. Conclusions BBAs of the ICA are difficult to treat surgically with high risk and complications. Thoughtful pre-operative evaluation of BBA and application of various surgical strategies during operation can signifi?cantly reduce the surgical risk and achieve good outcomes.

OBJECTIVETo observe the effect of naringin of Drynaria Rhizome, a Chinese medical component of Zhuanggu Jianxi Recipe (ZJR) containing serum on caveolin-p38MAPK signal factors (such as caveolin-1, p-p38, p-ATF-2, IL-1β, and TNF-α) in IL-1β induced rabbit degenerated chondrocytes, and further to explore its mechanism for protecting articular cartilages.

METHODSNaringin of Drynaria Rhizome was obtained and analyzed by HPLC-TOF/MS. Four weeks old New Zealand rabbits were killed and their bilateral knee joints were isolated aseptically. CDs were isolated and then cultured in vitro. The second generation of CDs were used for later experiment. The effect of naringin on CDs proliferation was detected by MTT assay. The effect of naringin on the expression of IL-1β-induced collagen II in CDs was detected by immunohistochemical method. The effect of naringin on caveolin-1, p-p38, and p-ATF-2 protein in IL-1β-induced CDs was detected by Western blot. The effect of naringin on mRNA expression of IL-1β and TNF-α in IL-1β-induced CDs was detected by RT-PCR.

RESULTSThe appearance time of naringin in flow graphs of naringin standard solution and ZJR containing serum was 23.5 min, and the molecular weight ranged between 581.0 and 581.5 m/z. Naringin could promote the proliferation of CDs, and inhibit the effect of IL-1β on collagen II in CDs. Compared with the model group, naringin could reduce the expression of caveolin-1, p-p38, p-ATF-2, IL-1β, and TNF-α in IL-1β induced CDs (P < 0.05), which was approximate to the level of the normal group.

CONCLUSIONSNaringin could not only promote the proliferation of CDs, but also protect IL-1β-induced CDs. Its mechanism might be associated with decreasing the expression of caveolin-1, p-p38, and p-ATF-2 proteins, inhibiting caveolin-p38MAPK signal pathway, and further reducing mRNA expression of IL-1β and TNF-α in the downstream of caveolin-p38MAPK signal pathway.

Animals ; Blotting, Western ; Cartilage, Articular ; Caveolins ; Chondrocytes ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Flavanones ; pharmacology ; Interleukin-1beta ; metabolism ; Polypodiaceae ; Rabbits ; Rhizome ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo evaluate the effect of Zhuanggu Jianxi Decoction (, ZGJXD) on interleukin-1 β (IL-1 β)-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen-activated protein kinase (MAPK) signal pathway, investigating the possible molecular mechanism that ZGJXD treats osteoarthritis.

METHODSSerum pharmacology was applied in the present study, where ZGJXD was orally administrated to New Zealand rabbits and then ZGJXD containing serum (ZGJXD-S) was collected for following in vitro experiments. CDs were isolated aseptically from New Zealand rabbits and then cultured in vitro. Upon IL-1 β stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type II collagen immunocytochemistry. After IL-1 β-stimulated CDs were intervened with blank control serum, ZGJXD-S, together with or without SB203580 (a specific inhibitor of p38 MAPK) for 48 h, caveolin-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL-1 β, tumor necrosis factor α (TNF-α), matrix metalloproteinase 3 (MMP-3) and MMP-13 were examined by real-time polymerase chain reaction.

RESULTSIL-1 β stimulation induced degeneration of CDs, increased caveolin-1 expression and p38 phosphorylation, up-regulated the mRNA level of IL-1 β, TNF-α, MMP-3 and MMP-13. However, the IL-1 β-induced activation of caveolin-p38 signaling and alteration in the expression of p38 downstream target genes were suppressed by ZGJXD-S and/or SB203580 in CDs.

CONCLUSIONZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.

Animals ; Base Sequence ; Blotting, Western ; Caveolins ; metabolism ; Chondrocytes ; drug effects ; enzymology ; metabolism ; DNA Primers ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Profiling ; Interleukin-1beta ; physiology ; MAP Kinase Signaling System ; Male ; RNA, Messenger ; genetics ; Rabbits ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

Objective To explore the effects of A DH1B and A LDH2 gene polymorphism and type of al-coholic beverage on ethanol metabolism, to provide data support for cases involving the interpretation of ethanol metabolism or back calculation of blood ethanol concentration in forensic practice. Methods A total of 81 volunteers were selected. The genotypes of A DH1B, A DH1C and A LDH2 were obtained by a multiplex SNaPshot genotyping method. Each subject was administered with 1.0 g/kg of alcohol. About 1 mL venous blood was collected before and after the alcohol consumption at 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h and 8 h, respectively. The concentrations of ethanol and acetaldehyde in blood were determined by headspace gas chromatography. The peak times of blood ethanol concentration (Tmax), the peak mass concentrations of ethanol (Cmax), the area under curve (AUC) of ethanol (AUCethanol), AUCacetaldehyde and ethanol elimination rates (β) were calculated. In order to eliminate the influence of A DH1C, the A DH1C*1/*1 carriers were grouped based on the genotype of A DH1B and A LDH2. The data of each group were evaluated by one-way analysis of variance and pairwise comparison tests were performed by least significant difference method. The gene interactions were evaluated by two-way analysis of variance. Each parameter of three kinds of alcoholic beverage (white wine, red wine and beer) among groups was analysed by variance analysis with randomized block design. Results There were no differences in the value of Tmax and Cmax between the groups with different A DH1B and A LDH2 genotype. The differences in the values of AUCethanol, β and AUCacetaldehyde among some groups carrying different A DH1B and A LDH2 geno-type had statistical significance, while no significant difference was observed in these parameters when one individual taking same dose of different alcoholic beverage type. Conclusion The ethanol metabolism is associated with the related gene polymorphism, which is barely affected by alcoholic beverage type.

OBJECTIVETo discuss the pathological characteristics of cervical spinal fracture complicating ankylosing spondylitis (AS) and the effect of combined anterior and posterior operation.

METHODSEighteen AS patients with traumatic cervical fracture-dislocation were treated operatively from January 2000 to January 2006. The symptom duration of AS was 14.5 years on average. Three cases had undergone osteotomy in lumbar spine. There were 4 cases of Grade A, 3 cases of Grade B, 9 cases of Grade C and 2 cases of Grade D according to Frankel's score. There were 15 cases of Grade III dislocation and 3 cases of Grade II. All patients underwent surgical procedures by combined anterior and posterior approach.

RESULTSThere were 4 anterior-posterior procedures, 8 anterior-posterior-anterior procedures and 6 posterior-anterior procedures. Seven patients had one stage operation and 11 cases underwent two stage surgeries. There was certain extent of neurological improvement in 14 incomplete paraplegic patients, but no improvement in 4 complete paraplegic patients. The follow-up period was 21.2 months on average and the time for bone fusion was 3.6 months. There were 4 complications during operation and a long-term complication in follow-up.

CONCLUSIONSThe study suggests that anterior combined with posterior approach makes the spine stable and relieves the pressure immediately. It is a reasonable surgical strategy for treatment of cervical spinal fracture-dislocation with AS.

Adult ; Cervical Vertebrae ; injuries ; Humans ; Joint Dislocations ; surgery ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Retrospective Studies ; Spinal Fractures ; surgery ; Spondylitis, Ankylosing ; complications