[HIV infection rate, high-risk behavior and pre-exposure prophylaxis/post-exposure prophylaxis in men who have sex with men in Beijing].

Objective: To understand the incidence of HIV infection, high risk behaviors and pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) utilization in men who have sex with men (MSM) in Beijing. Methods: Sample size was estimated to be 1 227 persons and 207 person year respectively in the survey and the cohort by using Epi Info 7.0 software. Using convenient sampling method, MSM were recruited by using Wechat app. Questionnaire was completed online to collect the information about demographic characteristics, high risk behavior, and utilization of PrEP/PEP of the MSM. MSM collected dry blood spot (DBS) samples by themselves, and mailed the DBS samples to laboratory for HIV nucleic acid testing. Open cohort was established and those with HIV negative nucleic acid testing results were followed up. Non-conditional binary logistic regression method was used to identify the associated factors for high risk anal sex in the last month and having multiple homosexual partners in the last month. Results: A total of 1 147 MSM were recruited, and follow up for 236 person years was conducted in 956 MSM with negative HIV nucleic acid testing results. The detection rate of new HIV infection was 1.3 per 100 person-years (3/236). During the last month, the proportions of consistent condom use in anal sex and oral sex were 50.7% (238/469) and 4.9% (23/469). In the MSM, 5.9% (43/723) had sex with HIV positive partners in the last month. 9.8% (103/1 049) used PrEP, and 8.7% (91/1 049) used PEP. The proportion of consistent condom use in PrEP and PEP were 34.3% (24/70) and 72.2% (39/54) respectively. Logistic regression analysis revealed that compared with those who used no PrEP/PEP, those who used PrEP/PEP were more likely to have unprotected anal sex in the last month (aOR=3.16, 95%CI:1.45-7.18), and more likely to have multiple homosexual partners in the last month (aOR=2.64, 95%CI:1.19-6.30), and compared with those who used no Rush Popper or drugs in the last month, those who used Rush Popper or drugs in the last month were more likely to have unprotected anal sex in the last month (aOR=2.34, 95%CI:1.67-3.30), and more likely to have multiple homosexual partners (aOR=2.42,95%CI:1.76-3.33). Conclusions: It is necessary to strengthen the health education to promote condom use and introduce the harm of drug use in MSM. In PrEP and PEP services, it is still necessary to suggest consistent condom use for MSM.

[Progress in research of influencing factors of prophylaxis drug use after non-occupational exposure to HIV].

Non-occupational post-exposure prophylaxis (nPEP), a biological means to block the transmission of HIV, is recommended by European countries, USA and WHO to use in HIV high-risk groups, but its utilization rate is still very low. The information-motivation-behavioral skills model (IMB) can accurately explain the prevalence and change of health behaviors. Based on this model, this paper summarizes the progress in research of the influencing factors for nPEP use to provide a basis for further research to promote the use of nPEP.

[Feasibility on the Internet-based HIV nucleic acid testing with dry blood spots and risk factors associated with HIV infection in men having sex with men in Beijing].

Objectives: To understand the prevalence of HIV nucleic acid using internet-based dry blood spots HIV testing strategy in men who had sex with men (MSM) and to probe the factors associated with HIV infection. Methods: Using convenient sampling method, 1 375 MSM were recruited and their dry blood spots samples were collected before being mailed to the laboratories for HIV nucleic acid testing. Results were showed to these MSM on a specific website by inputting their codes to it. Non-conditional binary logistic regression method was used to identify the associated factors on HIV infection. Results: The overall proportions of HIV nucleic acid positives appeared as 9.7% (131/1 349) and HIV antibody positives as 8.3% (112/1 349). Fresh infections accounted for 14.5% (19/131) among the newly-identified HIV nucleic acid positives, and the interval was ranging from 6 to 120 days, between the laboratory testings and the closest date that experiencing high risk behavior. Risk factors that related to HIV infection would include: 30 to 39 years of age (comparing to those under the age of 30, OR=1.88, 95%CI: 1.07-3.29), ≥8 000 Yuan of monthly income (comparing to those without income, OR=0.42, 95%CI: 0.19-0.96), inconsistent condom use during anal sexual contacts in the last six months (compared with those who had not anal sex or used condoms consistently in anal sex in the past six months, OR=2.22, 95%CI: 1.45-3.40), ever use of Rush Poppers (compared with those who never used Rush Poppers, OR=2.33, 95%CI: 1.49-3.64), addictive drug abuse (compared with those who never abused addictive drugs, OR=5.43, 95%CI: 2.32-12.69), and not having regular sexual partners (compared with having regular sexual partners, OR=1.74, 95%CI: 1.13-2.68) etc.. Conclusions: Dry blood spots HIV nucleic acid testing could help to identify the fresh HIV infections at an early stage, so as to prevent further transmission in the MSM population, among which fresh HIV infections accounted for a fairly large proportion. It is necessary to set up programs in reducing the abuse of drugs or Rush Poppers, and to promote condom use and advocate on stable sexual partnership etc., among the MSM population.

[Clinical presentations of neuromyelitis optica spectrum disorders with ultra-longitudinally extensive transverse myelitis].

Objective: To analyze the clinical presentations of neuromyelitis optica spectrum disorders (NMOSD) with ultra-longitudinally extensive transverse myelitis (uLETM), in order to improve the diagnostic accuracy of this disorder. Methods: Twenty-two uLETM patients was recruited and retrospectively analyzed for general clinical characteristics, laboratory tests and MRI characteristics, as well as therapeutic. Results: (1)The Male-to-female ratio was 1∶6. The median onset age was 31 years old. The duration from the first relapse to the onset was 5.5 months. (2)The positive rate of serum water channel aquaporin-4 antibody (AQP4-Ab) in the acute phase was 86.4%. The positive rate of cerebrospinal fluid (CSF) AQP4-Ab in the acute phase was 69.2%. The positive rate of autoimmune antibodies was 72.7%. There was a remarkable difference (Z=-12.632, P=0.000) in serum AQP4-Ab titer levels between with the acute and remission period (median titer of 1∶244.78 to 1∶139.63). There was a remarkable difference (Z=-20.161, P=0.000) in geometric mean of serum AQP4-Ab titer levels between with CSF AQP4-Ab positive (1∶289.8) and negative (1∶36.2). (3)63.6% of the uLETM patients had 10-15 contiguous segments, 31.8% had 16-19 contiguous segments and 4.5% had whole spinal cord affected. 72.7% of the lesions of uLETM were sliver. The detection rate of optic nerve lesion by MRI was 63.6% and brain sliver lesions was seen in 63.6% of the patients.(4) All patients improved after treatment with high-dose glucocorticoids (GCs) in the acute phase. 15 cases treated with long-term oral administration of low-dose GCs in remission stage of NMOSD. 6 cases treated with mycophenolate mofetil. 1 case treated with intravenous immunoglobulins. Conclusions: NMOSD with uLETM is predominantly seen in young woman. The high risk period of relapse is 5.5 months after the onset. A high portion of NMOSD patients with uLETM have serum and CSF AQP4-Ab in acute phase. The therapy of GCs is recommended in acute phase. Combination of GCs with immunosuppressant can achieve stable and satisfactory effect in remission period of NMOSD.

[A clinical analysis of 5 patients with infratentorial primary angiitis of central nervous system].

Objective: To explore the clinical characteristics of infratentorial primary angiitis in central nervous system(PACNS). Methods: A total of 5 cases diagnosed as infratentorial PACNS in the neurology department of Navy General Hospital of PLA in 2015 were enrolled in the study. The clinical, imaging and pathological data were collected and analyzed. Results: All the 5 cases were male with the median onset age of thirty-four. Five cases presented with dizziness, two with headache, three with walking unstable, two with facial numbness and one with dysarthria. Rising pressure of cerebrospinal fluid (CSF) (190-245 cmH(2)O, 1 cmH(2)O=0.098 kPa) was found in 4 cases by the lumbar puncture, mildly increased number of leukocyte in 2 cases [(12-28)×10(6)/L], increased CSF protein in 3 cases(540-979 mg/L) and increased IgG index in 3 cases(0.84-1.45). Pons lesions were revealed by magnetic resonance imaging(MRI)in 4 cases, brachium pontis lesions in 2 cases, cerebellum lesions in 2 cases, one with midbrain lesion in 1 case, unilateral lesions in 4 cases and bilateral lesion in 1 case. Different degree of edema and mass effect were shown in all lesions by MRI. Patch like enhancement was found by contrast MRI in 5 cases and meningeal enhancement in 2 cases. Elevation of choline(Cho)peak was found by magnetic resonance spectroscopy(MRS)in 4 cases, reduction of N-acetyl aspartate(NAA) peak in 3 cases, appearance of lactate peak in 1 case and lipid peak in another case. Arterial spin labeling(ASL) was performed in 4 cases and no hyperperfusion was found. Susceptibility weighted imaging(SWI) was performed in 3 cases and microhemorrhage in the lesions was found in 2 cases and normal in 1 case. Magnetic resonance arteriography(MRA) was performed in 1 case and no stenosis was found. Digital subtraction arteriography(DSA) was performed in 1 case and multiple stenosis of the intracranial arteries was showed. Two cases had taken the stereotactic brain biopsy and the histopathologic diagnosis was angiitis. Five cases were treated with methylprednisolone and cyclophosphamide was added on in 1 case. Good prognosis was found in all cases. Conclusions: Infratentorial PACNS mostly attacks middle-aged males. The lesions tend to locate in unilateral pons, brachium pontis, cerebellum and midbrain. Hemorrhage or microhemorrhage in lesions is often found by SWI and no hyperperfusion is shown by ASL, which would be useful to distinguish PACNS from malignant tumors. Given the limitations of brain biopsy in clinical practice, clinical and imaging features would be helpful to diagnose PACNS.

[Characteristics of sympathetic skin response in patients with multiple system atrophy].

Objective: To provide evidence for early clinical diagnosis of multiple system atrophy(MSA)by studying the characteristics of sympathetic skin responses(SSR) in the patients with MSA. Methods: A total of 47 MSA patients and 32 healthy individuals were enrolled as case group and normal control(NC) group, from in and out patients of Neurology Department of Navy General Hospital from July 2013 to August 2015. SSR was tested by Nicolet electromyography, the latency and abnormal and disappeared rate of SSR were compared. Results: The SSR latency of upper limbs and lower limbs in MSA group had statistical significance compared respectively with the NCgroup (upper limbs: SSR latency was(1 485±187)ms in MSA group, and(1 375±108)ms in NC group, P<0.05; lower limbs: SSR latency was(2 200±386)ms in MSA group, and(1 994±240)ms in NC group, P<0.05). Sex and age had no significant effect on the latency and the abnormal and disappeared rate of SSR in two groups (P>0.05). The upper and lower limb SSR latency in MSA patients with disease duration more than 2 years(SSR latency was (1 592±160)ms in upper limb and (2 268±254)ms in lower limb) were longer than those within 2 years(SSR latency was (1 453±184)ms in upper limb and (2 190±442)ms in lower limb), but only the upper limbs had significantly statistical differences (P<0.05). Both SSR abnormal rate and SSR disappeared rate in MSA patients whose disease duration were more than 2 years(SSR abnormal rate: 85.00%, SSR disappeared rate: 75.00%) were higher than those with shorter disease duration(SSR abnormal rate: 55.56%, SSR disappeared rate: 22.22%), and both were statistically significant (SSR abnormal rate: P<0.05, SSR disappeared rate: P<0.001). The upper and lower limb SSR latency of MSA-C subgroup had no statistical difference compared with MSA-P subgroup(P>0.05). The SSR abnormal rate in MSA-C subgroup(78.13%) was higher than that of MSA-P subgroup(46.76%), and were statistically significant (P<0.05). The SSR disappeared rate in MSA-C subgroup has no statistical difference compared with the MSA-P subgroup(P>0.05). Conclusions: SSR is helpful to diagnose MSA. The latency and the abnormal and disappeared rate of SSR are significantly increased with the extension of MSA duration. The SSR abnormal rate in MSA-C patients is higher than that in MSA-P patients, and symmetrically abnormal SSR is more supporting the diagnosis of MSA.

[Composition of potassium channels in normal rat coronary smooth muscle cells and activation effects of docosahexaenoic acid].

OBJECTIVE: To investigate the composition of potassium channels in normal rat coronary smooth muscle cells (CASMCs) and the activation effects of docosahexaenoic acid (DHA). METHODS: CASMCs were isolated by enzyme digestion.Effects of different types of potassium channel blockers and/or DHA on potassium channels currents were studied by whole-cell patch clamp technique. RESULTS: Potassium currents were significantly increased with 5 µmol/L DHA perfusion (P<0.05). The current density was increased from (52.80±6.68) pA/pF to (110.09±13.39) pA/pF (P<0.05) after DHA perfusion when the stimulation voltage was 100 mV.Compared with baseline, potassium currents were significantly decreased by various inhibitor perfusion (tetraethylammonium: (49.63±5.75) pA/pF vs. (13.96±2.18) pA/pF; ibritoxin: (50.67±7.89) pA/pF vs. (26.53±4.68) pA/pF; TRAM-34: (52.60±7.02) pA/pF vs. (46.05±7.60) pA/pF; apamin: (51.97±3.83) pA/pF vs. (44.89±5.04) pA/pF; 4-aminopyridine: (51.19±3.44) pA/pF vs. (29.92±2.81) pA/pF; glyburide: (49.67±1.77) pA/pF vs. (49.61±1.87) pA/pF, all P<0.05). In presence of different inhibitors, potassium channel current densities were increased after DHA perfusion except tetraethylammonium (tetraethylammonium: ( 12.79±1.89) pA/pF; ibritoxin: (67.08±5.54) pA/pF; TRAM-34: (117.91±21.79) pA/pF; apamin: (108.33±7.06) pA/pF; 4-aminopyridine: (127.73±20.56) pA/pF; glyburide: (121.53±13.83) pA/pF, all P<0.05 compared with baseline). CONCLUSIONS: Large-conductance calcium-activated potassium channel and voltage-gated potassium channel are the major constituents of potassium channels in CASMCs.DHA can activate potassium channels in CASMCs, mainly the large conductance calcium-activated potassium channel, thus dilate coronary arteries.

[The correlation factor analysis for conversion of clinically isolated syndrome to multiple sclerosis and neuromyelitis optica].

OBJECTIVE: To analyze the features of patients who converted from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and neuromyelitis optica (NMO) and explore the correlated factors. METHODS: A total of 151 patients admitted in our unit as CIS from January 2009 to December 2014 were enrolled in the study. All patients were divided into the following four groups by locations of the initial lesion, which were the spinal cord, the optic nerve, the brain stem and the multifocal lesions. Data were collected at the baseline including demographics, expanded disability status scale (EDSS) score, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OB) and serum aquaporin-4 antibody (AQP4-Ab), evoked potential (EP) and MRI lesions. The conversion rates from CIS to clinically definite MS or NMO were calculated and the correlated factors were explored. RESULTS: With a mean follow-up period of (44.11±17.62)months, 46/151(30.5%) patients converted to MS, 28/151 (18.5%) to definite NMO and 66/151 patients(43.7%)remained as CIS. Other patients were converted to optic neuritis(4/151), one-time transverse myelitis(3/151), acute disseminated encephalomyelitis (1/151) and Balo concentric sclerosis(3/151) . The EDSS score was significantly higher in patients converted to NMO than those converted to MS (P=0.003). The initial manifestation of optic neuritis significantly correlated with the conversion to NMO (P=0.000), while the initial manifestation of CIS with multifocal lesions significantly correlated with the conversion to MS (P=0.000). Neither the isolated BAEP (P=0.703), VEP (P=0.076), SEP (P=0.915) nor the combination of two (P=0.546)or three (P=1.000) of the above parameters could help to distinguish the conversion to MS or NMO. More patients with positive CSF-OB converted to MS (P=0.001), while more patients with positive serum AQP4-Ab converted to NMO (P=0.001). More patients were serum AQP4-Ab positive in those converted to NMO than those converted to MS (P=0.000). Lesions longer than three vertebral segments were dominant in patients converted to NMO (P=0.000). The logistic regression analysis revealed that factors correlated with conversion from CIS to MS were the initial CIS manifestation of multifocal lesions (OR=4.775, P=0.002), positive CSF-OB (OR=7.794, P=0.002) and VEP abnormality (OR=7.251, P=0.001). Factors correlated with conversion from CIS to NMO were female in gender (OR=12.536, P=0.019), positive serum AQP4-Ab (OR=36.410, P=0.002), lesions longer than three vertebral segments (OR=93.602, P=0.001), abnormal VEP and SEP (OR=18.448, P=0.002; OR=12.731, P=0.016). CONCLUSIONS: Factors correlated with the conversion from CIS to MS are initial CIS manifestation of multifocal lesions, positive CSF-OB and abnormal VEP, while those correlated with the conversion from CIS to NMO are female in gender, positive serum AQP4-Ab, initial CIS manifestation with optic nerve, lesions involved more than three vertebral segments and abnormal VEP and SEP.

[Docosahexaenoic acids activate large conductance calcium-activated potassium channels via phospholipase C- inositol triphosphate- calcium pathway in normal rat coronary smooth muscle cells].

OBJECTIVE: To investigate the mechanisms of docosahexaenoic acids (DHA) on activating large conductance calcium-activated potassium channels (BK channels) in normal rat coronary smooth muscle cells. METHODS: Normal coronary smooth muscle cells were isolated by enzyme digestion from Sprague-Dawley rats. BK currents were recorded by patch clamp in whole cell and single channel configurations, respectively. The effects of DHA on cytosolic calcium concentrations were examined by recording the changes of fluorescence intensity ratios. RESULTS: DHA (1 µmol/L) could activate BK channels. Open probabilities (NP0) of BK channels at test potential 60 mV, and calcium concentrations in external solution at 0, 0.01, 0.1, 1, 3, 10, 50 and 100 µmol/L were 0.002 7±0.000 4, 0.006 0±0.001 4, 0.097 2±0.010 6, 0.137 9±0.032 9, 0.468 7±0.163 7, 2.097 1±0.310 4 and 3.120 4±0.242 7, respectively (P<0.05, n=4). Before DHA perfusion, the fluorescence intensity ratio was 0.51±0.01, and the ratios were 0.53±0.02 and 0.55±0.01 after 0.001 and 0.01 µmol/L DHA perfusion, respectively (P>0.05, n≥5). The ratios were 0.64±0.01, 0.65±0.01, 0.70±0.01, 0.69±0.01, 0.68±0.01 and 0.67±0.02 after 0.1, 0.3, 1, 3, 5 and 10 µmol/L DHA perfusion, respectively, and EC50 was (0.04±0.02) µmol/L(P<0.05, n≥4). They were all higher than that before DHA perfusion. After incubating with phospholipase C (PLC) blocker U73122 and inositol triphosphate (IP3) blocker 2-APB, the ratios were 0.52±0.01 and 0.49±0.02 on the setting of 0.1 µmol/L DHA, respectively. Compared with control group(0.64±0.01), the ratios decreased after incubating with blockers (P<0.05, n≥4). CONCLUSIONS: Docosahexaenoic acids can activate large conductance calcium-activated potassium channels by the pathway of PLC-IP3-Ca(2+) to increase cytosolic calcium concentration in normal coronary smooth muscle cells, dilate the coronary vessels and bestow protective effects on cardiovascular system.

A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia

p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.

A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia.

p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.

Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition.

Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

Pharmacokinetics of tramadol in a diverse healthy Chinese population.

WHAT IS KNOWN AND OBJECTIVES: Drug disposition may show ethnicity and gender differences. The objective of this study is to assess whether there are gender and ethnic differences in the pharmacokinetics of tramadol. METHODS: Fifty healthy volunteers from five different ethnic Chinese groups (Han, Mongolian, Korean, Uygur and Hui) were recruited, and blood samples were obtained for up to 36 h after oral administration of a single 100 mg capsule of tramadol. The plasma concentration-time course of tramadol was measured by high-performance liquid chromatography and the pharmacokinetic estimated. RESULTS AND DISCUSSION: The mean maximum plasma concentration (C(max)) of tramadol was different between Chinese males and females. There were also statistically significant differences between Hui and the other ethnic groups in tramadol's clearance (CL/F), volume of distribution (V(d) /F), C(max) and area under the plasma concentration time curve (AUC(0-∞)) (P < 0·05). WHAT IS NEW AND CONCLUSION: The pharmacokinetics of tramadol was different in Hui subjects compared to the other Chinese ethnic groups. Tramadol CL/F may also show gender differences.

Pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 in five ethnic populations of China.

WHAT IS KNOWN AND OBJECTIVE: Interethnic variability in drug pharmacokinetics is well known. Our aim was to investigate whether the pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 vary between subjects of five Chinese ethnicities (Han, Mongolian, Korean, Hui and Uigur). METHODS: Fifty healthy subjects (five men and five women of each ethnicity) were recruited, and each received 50-mg dose of losartan in tablet form. Fourteen blood samples were collected for each subject over a 24-h period after drug administration. The concentrations of losartan and its active carboxylic acid metabolite E-3174 in plasma were determined by high-performance liquid chromatography/fluorescence (HPLC/FLU) method, and the pharmacokinetic parameters were calculated by DAS 2.0 software and compared by SPSS 16.0 software. Pharmacokinetic parameters, including area under the curve from 0h to the last measured point 24h [AUC((0-24))], area under the curve from 0h to infinite time [AUC((0-∞))], peak plasma concentration (C(max) ), time to reach C(max) (t(max) ), oral clearance (CL), oral volume of distribution (V(d)) and elimination half-life (t(1/2) ), were determined following a single oral dose of losartan. RESULTS AND DISCUSSION: The t(1/2) values of losartan and its active carboxylic acid metabolite E-3174 showed significant differences across the five ethnicities. After normalization by weight, no ethnicity-based difference was noted in the pharmacokinetic parameters of losartan. However, there were significant differences in C(max) and V(d) of the active carboxylic acid metabolite E-3174 for Han and Mongolian subjects, compared with the other three ethnic groups. There was a high linear correlation between weight and C(max) , AUC((0-24)) , AUC((0-∞)) , CL and V(d) . WHAT IS NEW AND CONCLUSION: Ethnicity was associated with significant differences in the single-dose pharmacokinetics of losartan's active carboxylic acid metabolite E-3174 in healthy subjects of the five main ethnic groups in China.

Pharmacokinetics of midazolam tablet in different Chinese ethnic groups.

WHAT IS KNOWN AND OBJECTIVES: Subjects of different ethnic groups may respond differently to drugs. The present study was conducted to compare the oral pharmacokinetics of midazolam among healthy volunteers from five different ethnic groups in China: Han, Mongolian, Uygur, Hui and Korean. METHODS: Healthy volunteers (10 Hans, 10 Mongolians, 10 Uygurs, 10 Huis and 9 Koreans) of Chinese nationality received a single oral tablet dose of 15 mg midazolam in an open label, parallel-group study. Blood samples were collected at intervals and analysed for midazolam by high performance liquid chromatography (HPLC). Ethnic differences in pharmacokinetic parameters of midazolam using non-compartmental methods and anova and Kruskal-Wallis rank test. RESULTS AND DISCUSSION: Midazolam maximum concentration (C(max) ) was significantly lower in Mongolians than that in Hans, Uygurs, Huis and Koreans (74·9 ± 33·7, 103·1 ± 26·4, 124·8 ± 50·0, 130·0 ± 38·3 and 189·0 ± 82·1 µg/L, respectively). C(max) for the Koreans were significantly greater, compared with Hans and Mongolians. The time to attain C(max) (t(max) ) for Hans was significantly longer as compared with Koreans and Uygurs (1·5 ± 0·7, 0·8 ± 0·5, 0·6 ± 0·7 h, respectively). Midazolam terminal half-life (t(1/2z)) were 3·0 ± 0·8, 2·2 ± 0·7, 1·9 ± 0·7, 3·5 ± 1·9, 3·8 ± 2·3 h for Hans, Mongolians, Uygurs, Huis and Koreans, respectively. The differences in half-life were significant between Koreans and Mongolians, Koreans and Uygurs, Uygurs and Huis, respectively. There were no differences between young males and females for all pharmacokinetic parameters. Double peaks in the concentration-time profiles were observed in some subjects. WHAT IS NEW AND CONCLUSION: There were some significant differences in midazolam pharmacokinetics between the five Chinese ethnic groups. However, the wide intra-ethnic variability observed in PK parameters makes predictions of midazolam kinetics, using ethnicity as predictor, unreliable.

The pharmacokinetics of fluconazole in healthy Chinese adult volunteers: influence of ethnicity and gender.

OBJECTIVE: The purpose of the present study was to investigate and compare the influence of ethnicity (including Han, Mongolian, Korean, Hui and Uygur) and gender on the pharmacokinetics of fluconazole in healthy adult volunteers after administration of 200-mg fluconazole tablet. METHODS: Ten healthy subjects (five males and five females) of each ethnicity were recruited and given a single 200-mg dose of fluconazole in tablet form. Blood samples were obtained before dosing and at various predetermined time points after administration up to 96 h. Drug levels were measured by high-performance liquid chromatography. The blood concentration-time profiles were analyzed using a non-compartmental approach to estimate the absorption parameters (AUC((0-96)), C(max) and t(max)), the distribution parameter (V(d)) and the disposition parameters (t(1/2) and CL). RESULTS: Ethnicity did not affect the parameter estimates, but gender did. However, the gender differences in pharmacokinetic parameter could be accounted for by differences in weight. There was a high linear correlation between weight and ln C(max), ln AUC (ln means natural logarithmic transformation), V(d) and CL. CONCLUSIONS: Ethnicity (Chinese Han, Mongolian, Korean, Hui and Uygur) influences the pharmacokinetics of fluconazole tablet. However, there were statistically significant gender differences in AUC, C(max), V(d) and CL. But these could be accounted for by weight differences. If fluconazole dose-adjustment is deemed necessary, this can be done on a weight basis rather than gender basis.

Reproductive health risks and HIV infection vulnerability of hostesses in metropolitan areas, China: a qualitative study.

In this paper, we describe sex-related health risks among hostesses in two metropolises in China based on data obtained from in-depth interviews. The data show that hostesses, many engaging in commercial sex, are vulnerable to HIV infection, unwanted pregnancies and reproductive tract infections. Nevertheless, many obstacles still are present that hinder them from engaging in safe sex. The findings from our study illustrate the need for targeted interventions in order to improve reproductive health and promote safe sex among this group.