[Consensus of experts on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)].

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients'suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aimsto establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. Temporomandibular joint disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Hydroponic barley supplementation fed with high-protein diets improves the production performance of lactating dairy cows.

The study investigated the effects of dietary protein level and the inclusion of hydroponic barley sprouts (HB) on lactation performance, blood biochemistry and N use efficiency in mid-lactation dairy cows. Treatments were arranged in a 2 × 2 factorial design with 2 CP levels (16.8% and 15.5% of DM), with HB (4.8% of DM, replacing 4.3% of alfalfa hay and 0.5% of distillers dried grains with solubles [DDGS]) or without HB. Forty-eight multiparous Holstein dairy cows (146 ± 15 DIM, 40 ± 5 kg/d of milk) were randomly allocated to 1 of 4 diets: high-protein diet (16.8% CP, HP), HP diet with HB (HP+HB), low-protein diet (15.5% CP, LP), or LP diet with HB (LP+HB). An interaction between CP × HB on DMI was detected, with DMI being unaffected by HB inclusion in cows fed the high-protein diets, but was lower in cows fed HB when the low-protein diet was fed. A CP × HB interaction was also observed on milk and milk protein yield, which was higher in cows fed HB with HP, but not LP. Inclusion of HB also tended to reduce milk fat content, and feeding HP resulted in a higher milk protein and MUN content, but lower milk lactose content. Feed efficiency was increased by feeding HP or HB diets, whereas N use efficiency was higher for cows fed LP or HB diets. There was an interaction on the apparent total-tract digestibility of DM and CP, which was higher when HB was fed along with HP, but reduced when fed with LP, whereas the digestibility of ADF was increased by feeding low-protein diets. In conclusion, feeding a low-protein diet had no adverse effect on cow performance, while feeding HB improved milk and milk component yield, and N efficiency when fed with a high-CP diet, but compromised cow performance with a low-CP diet.

[The mechanism of hyperbaric oxygen regulating HMGB1 in the prevention and treatment of encephalopathy after acute CO poisoning].

Objective: To study the expression of high mobility group protein 1 (HMGB1) in the brain of rats after hyperbaric oxygen (HBO) treatment of acute carbon monoxide poisoning (DEACMP) , and to explore the mechanism of HBO in the prevention and treatment of DEACMP pathological process by regulating HMGB1. Methods: 108 SD rats were randomly divided into control group (NC group) and co group (CO group) . HBO treatment group (HBO group) , 48 rats in each group. Co group and HBO group were used to establish CO poisoning model, HBO group were treated with hyperbaric oxygen once a day. Water maze test was used to detect and analyze the memory retention ability of three groups of rats in 3 d, 7 d, 14 d. ELISA was used to detect the plasma concentration of HMGB1、IL-6、TNF-α in three groups of rats on the 1 d, 3 d, 7 d, 14 d, 21 d Concentration. Western blotting was used to detect the expression of HMGB1 and Caspase-3 in the brain of the three groups on the 1 d, 3 d, 7 d, 14 d, 21 d. TUNEL staining was used to detect the apoptosis of hippocampal neurons in the three groups. Results: Compared with NC group, the average escape latency of rats in CO group and HBO group was significantly prolonged, and the activity time of platform quadrant in CO group was significantly shortened on 14 d and 21 d (P<0.05) ; compared with CO group, the average escape latency of HBO group on 7 d, 14 d and 21 d was significantly shortened (P<0.05) . Compared with NC group, plasma HMGB1 in CO group and HBO group were significantly increased (P<0.05) ; after 3 days, HBO group was significantly lower than co group, the difference was statistically significant (P<0.05) . The levels of IL-6 and TNF-α in HBO group and co group increased rapidly and then decreased gradually. The increased levels of IL-6 and TNF-α in HBO group were significantly lower than those in CO group (P<0.05) . Compared with NC group, the expression of HMGB1 and Caspase-3 in CO group was significantly increased on 3 d, 7 d and 14 d (P<0.05) ; the expression of HMGB1 and Caspase-3 in HBO group was significantly increased on 3 d, 7 d, 14 d and 21 d (P<0.05) ; compared with CO group, the expression of HMGB1 and Caspase-3 in HBO group decreased significantly on 3 d, 7 d, 14 d and 21 d (P<0.05) . The apoptotic index of nerve cells in CO group began to increase at 3 days, which was significantly different from that of NC group (P<0.05) , and the difference was still statistically significant on 21 d (P<0.05) ; the apoptotic index of nerve cells in HBO group was slightly increased, but there was no significant difference compared with NC group (P>0.05) , and the apoptotic index of 3 d, 7 d, 14 d and 21 d in HBO group was significantly lower than that in CO group (P<0.05) . Conclusion: acute CO poisoning can induce the release of HMGB1 and a variety of inflammatory factors. HMGB1 can promote the apoptosis of nerve cells after acute CO poisoning by up regulating the expression of caspase-3 protein, and participate in the pathological process of DEACMP. HBO can down regulate the expression of HMGB1, IL-6, TNF-α and caspase-3 protein, inhibit the apoptosis of nerve cells, and play a protective role on nerve cells.

[Clinical analysis of 96 cases of congenital cystic lung lesions in children].

Objective: To summarize the diagnosis, clinical manifestations, treatment and prognosis of congenital cystic lung lesions. Methods: A retrospective study described the clinical course of 96 patients (46 female and 50 male) diagnosed with congenital cystic lung lesions treated at the Tianjin Children's Hospital from January 2010 to March 2019. The clinical findings, imaging examinations, pathological findings, treatment and follow-up were analyzed. Results: Totally 96 patients (aged from 4 days to 13 years) with congenital cystic lung lesions were included in this study. Eighty-six patients (90%) were diagnosed when they had cough and fever symptoms. Forty (42%) patients exhibited congenital cystic adenomatoid malformation, 30 underwent surgical excision, two were at emergency operations and one dead. There were 12 (13%) patients with pulmonary sequestration and four were surgical treated. Twelve (13%) patients with bronchogenic cyst were included and 4 were surgically treated. There were 3 (3%) patients with congenital lobar emphysema and one was surgically treated. Another patient with pneumothorax was operated in other hospital 2 months after discharge. Twenty-nine (30%) patients with unclassified congenital cystic lung lesions could not be definitively diagnosed by CT. Some of them were difficult to be distinguished from necrotizing pneumonia. Finally, 2 patients were diagnosed as necrotizing pneumonia after 6, 10 months follow-up. After operation 37 out of 39 patients recovered well. Conclusions: The diagnosis of congenital pulmonary cystic disease depend on imaging and pathological examination. Most patients are diagnosed when they have respiratory tract infection. The main clinical manifestations are cough and fever. The prognosis of operative management is good.

MiR-325-3p promotes locomotor function recovery in rats with spinal cord injury via inhibiting the expression of neutrophil elastase.

OBJECTIVE: This study aims to investigate the potential function of miR-325-3p in vascular integrity and inflammatory response following spinal cord injury (SCI). MATERIALS AND METHODS: The protein levels of ANG-1, ANG-2, and caspase-3 in HUVECs incubated with 0, 100, 200, 400, and 800 ng/ml NE for 24 h were determined. The regulatory effect of overexpressed miR-325-3p on the protein levels of ANG-1 and ANG-2 was determined by Western blot. The SCI model in SD rats was established by spinal injury at T10. Subsequently, the relative levels of miR-325-3p, ANG-1, and ANG-2 were determined in SCI rats and controls. Furthermore, SCI rats were administrated with miR-325-3p mimics or negative control and the relative levels of miR-325-3p, ANG-1, and ANG-2 were examined as well. At day 14, the protein levels of iNOS and GFAP in SCI rats and those overexpressing miR-325-3p were detected. BBB (Basso, Beattie, and Bresnahan) locomotor rating scale was applied for evaluating the locomotor function recovery at day 1, 3, 7, 14, 21, and 28 following SCI. RESULTS: NE treatment in HUVECs downregulated ANG-1 and upregulated ANG-2 and caspase-3 in a dose-dependent manner. The overexpression of miR-325-3p upregulated NE-induced decreased the level of ANG-1 and downregulated NE-induced increased level of ANG-2. After the establishment of the SCI model in rats, the miR-325-3p level gradually decreased in SCI rats relative to controls in a time-dependent manner. ANG-1 level in SCI rats decreased to the lowest on the first day following SCI, and gradually increased at day 3, 5, and 7. ANG-2 level was firstly upregulated and achieved the peak on day 3, and then decreased at day 5 and 7. Moreover, SCI rats overexpressing miR-325-3p showed a higher level of ANG-1 and lower level of ANG-2 than those of SCI rats. Overexpression of miR-325-3p downregulated the protein levels of iNOS and GFAP in SCI rats. BBB scale showed elevated locomotor function recovery in SCI rats overexpressing miR-325-3p compared with SCI rats. CONCLUSIONS: MiR-325-3p protects the integrity of the vascular wall, reduces infiltration of inflammation, and improves locomotor function recovery at post-SCI.

The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia.

Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20 kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p = 4.37 × 10-8), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400 kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p = 1.89 × 10-7). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME_CHROMOSOME _MAINTENANCE, was significantly enriched by the genes that were identified in our study (p = 1.54 × 10-17). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.

[The effects and mechanisms of berberine on proliferation of papillary thyroid cancer K1 cells induced by high glucose].

Objective: To study the effect and mechanisms of berberine (BBR) on the proliferation of papillary thyroid cancer K1 cells induced by high glucose. Methods: K1 cells were cultured under 5.5 mmol/L or 25 mmol/L glucose condition with or without different concentration of BBR (0, 10, 40 and 80 µmol/L) for 24 hours. The proliferations of K1 cells in each condition were detected by MTT. Western blot was used to measure the expression of nuclear factor erythroid 2-related factor 2(Nrf2), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and phosphorylated-Akt (p-Akt). The distribution pattern of Nrf2 in K1 cells was determined using immunofluorescent staining. Results: Compared with 5.5 mmol/L condition, the proliferation rate [(126.64±5.41) % vs (87.31±3.67)%], expression levels of PI3K (0.425±0.019 vs 0.272±0.039), p-Akt/Akt (0.446±0.021 vs 0.168±0.035) and Nrf2 (0.597±0.014 vs 0.308±0.026), and Nrf2 distribution (93.0% vs 23.1%) in nuclear of K 1 cells under 25 mmol/L condition were significantly elevated, respectively (all P<0.01). Addition of BBR in 25 mmol/L condition dose dependently (10, 40, 80 µmol/L) lowered the proliferation rate of K1 cells [(111.76±4.10)%, (70.03±2.18)%, (32.41±3.76)% vs (126.64±5.41)%, all P<0.05], and suppressed the expression of PI3K, p-Akt/Akt, Nrf2, and Nrf2 nuclear distribution (P<0.05). Conclusions: BBR dose dependently inhibited the proliferation of high glucose-induced K1 cells. This effect was associated with the suppression on of PI3K/Akt signaling activation, Nrf2 expression and its nuclear translocation.

Effects of dietary neutral detergent fiber and starch ratio on rumen epithelial cell morphological structure and gene expression in dairy cows.

This study was designed to investigate the effect of dietary neutral detergent fiber to starch ratio on rumen epithelial morphological structure and gene expression. Eight primiparous dairy cows including 4 ruminally fistulated cows were assigned to 4 total mixed rations with neutral detergent fiber to starch ratios of 0.86, 1.18, 1.63, and 2.34 in a replicated 4 × 4 Latin square design. The duration of each period was 21 d including 14 d for adaptation and 7 d for sampling. Rumen epithelial papillae were collected from the ruminally fistulated cows for morphological structure examination and mRNA expression analysis using quantitative real-time PCR of several genes related to volatile fatty acid absorption and metabolism, and cellular growth. Increasing dietary neutral detergent fiber to starch ratio resulted in a linear increase in the thickness of the stratum spinosum and basale. In contrast, expression of HMGCS2 (encoding the rate-limiting enzyme in the synthesis of ketone bodies) decreased linearly, whereas the expression of MCT2 (encoding a transporter of volatile fatty acid) increased linearly with increasing dietary neutral detergent fiber to starch ratio. As dietary neutral detergent fiber to starch ratio increased, expression of IGFBP5 (a gene related to the growth of rumen epithelial papillae) decreased, whereas IGFBP6 expression increased. Both of these IGFBP genes are regulated by short-chain fatty acids. Overall, the data indicate that dietary neutral detergent fiber to starch ratio can alter the thickness of the rumen epithelial papillae partly through changes in expression of genes associated with regulating volatile fatty acid absorption, metabolism, and cell growth.

[Efficacy of thrombolytic therapy using reteplase in cases with acute ST-segment elevation myocardial infarction: results from a multicenter clinical trial].

Objective: To evaluate the efficacy and safety of intravenous thrombolytic therapy using reteplase in patients with acute ST-segment elevation myocardial infarction (STEMI). Method: A total of 73 hospitals from Henan province took part in this clinical trials during October 2012 to October 2014, 1 226 cases (1 014 male (82.7%), mean age 59.0 (51.0, 66.0) years) with acute STEMI received reteplase as thrombolytic agent.Reperfusion rate was judged according to the clinical symptoms, electrocardiogram, myocardial enzymes and heart rhythm, and the rate of cardiovascular events and bleeding events during hospitalization was also observed.Bleeding events were evaluated with global utilization of streptokinase and tissues plasminogen activator for occluded coronary arteries (GUSTO) criteria.Subgroup analysis was performed to compare the effects of various thrombolysis timing (time from onset to thrombolysis≤6 h or 6-12 h) on reperfusion rate, cardiovascular events and bleeding events rate. Results: The reperfusion rate was 89.3% (1 089/1 219) at 120 minutes after the thrombolysis, average recanalization time was (59.96±26.86) minutes.The reperfusion rate of ≤6 h thrombolysis group was significantly higher than in 6-12 hours group (90.3% (988/1094) vs. 80.8% (101/125), P=0.001), while in-hospital mortality (2.6%(28/1 094) and 0.8% (1/125), P=0.352) and rate of bleeding (5.9%(64/1 094) and 5.6%(7/125), P=0.910) were similar between the two groups. The total in-hospital mortality after thrombolysis was 2.4% (29/1219), which was significantly higher in failed recanalization group than in recanalization group (10.8%(14/130) vs. 1.4%(15/1089), P< 0.001). The total rate of bleeding after thrombolysis was 5.8% (71/1219), there were 3 severe bleeding cases according to GUSTO classification (0.2%), all of them were cerebral hemorrhage, and 2 out of 3 cases died. Conclusions: Reteplase use is related to high recanalization rate and low cardiovascular events and bleeding rate and our results thus show that reteplase is a safe and effective thrombolytic agent for STEMI patients.

Performance of peanut mutants and their offspring generated from mixed high-energy particle field radiation and tissue culture.

To develop new ways to breed peanut, we irradiated seeds of the Luhua 11 cultivar with a mixed high-energy particle field at different doses. The embryonic leaflets were extracted as explants and incubated on somatic embryo induction medium and then on somatic embryo germination and regeneration medium. After being grafted, the M1-generation plants were transplanted, and seeds from each M1-generation plant were harvested. In the following year, the M2-generation seeds were planted separately. Some M2-generation plants showed distinct character segregation relative to the mutagenic parent in terms of vigor, fertility, plant height, branch number, and pod size and shape. M2-generation plants that had a high pod weight per plant tended to produce M3-generation offspring that also had a high pod weight per plant, much higher than that of the mutagenic parent, Luhua 11. M4-generation seeds varied greatly in quality, and 35 individuals with an increased fat content (>55%) were obtained. Overall, the results indicate that the combination of mutagenesis via mixed high-energy particle field exposure and tissue culture is promising for peanut breeding.

Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis.

Numerous studies have evaluated the association between the angiotensinogen (AGT) G-217A gene polymorphism and essential hypertension risk. However, the results have been inconsistent. We examined whether the AGT G-217A gene polymorphism confers essential hypertension risk by conducting a meta-analysis. We conducted a literature search of the Google Scholar, PubMed, and China National Knowledge Infrastructure databases for relevant studies that examined the G-217A polymorphism and risk of essential hypertension. Statistical analyses were carried out using Stata 12.0 to combine all relevant studies. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the strength of this association. A total of 2017 patients with psoriasis and 1708 controls from 7 comparative studies were included in this meta-analysis. We found a significant association between the AGT G-217A gene polymorphism and the risk of essential hypertension (AA vs GG: OR = 2.52, 95%CI = 1.68-3.78; AA vs GA: OR = 2.26, 95%CI = 1.48-3.45; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.20, 95%CI = 1.03-1.39). Further stratified analyses were conducted by ethnicity and sample size and produced similar results. No evidence of publication bias was found. This meta-analysis confirms that the AGT G-217A gene polymorphism is associated with essential hypertension susceptibility.

Intrahepatic IFN-alpha expression in liver specimens from HBV-infected patients with different outcomes.

BACKGROUND: Interferon-alpha (IFN-α), an active cytokine, plays an important role in antiviral host responses, including protection against hepatitis B virus (HBV) infection. This study was designed to investigate the correlation between intrahepatic IFN-α expression levels and disease severity using liver biopsy specimens from HBV-infected patients with different outcomes. PATIENTS AND METHODS: Immunohistochemistry (IHC) was performed to detect intrahepatic IFN-α expression in liver biopsy specimens obtained from 69 HBV-infected patients with different outcomes (including 23 cases with chronic hepatitis B [CHB], 18 cases with severe hepatitis B [SHB], and 28 cases with liver cirrhosis [LC]). In situ hybridization (ISH) was carried out to measure the levels of HBV DNA in liver samples. In addition, the liver specimens of 33 healthy liver transplant donors without detectable liver diseases comprised a normal control (NC) group. RESULTS: The intrahepatic expression levels of IFN-α were higher in the HBV-infected patients than the NC group (p = 0.001). Intrahepatic IFN-α expression was also significantly higher in the SHB and CHB groups compared to the NC group (p = 0.001 and p = 0.001, respectively), while the intrahepatic HBV DNA levels of the SHB patients were higher than those of LC patients (p = 0.013). Furthermore, intrahepatic IFN-α expression was positively correlated with serum alanine aminotransferase (ALT) levels in CHB patients; no significant correlations were discovered between intrahepatic IFN-α expression and intrahepatic HBV DNA levels in all other sub-groups. CONCLUSIONS: Intrahepatic IFN-α expression may correlate with liver inflammation after hepatitis B virus infection, and IFN-α may play a vital role in the occurrence of SHB.

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.

Association between plasma osteoprotegerin concentrations and urinary albumin excretion in Type 2 diabetes.

AIMS: Osteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicate that OPG is also associated with endothelial dysfunction in Type 2 diabetes. The aim was to investigate the relationship between plasma OPG levels and urinary albumin excretion (UAE) in Type 2 diabetic patients. METHODS: This study included 154 newly diagnosed Type 2 diabetic patients and 46 healthy subjects. Plasma OPG and 24-h UAE were measured. High-resolution ultrasound was used to measure flow-mediated (endothelium-dependent arterial) dilation (FMD). RESULTS: Compared with the normoalbuminuric subgroup, OPG levels in the microalbuminuric subgroup were significantly higher, and OPG levels in macroalbuminuria subgroup were significantly higher than those in the normoalbuminuria and albuminuria subgroups. Multiple regression analysis showed that only FMD (r = -0.26), C-reactive protein (r = 0.23), fasting blood glucose (r = 0.25), 2-h blood glucose (r = 0.21), HbA(1c) (r = 0.28), UAE (r = 0.27) and retinopathy (r = 0.27) were significant factors associated with OPG. Pearson's correlation analyses showed a positive correlation between OPG and logUAE (r = 0.440) and negative correlations between OPG and FMD (r = -0.284), and between FMD and logUAE (r = -0.602). CONCLUSIONS: Plasma OPG levels are significantly associated with UAE in Type 2 diabetic patients.

Interracial comparative study of prostate cancer in the United States, China, and Japan.

The interracial differences of prostate cancer progression have long been documented; however, underlying molecular and cellular mechanisms remain obscure. This study focuses on the histopathologic, immunohistochemical, biochemical, and molecular characterization of prostate cancer tissues unselectively obtained from US, Chinese, and Japanese men. Histopathologic analyses indicate that 74.5% of the prostate cancers in Chinese patients were poorly differentiated, compared with 28.6 and 32.8% of the prostate cancers in US and Japanese men, respectively. These differences cannot be attributed to patient age, clinical stage of disease, or methods of tissue sampling. Furthermore, the high proportion of poorly differentiated prostate cancer tissues in the Chinese group was not related to the patients' access to medical service or their geographic origins within China. We found significantly higher levels of tumor angiogenesis (2- to 4-fold), serotonin (2- to 20-fold), and bombesin (7- to 16-fold), but not chromogranin A, in tissue specimens obtained from Chinese prostate cancer patients compared with those from US and Japanese patients. We also found marked differences in p53 protein accumulation among various ethnic groups. The p53 protein was frequently detected in prostate cancer tissue specimens from Chinese (90.2%), but less frequently in US black (3.7%), US white (17.4%), and Japanese (7.1%) men. Further analysis of 31 prostate cancer tissues from Chinese men indicated that mutational changes in the p53 gene occurred between exons 5 and 8.

Nicorandil augments regional ischemia-induced monophasic action potential shortening and potassium accumulation without serious proarrhythmia.

Nicorandil is a clinically used nitrovasodilator that has a property as an opener of ATP-sensitive potassium (KATP) channels in vitro. We examined whether nicorandil at a clinically used dose augmented regional ischemia-induced monophasic action potential (MAP) shortening and increase in extracellular potassium concentration ([K+]o), and how it affected arrhythmia occurrence. Five-minute occlusion of a distal site of the left anterior descending coronary artery (LAD) was repeated at 30-min intervals in anesthetized open-chest dogs while recording MAP or measuring [K+]o with a potassium-sensitive valinomycin electrode from the epicardial center of the ischemic myocardium. Nicorandil (0.2-0.5 mg/kg) was administered intravenously (i.v.) 5 min before the third occlusion, and the data were compared with those during the second occlusion (control). During the second occlusion, MAP duration at 90% repolarization (APD90) shortened (mean rate for 5 min, 13 +/- 3%, n = 11) and [K+]o increased from 3.7 +/- 0.1 to 6.2 +/- 0.8 mM at 5 min (n = 12). These changes were reversed < or = 3 min after reperfusion. Before the third occlusion, baseline APD90 and [K+]o were not altered by nicorandil; however, the extent of occlusion-induced shortening of APD90 (25 +/- 4%) and [K+]o increase (7.8 +/- 1.6 mM) was augmented by the pretreatment. The drug effect was attenuated by a concomitant pretreatment with 5-hydroxydecanoate, a specific blocker of KATP channels (n = 2). The prevalence of ventricular fibrillation (VF) during occlusion/reperfusion sequence was reduced after nicorandil (1 of 25 vs. 5 of 25) without de novo VF. These results suggest that nicorandil at a clinical dose facilitates regional ischemia-induced activation of myocardial KATP channels without causing serious proarrhythmia. Such a property might help protect the myocardium against ischemia/reperfusion damage.