Suanzaoren Decoction for the treatment of chronic insomnia: a systematic review and meta-analysis.

OBJECTIVE: Suanzaoren decoction (SZRD) in Traditional Chinese Medicine is a common prescription for chronic insomnia. This study systematically and accurately evaluated the safety and efficacy of SZRD in the treatment of chronic insomnia, thus providing a reference for its clinical application. MATERIALS AND METHODS: From the establishment of the corresponding database until May 2022, we systematically queried EMbase, PubMed, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang Database. Randomized control trials (RCTs) were included in this study, and the results that qualified for inclusion were screened and cross-checked by two researchers. After the relevant data were extracted, a meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 1,311 patients with chronic insomnia from 12 RCTs were enrolled in the meta-analysis, showing that the use of SZRD alone or in combination was superior to the control group in improving the clinical effective rate (RR=1.22, 95%CI [1.16, 1.29], p<0.00001), reducing the recurrence rate (RR=0.47, 95%CI [0.28, 0.80], p=0.005), and lowering the Pittsburgh Sleep Quality Index (PSQI) scores (MDSZRD+WM=-3.35,95%CI [-5.22, -1.47], p<0.00001); (MDSZRD=-1.94, 95%CI [-3.80, -0.07], p = 0.04). SZRD also could reduce the adverse effects rate (RR=0.30, 95% CI [0.22, 0.40], p<0.00001). CONCLUSIONS: It was therefore concluded that SZRD alone or in combination with Western medicine can increase the clinical effective rate, reduce the recurrence rate, improve the quality of life of chronic insomnia patients, and decrease the incidence of adverse effects. However, studies included in this analysis varied in quality, and more large-sample, high-quality, multi-center RCTs are still needed to verify the above conclusions.

[Effects of the composite of buckwheat-oat-pea on blood glucose in diabetic rats].

OBJECTIVE: To study the effects of buckwheat-oat-pea (BOP) composite flour [buckwheat ∶ oats ∶ peas=6 ∶ 1 ∶ 1 (quality ratio)] on blood glucose in diabetic rats. METHODS: In this study, 64 male Sprague-Dawley rats were divided into 8 groups by fasting blood glucose (FBG) and body weight: normal control group, model control group, metformin group, buckwheat group, oats group, BOP low-dose group (BOP-L), medium-dose group (BOP-M), and high-dose group (BOP-H). The rats in the normal control group were fed with normal diet, the rats in the model control group and metformin group were fed with a high-fat diet (HFD), and the rats in the buckwheat group, oats group, and BOP-L, BOP-M, BOP-H groups were fed with HFD containing 10% buckwheat flour, 10% oat flour, 3.3% BOP, 10% BOP, 30% BOP, respectively. The HFD in all the groups had the same percentage of energy from fat (45%). After 30 days, the rats fed with HFD received intraperitoneal injection of streptozotocin (30 mg/kg, once a week for two weeks) to establish diabetes mellitus. After the model was successful established, the rats were fed for another 28 days. During the study, the body weight, food intake/body weight (FI/BW) and water intake/body weight (WI/BW), food utilization rate, 24 h urine volume, FBG, glucose area under curve (GAUC) of oral glucose tolerance test were measured regularly. At the end of the study, the fasting serum glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS: With the inducing of HFD and streptozotocin, compared with the normal control group, the rats in the model control group had higher FI/BW, WI/BW, 24 h urine volume, FBG, GAUC, HOMA-IR (P < 0.05), and lower body weight, food utilization rate (P < 0.05). Compared with the model control group, the rats in the three BOP groups all had higher body weight, food utilization rate (P < 0.05), and lower WI/BW, HOMA-IR (P < 0.05); the rats in the BOP-L and BOP-M groups had lower FI/BW, 24 h urine volume, FBG (P < 0.05), and the rats in the BOP-M group also had lower GAUC (P < 0.05). After the establishment of diabetes, there was no significant difference in blood glucose and the other indicators between the rats in the three BOP groups and the buckwheat group or the oats group (P>0.05). CONCLUSION: The BOP had the effects of reducing blood glucose, insulin resistance and diabetic symptoms on diabetic rats, and had the value for further development and utilization.

Novel variants and uncommon cases among southern Chinese children with X-linked hypophosphatemia.

PURPOSE: X-linked hypophosphatemia (XLH) is the most common inherited renal phosphate wasting disorder and is often misdiagnosed as vitamin D deficiency. This study aims to provide clinical and mutational characteristics of 65 XLH pediatric patients in southern China. METHODS: In this work, a combination of DNA sequencing and qPCR analysis was used to study the PHEX gene in 80 pediatric patients diagnosed with hypophosphatemia. The clinical and laboratory data of confirmed 65 XLH patients were assessed and analyzed retrospectively. RESULTS: In 65 XLH patients from 61 families, 51 different variants in the PHEX gene were identified, including 23 previously reported variants and 28 novel variants. In this cohort of XLH patients, the c.1601C>T(p.Pro534Leu) variant appears more frequently. Fourteen uncommon XLH cases were described, including four boys with de novo mosaic variants, eight patients with large deletions and a pair of monozygotic twins. The clinical manifestations in this cohort are very similar to those previously reported. CONCLUSION: This study extends the mutational spectrum of the PHEX gene, which will contribute to accurate diagnosis. This study also suggests a supplementary qPCR or MLPA assay may be performed along with classical sequencing to confirm the gross insertion/deletion.

Effects of dietary rapeseed meal inclusion levels on growth performance, organ weight, and serum biochemical parameters in Cherry Valley ducks.

The aim of this study was to investigate the effects of the inclusion levels of different types of rapeseed meal (RSM) on performance, organ weight, and serum biochemical parameters in Cherry Valley ducks in the starter period and grower-finisher period. In Exp. 1, a total of 750 seven-day-old male ducklings were divided into 5 dietary treatments with 6 replicate pens of 25 birds per pen. The starter diets with the inclusion of 0, 5, 10, 15, or 20% of double-low RSM contained 0, 1.37, 2.15, 3.46, or 5.31 µmol glucosinolates (GLS)/g in the finished feed (from day 7 to 21). In Exp. 2, a total of 900 fifteen-day-old male ducklings were divided into 6 dietary treatments with 6 replicate pens of 25 birds per pen. The grower-finisher diets with the inclusion of 0, 5, 10, 15, 20, or 25% of Indian RSM contained 0, 7.67, 15.34, 24.66, 31.21, or 38.44 µmol GLS/g in the finished feed (from day 15 to 42). For ducklings in the starter period (Exp. 1), body weight gain and feed intake decreased linearly as the dietary double-low RSM inclusion level increased at day 7 to 14, while growth rate was not influenced by dietary double-low RSM inclusion levels at day 15 to 21 and day 7 to 21. For ducks in the grower-finisher period (Exp. 2), growth performance decreased linearly as the dietary RSM inclusion level increased from 5 to 20%. In addition, dietary RSM inclusion levels induced liver enlargement in ducklings at day 21 (5 to 20% double-low RSM with 1.37 to 5.31 µmol/g GLS) and thyroid enlargement accompanied by increased serum AST and ALP activities in ducks at day 42 (5 to 15% Indian RSM with 7.67 to 23.66 µmol/g GLS). Therefore, our results indicated that the upper limit of using RSM sources in feed formulation should consider the anti-nutritional factor of GLS content at different stages of duck growth.

[Clinical characteristics and outcome comparison between atrial fibrillation patients underwent catheter ablation under general aesthesia or local anesthesia and sedation].

Objective: To compare the outcome of radiofrequency catheter ablation under local anesthesia/sedation (S) or general anesthesia(GA) in atrial fibrillation patients. Methods: Data of 498 patients with atrial fibrillation undergoing radiofrequency catheter ablation in our departmentfrom January 2014 to December 2015 were retrospectively analyzed. Two hundred and twenty patients assigned to the GA group, the other 278 patients to the S group. Patients were followed clinically every 3 months within one year after procedure. Immediate electrocardiogram was performed in patients with palpitation or choking sensation in chest. The end point of the study was recurrence of any atrial tachyarrhythmia lasting >30 seconds in device interrogation, 24-hour Holter monitoring or 12-lead electrocardiogram after a single procedure. After the ablation procedure, a blanking period of 3 months was allowed according to the guidelines. Procedure time, radiofrequency time, fluoroscopy time, the detection of paroxysmal supraventricular tachycardia, the success rate and the complications were compared between the two groups. Results: There was no difference in the baseline characteristics between the two groups, such as age, gender, BMI, complications, LVEF, LAD (all P>0.05). The duration of procedure ((117.8±51.7)minutes vs.(115.4±36.9)minutes, P=0.79), duration of fluoroscopy((12.5±11.2)minutes vs. (10.4±10.2)minutes, P=0.35), duration of radiofrequency((40.1±12.9)minutes vs. (48.6±44.3)minutes, P=0.48) were similar between the two groups (P>0.05). Compared with S group, discovery of the frequency of atrioventricular node reentrant tachycardia (AVNRT) was significantly lower in GA group (0 vs. 3.6%(10/278), P<0.01), but the difference disappeared with repeat electrophysiological examination when patients become conscious from GA(3.2%(7/220) vs. 3.6%(10/278), P=0.311). The difference of atrioventricular reentrant tachycardia (AVRT) was similar between the two groups(0.9%(2/220) vs. 0.7%(2/278), P=0.841). Compared with S group, reflection of vagus nerve was less in GA group (1.4%(3/220) vs. 8.6%(24/278), P=0.026). After following up of (356±92) days, freedom from atrial fibrillation/atrial flutter/atrial tachyarrhythmia was similar between the two groups(77.9%(162/208) vs. 79.9%(215/269), P=0.818). Conclusion: General anesthesia is a promising method to atrial fibrillation ablation, in view of stable patient status and safety for the procedure. There is no difference in complications, recurrence of arrhythmia between the two groups, but detection rate of AVNRT is lower in GA group.

[Interaction between passive smoking and folic acid supplement during pregnancy on autism spectrum disorder behaviors in children aged 3 years].

OBJECTIVE: To explore the interaction between passive smoking and folic acid supplement during pregnancy on children autism spectrum disorder(ASD)behaviors. METHODS: Children aged about 3 years were enrolled at kindergarten entrance in Longhua district of Shenzhen in 2014. Self-administered questionnaires were completed by their primary caregivers and the information about children' s age, gender, history of preterm birth and low birth weight, parents' education level, parents' reproductive age and family income were collected. The children ASD behaviors were assessed with Autism Behavior Checklist(ABC). According to the cut point of ABC, the children were divided into normal group with score less than 31, sub-clinical group with score ranging from 31 to 61 and suspect clinical group with score no less than 62. After controlling for potential confounders, multivariate logistic regression analysis was performed to evaluate the main effects and the interaction between passive smoking and folic acid supplement during pregnancy on children ASD behaviors. RESULTS: Maternal passive smoking during pregnancy was significantly associated with children ASD behaviors(sub-clinical group: OR=1.48; suspect clinical group: OR= 2.85), and maternal folic acid supplement during pregnancy was not related to children ASD behaviors(sub-clinical group: OR=1.04; suspect clinical group: OR=0.75). Stratified analysis showed that folic acid supplement during pregnancy was negatively associated with children ASD behaviors(suspect clinical group: OR=0.30)among children without mothers' passive smoking during pregnancy, and that mothers' passive smoking during pregnancy was positively associated with children ASD behaviors(sub-clinical group: OR=1.52; suspect clinical group: OR=4.45)among the children whose mothers had folic acid supplement during pregnancy. Furthermore, an interaction effect on children ASD behaviors was found between passive smoking and folic acid supplement during pregnancy(suspect clinical group: OR=5.30). CONCLUSION: Passive smoking and folic acid supplement during pregnancy were related to children ASD behaviors and had an interaction on children ASD behaviors.

Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-ß1 in ovariectomized rats.

OBJECTIVE: To explore the effect of vitamin D on turnover of articular cartilage with ovariectomy (OVX) induced OA, and to investigate transforming growth factor-ß1 (TGF-ß1) as a possible underlying mechanism mediated by 1α,25(OH)2D3. DESIGN: Sixty-six rats were randomly allocated into seven groups: sham plus control diet (SHAM+CTL), OVX+CTL diet, sham plus vitamin D-deficient (VDD) diet, OVX+VDD diet, and three groups of ovariectomized rats treated with different doses of 1α,25(OH)2D3. The cartilage erosion and the levels of serum 17ß-estradiol, 1α,25(OH)2D3 and C-telopeptide of type II collagen (CTX-II) were measured. TGF-ß1, type II Collagen (CII), matrix metalloproteinases (MMP)-9,-13 in articular cartilage were assessed by immunohistochemistry. TGF-ß1 and CTX-II expression were measured in articular cartilage chondrocytes treated with/without tumor necrosis factor (TNF-α), 1α,25(OH)2D3, and TGF-ß receptor inhibitor (SB505124) in vitro. RESULTS: Cartilage erosion due to OVX was significantly reduced in a dose-dependent manner by 1α,25(OH)2D3 supplementation, and exacerbated by VDD. The expressions of TGF-ß1 and CII in articular cartilage were suppressed by OVX and VDD, and rescued by 1α,25(OH)2D3 supplementation. The expression of MMP-9,-13 in articular cartilage increased with OVX and VDD, and decreased with 1α,25(OH)2D3 supplementation. In vitro experiments showed that 1α,25(OH)2D3 increased the TGF-ß1 expression of TNF-α stimulated chondrocytes in a dose-dependent manner. 1α,25(OH)2D3 significantly counteracted the increased CTX-II release due to TNF-α stimulation, and this effect was significantly suppressed by SB505124. CONCLUSION: VDD aggravated cartilage erosion, and 1α,25(OH)2D3 supplementation showed protective effects in OVX-induced OA partly through the TGF-ß1 pathway.

A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.

Nickel-responsive regulation of two novel Helicobacter pylori NikR-targeted genes.

Nickel is an essential transition metal for the survival of Helicobacter pylori in the acidic human stomach. The nickel-responsive transcriptional regulator HpNikR is important for maintaining healthy cytosolic nickel concentrations through the regulation of multiple genes, but its complete regulon and role in nickel homeostasis are not well understood. To investigate potential gene targets of HpNikR, ChIP sequencing was performed using H. pylori grown at neutral pH in nickel-supplemented media and this experiment identified HPG27_866 (frpB2) and HPG27_1499 (ceuE). These two genes are annotated to encode a putative iron transporter and a nickel-binding, periplasmic component of an ABC transporter, respectively. In vitro DNA-binding assays revealed that HpNikR binds both gene promoter sequences in a nickel-responsive manner with affinities on the order of ∼10(-7) M. The recognition sites of HpNikR were identified and loosely correlate with the HpNikR pseudo-consensus sequence (TATTATT-N11-AATAATA). Quantitative PCR experiments revealed that HPG27_866 and HPG27_1499 are transcriptionally repressed following growth of H. pylori G27 in nickel-supplemented media, and that this response is dependent on HpNikR. In contrast, iron supplementation results in activation of HPG27_1499, but no impact on the expression of HPG27_866 was observed. Metal analysis of the Δ866 strain revealed that HPG27_866 has an impact on nickel accumulation. These studies demonstrate that HPG27_866 and HPG27_1499 are both direct targets of HpNikR and that HPG27_866 influences nickel uptake in H. pylori.

Efficacy of low-level laser therapy for accelerating tooth movement during orthodontic treatment: a systematic review and meta-analysis.

This review aimed to evaluate the efficacy of low-level laser therapy (LLLT) for accelerating tooth movement during orthodontic treatment. An extensive electronic search was conducted by two reviewers. Randomized controlled trials (RCTs) and quasi-RCTs concerning the efficacy of LLLT for accelerating tooth movement during orthodontic treatment were searched in CENTRAL, Medline, PubMed, Embase, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), and Google Scholar. Six RCTs and three quasi-RCTs, involving 211 patients from six countries, were selected from 173 relevant studies. All nine articles were feasible for the systematic review and meta-analysis, five of which were assessed as moderate risk of bias, while the rest were assessed as high risk of bias. The mean difference and the 95 % confidence interval (95 % CI) of accumulative moved distance of teeth were observed among all the researches. The results showed that the LLLT could accelerate orthodontic tooth movement (OTM) in 7 days (mean difference 0.19, 95 % CI [0.02, 0.37], p = 0.03) and 2 months (mean difference 1.08, 95 % CI [0.16, 2.01], p = 0.02). Moreover, a relatively lower energy density (5 and 8 J/cm(2)) was seemingly more effective than 20 and 25 J/cm(2) and even higher ones.

Prognostic impact of pERK in advanced hepatocellular carcinoma patients treated with sorafenib.

BACKGROUND: Sorafenib represents the standard of care targeted therapy for patients with advanced hepatocellular carcinoma (HCC). However, biomolecules that predict a patient's response to sorafenib treatment for HCC remain largely unknown. Thus, this study was designed to investigate whether phosphorylated ERK (pERK) and members of the sorafenib target or PI3K/Akt/mTOR signaling pathway predict the efficacy of sorafenib in advanced HCC patients. METHODOLOGY: From December 2008 to October 2011, pathological specimens from 54 advanced HCC patients received sorafenib treatment were obtained. Clinicopathological variables, treatment response, survival and time to progression (TTP) were recorded. Immunophenotypical analysis was carried out using antibodies against pERK, phosphorylated S6K (pS6K), VEGFR2 and PTEN. RESULTS: The median overall survival (OS) and TTP were 14.2 and 3.4 months, respectively, and the disease control rate (DCR) was 59.3%. Better Eastern Cooperative Oncology Group Performance Status (ECOG PS) (95% CI: 3.27-4.93 m vs. 1.15-2.85 m, p = 0.01), Child-Pugh class A score (95% CI: 3.47-4.53 vs. 1.14-2.06 m, p < 0.01), and higher pERK (3.34-6.66 m vs. 1.33-2.67 m, p = 0.03) and VEGFR2 (3.49-6.52 m vs. 2.15-2.73 m, p = 0.04) immunohistochemical staining score were associated with increased TTP by univariate analysis. The ECOG PS (p = 0.022), Child-Pugh class (p = 0.045) and pERK staining score (p = 0.012) were found to be associated with TTP using multivariate analysis. CONCLUSION: Sorafenib treatment outcome is favorable in advanced HCC patients who received tumor resection and who have a good ECOG PS and Child-Pugh class A liver function. The pERK immunohistological staining score, ECOG PS and Child-Pugh class may be helpful in determining patients most likely to benefit from sorafenib therapy.

Improved post-prandial ghrelin response by nateglinide or acarbose therapy contributes to glucose stability in Type 2 diabetic patients.

BACKGROUND: Recent studies highlight an important role of ghrelin in glucose homeostasis, while the association between ghrelin regulation and glucose fluctuation is unclear. AIM: We compared the effects of two postprandial hypoglycemic agents on ghrelin response and determined the contribution of ghrelin response to glucose stability in Type 2 diabetic (T2DM) patients. SUBJECTS AND METHODS: Forty newly- diagnosed T2DM patients were randomly allocated to receive nateglinide or acarbose for 4 weeks, with twenty body mass index (BMI)-matched normoglycemic subjects as controls. Mean glucose values and daily average glucose excursion were assessed using continuous glucose monitoring system. Serum ghrelin levels were determined by enzyme-linked immunosorbent assay. RESULTS: T2DM patients had similar fasting ghrelin levels (p=0.546), while their postprandial ghrelin suppressions at 30 min and 120 min were reduced as compared to BMI-matched normoglycemic controls (p<0.01). Both nateglinide and acarbose increased post-prandial ghrelin suppression at 120 min and reduced ghrelin area under the curve (AUCGHRL) (p<0.05), while only nateglinide increased postprandial ghrelin suppression at 30 min (p<0.01), which was positively correlated with the increased early-phase insulin secretion by 4 weeks of nateglinide therapy (r=0.48, p=0.05). The decrease in AUCGHRL was positively correlated with the decrease in daily average glucose excursion and mean glucose values either by 4 weeks of nateglinide or acarbose therapy (p<0.05). CONCLUSIONS: Both nateglinide and acarbose increase post-prandial ghrelin suppression. Improved ghrelin regulation is most likely to play a role in glucose stability in T2DM patients with nateglinide or acarbose therapy.

Efficacy of low-level laser therapy in the management of orthodontic pain: a systematic review and meta-analysis.

This review aimed to identify the efficacy of low-level laser therapy (LLLT) in the management of orthodontic pain. This systematic review and meta-analysis was carried out in accordance with Cochrane Handbook and the PRISMA statement. An extensive literature search for RCTs, quasi-RCTs, and CCTs was performed through CENTRAL, PubMed, Embase, Medline, CNKI, and CBM up to October 2011. Risk of bias assessment was performed via referring to the Cochrane tool for risk of bias assessment. Meta-analysis was implemented using Review Manager 5.1. As a result, four RCTs, two quasi-RCTs, and two CCTs were selected from 152 relevant studies, including 641 patients from six countries. The meta-analysis demonstrated that 24% risk of incidence of pain was reduced by LLLT (RR = 0.76, 95% CI range 0.63-0.92, P = 0.006). In addition, compared to the control group, LLLT brought forward "the most painful day" (MD = -0.42, 95% CI range -0.74- -0.10, P = 0.009). Furthermore, the LLLT group also implied a trend of earlier end of pain compared with the control group (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18) and the pseudo-laser group (MD = -1.04, 95% CI range -4.22-2.15, P = 0.52). However, because of the methodological shortcomings and risk of bias of included trials, LLLT was proved with limited evidence in delaying pain onset and reducing pain intensity. In the future, larger and better-designed RCTs will be required to provide clearer recommendations.

No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY).

AIMS/HYPOTHESIS: The aim of the study was to investigate the association between vitamin D intake and status and the risk of islet autoimmunity (IA) and subsequent type 1 diabetes in children at increased risk of type 1 diabetes. METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) in Denver, CO, USA, has been following children at increased risk of diabetes since 1993. As of February 2011, 198 children developed IA during follow-up of 2,644 DAISY children. Vitamin D intake and plasma 25-hydroxyvitamin D [25(OH)D] were measured longitudinally. Proportional hazards regression analyses of time to IA, or type 1 diabetes in IA-positive children, were conducted, with vitamin D intake and 25(OH)D as time-varying covariates. HRs were calculated for a standard deviation difference in exposure, with adjustment for confounders. RESULTS: Intake of vitamin D was not associated with the risk of IA (adjusted HR 1.13; 95% CI 0.95, 1.35; p = 0.18) nor progression to diabetes in IA-positive children (adjusted HR 1.30; 95% CI 0.91, 1.86; p = 0.15). Moreover, 25(OH)D level was not associated with the risk of IA (adjusted HR 1.12; 95% CI 0.88, 1.43; p = 0.36), nor progression to diabetes in IA-positive children (adjusted HR 0.91; 95% CI 0.68, 1.22; p = 0.54). In the 128 children in whom we measured 25(OH)D at 9 months of age, 25(OH)D was not associated with risk of IA (n = 30 IA-positive children) (adjusted HR 1.02; 95% CI 0.96, 1.07; p = 0.58). CONCLUSIONS/INTERPRETATION: Neither vitamin D intake nor 25(OH)D levels throughout childhood were associated with the risk of IA or progression to type 1 diabetes in our population.

High performance liquid chromatographic determination of a new antifungal compound, ADKZ in rat plasma.

A high performance liquid chromatography (HPLC) method was developed and validated for the determination of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl) -3-[N-methyl-N-(4-iodo-benzyl)amino]-2-propanol) in rat plasma. The compound was extracted from plasma samples by liquid-liquid extraction, and an isomeric compound of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-[N-methyl-N -(3-iodo-benzyl)amino]-2-propanol) was used as the internal standard (IS), which were analyzed on a reversed-phase C18 column (5 microm, 200 mm x 4.6 mm i.d.). The extracted plasma samples were eluted with acetonitrile-0.018 M triethylamine solution adjusted to pH 3.2 with phosphoric acid (35:65, v/v). The effluent was monitored by a UV detector at 230 nm. The retention time of ADKZ was 7.1 min and IS 8.2 min. The calibration curves were linear in the concentration range of 0.02-2.00 microg/ml with the correlation coefficients greater than 0.999. The quantification limit of ADKZ in rat plasma was 0.02 microg/ml. Intra- and inter-day precision ranged from 2.6 to 7.9% and 3.1 to 9.6%, respectively. The extraction recovery from plasma was no less than 80%. No endogenous interferences were observed with either ADKZ or IS. The method has been successfully used to support the pre-clinical pharmacokinetic studies of ADKZ in rats.

Intratumoral injection of boiling carboplatin (BCBP) solution for treatment of liver cancer in the animal model.

BACKGROUND/AIMS: To develop a new modality of local hyperthermal chemotherapy for liver cancer. METHODOLOGY: Carboplatin solutions of various concentrations were heated at 60 degrees C, 80 degrees C and 100 degrees C, and carboplatin content, pH value and ultraviolet absorption spectrum were assayed before and after heating. By establishing BALB/c murine model of subcutaneous transplant liver cancer, intratumoral injection of boiling carboplatin solution (group A), 45 degrees C carboplatin solution (group B), room-temperature carboplatin solution (group C), boiling distilled-water (group D) and room-temperature distilled-water (control group) was carried out, and tumor growth curve, tumor regression rate and pathohistological features following treatment were evaluated. RESULTS: Carboplatin content remained stable, ultraviolet absorption spectrum presented no remarkable changes and pH value showed a slight decline after being heated for up to 20 min. Following treatment, all 16 tumors in group A were completely regressed up to day 21. In groups B, C and control group, no tumors became fully regressed and a size of 1.98 +/- 1.11 cm2, 1.50 +/- 0.58 cm2 and 4.83 +/- 0.37 cm2 was presented on day 21, respectively. In group D, though all tumors grossly disappeared during the early post-treatment days, 12 out of 16 recurred on day 21. The tumor regression rate in group A was significantly lower as compared with that of groups B, C, D and control group (all P < 0.01). Histological examination revealed massive necrosis with some degenerated tumor cells at the tumor margin in groups A and D, and only focal necrosis with more viable tumor cells at the center and margin in groups B and C on post-treatment day 1 and 3. Twenty-one days after injection, all tumors in group A presented complete necrosis and were partly replaced by fibrotic tissue. Except for 4 regressed tumors in group D which had the same histological features as those in group A, all other tumors in groups B, C, D and control group presented the same histological features as those untreated. CONCLUSIONS: Carboplatin solution remained stable at boiling status. Intratumoral injection of boiling carboplatin solution could completely devitalize liver cancer tissue via synergistic effects of direct tumoricidal role of heat and the heat-enhanced tumoricidal role of carboplatin.

[Clinical study on treatment of middle-advanced stage liver cancer by combined treatment of hepatic artery chemoembolization with gan'ai no. I and no. II].

OBJECTIVE: To observe the clinical effect of combined treatment of hepatic artery chemoembolization (HACE) and Chinese herbal medicine (CHM) in treating middle-advanced stage liver cancer. METHODS: Sixty patients with middle-advanced stage liver cancer were randomly divided into two groups. The 30 patients in Group A were treated with combined HACE and Chinese herbal medicine (Gan'ai No. I and No. II) and the other 30 in Group B were treated with HACE alone. All patients were followed up for over 3 years. RESULTS: The 0.5-, 1- and 2-year survival rate in Group A was 76.7%, 56.7% and 30.0% respectively, and those in Group B was 50.0%, 33.3% and 16.7% respectively. The 1- and 2-year recurrence rate in Group A was 43.3%, 66.7% and that in Group B was 66.7%, 90.0% respectively. Moreover, Group A was significantly superior to Group B in tumor shrinking, AFP decreasing and blood leucocyte reducing (P < 0.01), as well as in improving clinical symptoms. CONCLUSION: The combined treatment has obvious effect in treating middle-advanced stage liver cancer.

Cloning and characterization of PHIP, a novel insulin receptor substrate-1 pleckstrin homology domain interacting protein.

Insulin receptor substrate-1 (IRS-1) protein is a major substrate of the insulin receptor tyrosine kinase and is essential for transducing many of the biological effects of insulin including mitogenesis, gene expression, and glucose transport. The N terminus of IRS-1 contains a pleckstrin homology (PH) domain that is critical for recognition and subsequent phosphorylation of IRS-1 by the activated insulin receptor. Here we report the isolation of a novel protein, PHIP (PH-interacting protein), which selectively binds to the PH domain of IRS-1 in vitro and stably associates with IRS-1 in vivo. Importantly, mutants of the IRS-1 PH domain that disrupt the PH fold fail to bind to PHIP. Anti-phosphotyrosine immunoblots of PHIP revealed no discernible insulin receptor-regulated phosphorylation, suggesting that PHIP is not itself a substrate of the insulin receptor. In contrast to full-length PHIP, overexpression of the PH-binding region of PHIP has a pronounced inhibitory effect on insulin-induced IRS-1 tyrosine phosphorylation levels. Furthermore, expression of this dominant-negative PHIP mutant leads to a marked attenuation of insulin-stimulated mitogen-activated protein kinase activity. We conclude that PHIP represents a novel protein ligand of the IRS-1 PH domain that may serve to link IRS-1 to the insulin receptor.

Determination of glycyrrhizin in radix glycyrrhizae and its preparations by capillary zone electrophoresis.

A capillary zone electrophoresis method was set up for the separation and determination of glycyrrhizin in Chinese medicinal preparations. Concentrations of Na(2)B(4)O(7) were optimized, which showed that glycyrrhizin in the sample could be separated from interference in the running buffer of 30 mmol/L Na(2)B(4)O(7). Using declofenac as internal standard, the simple method was linear in the range 25-300 microg/mL of glycyrrhizin, and good reproducibility was obtained. The extracts of Radix glycyrrhizae and its preparations could be injected directly for analysis without any pretreatment.