Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy / 医学前沿

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Efficacy of percutaneous curved kyphoplasty in the treatment of osteoporotic vertebral compression fracture / 中华创伤杂志

Objective:To evaluate the efficacy of percutaneous curved kyphoplasty (PCKP) for the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 70 patients with OVCF admitted to Third People′s Hospital of Datong from May 2020 to December 2021, including 32 males and 38 females, aged 60-89 years [(73.0±8.7)years]. The patients were treated with PCKP (PCKP group, n=20) or percutaneous vertebroplasty (PVP) (PVP group, n=50). The operation time, intraoperative blood loss, length of hospital stay, excellent rate of bone cement distribution at postoperative 1 day, and leakage rate of bone cement were compared between the two groups. In addition, anterior height ratio of the injured vertebrae, upper and lower Cobb angle, visual analogue scale (VAS), and Oswestry dysfunction index (ODI) were measured preoperatively and at postoperative 24 hours and 3 months. Results:All patients were followed up for 3-4 months [(3.0±0.6)months]. There were no significant differences in the operation time, intraoperative blood loss, and length of hospital stay between the two groups (all P>0.05). At postoperative 1 day, the excellent rate of bone cement distribution was 100% in PCKP group (excellent in 13 patients, good in seven, poor in zero), significantly higher than 82% in PVP group (excellent 21 patients, good in 20, and poor in nine). The leakage rate of bone cement was 0%(0/20) in PCKP group, lower than 20% (10/50) in PVP group ( P<0.05). There were no significant differences in the anterior height ratio of injured vertebrae, upper Cobb angle, lower Cobb angle, VAS and ODI between the two groups before operation (all P>0.05). At postoperative 1 day, PCKP group showed significantly higher anterior height ratio of injured vertebrae and significantly lower upper Cobb angle, lower Cobb angle, VAS, and ODI than those in PVP group ( P<0.05 or 0.01). At postoperative 3 months, PCKP group still showed significantly higher anterior height ratio of injured vertebrae and significantly lower upper Cobb angle and lower Cobb angle than those in PVP group ( P<0.05 or 0.01), but there was no significant difference in VAS and ODI between the two groups (all P>0.05). In PCKP group, the anterior height ratio of the injured vertebrae was significantly increased and the upper Cobb angle, lower Cobb angle, VAS, and ODI index were significantly decreased at postoperative 1 day and 3 months when compared with those before operation (all P<0.05). In PVP group, there were no significant changes in the anterior height ratio of the injured vertebrae, upper Cobb angle, and lower Cobb angle at postoperative 1 day and 3 months when compared with those before operation (all P>0.05), but the VAS and ODI were significantly lowered at postoperative 1 day and 3 months when compared with those before operation (all P<0.05). Conclusion:Compared with PVP, PCKP has better diffusion effect of bone cement in the injured vertebrae and lower incidence of bone cement leakage in the treatment of OVCF, which can effectively promote height recovery of the injured vertebrae, relieve the pain early, and improve spinal function.

Application of the SNAP-Ⅳ and the Integrated Visual and Auditory Continuous Performance Test in evaluating attention deficit hyperactivity disorder / 中华实用儿科临床杂志

Objective:To analyze the consistency and correlation between the Chinese Version of Swanson Nolan and Pelham, Version Ⅳ Scale (SNAP-Ⅳ) and the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) in the assessment of attention deficit hyperactivity disorder (ADHD), thus providing a reliable basis for the diagnosis of ADHD, and reducing the misdiagnosis rate and missed diagnosis rate.Methods:Clinical data of children to be diagnosed as ADHD in the Department of Children′s Rehabilitation, Yuying Children′s Hospital of the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to July 2020 were collected.A total of 282 SNAP-Ⅳ and IVA-CPT profiles were collected, and the Kappa test and Pearson test were used to retrospectively analyzed for their consistency and correlation in the diagnosis of ADHD. Results:SNAP-Ⅳ and IVA-CPT were consistent in the diagnosis of ADHD (Kappa value=0.514, total coincidence rate=65.6%, P<0.000 1). Inattention subset scores of SNAP-Ⅳ were consistent with the assessment of ADHD by IVA-CPT (Kappa value=0.485, total coincidence rate=75.5%, P<0.000 1). Inattention subset scores of SNAP-Ⅳ were negatively correlated with the Full Scale Attention Quotient (FAQ) in IVA-CPT ( r=-0.71, P<0.000 1). Hyperactivity-impulsive subscale in the SNAP-Ⅳ and IVA-CPT were consistent in the assessment of hyperactivity-impulsive behavior (Kappa value=0.585, total coincidence rate=81.6%, P<0.000 1). Hyperactivity-impulse subset scores were negatively correlated with the Full Scale Response Control Quotient (FRCQ) in IVA-CPT ( r=-0.74, P<0.000 1). Conclusions:Both SNAP-Ⅳ and IVA-CPT have certain diagnostic potential of ADHD, showing good consistency and correlation.They can be both used to provide a more comprehensive diagnosis basis, thereby reducing the misdiagnosis rate and missed diagnosis rate of ADHD.

Comparison of prediction accuracy between warfarin PPK/PD model and multiple regression dose models / 中国临床药理学与治疗学

AIM: To provide reference for clinical application of warfarin PPK/PD model, the prediction accuracy of warfarin PPK/PD model and 6 dose models established by multiple linear regression were compared. METHODS: Clinical data of inpatients who took warfarin tablets for oral anticoagulant therapy in our hospital were collected, and the predictive values were simulated by PPK/PD model and other 6 models, respectively. SPSS 23.0 software was used for paired t-test of measured value and predicted value. MAE and percentage of prediction deviation were used to evaluate the results, and the prediction deviation box-plot was drawn to compare the total data, different dose groups and different genotypes. RESULTS: A total of 50 patients were included in the study. Among 7 models, only PPK/PD model, Wen et al., and Du Liping et al.'s model had no statistical difference in predicted values and measured values (P>0.05). The prediction accuracy of PPK/PD model was higher among the total data, low and medium doses, and patients with different genotypes.The prediction accuracy of Wen et al. 's model and Li Chuanbao et al.'s model was higher in the high-dose group. CONCLUSION: The PPK/PD model of warfarin has good clinical prediction performance, which is expected to provide reference for accurate administration of warfarin.

Investigation on Drugs for Asthma Control Administered by Pediatric Clinicians-Selection of Inhaled Corticosteroids and Compliance Evaluation of Patients / 中国药房

OBJECTIVE： To provide reference for the selection of inhaled corticosteroids （ICS） in clinic. METHODS： A questionnaire survey was conducted among pediatricians from medical institutions of 11 provinces （districts， cities） to analyze the drug selection and reasons， dosage form selection [by comprehensive score （CS）] of 3 kinds of ICS as budesonide （BUD）， beclomethasone （BDP） and fluticasone （FP）， medication compliance and influential factors （by CS）. RESULTS： A total of 200 questionnaires were sent out， and 196 valid questionnaires were collected with effective rate of 98.00％. Pediatric clinicians preferred BUD as a control drug for asthma in children （158 cases， 80.61％）， followed by FP （22 cases， 11.22％） and BDP （2 cases， 1.02％） and the rest had no tendency （14 cases， 7.14％）. Clinicians who chose BUD mainly believed that the drug had better clinical efficacy， and was more recommended by guidelines and experts， more recognized by patients and so on. In addition， of all inhalation equipment for children asthma， pediatric clinicians believed that parents or children were more easier to master atomizer （CS： 4.04）， followed by pressurized metered dose inhalers （pMDI） （with spacer） （CS： 2.75）， pMDI （without spacer） （CS： 1.71）， dry powder inhalers （DPI） （turbuhaler） （CS： 1.46） and DPI （accuhaler） （CS： 1.08）. For the evaluation of patients’ medication compliance， 48 （24.49％）， 88 （44.90％）， 58 （29.59％） pediatricians thought that the actual administration accounted for ＜50％， 50％-74％， 75％-99％ of the medical order dosages， respectively. Only 2 （1.02％） subjects thought that the patients would fully obey. The main factors affecting children’s medication compliance were worrying about side effects of long-term medication （CS： 9.19）， drug withdrawal after improvement （CS： 8.16）， and children’s treatment incompatibility （CS： 7.82）. CONCLUSIONS： Pediatricians tend to choose BUD as drug for asthma control， and atomizer is treated as the easiest inhalation equipment for children. At the same time， pediatricians have low evaluation on the medication compliance of parents and children.

Genomic DNA detection frequently-used chemotherapeutic drugs and their adverse drug reactions in children with rhabdomyosarcoma / 中华实用儿科临床杂志

Objective To analyze and summarize the results of genomic DNA test findings of chemotherapeutic drugs commonly used in pediatric rhabdomyosarcoma (RMS) in children,and to analyze the relationship between adverse reactions to chemotherapy toxicity and genomic DNA polymorphisms,so as to provide evidence for guiding treatment.Methods Retrospective analysis was conducted in RMS children admitted at Hematology Oncology Center,Beijing Children's Hospital,Capital Medical University from January 2017 to June 2018.The criteria for enrollment were definite diagnosis of RMS,regular treatment and follow-up at Hematology Oncology Center,Beijing Children's Hospital,Capital Medical University,and detection of peripheral blood DNA fluorescence hybridization sequence for several commonly chemotherapy drugs.The toxicity of chemotherapeutic drugs was detected based on the National Cancer Institute routine toxicity criteria (NCI-CTCAE version 4.0).Summary and analysis indicators included primary and metastatic site,size,international RMS clinical stage (TNM-UICC),Intergroup Rhabdomyosarcoma Study (IRS) Clinical Grouping Classification,risk grouping,pathological type,changes in major organ functions,as well as processes of surgery,chemotherapy and radiotherapy,and the association between toxicity and DNA polymorphism of drug genes was analyzed.SPSS 22.0 software was used for x2 test.Results A total of 32 children were enrolled,and 20 cases were male and 12 cases were female,their median age was 50 months (15-120 months).The primary tumor of 9 cases were sited in the chest,abdomen and basin,8 cases in the head and neck (non-meningeal),7 cases in bladder prostate,3 cases in limbs,2 cases in the meningeal area,1 case in urogenital tract (non-bladder prostate),2 cases in other parts.Seventeen cases were embryonic type and 15 cases were alveolar type.Five cases were TNM-Ⅰ stage,5 cases were TNM-Ⅱ stage,10 cases TNM-Ⅲ stage,12 cases were TNM-Ⅳ stage,21 cases were IRS-Ⅲ,11 cases were IRS-Ⅳ.Twenty-two cases were moderate-risk (MR),10 cases were high-risk (HR).Twenty-two cases were detected UGT1A1 * 6 gene,18 cases in GG type,13 cases in GA type,and 1 case in AA type.ABCB1 gene monitoring was performed in 27 children,14 cases of CT type and 13 cases of TT type;29 cases were detected GSTP1 gene,7 cases of GA type and 2 cases of GG type,19 cases of AA type,1 case of AG type;30 cases were detected CYP3A5 gene,2 cases of GA type,13 cases of GG type,AG 15 cases.All patients were treated according to the BCH-RMS-2007 protocol using VAC (Vincristine,Doxorubicin,and Cyclophosphamide) as the basis for chemotherapy.From 2017,VAC and Ⅵ regimen (Vincristine,Irinotecan) were defined as the standard of backbone chemotherapeutic regimen for MR.Nine cases underwent surgery before chemotherapy and 10 cases had surgery after chemotherapy,among them,5 cases underwent twice operation.Local radiotherapy was performed on the 12th week of chemotherapy,and the central nervous system involvement cases started in the first week.Hematological toxicity was mainly caused by neutropenia,with 2 cases of grade 3 and 30 cases of grade 4.Liver function damage of grade 2 was 6 cases,grade 3 was 3 cases.Four patients with grade 1 diarrhea,3 patients with grade 2,5 patients with grade 3,3 patients with grade 4.There was significant difference between the severity of diarrhea and UGT1A1 * 6 genotype polymorphism (P ＜ 0.05).Conclusions Chemotherapy for RMS patients is highly safety.If the genomic DNA test of chemotherapy drugs show a slow metabolism type,the dose of chemotherapy should be reduced,and the toxicity of chemotherapy drugs should be monitored dynamically.

Genomic DNA detection frequently-used chemotherapeutic drugs and their adverse drug reactions in children with rhabdomyosarcoma / 中华实用儿科临床杂志

Objective@#To analyze and summarize the results of genomic DNA test findings of chemotherapeutic drugs commonly used in pediatric rhabdomyosarcoma (RMS) in children, and to analyze the relationship between adverse reactions to chemotherapy toxicity and genomic DNA polymorphisms, so as to provide evidence for guiding treatment.@*Methods@#Retrospective analysis was conducted in RMS children admitted at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from January 2017 to June 2018.The criteria for enrollment were definite diagnosis of RMS, regular treatment and follow-up at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University, and detection of peripheral blood DNA fluorescence hybridization sequence for several commonly chemotherapy drugs.The toxicity of chemotherapeutic drugs was detected based on the National Cancer Institute routine toxicity criteria (NCI-CTCAE version 4.0). Summary and analysis indicators included primary and metastatic site, size, international RMS clinical stage (TNM-UICC), Intergroup Rhabdomyosarcoma Study(IRS) Clinical Grouping Classification, risk grouping, pathological type, changes in major organ functions, as well as processes of surgery, chemotherapy and radiotherapy, and the association between toxicity and DNA polymorphism of drug genes was analyzed.SPSS 22.0 software was used for χ2 test.@*Results@#A total of 32 children were enrolled, and 20 cases were male and 12 cases were female, their median age was 50 months (15-120 months). The primary tumor of 9 cases were sited in the chest, abdomen and basin, 8 cases in the head and neck (non-meningeal), 7 cases in bladder prostate, 3 cases in limbs, 2 cases in the meningeal area, 1 case in urogenital tract (non-bladder prostate), 2 cases in other parts.Seventeen cases were embryonic type and 15 cases were alveolar type.Five cases were TNM-Ⅰ stage, 5 cases were TNM-Ⅱ stage, 10 cases TNM -Ⅲ stage, 12 cases were TNM-Ⅳ stage, 21 cases were IRS-Ⅲ, 11 cases were IRS-Ⅳ.Twenty-two cases were moderate-risk (MR), 10 cases were high-risk (HR). Twenty-two cases were detected UGT1A1*6 gene, 18 cases in GG type, 13 cases in GA type, and 1 case in AA type.ABCB1 gene monitoring was performed in 27 children, 14 cases of CT type and 13 cases of TT type; 29 cases were detected GSTP1 gene, 7 cases of GA type and 2 cases of GG type, 19 cases of AA type, 1 case of AG type; 30 cases were detected CYP3A5 gene, 2 cases of GA type, 13 cases of GG type, AG 15 cases.All patients were treated according to the BCH-RMS-2007 protocol using VAC (Vincristine, Doxorubicin, and Cyclophosphamide) as the basis for chemotherapy.From 2017, VAC and VI regimen (Vincristine, Irinotecan) were defined as the standard of backbone chemotherapeutic regimen for MR.Nine cases underwent surgery before chemotherapy and 10 cases had surgery after chemotherapy, among them, 5 cases underwent twice operation.Local radiotherapy was performed on the 12th week of chemotherapy, and the central nervous system involvement cases started in the first week.Hematological toxicity was mainly caused by neutropenia, with 2 cases of grade 3 and 30 cases of grade 4.Liver function damage of grade 2 was 6 cases, grade 3 was 3 cases.Four patients with grade 1 diarrhea, 3 patients with grade 2, 5 patients with grade 3, 3 patients with grade 4.There was significant diffe-rence between the severity of diarrhea and UGT1A1*6 genotype polymorphism(P<0.05).@*Conclusions@#Chemothe-rapy for RMS patients is highly safety.If the genomic DNA test of chemotherapy drugs show a slow metabolism type, the dose of chemotherapy should be reduced, and the toxicity of chemotherapy drugs should be monitored dynamically.

Olprinone alleviates myocardial ischemia/reperfusion injury via regulating autophagy in rats / 中华急诊医学杂志

Objective To observe the effects of olprinone on ischemia/reperfusion (I/R) induced myocardial injury in male (Sprague-Dawley, SD rats) and explore its mechanisms. Methods Rats were subjected to a 30-min coronary arterial occlusion followed by 24-hour reperfusion. The survival rats were randomly divided into sham group (n=6), ischemia reperfusion group (I/R group, n=9), ischemia reperfusion+low dose of olprinone group(IR+olprinone-L group, n=6), ischemia reperfusion+medium dose of olprinone group (IR+olprinone-M group, n=6),ischemia reperfusion +high dose of olprinone group (IR+olprinone-H group, n=6). A MAP heart function analysis system was used to measure hemodynamic parameters; TTC staining method was used to detect the myocardial infarct size;24-hour mortality of SD rats was recorded; western blot was used to detect the levels of Caspase-3, Bax,Bcl-2, LC3B/LC3A,Beclin-1. Results Cardiac function in I/R group was lower than that in sham group, which was significantly improved by pretreatment with olprinone (P＜0.01),but systolic arterial pressure (SAP) diastolic arterial pressure (DAP) mean arterial pressure (MAP) mean pressure developed in left ventricle (Pmean) had no significant difference (P＞0.05). The percentage of myocardial infarct size in olprinone-M and olprinone-H group was lower than that in I/R group (P＜0.05).There was no significant difference in mortality among groups within 24 hours. Compared with sham group, the expressions of Caspase-3 and Bax were obviously up-regulated in I/R group (P＜0.01), whereas caspase-3 was down-regulated in olprinone-M group (P＜0.05) and Bax was inhibited by different doses of olprinone (P＜0.05), but the expression of Bcl-2 increased (P＜0.05); furthermore, the ratio of Bcl-2/Bax decreased in I/R group (P＜0.01) and increased with different degrees in different doses of olprinone (P＜0.05). Meanwhile, compared with sham group, the expression of Beclin-1 was up-regulated in I/R group(P＜0.05),and also increased in olprinone-L and olprinone-M groups(P＜0.05), but the ratio of Bcl-2 /Beclin-1 decreased in different doses of olprinone making statistically significant difference only in olprinone-M group (P＜0.05). Moreover, different doses of olprinone elevated the different ratios of LC3B/LC3A (P＜0.05), and this elevated ratio in olprinone-M group at median among groups. Conclusions Olprinone can strengthen the cardiac function after myocardial ischemia/reperfusion injury, without leading to disorders in hemodynamics; by regulating autophagy with anti-apoptotic protein, olprinone can make autophagy to an appropriate level using the mechanism of autophagy to preventing the myocardium from injury.

Establishing the pediatric clinical medicine comprehensive evaluation system:exploration of the method and path / 国际药学研究杂志

Due to the weak foundation of clinical trials,the pre-market data of pediatric medicine is insufficient. Therefore,a comprehensive evaluation system of pediatric clinical medicine is urgently needed to safeguard the children′s medication safety. This article provides the method and builds path to establish the comprehensive evaluation system from the aspects of biulding organization?al structure,operational process and evaluation methodology,respectively. Further,based on the concept ofEvidence-based or other?wise evidence-created,and following the example of“Mini-Sentinel”of the United States,the big data in medicine can be used to overcome the“Evidence-created”difficulty in the evaluation of pediatric medication. Thus more extensive comprehensive evaluation can be made through collecting the clinical data generated from the real world for the pediatric medication. In the future ,the compre?hensive evaluation system of pediatric clinical medicine established on the basis of big data can be linked to thePrecision MedicineProject in our country,the evaluation bases can be the Mini-Sentinel to collect big medical data and biological samples,thus to bring a steady flow of power for promoting the pediatric medicine active surveillance and pediatric precision medicine ,and finally to safeguard the children′s health in our country.

Influence factors of depression in patients with diabetic foot / 实用医学杂志

Objective To investigate the prevalence of depression among the patients with diabetic foot and analyze the influence factors. Methods One hundred and ten patients with diabetic foot were inquired and assessed with patient health questionnaire for self-administered measurement (PHQ-9), meanwhile, the demo-graphic data, metabolic data and diabetes behaviors were also investigated. Results Prevalence of depression was 47.3%. Logistic regression analysis showed that alternation of diarrhea and astriction (OR = 6.901, P =0.017) and formication (OR = 23.401, P = 0.009) were risk factors, and medical insurance (OR = 0.217, P =0.007) was a protective factor. Conclusions Depression is a frequent mental disorder in patients with diabet-ic foot and its influence factors include alternation of diarrhea and astriction , formication and medical insur-ance .

Electro-acupuncture combined with surface gastric pacing in the treatment of gastrointestinal dysfunction after spinal cord injury / 中华物理医学与康复杂志

Objective To explore the effects of electro-acupuncture combined with surface gastric pacing on gastrointestinal dysfunction for patients with spinal cord injury (SCI).Methods Seventy-five SCI patients with gastrointestinal dysfunction were divided randomly into an electro-acupuncture group (group A),a gastric pacing treatment group (group B) and a group for which electro-acupuncture was combined with gastric pacing (group C).There were 25 cases in each group.Members of group A were given 30 minutes of electro-acupuncture per day ; those of group B had 30 minutes of gastric pacing treatment twice per day ; group C was provided with both 30 minutes of electro-acupuncture and one 30-minute gastric pacing treatment per day.All of the interventions lasted ten days.Before and after the treatment,all patients were assessed using a clinical symptoms score and with electrogastrograms,and any adverse effects were observed.Results There was a significant improvement in upper abdominal pain and epigastric discomfort,bloating and early satiety,nausea,vomiting,as well as belching and loss of appetite in each group after treatment.Before treatment there was no significant difference in the average clinical symptom scores of the three groups.After treatment the values had decreased,and those of group C were significantly lower than group A or B.The average scores of groups B and A were not significantly different.The electrogastrogram results showed than after treatment there was significant improvement in N％ and T％ in groups A and B,and also significant improvement in N％,B％ and T％ in group C compared to before treatment.Group C's improvements were all significantly greater than those observed in groups A and B.Conclusion Electro-acupuncture or gastric pacing alone can give some improvement in gastrointestinal function and its electrophysiological indicators,but their combined effects are better than when either is used alone.

The combined effect of hyperbaric oxygen and borneol on the permeability of the blood-brain barrier to sodium valproate / 中华物理医学与康复杂志

Objective To observe the effect of hyperbaric oxygen (HBO) combined with borneol on the permeability of the blood-brain barrier to sodium valproate in rats.Methods Fifty-six male,healthy Sprague Dawley rats were randomly divided into a control group which received an intraperitoneal injection of sodium valproate (0.1 g/kg),an HBO-1 group to which HBO was administered 0.5 hours before an equivalent injection of sodium valproate,an HBO-2 group where the HBO and sodium valproate were administered together,an HBO-3 group which received HBO 0.5 hours after the injection,a low dosage borneol group (L-borneol) which received 0.125 g/kg of borneol by oral perfusion 0.5 hours before an injection of sodium valproate (0.1 g/kg),a high dosage borneol group which received 0.25 g/kg of borneol 0.5 hours before an injection of sodium valproate (0.1 g/kg) and a combined group which received the HBO-3 group's treatment supplemented with the borneol dose of the L-borneol group.There were 8 rats in each group.Blood and cerebrospinal fluid (CSF) were collected 1.5 h after the sodium valproate injection and the concentrations of sodium valproate were measured by high performance liquid chromatography.Results Compared with the control group,the CSF concentrations of sodium valproate in the HBO-2 and HBO-3 groups had increased significantly more (to 97.43 ± 12.09 mg/L and 100.10 ± 13.54 mg/L respectively).The ratios of the CSF to plasma (C/P) concentrations had also increased significantly more.The CSF concentration of sodium valproate in the H-borneol group (91.09 ± 9.45 mg/L) and the C/P ratio (0.577 ± 0.051) had increased significantly more than in the control group.Compared with the L-borneol group,there were significantly greater increases in the HBO-3 group and the combined group in the concentration of sodium valproate in the rats' CSF.Compared with the HBO-3 group,the average concentration of sodium valproate in the CSF of the combined group (112.43 ± 11.52 mg/L) and the C/P ratio (0.698 ±0.058) had increased significantly more.There was no significant difference among the groups in the plasma concentrations of sodium valproate.Conclusions HBO can increase the permeability of the blood-brain barrier to sodium valproate,at least in rats.Combining HBO with a low dose of borneol has an additional effect.

A method to determine the structure of the complex of enzyme and its substrate using 6-phosphate-beta-glucosidase at low temperature / 生物工程学报

To capture a state of the enzyme in complex with an intact substrate, we developed and adopted a novel freezing method in crystal preparation procedure. Neither the elimination of the catalytically indispensable ligands, nor mutation or modification of the active site is required. At -20 degrees C, we soaked the crystal of 6-phosphate-beta-glucosidase (Bg1A) in the liquor containing p-nitrophenyl-beta-D-glucopyranoside-6-phosphate (pNPbetaG6P). The diffraction data at 2 A resolution was collected and an intact and unambiguous electron density map of pNPbetaG6P was obtained. These results provide an effective method for the research of cryoenzymology and the intermediate state of enzyme-substrate complex in the future.

Expression, purification and interaction of human leukocyte antigen F and cluster of differentiation 8alpha homodimers / 生物工程学报

To obtain large quantity of human leukocyte antigen F (HLA-F) and cluster of differentiation 8alpha homodimers (CD8alphaalpha) proteins and to study their relationship, HLA-F and CD8alpha genes with rare codon in Escherichia coli were cloned using an N-terminal synonymous mutation method. High-efficiency expression protein inclusion bodies were acquired. The proteins were refolded using the dilution method and purified with gel-filtration and anion exchange chromatography. The results of gel-filtration and native-PAGE indicate that HLA-F interacts with CD8alphaalpha. This interaction may affect the binding between CD8alphaalpha and other MHC molecules to regulate immune responses. These results provide a basis for further research of HLA-F.

Purification and Functional Analysis of Recombinant Nisin Resistance Protein (NSR) Expressed in Escherichia coli / 微生物学通报

Nisin is a cationic antimicrobial peptide produced by some lactic acid bacteria. However, expression of nisin resistance protein (NSR) could confer nisin resistance on some non-nisin-producing Lactococcus lactis. To deeply elucidate molecular mechanism underlying NSR-mediated nisin resistance, an NSR mutant with N-terminal 38 amino acid residues deleted (NSR?38) was overexpressed in Escherichia coli by fusion with GST. Purified NSR?38 was obtained through glutathione (GSH) affinity chromatography followed by cleavage of GST tag. Putative proteolytic activity of NSR?38 was determined in vitro against nisin. Antimicrobial activity analysis revealed that nisin lost its bactericidal activity after incubation with NSR?38. Further reversed-phase high performance liquid chromatography (RP-HPLC) analysis indicated that NSR?38 displayed proteolytic activity against nisin, thus inactivating the antimicrobial peptide. The current study paves the way for in-depth functional studies on NSR.

Compatible Stability of Isosorbide Mononitrate Injection and Dopamine Hydrochloride Injection / 中国药房

OBJECTIVE:To investigate the compatible stability of isosorbide mononitrate(ISO) and dopamine(DA) hydrochloride in glucose injection.METHODS:The contents of ISO and DA in the mixture of ISO and DA at 20 ℃ and 30 ℃ under natural illumination within 24 h,and the pH and appearance of the mixture were monitored.RESULTS:No significant change was noted in the concentrations of ISO and DA,the pH and the appearance of the mixture at 20 ℃ or 30 ℃.CONCLUSION:The mixture of ISO and DA in glucose injection was stable at 20 ℃ or 30 ℃,but which should be used up within 18 h after mixing.

Determination of floxuridine in plasma by HPLC / 中国生化药物杂志

Purpose　 The aim is to establish the HPLC method for the determination of Fluoro-deoxyuridine in plasma.Methods　The Chromatography conditions include: Chromatography column: Nova-pak C18(3.9mm×150mm,4μm), mobile phase: 0.05mol/L sodium phosphate monobasic -methanol-water(0.5∶7∶92.5)， UV detection at 260nm， FUDR was extracted with ethyl acetate. Results　The average recoveries were 96.4%，96.5%，97.8% for concentration 0.23、1.67、20.0μg/ml (n=5).The corresponding reproducibility were RSD 1.61%, 1.98%, 3.17% respectwely for iner-day and RSD 3.56%, 1.90%, 2.63% for the intra-day(n=5). The FUDR concentration was linear with a correlation coefficient of 0.999　4 over the range of 0.099～20.0μg/ml. Conclusion　 The method was sensitive and accurate and suitable for pharmacokinetics and bioavailability study of FUDR.

Compatible Stability of Gatifloxacin for Injection and Tinidazole Injection / 中国药房

OBJECTIVE:To study the compatible stability of gatifloxacin for injection with tinidazole injection.METHO_DS:Contents changes of gatifloxacin and tinidazole within 48h after mixing were determined by HPLC;and the appearance,pH value were observed and determined.RESULTS:The contents changes for both gatifloxacin and tinidazole were less than 5%. The mixed solution was clear in appearance yet without generation of gas and sediments.No significant changes were noted in pH value,color and smell.CONCLUSION:The mixed solution of gatifloxacin for injection with tinidazole injection is stable at room temperature within 48h and which can be applied in combination.

Measurement of anaerobic threshold for evaluation of chronic cardiac failure / 中国病理生理杂志

Cardio-pulmonary exercise was performed in 43 normal subjects and 175 patients with cardiac disease in order to evaluate the severity of heart failure. AT could be determined easily during bicycle ergometer exercise by measuring minute ventination (V_E), oxygen uptake (V_(O2)) and carbon dioxide output (V_(CO2)). Peak V_(O2) and % AT were also determined, Both AT(ml/min/kg) and peak V_(O2) (ml/min/kg) declined with age, how ever male showed higher values than femal in both indiceS, % AT (determined by the predicted AT values of each age and sex), decreased as class of NYHA progressed (i. e. 85.3?10.3% in class Ⅰ, 74.7?14.1% in class Ⅱ, and 58.8?12.8% in class Ⅲ). The reproducibility of AT was excellent in two testing With in a 3-hour interval. These results suggested that indices from cardio-pulmonary exercise testing, especially AT, were closely related to the pathophysiology of heart failure so that they might be used as an objective parameters and were reliable for evaluation of the severity of heart failure and are sensitive enough to detect the efficacy of therapuetic intervention for heart failure.