Research progress on bone defect repair materials / 中国骨伤

In the process of repairing of bone defects, bone scaffold materials need to be implanted to restore the corresponding tissue structure at the injury. At present, the repair materials used for bone defects mainly include autogenous bone, allogeneic bone, metal materials, bioceramics, polymer materials and various composite materials. Different materials have demonstrated strong reconstruction ability in bone repair, but the ideal bone implants in the clinic are still yet to be established. Except for autogenous bone, other materials used in bone defect repair are unable to perfectly balance biocompatibility, bone formation, bone conduction and osteoinduction. Combining the latest advances in materials sciences and clinical application, we believe that composite materials supplementedwith Chinese medicine, tissue cells, cytokines, trace elements, etc. and manufactured using advanced technologies such as additive manufacturing technology may have ideal bone repair performance, and may have profound significance in clinical repair of bone defects of special type. This article reviewed to the domestic and foreign literature in recent years, and elaborates the current status of bone defect repair materials in clinical application and basic research in regard to the advantages, clinical options, shortcomings, and how to improve the autogenous bone, allogeneic bone and artificial bone materials, in order to provide a theoretical basis for clinical management of bone defects.

General considerations of model-based meta-analysis / 中国临床药理学与治疗学

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Reversed vascularized second metatarsal flap for reconstruction of Manske type IIIB and IV thumb hypoplasia with reduced donor site morbidity / 中华医学杂志(英文版)

BACKGROUND@#The predominant method for Manske type IIIB and IV thumb hypoplasia is pollicization. However, for those who are not willing to sacrifice the index finger, a method that could reconstruct a functionally capable and aesthetically acceptable thumb remains desirable. This study aimed to investigate and assess the functional and radiographic outcomes of utilizing a reversed vascularized second metatarsal composite flap for thumb reconstruction as a new alternative.@*METHODS@#From May 2014 to January 2017, 15 patients with Manske type IIIB or IV thumb hypoplasia who were admitted to the Department of Hand Surgery, Beijing Jishuitan Hospital were included in this study. An osteocutaneous flap containing a section of second metatarsal and its distal head was transferred in reversed position to reconstruct carpometacarpal joint. The donor site was reconstructed by a split half of the third metatarsal. Various functional reconstructions were commenced at second stage. The reconstructed thumbs were evaluated using the Kapandji score, pinch force, and the capacities of performing daily activities through a detailed questionnaire.@*RESULTS@#Among these 15 patients (seven type IIIB and eight type IV), there were ten boys and five girls with median age of 4.2 years (range: 2.0-7.0 years). There were seven right, three left, and five bilateral thumbs for whom only the right thumb received surgery. There were 14 metatarsal flaps survived (14/15). With an average follow-up of 19.2 months, the reconstructed thumbs had acceptable functional and aesthetic outcomes and the donor foot presented in decent appearance without signs of impaired function. All 15 children have improved the Kapandji score (from 0 to an average of 6.7), pinch force (from 0 to an average of 1.5 kg), with ability of grip and pen holding. X-ray indicated continuous bone growth. Patients and parents had good acceptance of the new thumb.@*CONCLUSIONS@#Reconstruction of an unstable hypoplastic thumb (Manske type IIIB and IV) with use of a vascularized metatarsal is an effective strategy. It offers an alternative solution for parents insisting on saving the thumb.

Up-Regulation of MiR-1915 Inhibits Proliferation, Invasion, and Migration of Helicobacter pylori-Infected Gastric Cancer Cells via Targeting RAGE

PURPOSE: Helicobacter pylori (HP)-infected gastric cancer (GC) is known to be a fatal malignant tumor, but the molecular mechanisms underlying its proliferation, invasion, and migration remain far from being completely understood. Our aim in this study was to explore miR-1915 expression and its molecular mechanisms in regulating proliferation, invasion, and migration of HP-infected GC cells. MATERIALS AND METHODS: Quantitative real-time PCR and western blot analysis were performed to determine miR-1915 and receptor for advanced glycation end product (RAGE) expression in HP-infected GC tissues and gastritis tissues, as well as human gastric mucosal cell line GES-1 and human GC cell lines SGC-7901 and MKN45. CCK8 assay and transwell assay were performed to detect the proliferation, invasion, and migration capabilities. MiR-1915 mimics and miR-1915 inhibitor were transfected into GC cells to determine the target relationship between miR-1915 and RAGE. RESULTS: MiR-1915 was under-expressed, while RAGE was over-expressed in HP-infected GC tissues and GC cells. Over-expressed miR-1915 could attenuate cellular proliferation, invasion, and migration capacities. RAGE was confirmed to be the target gene of miR-1915 by bioinformatics analysis and luciferase reporter assay. Moreover, HP-infected GC cellular proliferation, invasion, and migration were inhibited after treatment with pcDNA-RAGE. CONCLUSION: MiR-1915 exerted tumor-suppressive effects on cellular proliferation, invasion, and migration of HP-infected GC cells via targeting RAGE, which provided an innovative target candidate for treatment of HP-infected GC.

Reversed vascularized second metatarsal flap for reconstruction of Manske type IIIB and IV thumb hypoplasia with reduced donor site morbidity / 中华医学杂志(英文版)

Background@#The predominant method for Manske type IIIB and IV thumb hypoplasia is pollicization. However, for those who are not willing to sacrifice the index finger, a method that could reconstruct a functionally capable and aesthetically acceptable thumb remains desirable. This study aimed to investigate and assess the functional and radiographic outcomes of utilizing a reversed vascularized second metatarsal composite flap for thumb reconstruction as a new alternative.@*Methods@#From May 2014 to January 2017, 15 patients with Manske type IIIB or IV thumb hypoplasia who were admitted to the Department of Hand Surgery, Beijing Jishuitan Hospital were included in this study. An osteocutaneous flap containing a section of second metatarsal and its distal head was transferred in reversed position to reconstruct carpometacarpal joint. The donor site was reconstructed by a split half of the third metatarsal. Various functional reconstructions were commenced at second stage. The reconstructed thumbs were evaluated using the Kapandji score, pinch force, and the capacities of performing daily activities through a detailed questionnaire.@*Results@#Among these 15 patients (seven type IIIB and eight type IV), there were ten boys and five girls with median age of 4.2 years (range: 2.0-7.0 years). There were seven right, three left, and five bilateral thumbs for whom only the right thumb received surgery. There were 14 metatarsal flaps survived (14/15). With an average follow-up of 19.2 months, the reconstructed thumbs had acceptable functional and aesthetic outcomes and the donor foot presented in decent appearance without signs of impaired function. All 15 children have improved the Kapandji score (from 0 to an average of 6.7), pinch force (from 0 to an average of 1.5 kg), with ability of grip and pen holding. X-ray indicated continuous bone growth. Patients and parents had good acceptance of the new thumb.@*Conclusions@#Reconstruction of an unstable hypoplastic thumb (Manske type IIIB and IV) with use of a vascularized metatarsal is an effective strategy. It offers an alternative solution for parents insisting on saving the thumb.

PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China / 亚洲男科学杂志(英文版)

Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.

Bilateral maxillary bisphosphonate-related osteonecrosis of the jaw: a case report / 北京大学学报(医学版)

Bisphosphonate-related osteonecrosis of the jaw (BRONJ),as one serious side-effect of bisphosphonate therapy,has been known for more than ten years since it was first reported in 2003.In the majority of the cases,BRONJ occurs more commonly in the mandible.Those involving the maxilla are relatively few.This paper reported a case that a patient with multiple myeloma developed bilateral maxillary BRONJ after tooth extraction.The patient had used bisphosphonates for more than three years,meanwhile with uncontrolled diabetes mellitus.The patient recovered completely after surgical treatment,in combination with diabetes disease control and antibiotics application.Two key factors to ensure the success of surgical treatment are as follows:sufficient removal of infected and necrotic tissue,and good blood-supply for the local flap to help completely close the wound.The literature was reviewed to analyze the reasons why bone necrosis related to bisphosphonates was most likely to occur in the jaw,especially in the mandible,according to the pathogenesis of this disease.Furthermore,the related risk factors of BRONJ presented in this case were discussed,such as tooth extraction,oral infection and diabetes mellitus,etc.We summarized adjuvant prophylaxes for prevention of BRONJ after tooth extraction,for example,drug holiday that could be used in the dental clinic.This case report reminds us that it's of great importance to establish the awareness that the osteonecrosis of the jaw may be related to the use of some bone-stabilizers.As for patients with a history of exposure to antiresorptive or antiangiogenic agents,dentists are supposed to be cautious.It's recommended to take appropriate measures in perioperative period of oral surgical treatment to prevent BRONJ.

UPLC-MS/MS determination of tanshinone ⅡA, salvianolic acid B and ginsenoside Rg₁ in Fufang Danshen preparation in rat plasma and brain tissues / 中国中药杂志

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of tanshinone ⅡA(TSⅡA), salvianolic acid B(SAB) and ginsenoside Rg₁ (GRg₁) in rat plasma and brain tissues. Male healthy Sprague-Dawley(SD) rats were orally given single dose of Fufang Danshen preparation (TS ⅡA 60 mg•kg⁻¹, SAB 300 mg•kg⁻¹, GRg₁ 150 mg•kg⁻¹, borneol 300 mg•kg⁻¹), and their blood samples and brain tissues were collected at different time points. The drug plasma and brain tissue concentrations of the three analytes were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma and brain tissues were calculated by using Phoenix WinNolin 6.1 software. The methodological test showed that all of analytes in both plasma and brain homogenate exhibited a good linearity within the concentration range(r>0.992 2). Their mean recoveries were between 58.86% and 112.1%. Intra-day and inter-day precisions of the investigated components exhibited RSD≤9.7%, and the accuracy(RE) ranged from -9.68% to 8.20% at all quality control levels. The results of accuracy and stability meet the requirements for biopharmaceutical analysis. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.58±0.081) h, (725.4±88.20) μg•L⁻¹, (2 101.3±124.85) μg•h•L⁻¹ and (3.66±0.05) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.29±0.21) h, (307.9±46.75) μg•L⁻¹, (537.4±88.24) μg•h•L⁻¹ and (2.08±0.11) h, respectively. For GRg₁, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.42±0.20) h, (460.38±154.60) μg•L⁻¹, (383.4±88.16) μg•h•L⁻¹ and (1.87±0.046) h, respectively. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the brain tissue were (0.75±0.22) h, (1.41±0.42) ng•g⁻¹, (4.34±2.48) ng•h•g⁻¹ and (4.00±1.90) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.08±0.20) h, (21.09±4.850) ng•g⁻¹, (14.83±3.160) ng•h•g⁻¹ and (0.99±0.08) h, respectively. For GRg₁, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (0.50±0.16) h, (130.96±54.220) ng•g⁻¹, (136.24±34.350) ng•h•g⁻¹ and (2.87±0.33) h, respectively. The developed method was successfully applied in pharmacokinetic studies on content of TS ⅡA, SAB and GRg₁ in rat plasma and brain tissues.

Modeling and simulation activities to design sampling scheme for population pharmacokinetic study on amlodipine / 药学学报

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.

Effect of nicotinamide mononucleotide on insulin secretion and gene expressions of PDX-1 and FoxO1 in RIN-n5f cells / 中南大学学报(医学版)

Objective To investigate the effect of nicotinamide mononucleotide (NMN) on insulin secretion and gene expressions of pancreatic and duodenal homeobox 1 ( PDX-1 ) and forkhead box-containing protein O-1 ( FoxO1 ),which were important transcription factors for insulin secretion.Methods Insulin secretion level in RIN-m5f cells was detected by rat insulin ELISA detection kit.The mRNA expression levels of PDX-1 and FoxO1 in RIN-m5f cells were analyzed by real-time PCR.The protein expression of PDX-1 was measured by Western blot.Results Insulin secretion levels in RIN-m5f cells treated with repaglinide ( 10 nmol/L) plus NMN ( 100 μnol/L) was significantly higher than those in the blank control,the DMSO control group,and the NMN (50μmol/L) treated group (P ＜0.05 ).The mRNA expression levels of PDX-1 in RIN-m5f cells treated with NMN ( 10,50 and 100 μmol/L) for 36 h were significantly higher than those in the control group (P ＜0.05,P ＜ 0.01,and P ＜ 0.001,respectively).There was marked differences in the mRNA expression levels of PDX-1 among different concentrations of NMN (P ＜0.001 ),but no significant differences in the mRNA expression level of FoxO1 ( P ＞ 0.05).No significant difference was found in the protein expression levels of PDX-1 in RIN-m5f cells treated by NMN (50,100,and 200 μmol/L) for 36 or 48 h compared with the control group (P ＞ 0.05).Conclusion NMN can stimulate insulin secretion and upregulate the mRNA expression of PDX-1 in RIN-m5f cells.

High-performance liquid chromatography-mass spectrometry for determining olmesartan in human plasma / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a simple and rapid HPLC-MS method for determining the contents of olmesartan in human plasma.</p><p><b>METHODS</b>Plasma were precipitated with trifluoroacetic acid, then analyzed on an HyPurity C(18) column (150 mm 2.1 mm, 5 microm). Samples at 40 degrees celsius;. The mobile phase consisted of water-methanol- acetonitrile(14:60:26) with a flow rate of 0.22 ml/min.</p><p><b>RESULTS</b>The lower limit of qualification was 25 microg/L. The calibration curve was linear over the range of 25-3200 microg/L (r=0.9998), with the intra-day and inter-day RSD less than 15%.</p><p><b>CONCLUSION</b>The method is sensitive, rapid and suitable for the study of pharmacokinetics and bioavailability of olmesartan.</p>

Determination of amodiaquine in human plasma by high performance liquid chromatography / 中国新药与临床杂志

AIM:To establish HPLC method for the determination of amodiaquine in human plasma.METHODS: Amodiaquine and internal standard(hydroxychloroquine) were analyzed on C18 column(150 mm ×4.6 mm, 5 μm) with methanol: water:triethylamine: orthophosphoric acid (21:77.5:1:0.5 )as mobile phase at the flow rate of 1.0 mL · min-1The UV detector was set at 294 nm. RESULTS: The retention times of amodiaquine and internal standard were 5.82, 8.56 min, respectively. The calibration curve was linear in the range from 10 to 1 000 μg ·L- 1 ( r = 0.999 8, n = 9 ). The limit of quantitation was5 μg· L-1. The extraction recovery was between 75.5 % and 82.7 %, and the methodological recovery was between 97.0 % and 104.8 %. The intra-day and inter-day RSD were less than 6.0 % and 7.5 %, respectively. CONCLUSION: This HPLC method is simple, sensitive and suitable for pharmacokinetic study of amodiaquine.

Study on the relative bioavailability of diclofenac sodium extended action tablet in human body / 中国医师杂志

0.05)in healthy volunteers.

Content Determination of Gatifloxacin in Human Plasma by HPLC / 中国药房

OBJECTIVE: To establish a HPLC method for content determination of gatifloxacin in human plasma.METHODS: The Analytical column was C18,the mobile phase consisted of acetonitrile-30mmol/L ammonium acetate-triethylamine-orthophosphoric acid (20∶80∶1.0∶0.7) with a flow rate of 1.0ml/min,the detection was performed at UV 294nm.RESULTS: The calibration curve was linear in the concentrations ranging from 0.1 to10.0?g /ml (r=0.9 992).The detection limit was 0.05?g/ml.The intraday RSD was less than 8% and interday RSD was less than 10%.The average recovery was (101.67?3.06)%.CONCLUSION: The method is simple, sensitive, accurate and suitable for determination of gatifloxacin in human plasma and pharmacokinetic study.

Reversal effect of cinobufacine on adriamycin resistancehuman breast cancer cells / 中国药理学通报

Aim To investigate the reversal effect of cinobufacine(Cino)on adrimycin(ADM)resistant human breast cancer cell line MCF-7/ADM.Methods The cytotoxic effect of Cino or ADM and the sensitivity of ADM to cells was determined by MTT assay.The intracellular concentration of ADM was detected by HPLC. The expression of P-glycoprotein(P-gp)was examined by flow cytometric(FCM) .Results The maximum non-toxic dose Cino(15 mg?L-1) increased the sensitivity of ADM in MCF-7/ADM,decreased the IC50 of ADM in MCF-7/ADM from 38.14 mg?L-1 to 12.93 mg?L-1, and significantly increased the intracellular concentration of ADM in MCF-7/ADM and reduced the expression of P-glycoprotein.Conclution The results showed that Cino can partially reverse multidrug resistance(MDR)of MCF-7/ADM cells and the mechanism might be associated with the increase of intracellular accumulation of ADM and the reduced expression of P-glycoprotein(P-gp)in MCF-7/ADM cells.

A STUDY ON THE NUTRITIVE VALUE OF INFANT STAPLE FOOD SPRAYS IN RATS / 营养学报

Three infant staple food sprays were studied. Preparation A contained 17.5% cow's milk powder, preparations B and C contained 30% and 26% soybean powder respectively, preparations A and B both contained 22% cane sugar; while C was without cane sugar. Other components in these 3 sprays were mainly rice powder and a little amount of soybean oil and whole egg powder. 3 preparations were fed to 3 groups of male weaning rats for 4 weeks. As indicated by parameters such as body weights gained, FE, CE and PER, preparation C had a significantly higher value than A and B. A and B got a practically similar results. Those effects were also true in a repletion test. The BV and nitrogen balance values were similar among these 3 preparations. There was no prominent effect on serum osmotic pressure in rats fed 22% cane sugar for 4 weeks, but had a lower caloric utilization in group A and B as compared with group C