Thinking and practice of risk-based monitoring strategies in Investigator initiated Trials / 中华医学科研管理杂志

Objective:To discuss the scientificity and feasibility of risk-based monitoring strategies in Investigator initiated Trials.Methods:" Guideline for Good Clinical Practice" promulgated by NMPA, " Oversight of Clinical Investigations-a Risk-based Approach to Monitoring" and " A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers Guidance for Industry DRAFT GUIDANCE" promulgated by the US FDA and other documents were analyzed, the practical experience of Investigator initiated Trials was also summarized.Results:It was recommended that clinical investigators use risk-based monitoring strategies in Investigator initiated Trials. The main idea of risk-based monitoring is to determine the key process and key data of the study, carry out risk rating on the project, and adopt corresponding monitoring methods according to the risk level when formulating the monitoring plan. At the same time, during the clinical trial development process, the risk and data quality of the research center should be regularly evaluated to grasp the risk changes of different centers. In accordance with trends, adjust the method, content and frequency of monitoring.Conclusions:To apply risk-based monitoring strategies in Investigator initiated Trials is scientificity and feasibility. Risk based monitoring can meet the data quality requirements of clinical trials, without affecting the analysis results of the main outcomes, and can further improve the efficiency and effectiveness of monitoring.

Analgesic effect of buccal acupuncture on patients after lumbar spinal fusion: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of buccal acupuncture on pain after lumbar spinal fusion.@*METHODS@#Sixty patients undergoing lumbar spinal fusion were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 1 case was eliminated). The patients in the control group were treated with routine anesthesia. On the basis of the control group, the patients in the observation group were treated with buccal acupuncture at bilateral back point, waist point, and sacral point for 30 min per treatment. The first acupuncture was given before anesthesia induction, and then once a day postoperation for two days, totally 3 treatments. The dosage of sufentanil, the number of remedial analgesia, and the incidence of nausea and vomiting within 48 h after surgery were compared between the two groups; rest and motion visual analogue scale (VAS) scores at 2 (T1), 8 (T2), 12 (T3), 24 (T4), and 48 (T5) h after surgery were observed; the quality of recovery-15 scale (QoR-15) at 24 and 48 h after surgery were evaluated.@*RESULTS@#The dosage of sufentanil and the number of remedial analgesia within 48 h after surgery in the observation group were lower than those in the control group (P<0.01). There was no significant statistically difference in rest and motion VAS scores between the two groups in T1, T2, T3, T4 and T5 (P>0.05). The QoR-15 scores in the observation group at 24 and 48 h after surgery were higher than those in the control group (P<0.01). The incidence of nausea in the observation group was lower than that in the control group (P<0.05).@*CONCLUSION@#Buccal acupuncture could reduce the amount of postoperative analgesic drugs of patients after lumbar spinal fusion, and promote early postoperative recovery.

Discussion on management strategies of multi-center pharmaceutical clinical study initiated by investigator / 中华医学科研管理杂志

Objective:Discuss the problems of multi-center pharmaceutical clinical trial which initiated by investigator (IIT), providing references for developing study management strategies.Methods:By analyzing the site recruitment, academic and ethical review, study contract, study training, quality control, influencing factors of subject enrollment, proposed management strategies of multi-center pharmaceutical clinical study which initiated by investigator.Results:While conducting multi-center pharmaceutical clinical study initiated by investigator, the study experiences, study team, hospital equipment, and the internal process of hospitals are the factors which ensure the progress and quality of clinical study. Most of the sites have no clear statement of scientific review, but most of the high-level hospitals do not use the ethical review results of the head hospitals, the ethics must be reviewed repeatedly; Contract also has different requirements due to different management departments. During the preparation and implement of IIT, the investigators should undergo a rigorous training which is a key element to ensure the quality of the study. Research quality and progress restrict each other and are affected by many factors, detailed quality control measures should be developed, training and inspection, and the cooperation of project management and data management, also with discover the data problems of sites and communicate with investigators timely to ensure the improvement measures are implemented.Conclusions:There are many factors have impact on study progress and quality of multi-center pharmaceutical clinical trial of IIT. Before conducting research, protocols should be developed scientifically, and fully assessing its feasibility, screening study sites strictly, shorten the time of ethical review and contract preparation. Study training, inspection, data management, risk management and document management should be implement strictly, and make full use of information platforms and means, improve management efficiency and IIT progress and quality.

Incidence of major autoimmune diseases of the nervous system in China / 中华神经科杂志

Autoimmune diseases of the nervous and muscle systems constitute a major disease category in neurology, characterized by high disability and heterogeneity. However, incidences for this group of disorders are still unknown in China at the national level. The emergence of the national Hospital Quality Monitoring System (HQMS) provides comprehensive data for epidemiological studies of rare diseases, and the systematism, accuracy and consistency during data collection of HQMS information provide a unique advantage for the investigation of the incidence of rare diseases. Currently, the incidence of major neurological autoimmune diseases based on HQMS has been accomplished and published. In conjunction with clinical practice and research progress of this field, the incidence studies of multiple sclerosis, neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, Guillain-Barré syndrome, and myasthenia gravis are summarized. The completion of survey of disease incidence is instrumental to investigate the prevalence of this group of diseases. Ultimately, the outcome would benefit neurologists as well as health care policy makers.

Construction and mechanism of dry eye model in mice with ocular surface iron overload / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish a dry eye mouse model of iron overload by intraperitoneal injection of iron dextran and preliminarily explore its possible mechanism.METHODS: A total of 40 male C57BL/6 mice(taking the right eye as the experimental eye)were divided into 4 groups by random number table method: There were 10 mice in the control group, each time by intraperitoneal injection of 0.2mL of normal saline; Low-dose group, middle-dose group and high-dose iron group with 10 mice in each group were the model group. Each time, 0.2mL of iron dextran solution with concentrations of 12.5, 25, and 50 mg/mL was injected intraperitoneally. One injection 3d for a total of 28d. We observed the ocular surface inflammation index, corneal fluorescein staining, tear break-up time(BUT)and Schimer I test(SIt)on the 7, 14 and 28d after injection and evaluated the degree of dry eye and ocular surface inflammation. After 28d, the mice were sacrificed for cornea, conjunctiva and lacrimal glands tissue for HE staining, Prussian blue staining and tissue iron detection, to evaluate the inflammatory reaction and iron overload. The expression of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α)and matrix metallo proteinase-9(MMP-9)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS: Compared with the control group, the mice in the model group showed a series of dry eye symptoms, the inflammation index of ocular surface in mice were increased, the score of corneal fluorescein staining increased, the BUT shortened and the amount of tear secretion decreased(all P&#x003C;0.05). The cornea, conjunctiva and lacrimal gland tissues of the mice were damaged to varying degrees, the iron deposition on the eye surface of the model group was more serious than that of the control group, and the iron content of the tissue was significantly increased than the control group(all P&#x003C;0.01). The contents of inflammatory factors(IL-1β, TNF-α, MMP-9)in the cornea, conjunctiva and lacrimal gland tissue of the mice in the model group were significantly higher than those of the control group(all P&#x003C;0.01). With the increase of injection time and concentration of iron dextran, the degree of dry eye and ocular surface inflammation in mice gradually increased. CONCLUSION: The mouse iron overload dry eye model was successfully established by intraperitoneal injection of iron dextran, the mechanism may be related to the ocular surface inflammation aggravated by iron overload.

Efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore whether efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization. METHODS: A total of 50 healthy C57BL/6 male mice aged 6-8wk were randomly divided into normal control group, iron group, inhibitor group, enhancer group and solvent control group, with 10 mice in each group. The normal control group was injected intraperitoneally with 0.2mL of normal saline, and the other groups were injected intraperitoneally with 50mg/mL iron dextran of 0.2mL, once every 3d. From the 14d, the inhibitor group, the enhancer group and the solvent control group were injected intraperitoneally with the same volume(0.2mL)50mg/kg XMD8-92, 10mg/kg simvastatin and 50% DMSO solvent once a day, respectively. The anterior segment of the eyes was observed under slit lamp microscope on the 7, 14, 28d after intraperitoneal injection, and the ocular surface inflammation index and corneal fluorescein staining score were evaluated. The cornea, conjunctiva and lacrimal gland tissues were taken at 28d for the HE staining and immunofluorescence staining, and RT-PCR were used to detect the expression of macrophage polarization related indexes(CD86, CD206, iNOS, Arg-1); Western blot were used to detect the expression of efferocytosis related signal factors(Gas6, MerTK); ELISA was used to detect the expression of inflammatory factors(IL-1β, TNF-α, MMP-9).RESULTS: After injection for 28d, compared with the normal control group, the ocular surface inflammatory index and corneal fluorescein staining score were increased in the iron group and the solvent control group. HE staining showed incomplete corneal epithelium, reduced conjunctival goblet cells, unclear lacrimal gland structure and relatively disordered arrangement of cells. In all tissues, the expressions of polarization related indexes of M1 macrophages such as CD86 and iNOS were up-regulated, while those of M2 macrophages such as CD206 and Arg-1 were down-regulated, and the expressions of inflammatory factors such as IL-1β, TNF-α and MMP-9 were up-regulated(all P&#x003C;0.05). Compared with the iron group and the solvent control group, the ocular surface inflammation index and corneal fluorescein staining score of the inhibitor group were further increased. HE staining showed obvious exfoliation of corneal epithelium, further decrease or even disappearance of conjunctival goblet cells, disorder of lacrimal gland structure and irregular arrangement of cells. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was down-regulated(all P&#x003C;0.05), the expression of polarization related indexes of M1 macrophages such as CD86 and iNOS and the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 were further up-regulated(all P&#x003C;0.05). But the ocular surface inflammation index and corneal fluorescein staining score decreased in the enhancer group. HE staining showed the integrity of corneal epithelial, the increase of conjunctival goblet cells and the improvement of lacrimal gland structure and morphology. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was up-regulated(all P&#x003C;0.05), and the expression of polarization related indexes of M2 macrophages such as CD206 and Arg-1 was up-regulated, while the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 was down-regulated(all P&#x003C;0.05). CONCLUSION: High-iron environment induces macrophages polarize to M1, which aggravates ocular surface inflammation and tissue damage. Efferocytosis by regulating the polarization of macrophages impact the occurrence of ocular surface inflammation in high-iron environment.

Effect and Involved Mechanism of RSL3-induced Ferroptosis in Acute Leukemia Cells MOLM13 and Drug-resistant Cell Lines / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect and involved mechanism of RSL3 on ferroptosis action in acute leukemia cells MOLM13 and its drug-resistant cells.@*METHODS@#After MOLM13 treated with RSL3, CCK-8 assay was performed to detect cell viability, flow cytometry was used to detect the reactive oxygen species (ROS) level of the cells, RT-qPCR and Western blot were used to detect the expression of glutathione peroxidase 4 (GPX4). After MOLM13/IDA and MOLM13/Ara-C, the drug-resistant cell lines were constructed, the ferroptosis induced by RSL3 was observed. Bone marrow samples were collected from patients with acute monocytic leukemia. RT-qPCR and Western blot were performed to detect the expression of related genes and proteins involved in ferroptosis pathway.@*RESULTS@#RSL3 significantly inhibited the cell viability of MOLM13 and increased the intracellular ROS level, which were partially reversed by ferrostatin-1. The mRNA and protein expression of GPX4 decreased in MOLM13 treated with RSL3. RSL3 inhibited the viability of MOLM13/IDA and MOLM13/Ara-C cells more strongly than that of non-drug resistant cells, also increased the intracellular ROS level . The cytotoxic effects were partially reversed by ferrostatin-1. The mRNA and protein expressions of GPX4 in MOLM13/IDA and MOLM13/Ara-C cells were higher than those in non-drug resistant cells. The mRNA and protein levels of GPX4 in bone marrow of relapsed/refractory acute mononuclear leukemia patients were higher than those of ordinary acute mononuclear leukemia patients.@*CONCLUSION@#RSL3 can induce non-drug resistant cells MOLM13 ferroptosis by inhibiting GPX4 activity. MOLM13/IDA and MOLM13/Ara-C are more sensitive to RSL3 compared with non-drug resistant cells MOLM13, which may be caused by the differences in GPX4 expression. The expressions of GPX4 mRNA and protein in relapsed/refractory acute mononuclear leukemia are higher than those in ordinary acute mononuclear leukemia.

Effect of molecular weight of polyethylene glycol on pharmacokinetics of baicalin / 药学学报

The aim of this study was to investigate the effects of polyethylene glycol (PEGs) with different molecular weights (MW: 400, 1 000, 4 000) on the pharmacokinetics of baicalin, and preliminarily analyze its mechanism. Rats were gavaged with baicalin (168 mg·kg-1) + aqueous solution or baicalin + PEGs solution and plasma samples were collected from 0 to 24 h after administration. The concentration of baicalin and its main metabolite baicalein 6-O-β-D-glucuronide (B6G) were determined at different time points by UPLC-MS/MS, and the pharmacokinetic parameters were calculated with DAS 3.0 software. The results showed that PEGs with different molecular weights could effectively increase the AUC0-t of baicalin and B6G, increase the Cmax, and prolong the t1/2, effectively increasing the concentration of baicalin and B6G in vivo. The mechanism may be by promoting the activity of uridine diphosphate glucuronosyl-transferases 1A8 (UGT1A8) and 1A9 (UGT1A9), thereby increasing the transformation rate of baicalin and B6G. The rate of metabolism of B6G was faster than that of baicalin, suggesting that PEGs had a higher affinity for UGT1A8, and PEG400 had the most significant effect. The purpose of this study was to provide a basis for the clinical safe use of baicalin and other flavonoids and the design of new dosage forms with the participation of PEGs. The animal experiment protocol in this study was approved by the Experimental Animal Ethics Committee of Guizhou Medical University.

Key points for establishing a whole-process clinical research management system / 中华医学科研管理杂志

Objective:To explore the key points and implementation of establishing a whole-process clinical research management system.Methods:Based on the problems in practice, combined with project management experiences, this article analyzed the construction of the whole-process clinical research management system.Results:The establishment of the management system provides a comprehensive and sustainable safeguard for clinical research, as well as the improvement of efficiency and quality of clinical research.Conclusions:The establishment of an effective whole-process management system for clinical research project is a useful exploration of the research service model in China.

Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention / 대한뇌졸중학회지

Background@#and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk. @*Methods@#Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months. @*Results@#Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk. @*Conclusions@#There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

Effect of Polyethylene Glycol 400 on Bile Excretion of Baicalin and Its Main Metabolite / 中国实验方剂学杂志

Objective::To investigate the effect of polyethylene glycol 400 (PEG400) on rat bile excretion of baicalin and its main metabolite [baicalein 6-O-β-D-glucuronide (B6G)], and to analyze its mechanism of action. Method::Rats were randomly divided into baicalin+ water group and baicalin+ PEG400 group, the anesthesia was induced by intraperitoneal injection of 10% chloral hydrate (dose of 4 mL·kg-1) to prepare a rat bile duct intubation model. After the rats were fully awake, rats were given baicalin aqueous solution and baicalin PEG400 solution with dose of 168 mg·kg-1 for baicalin, respectively. And bile was collected from 0 h to 12 h after administration. UPLC-MS/MS was used to determine the concentration of drug excreted through bile at different time periods. Thermo Hypersil GOLD C18 column was used with acetonitrile (A)-0.1% formic acid solution (B) as the mobile phase for gradient elution (0-9 min, 90%-27%B; 9-10 min, 27%-90%B; 10-12 min, 90%B), the flow rate was 0.3 mL·min-1, the column temperature was 30 ℃, the injection volume was 5 μL. The mass spectra were obtained in positive ion mode with electrospray ionization (ESI). The effects of PEG400 on the activities and expressions in rat liver of uridine diphosphate glucuronyltransferase (UGT) 1A8 and UGT1A9 were studied in vitro incubation assay and enzyme linked immunosorbent assay (ELISA). Result::Compared with the baicalin+ water group, in the baicalin+ PEG400 group, the bile cumulative excretions of baicalin and B6G increased by 1.8 times and 2.1 times within 12 h, respectively. PEG400 increased the enzyme activities of UGT1A8 and UGT1A9 by 2.0 times and 1.5 times, and their concentrations in liver were increased by 2.2 times and 1.3 times, respectively. Conclusion::PEG400 can significantly increase the bile excretion of baicalin and its main metabolite B6G by enhancing the activities and expressions of UGT1A8 and UGT1A9, and its promoting effect on bile excretion of B6G is greater than that of baicalin, which provides a basis for the rational clinical application of PEG400 and the design of new dosage forms of flavonoids such as baicalin.

Expression and clinical significance of Cripto-1 and mTOR in cervical cancer / 中国医师杂志

Objective:To study the expression and clinical significance of teratocarcinoma-derived growth factor 1 (Cripto-1) and mammalian target of rapamycin (mTOR)in cervical cancer (CC)cancer tissues.Methods:From January 2012 to May 2017, 152 patients with CC in the 2nd Affiliated Hospital of Chengdu Medical College were selected as CC group, and 40 patients with uterine fibroids as control group. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Cripto-1 and mTOR in 152 cases of CC tissues and 40 cases of normal cervical tissues. The expression difference between the two and their relationship with pathological features and prognosis were statistically analyzed.Results:The relative expression of Cripto-1 and mTOR in CC tissues was significantly higher than that in normal cervical tissues ( P<0.05). There was a significant positive correlation between Cripto-1 and mTOR expression in CC tissues ( r=0.634, P<0.05). The expression of Cripto-1 and mTOR protein in CC tissues were associated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor grade ( P<0.05), but not with age, pathological type, depth of invasion and lymph node metastasis ( P>0.05). The 3-year overall survival (OS) rate of patients with high Cripto-1 expression was not significantly different from that of patients with low Cripto-1 expression ( P>0.05), while the 3-year OS of high mTOR expression group was significantly lower than that of low mTOR expression group (χ 2=5.808, P=0.016). Conclusions:The expression of Cripto-1 and mTOR is increased in CC tissues.Both of them are related to FIGO stage and tumor grade, which may become a new molecular marker for diagnosis, treatment and evaluation of CC.

Content Determination of Nine Constituents in Different Medicinal Parts of Pimpinella thellungiana / 中国实验方剂学杂志

Objective:To develop a method to quantify nine constituents in different medicinal parts of Pimpinella thellungiana, in order to compare the content difference of the nine constituents, namely protocatechuic acid,gallic acid,neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,luteolin-7-O-β-D-glucuronide,isochlorogenic acid A,apigenin-7-O-β-D-glucuronide and isochlorogenic acid C. Method:The analysis was performed on an Agilent TC-C18 column (4.6 mm×250 mm,5 μm) with acetonitrile and mixed acid solution (0.1% phosphoric acid-0.1% glacial acetic acid) as mobile phase for gradient elution. The handover detection wavelengths were at 265 and 325 nm. The column temperature was 20℃, and the flow rate was 1.0 mL·min-1. The experiment data was analyzed using the software of Markerlynx XS. Result:The nine constituents of protocatechuic acid,gallic acid,neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid, luteolin-7-O-β-D-glucuronide,isochlorogenic acid A,apigenin-7-O-β-D-glucuronide and isochlorogenic acid C had a good degree of separation and a good linearity in their respective linear ranges(r>0.999 8). The average recoveries ranged from 99.11% to 100.76%,and the RSD ranged from 0.9% to 2.0% 。The results showed that the contents of the nine constituents had significant differences in different medicinal parts of P. thellungiana. The average contents of the nine constituents were the highest in leaves,which was followed by stem,and the lowest was in root. Conclusion:The study could provide evidence for the quality control,clinical application,and scientific resources utilization of P. thellungiana.

Effect of PEG400 on pharmacokinetics of baicalin and baicalein in gut microbiotadysbiosis rats / 中国中药杂志

The study aimed to establish an UPLC-MS/MS method for the determination of baicalin in rat plasma,in order to study the effect of PEG400 on pharmacokinetics of baicalin and baicalein in normal and gut microbiotadysbiosis rats. Plasma was precipitated with ethyl acetate and determined by UPLC-MS/MS method,with genistein as an internal standard. In terms of specificity,linearity,range,accuracy,precision and stability,the method was suitable for the determination of baicalin in plasma. The gut microbiotadysbiosis rat model was induced through the oral administration with lincomycin hydrochloride(5 g·kg-1·d-1) for one week. Samples of plasma of rats were obtained at different time points,after the rats were administrated with baicalin,baicalin and PEG400. Baicalin in rats were detected by UPLC-MS/MS method,and pharmacokinetic parameters were calculated by DAS 3. 2. 2 software. The results showed that the β-glucosidase activity and the number of colonies in the feces of gut microbiotadysbiosis rats induced by lincomycin hydrochloride were significantly reduced. The Cmaxand AUC0-tof the baicalinand PEG400 group in the intestinal flora were significantly lower than those in the normal rat baicalin and PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the baicalin group and the baicalin+PEG400 group of gut microbiotadysbiosis rats. The Cmaxand AUC0-tof the normal rats baicalin group were significantly higher than those of the gut microbiotadysbiosis rats baicalin group and the baicalin + PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the normal rat baicalein and PEG400 group and the baicalein group. The Cmaxand AUC0-tof the baicalein group in the gut microbiotadysbiosis rats were lower than those in the normal baicalein group,but significantly higher than those in the baicalein and PEG400 group. PEG400 could increase the absorption of baicalin in normal rats,but is ineffective in gut microbiotadysbiosis rats,with no impact on the absorption of baicalein in rats.

Efficacy of Recombinant Human Thrombopoietin and Recombinant Human Interleukin 11 for Treatment of Chemotherapy Indu-ced Thrombocytopenia in Acute Myeloid Leukaemia Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate and compare the clinical efficacy and safety of recombinant human thrombopoietin(rhTPO) and recombinant human interleukin11(rhIL-11) for the treatment of chemotherapy-induced thrombocytopenia in adult acute myeloid leukaemia patients.</p><p><b>METHODS</b>Total of 96 adult acute myeloid leukaemia patients were divided into 3 groups according to randomized controlled method: rhTPO group, rhIL-11 group and control group, 32 cases in each group. The patients in rhTPO group and rhIL-11 received rhTPO of 15000 IU/d and rhIL-11 of 1.5 mg/d, respectively after the standard combined chemotherapy within 24 hours, and patients in control group, received nothing drugs to promote thrombocyte recovery. And rhTPO and rhIL-11 should be stopped when the Plt≥100× 10/L. After chemotherapy, the platelet recovery degree, duration of Plt<50× 10/L, ≥50× 10/L and ≥100× 10/L, the count of infusion thrombocytes, and incidence of adverse reactions all were compared.</p><p><b>RESULTS</b>The duration of Plt<50× 10/L was obviously less than that in control group(P<0.01). The duration of rhIL-11 was less than that in control group, but there was no statistical significance(P>0.05). As compared with that in control group, the Plt count in rhTPO and rhIL-11 groups can faster increase to Plt≥50× 10/L (P<0.01, P<0.05), among them the Plt count in rhTPO group faster increase, but there was no statistical signiticance. As compared with that in control group, the Plt count in rhTPO group and rhIL-11 group can increase to Plt≥100× 10/L (P<0.01), the Plt count in rhTPO group was more obviously increase than that in rhIL-11 group(P<0.05). The count of infusion Plt in rhTPO and rhIL-11 groups was lese than that in control group(P<0.01, P<0.05), and the count of infusion Plt in rhTPO group was less than that in rhIL-11 group(P<0.05). After using rhTPO and rhIL-11, the adverse reactions, such as low fever, induration of injection site, athralgia, nausea and vomiting occured in rhTPO group and rhIL-11 group, but all can be tolerated.</p><p><b>CONCLUSION</b>Both rhTPO and rhIL-11 can reduce the duration of thrombocytopenia and the amount of infused thrombocyte, promote platelet recovery in the patients with acute myeloid leukaemia after chemotherapy, to decreae the risk of bleeding, and reduce incidence of adverse reactions, both of them can be tolerated by patients, and rhTPO is more advantage than rhIL-11, worthy of clinical popularization and application.</p>

Long-term follow - up of percutaneous balloon pulmonary valvuloplasty in pulmonary valve stenosis in 230children / 中华实用儿科临床杂志

Objective To evaluate the safety and efficacy of percutaneous balloon pulmonary valvuloplasty (PBPV)in the treatment of the children with pulmonary stenosis (PS),and to observe the long - term prognosis and analyze the influencing factors. Methods The total of 230 children were collected,who had been diagnosed with pul-monary valve stenosis and had undergone percutaneous balloon pulmonary valvuloplasty between November 1987 and November 2015 in Shandong Provincial Hospital Affiliated to Shandong University. Their ages ranged from 4 months to 17 years,and the follow - up duration lasted from 1 month to 29 years. The data included clinical data and long - term follow - up data of hospitalized children,and the echocardiography data from the healthy peers in the same period. Then the data were analyzed statistically. Results In this study,228 cases of children were successfully performed PBPV, and the success rate was 99％(228 / 230 cases). The pulmonary transvalvular gradient (△P)of preoperation,24 hours postoperatively,half a year postoperatively,2 years postoperatively,5 years postoperatively,and 10 years postope-ratively was (63. 5 ± 23. 8)mmHg (1 mmHg = 0. 133 kPa),(26. 2 ± 11. 1)mmHg,(24. 8 ± 9. 8)mmHg,(20. 9 ± 8. 9)mmHg,(18. 1 ± 8. 7)mmHg,(15. 3 ± 7. 3)mmHg and (15. 3 ± 7. 3)mmHg,respectively. The immediate post-operative △P was significantly lower than that of preoperation (P < 0. 01),and the △P of the most children decreased in the long - term follow - up. The results of Logistic regression analysis showed that valve dysplasia with right ventricu-lar outflow tract stenosis and the immediate postoperative residual transvalvular gradient degree were the risk factors for long term curative effect of PBPV in children who could not reach the best standard. The restenosis rate was 4. 6％(3 /65 cases)with children followed up for more than 10 years. The incidence of long - term follow - up pulmonary valve regurgitation (83％)was significantly higher than that before operation (58％)and short term (68％)after operation, and the degree of regurgitation also increased (P < 0. 05),while the degree of regurgitation of the tricuspid regurgitation decreased gradually during the follow - up (P < 0. 05);the right ventricular diastolic diameter of the patients at 10 years or more after the operation was measured as (19. 27 ± 3. 03)mm,which was significantly higher than that (15. 24 ± 2. 89)mm of the healthy children of at the same term healthy age (P < 0. 05). Conclusions The PBPV has a high success rate in the treatment of children with PS,and it has good medium - long - term curative effect,less com-plications and lower restenosis rate. Therefore,PBPV can be used as the first choice for PS. However,the incidence and degree of pulmonary regurgitation has an increasing trend after PBPV and the right ventricular diastolic diameter is still larger than that of the healthy children. Therefore,the long - term follow - up is necessary out of the hospital.

Specialized division of labor system in effect evaluation of clinical research / 中华医学科研管理杂志

Objective To establish a specialized division of labor system for cerebrovascular disease clinical research and verify the effectiveness of specialized division of labor system in the management of cerebrovascular disease clinical research.Methods Using Delphi method to establish the specialized division of labor system of clinical research,identify personnel responsibilities,access mechanism and access standards.Compare two clinical studies that using and not using this system in terms of clinical research management efficiency,effectiveness of the clinical research progress and quality control.Results Specialized division of labor system can reduce the time spent for research design and preparation,improve the research progress and data integrity,reduce the protocol deviation and the loss of subject follow up.Conclusions Specialized division of labor system can improve the efficiency of clinical research management and improve the research progress and quality.

Miaoling Natto Capsules in protection against myocardial ischemia-reperfusion injury in rats / 中成药

AIM To investigate the protective effects of Miaoling Natto Capsules (MNC) on myocardial ischemia-reperfusion injury (MIR) in rats.METHODS Forty-eight healthy male Sprague-Dawley (SD) rats randomly divided into sham group,model group,positive control group (propranolol),MNC groups (low dose,medium dose,and high dose groups) underwent corresponding 7-day oral administration at a frequency of twice daily (rats of the sham group and the model group were dosed with saline water at 1 mL/100 g).Anesthetized by 8％ chloral hydrate,rat models were made by left anterior descending coronary artery ligation,30 min coronary occlusion followed by 3 h of reperfusion for ST segments and T waves monitoring,and rats in the sham group were performed opening and suture procedures.The rats had their serum levels of acetic transaminase (AST),lactate dehydrogenase (LDH),creatine kinase isoenzyme (CK-MB),cardiac troponin-Ⅰ (cTn-Ⅰ),superoxide dismutase (SOD),malondialdehyde (MDA),and tumor necrosis factor-α (TNF-α) detected,real time ECG changes monitored and myocardial infarction area assessed by TTC.RESULTS Compared with the sham group,the model group was observed with markedly elevated ST segments or high T waves rise,significantly increased activities of CK-MB,LDH,AST and the content of cTnⅠ,MDA,TNF-α,and decreased activity of SOD (P ＜ 0.01 or P ＜ 0.001).Compared with the model group,the positive control group and the low,medium and high dose MNC groups achieved controlled ST segments elevation or greater T waves amplitude,significantly decreased activities of CKMB,LDH,AST and the content of cTnⅠ,MDA,TNF-α increased activity of SOD (P ＜0.01 or P ＜0.05) and mycocardial infact range reduction (P ＜ 0.001).CONCLUSION MNC is protective to rats with myocardial ischemia-reperfusion injury.

The association of lipid profile and bleeding in patients with minor stroke or transient ischemic attack on antiplatelet therapy: subgroup analysis of CHANCE / 中华内科杂志

Objective Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results A total of 59 (1.9％) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95％CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04;95％CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05;95％CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.

Effects of elderly patients with long-term use of proton pump inhibitors for osteoporosis / 重庆医学

Objective To investigate the effect of long-term proton pump inhibitor on osteoporosis in elderly patients.Methods A total of 150 patients with peptic ulcer treated in our hospital from January 2011 to January 2015 were selected as the observation group.150 healthy subjects were selected as the control group.The age,height,body weight and PPI time of the two groups were recorded.The changes of bone mineral density before and after treatment were measured by bone mineral density analyzer,ineluding lumbar L1-4,radial density and ulna density.The changes of bone mineral density were observed and recorded in the observation group before treatment,six months,1 year and 2 years after treatment.Results After treatment,the levels of gastrin were significantly increased in the observation group,and the serum calcium concentration and bone mineral density were significantly decreased (P＜0.05).The density of lumbar vertebrae,radius and ulna was significantly lower in observation group than those of control group (P＜0.05).With the prolongation of PPIs,lumbar vertebrae,radius and ulna density in observation group showed a decreasing trend.Conclusion Long-term application of proton pump inhibitors in elderly patients can cause bone loss.