BACKGROUND: Calcium sulfate/poly amino acid compound materials carrying triple anti-tuberculosis drugs have been proved to have excellent slow release performance based on our preliminary studies on the physical and chemical properties and the release properties of the compound materials.OBJECTIVE: To observe the slow release performance of the calcium sulfate/poly(amino acid) compound material carrying triple anti-tuberculosis drugs in a rabbit model of spinal tuberculosis.METHODS: Twenty-four New Zealand white rabbits were used to make L4-5 spinal tuberculosis models and divided into two groups in a random way following removal of tuberculosis lesions. Calcium sulfate/poly amino acid compound material carrying isoniazide, rifampicin, pyrazinamide or calcium sulfate/poly(amino acid)compound material with no drugs was implanted into the defect in the experimental or control group,respectively. At 2, 4, 6 and 8 weeks after implantation, the concentrations of isoniazid, rifampicin and pyrazinamide in the defect region, including the bone tissue, adjacent psoas major and inferior vena cava,were measured.RESULTS AND CONCLUSION: In the experimental group, the isoniazid levels in the damaged bone tissue and psoas major were kept in minimum bactericidal concentration (MBC) at 8 weeks after implantation and in the minimum inhibitory concentration (MIC) at the end of 12 weeks after implantation, while its level in the vein was kept in MBC at 2 weeks and in MIC at 8 weeks. The rifampicin levels in the bone tissue and psoas major were kept in MBC at 4 weeks after implantation and in the MIC at 8 weeks after implantation, while its level in the vein was kept MIC at 4 weeks.The pyrazinamide levels in the damaged bone tissue and psoas major were kept in MBC at 8 weeks after implantation and in the MIC until 8 weeks after implantation, while its level in the vein was kept MIC at 8 weeks. In the control group,there were no levels of isoniazid, rifampicin and pyrazinamide in the damaged bone tissue, adjacent psoas major and inferior vena cava in comparison with the baseline. These results show that isoniazid, rifampicin and pyrazinamide in the defect region can achieve sustained slow release in the rabbit model of spinal tuberculosis after implantation of the calcium sulfate/poly(amino acid) compound material carrying triple anti-tuberculosis drugs. In addition, the local drug concentration and duration in the defect region are better than those in the blood.

Objective: To explore the effect of intravenous recombinant human brain natriuretic peptide (rhBNP) on regional myocardium deformability in patients with anterior acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI). Methods: A total of 35 patients with anterior AMI who received primary PCI within 12 hours of symptom onset in our hospital from 2013-06 to 2013-12 were enrolled in this study and randomized into 2 groups: rhBNP group, the patients received intravenous rhBNP,n=18, Control group, the patients received standard intravenous nitrates,n=17, and the intravenous pumping administration maintained for 72 hours in both groups. The echocardiography was conducted at immediately, 7 days and 1 month after PCI respectively to compare the relative parameters. The occurrence of major adverse cardiac events (MACE) were followed-up for 6 months in all patients. Results: The baseline condition was similar between the two groups,P>0.05 , the parameters of echocardiography as LVEF and WMSI at immediately and 7 days after PCI were similar between the two groups,P>0.05. Compared with Control group, rhBNP group had the increased LVEF and decreased WMSI at 1 month after PCI ,P<0.05; rhBNP group had increased SRs at 7 days after PCI,P<0.05, while SRe and SRa were similar between the two groups,P>0.05; SRs, SEe and Sra were increased at 1 month after PCI, allP<0.05. The cTnI value in rhBNP group was lower than that in Control group as (50.09 ± 16.88) ng/ml vs (63.24 ± 18.60) ng/ml,P=0.036. The occurrence of MACE was similar between the two group,P>0.05. Conclusion: Intravenous administration of rhBNP could improve the regional myocardium deformability and the systolic/diastolic function in patients with anterior AMI after primary PCI.

Objective:To understand the views of various relevant personnel on the standardized training mode of resident doctors after the implementation of Beijing′s medical education synergy policy, so as to provide references for further improvement of China′s medical education synergy policy.Methods:From January to May 2019, a semi-structured interview method was used to investigate the resident training students, clinical teachers(professional postgraduate tutors and resident training trainees′ guiding doctors)as well as resident training managers in 35 resident training bases in Beijing. The original data of the interviews were sorted out, coded and analyzed by taking root theory and main frame method descriptive analysis.Results:A total of 687 valid interview results were received, of which 71.86% of the resident training managers thought that the mode was more reasonable and the advantages outweighed the disadvantages; 38.07% of the resident training students and 45.45% of the graduate supervisors mentioned that the mode effectively shortened the training time of clinical talents; however, 31.98% of the resident training students and 22.92% of the resident training students′ guiding physicians mentioned it was difficult to balance courses, scientific research and clinical work under this mode, 61.62% of graduate supervisors pointed out that the students were lack of time and energy to engage in scientific research.Conclusions:The training mode of the integration of the standardized training of resident doctors and the postgraduate training of master′s degree in clinical medicine, given its necessity and institutional advantages, is found with room of improvement in its mode setting, arrangement of scientific research courses and clinical rotation, supervision and assessment of the process.

Objective: To observe the effect of ticagrelor for non-ST-segment elevation acute coronary syndrome after percutaneous coronary intervention (PCI). Methods: A total of 200 patients with non-ST-segment elevation acute coronary syndrome after PCI were enrolled in this study.And the patients were randomly divided into the observation group (18 months treatment group, 100 cases) and control group (12 months treatment group, 100 cases) according to the digital table.The control group was given dual antiplatelet therapy (DAPT) for 12 months, and then, suspended the usage of ticagrelor.The observation group was treated by DAPT for 18 months.The major adverse cardiovascular events (MACCE) and the secondary end point events were observed. Results: The incidence rate of MACCE between the two groups had no statistically significant difference (χ²=0.298, P=0.862). And there was no statisticallysignificant difference in the incidence of the secondary end point events between the two groups (χ²=1.963, P=0.375). Conclusion The usage of DAPT beyond or equal 12 months doesn't reduce the incidence of MACC and it will not increase the blooding rate.The use of DAPT (aspirin and ticagrelor) should be used less than 12 months.

Compound homozygous or heterozygous mutations in WFS1 can lead to autosomal recessive Wolfram syndrome (WS),and heterozygous mutations in WFS1 can lead to autosomal dominant non-syndromic low frequency sensorineural hearing loss (LFSNHL).In addition,mutations in the WFS region has relationship with diabetes and psychiatric diseases.In this paper,we provide an overview of genetic research with different phenotypes,including WS and LFSNHL.

Objective:To explore the effects of Nd 2O 3 exposure to rare earth particles on the secretion of sex hormones, cytochrome P450 family member 11A1 (CYP11A1) , spermatogenesis markers promyelocytic leukemia zinc finger protein (PLZF) and retinoic acid stimulating gene 8 (STRA8) protein in C57 BL/6J male mice. Methods:In March 2021, Forty-eight male C57 BL/6J mice aged 6-8 weeks divided into control group and Nd 2O 3 exposure low, medium and high dose groups (exposing doses of 62.5, 125.0, 250.0 mg/ml Nd 2O 3) , 12 per group. The mice in the Nd 2O 3 groups were perfused with different doses of Nd 2O 3 suspension by a one-time non-exposing tracheal instillation method, and the control group was perfused with an equal volume of normal saline, with a volume of 0.1 ml, to establish a mouse reproductive function injury model. After 28 days of exposure, the mice's body weight, testes and epididymis were weighed, and the organ coefficients were calculated; the two epididymis were taken to make a sperm suspension to determine the sperm count, survival rate, and deformity rate; inductively coupled plasma mass spectrometry (ICP-MS) method was used to detect the content of Nd in mouse testis tissue; HE staining was used to detect testicular tissue pathological changes and quantitative analysis; enzyme-linked immunosorbent assay (ELISA) method was used to detect serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) and testosterone (T) content; western blot was used to detect the protein levels of CYP11A1, PLZF and STRA8 in testicular tissues. Results:Compared with the control group, with the increase of the exposure dose, the Nd content in the testis of the mice showed an increasing trend, the sperm survival rate and LH showed a decreasing trend, and the sperm deformity rate showed an increasing trend ( P<0.05) ; Pathological showed that the number of sperm in the seminiferous tubules of the testicular tissue in the Nd 2O 3 medium and high dose groups was significantly reduced, and the germinal epithelial disintegration, intraepithelial vacuolization, and exfoliation of spermatogenic cells and supporting cells occurred; The height of germinal epithelium was significantly reduced, and the percentage of damaged seminiferous tubules showed an increasing trend ( P<0.05) ; FSH and T levels in serum in the middle and high dose groups of Nd 2O 3, and CYP11A1, PLZF and STRA8 proteins in testicular tissues showed a downward trend with increasing dose ( P<0.05) . Conclusion:The rare earth particulate Nd 2O 3 may interfere with the expression of CYP11A1, PLZF and STRA8 protein, thereby causing the disorder of sex hormone secretion in the body, the maintenance of spermatogonia and the obstruction of the process of meiosis, causing reproductive function damage.

【Objective】 To evaluate the efficacy of sacral neuromodulation (SNM) in the treatment of neurogenic bladder (NB) with Meta-analysis, so as to provide reference for clinical treatment options for NB. 【Methods】 Relevant literatures regarding the efficacy of SNM in treating NB during Jan.2010 and Dec.2022 were collected from the PubMed and CNKI databases, and screened with inclusion and exclusion criteria.After the quality of literatures was assessed, data were extracted and then analyzed using Review Manager 5.3. 【Results】 The research included 14 studies involving 601 patients.Meta-analysis showed that SNM significantly improved urinary frequency (WMD=4.30, 95%CI: 2.84-5.77, P<0.01), daily episodes of urinary incontinence (WMD=2.92, 95%CI: 2.76-3.07, P<0.01), single void volume (WMD=-113.93, 95%CI: -159.91- -67.98, P<0.01), maximum flow rate (WMD=-3.23, 95%CI: -4.04- -2.42, P<0.01), residual urine (WMD=111.79, 95%CI: 79.93-143.64, P<0.01), maximum bladder capacity (WMD=-65.63, 95%CI: -84.38- -46.88, P<0.01), and bladder compliance (WMD=-4.65, 95%CI: -8.75- -0.55, P=0.03). 【Conclusion】 SNM is effective in the treatment of NB, but more randomized controlled trials are needed to verify the efficacy.

Objective:To explore the effects of Nd 2O 3 exposure to rare earth particles on the secretion of sex hormones, cytochrome P450 family member 11A1 (CYP11A1) , spermatogenesis markers promyelocytic leukemia zinc finger protein (PLZF) and retinoic acid stimulating gene 8 (STRA8) protein in C57 BL/6J male mice. Methods:In March 2021, Forty-eight male C57 BL/6J mice aged 6-8 weeks divided into control group and Nd 2O 3 exposure low, medium and high dose groups (exposing doses of 62.5, 125.0, 250.0 mg/ml Nd 2O 3) , 12 per group. The mice in the Nd 2O 3 groups were perfused with different doses of Nd 2O 3 suspension by a one-time non-exposing tracheal instillation method, and the control group was perfused with an equal volume of normal saline, with a volume of 0.1 ml, to establish a mouse reproductive function injury model. After 28 days of exposure, the mice's body weight, testes and epididymis were weighed, and the organ coefficients were calculated; the two epididymis were taken to make a sperm suspension to determine the sperm count, survival rate, and deformity rate; inductively coupled plasma mass spectrometry (ICP-MS) method was used to detect the content of Nd in mouse testis tissue; HE staining was used to detect testicular tissue pathological changes and quantitative analysis; enzyme-linked immunosorbent assay (ELISA) method was used to detect serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) and testosterone (T) content; western blot was used to detect the protein levels of CYP11A1, PLZF and STRA8 in testicular tissues. Results:Compared with the control group, with the increase of the exposure dose, the Nd content in the testis of the mice showed an increasing trend, the sperm survival rate and LH showed a decreasing trend, and the sperm deformity rate showed an increasing trend ( P<0.05) ; Pathological showed that the number of sperm in the seminiferous tubules of the testicular tissue in the Nd 2O 3 medium and high dose groups was significantly reduced, and the germinal epithelial disintegration, intraepithelial vacuolization, and exfoliation of spermatogenic cells and supporting cells occurred; The height of germinal epithelium was significantly reduced, and the percentage of damaged seminiferous tubules showed an increasing trend ( P<0.05) ; FSH and T levels in serum in the middle and high dose groups of Nd 2O 3, and CYP11A1, PLZF and STRA8 proteins in testicular tissues showed a downward trend with increasing dose ( P<0.05) . Conclusion:The rare earth particulate Nd 2O 3 may interfere with the expression of CYP11A1, PLZF and STRA8 protein, thereby causing the disorder of sex hormone secretion in the body, the maintenance of spermatogonia and the obstruction of the process of meiosis, causing reproductive function damage.

Objective To analyze the hot spots,rules and distribution on safety research of inhalation preparations at home and abroad in the past 20 years,and to summarize the current status of safety and risk control research on inhalation preparations.Methods This reaserch is based on the literature related to the safety and risk control of inhalation preparations in the core collection database of the Web of Science.With the help of Excel 2021 and CiteSpace6.1.R3,visualized processing and analysis were carried out on the annual number of publications,countries,institutions,authors,co-occurrence of keywords,clustering and prominence.Results A total of 365 articles were included,the annual publication number in the field of the safety and risk control of inhalation preparations was less than 30 per year from 2002 to 2018.But since 2019,the number of articles published this year has exceeded 30.Through the analysis of the cooperation network of countries and institutions,the top four countries in terms of publication volume are the United States,the United Kingdom,Germany,and China,and the top three institutions are AstraZeneca,GlaxoSmithKline and Pfizer.Through the analysis of the author cooperation network,the cooperation network between European and American authors was formed earlier,and a certain research group has appeared in 2002.In contrast,a more concentrated cooperation network has been formed in China in 2020.Conclusions In the past 20 years,the research on inhalation preparations has mainly focused on their safety and efficacy,while there are few studies on their risk control.There is a disconnect between safety assessment and risk assessment,and the future focus maybe focused on the adverse reaction assessment and risk management research of inhalation preparations.

Objective:To evaluate the effect of sodium sivelestat on the expression of specialized pro-resolving mediators (SPMs) synthesis enzymes in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Eighteen SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=6 each) using a random number table method: control group (C group), LPS-induced ALI group (ALI group), and LPS-induced ALI + sodium sivelestat group (ALI+ SV group). ALI was induced by intravenous injection of LPS 15 mg/kg through the tail vein. Sodium sivelestat 50 mg/kg was intraperitoneally injected at 1 h after LPS administration. At 12 h after LPS administration, blood samples were collected from the eyeballs for routine blood tests, and the remaining blood was processed for serum extraction. The mice were sacrificed after anesthesia, and lung tissues were collected to determine the wet/dry weight (W/D) ratio, serum concentrations of interleukin-1beta (IL-1β) and IL-10 (by enzyme-linked immunosorbent assay), expression of neutrophil elastase (NE) and SPMs synthesis enzymes 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX), and 15-lipoxygenase (15-LOX) in lung tissues (by Western blot) and to examine the pathological changes of lung tissues which were scored. Results:Compared with C group, the lung injury scores, W/D ratio, white blood cell counts, percentage of neutrophil, and serum IL-1β and IL-10 concentrations were significantly increased, the expression of NE was up-regulated, and the expression of 5-LOX, 12-LOX and 15-LOX was down-regulated in ALI group ( P<0.05). Compared with ALI group, the lung injury scores, W/D ratio, white blood cell counts, percentage of neutrophil, and serum IL-1β concentration were significantly decreased, the serum IL-10 concentration was increased, the expression of NE was down-regulated, and the expression of 5-LOX, 12-LOX and 15-LOX was up-regulated in ALI+ SV group ( P<0.05). Conclusions:The mechanism by which sodium sivelestat alleviates LPS-induced ALI may be related to up-regulating the expression of SPMs synthesis enzyme and promoting the resolution of pulmonary inflammation in mice.