A retrospective analysis to estimate trough concentrations of teicoplanin in patients with suspected or documented Gram-positive infections

Abstract Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.

Comparison of effect between internal fixation and total hip replacement in the treatment of displaced femoral neck fracture in middle age patients / 中国骨伤

OBJECTIVE@#To analyze and compare the clinical efficacy of internal fixation and total hip replacement in the treatment of displaced femoral neck fracture from 55 to 65 years.@*METHODS@#From September 2016 to August 2020, 86 patients with Garden type Ⅲ or Ⅳ femoral neck fracture were divided into two groups according to different surgical methods. Among them, 38 patients were treated with lag screws for internal fixation, there were 26 males and 12 females, aged 55 to 64 years old with an average of(60.2±3.1) years;the other 48 patients were treated with total hip replacement, including 28 males and 20 females, aged from 57 to 65 years old with an average of(61.3±3.8) years. The time from injury to operation ranged from 1 to 3 days. The reoperation rate, incidence of deep infection, Harris score of hip joint function, visual analogue scale(VAS) of pain and patients reported outcome scores(European five-dimensional Health Questionnaire, EQ-5D) were compared between two groups.@*RESULTS@#All patients were followed up for 24 to 54 months with an average of (35.8±10.3) months. There was significant difference in reoperation rate between two groups (P<0.05). There was no significant difference on the incidence of deep infection, hip Harris score and VAS between two groups(P>0.05) . The postoperative EQ-5D score of patients with internal fixation was lower than that of total hip replacement, and the difference was statistically significant(P<0.05).@*CONCLUSION@#Both the surgery of internal fixation and total hip replacement have similar effect in short-and medium term among the patients aged 55 to 65 years old. However, for the reoperation rate, the group of internal fixation was higher than that of total hip replacement. For the subjective functional score of patients, the group of internal fixation was lower than that of total hip replacement.

Emerging immunological strategies: recent advances and future directions / 医学前沿

Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.

The Clinical Value of Combined Detection of RBC, Ret-He and HbA2 for Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution of Ret-He and RBC in thalassemia and the value of combining HbA2 in the detection of thalassemia among patients with microcytic or hypochromic.@*METHODS@#145 patients with microcytic or hypochromic outpatient or hospitalization in our hospital from May 2018 to December 2019 were selected and were divided into the thalassemia group(68 cases) and the non-thalassemia group (77 cases), and at the same time, the patients were divided into four groups of the non-anemia, mild anemia, moderate anemia and severe anemia group according to the degree of anemia. The Ret-He, RBC, RDW-CV and HbA2 in patients were detected, and the distribution of these parameters were compared, and the joint detection of Ret-He, RBC and HbA2 about its sensitivity, specific and other indicators of auxiliary diagnosis of thalassemia were analyzed.@*RESULTS@#Among patients with microcytic or hypochromic, according to the anemia grade Ret-He gradually decreased from the non-anemia group to the severe anemia group (P<0.05); while RDW-CV was increased gradually from the mild anemia group to the severe anemia group (P<0.05); both RBC and Ret-He were increased in the thalassemia group as compared with the non- thalassemia group (P<0.05); while RDW-CV was decreased in the thalassemia group as compared with the non-thalassemia group (P<0.05); meanwhile Ret-He in the α-thalassemia group was higher than that in the β-thalassemia group. ROC curve analysis showed that combined with HbA2, the specificity was 93.51%, the sensitivity was 66.18%, the positive predictive value was 90% and the negative predictive value was 75.189% when Ret-He was truncated with 19.25 pg and RBC was truncated with 4.95×10@*CONCLUSION@#Among patients with microcytic or hypochromic, the distribution of RBC, Ret-He and RDW-CV was different in the thalassemia group and the non-thalassemia group, and was also affected by the degree of anemia. Combined Ret-He and RBC could improve the diagnostic specificity for thalassemia, which were screened by HbA2 in patients with microcytic or hypochromic.

Effect of butylphthalide combine edaravone on the dynamic change of Drp1 and Mfn2 in rats with focal cerebral ischemia and its protection mechanism / 医学研究生学报

Objective Apoptosis was induced by oxidative stress in nerve cells after cerebral ischemia. It further breaks the dy-namic balance of mitochondrial division of fusion. This study aimed to investigate the effect of butylphthalide combined with edaravone treat-ment on the dynamic change of Drp1 and Mfn2 in rats with focal cere-bral ischemia cells and its protection mechanism. Methods 96 rats were divided into 4 groups according to random number table. The 4 groups were ischemia group,butylphthalide group,edaravone group and butylphthalide combined with edaravone groups(combine group),each group divided into three subgroups(3 d,7 d,14 d). Longa-Zea suppository method is adopted to establish the middle cerebral artery occlusion(MCAO)model.Butylphthalide group,edar-avone group and combine group were injected butylphthalide(0.4 g/kg)and/or edaravone(10 mL/kg)peritoneally 2 hours before surgery and 1 day after surgery. The same volume of isotonic saline was given at the same time of the other 3 groups in ischemia group. The cerebral cortex of the left ischemic region was obtained at the day 3,7,14. The evaluation of the curative effect was evaluated with neurological function score.HE staining was used to observe the cerebral cortex neuron morphological structure,protein and mRNA lev-el of Drp1 and Mfn2 was measured by western blot and RT-PCR. Results At the day 3,7,and 14,the neurological function score was higher in ischemia group than the other 3 groups(P<0.05). Compared with the combine group at day 3,7,and 14[(1.06± 0.18),(0.82±0.13),(0.57±0.10)],the neurological function score was elevated in butylphthalide group[(2.02±0.18),(1.23± 0.13),(0.86±0.10)]and edaravone group[(2.08±0.17),(1.23±0.13),(0.85±0.12)](P<0.05). At the same time point,com-pared with the ischemia group,Drp1 protein and mRNA levels were lower in the other 3 groups(P < 0.05)while Mfn2 protein and mRNA levels were elevated(P<0.05). Compared with the butylphthalide group and edaravone group,Drp1 protein and mRNA levels were lower in combine group(P<0.05)while Mfn2 protein and mRNA levels were elevated(P<0.05). Conclusion The protective effect of edaravone combined with butylphthalide is better than single use. Its mechanism may be related to the removing of oxygen free radicals and reducing oxidative stress by edaravone,and the protection of the mitochondria by butylphthalide.

The Advanced Progress on the Analgesic Mechanism of Oxytocin / 昆明医科大学学报

Oxytocin (OT) is a 9-amino-peptide hormone synthesized mainly in the Paraventricular Nucleus (PVN) and Supraoptic Nucleus (SON) of mammals'hypothalamus. Small part of OT is synthesized in peripheral organs. In addition to promoting the lactation and uterine contraction, OT has many other physiological functions, such as analgesia. It has been proved that neuropeptide can exert analgesic effect. OT is indeed a neuropeptide secreted naturally by mammals. Sdudies have shown that OT plays an important role in relieving pain and can avoid problems like addiction and other side effects.However, its underlying mechanism of analgia is still unclear. Therefore, further study of the analgesic mechanism of oxytocin has a great theoretic significance and very broad clinical prosperities.

Pharmacology and pharmacokinetics studies of MBX-2982, a novel GPR119 agonists / 中国药学杂志

OBJECTIVE: To observe the glucose tolerance and evaluate the hypoglycemic effect of MBX-2982 respectively in the normal mice and in the KK-Ay mice. And further pharmacokinetics investigation was experimented in rats. METHODS: The influence of glucose tolerance was evaluated in KM mice which underwent a single dose of MBX-2982. Body weight, fasting blood glucose, glucose tolerance, triglyceride, serum insulin were all tested in order to evaluate the hypoglycemic effect on KK-Ay mice. The pharmacokinetics of MBX-2982 suspension and solution were investigated in rats to calculate the oral bioavailability. RESULTS: The blood glucose of each test point were all reduced after MBX-2982 (3, 10, 30 mg · kg-1) were administered orally to KM mice. After MBX-2982 (10, 30 mg · kg-1) treatment to KK-Ay mice for 4 weeks, the fasting blood glucose and triglyceride were significantly reduced and the serum insulin was remarkably increased. Meanwhile the area under glucose curve was significant reduced of 30 mg · kg-1. After oral administration of MBX-2982 (4 mg · kg-1) in rats, the oral bioavailability of suspension (0.4% CMC) and solution (DMSO-Cremopor EL-NS = 1:1:8) were 35.2% and 98.2% receptively. CONCLUSION: Animal experiment results show that the MBX-2982 as a GPR119 agonists had a good hypoglycemic effect. The absolute bioavailability of the solution is closed to 100%, which is higher than that of suspension.

Genetic analysis on S segment of hantaviruses in rodent hosts from Wuhan area, Hubei province / 中华流行病学杂志

Objective To investigate the infection and genotype of hantaviruses in rodents from Wuhan area,Hubei province.Methods Rodents were trapped in fields and residential areas of Xinzhou and Jiangxia districts of Wuhan in autumn and winter seasons,from 2000 to 2003 and from 2009 to 2011.Trapped rodents were identified,and hantavirus antigens were detected in the lung tissues with indirect immunofluorescence assay (IFA).Partial S segment sequences were amplified with RT-PCR in hantavirus antigen positive samples and then sequenced.Phylogenetic tree was constructed to analyze the genetic characteristics of hantaviruses.Results From 2000 to 2003,437 rodents were trapped,with 24 (5.49％) lung tissues showed hantavirus antigen positive.From 2009 to 2011,173 rodents were trapped and 7 (4.05％) were hantavirus antigen positive.Rattus norvegicus were the dominant species of rodents.Partial S segment sequences were amplified from 22 samples with Hantaan and Seoul viruses specific primers and sequenced.Partial S segments of Seoul viruses (nucleotide 588-1147) were amplified from 17 rodents (13 R.norvegicus and 4 Apodemus agrarius).Seven of these sequences belonged to 3 genetic lineage,while two novel genetic lineages were formed by 9 and 1 sequences,respectively.Partial S segments of Hantaan viruses (nucleotide 615-1141 ) were amplified from 5 A.agrarius.One of these sequences belonged to 7 genetic lineages,and 4 sequences formed one novel genetic subtype.Conclusion Hantaan and Seoul viruses co-circulated in Wuhan area.Hubei province.Novel genetic lineages were identified in this study and Seoul virus might have caused spillover infection in A.agrarius.

Anti-tumor effect of type Ⅲ interferon / 国际肿瘤学杂志

It is reported that type Ⅲ interferon (IFN-λ) has an anti-tumor effect on melanoma,hepatocellular carcinoma,esophageal carcinoma and fibrosarcoma in recent years.IFN-λ could not only inhibit melanoma metastasis,but also induce cell apoptosis;its constitutively expression could activate natural killer cells,affecting hepatocellular carcinoma growth;IFN-λ could induce cells of G1 phase in esophageal carcinoma directly to stagnation or apoptosis;IFN-λ could cause native and adaptive immune response to suppress fibrosarcoma growth.Research on the anti-tumor mechanisms of IFN-λ will provide new ideas for clinical tumor therapy.

Detection of minimal residual disease in childhood acute lymphoblastic leukemia by using real-time quantitative PCR / 中国实验血液学杂志

This study was purposed to detect the minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) by using real time quantitative PCR (RQ-PCR) . The Ig and TCR gene rearrangements were amplified by using 18 primer sets in B-ALL, 8 primer sets in T-ALL; the ALL-MRD levels were quantified by using RQ-PCR with SYBR green dye staining and clone specific Ig/TCR gene rearrangements as molecular markers. The results indicated that there were 8 cases showing gene rearrangements in 9 B-ALL patients, marker detection rate for all samples was 88.8%, the MRD level on day 33 during induction treatment decreased significantly. It is concluded that Ig/TCR gene rearrangements can be used as a marker to detect MRD in childhood ALL; the technique of QR-PCR with SYBR green dye staining is reliable, relatively sensitive and easy performable method which can be used in routine detection for childhood ALL.

Association of hemorrhagic fever with renal syndrome and HLA-DRB allele polymorphisms in Han nationality, Hubei province / 中华流行病学杂志

Objective To understand the association of human leukocyte antigen (HLA)-DRB polymorphism and patients diagnosed as hemorrhagic fever with renal syndrome (HFRS). Methods HLA-DR allele polymorphism was detected by PCR-sequence specific primers (PCR-SSP). Hantavirus (HV) typed as Hantaan virus (HTNV) and Seoul virus (SEOV) in patients were detected by RT-heminested PCR. Results The gene frequency of DRB1*0401-0411, *1001 and *1101-1105 in HFRS case group were 3.1%, 2.2% and 15.7% respectively. Compared with control group, it was significant higher in HFRS case group (RR=13.87, 9.72 and 2.00 respectively with Chi-square value as 10.006,6.324 and 6.472 respectively, P<0.05). When compared with HFRS case group, the gene frequency of DRB1*1501-1502, DRB4 and DRB5 in control group were 11.0%, 19.0% and 16.9% respectively, markedly lower than in patients (RR=0.45, 0.58 and 0.23 respectively. Chi-square values were 6.138, 4.583 and 21.076 respectively, P<0.05). There was no significant difference in other HLA-DR gene frequencies. Mixed infection was found in Hubei, with HTNV slightly more than SEOV. Distinct hantaviruses could coexist in either different or the same geographic or ecological zores in Hubei province. Patients with HLA-DRB1*1101-1105 alleles were 81.8%(27/33) infected by HTNV and only 18.2% infected by SEOV, which had significant difference (P<0.05). Conclusion DRB1*0401-0411,*1001 and *1101-1105 were possibly associated with increased susceptibility to HV infection. On the other hand there was an inverse correlation among HFRS, DRB1*1501-1502, DRB4 and DRB5.

Effect of Xinmaitong capsule on serum matrix metalloproteinases-9, high sensitive C-reactive protein levels in patients with acute coronary syndrome / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the influence of Xinmaitong capsule (XMT) on serum matrix metalloproteinases-9, high sensitive C-reactive protein levels in patients with acute coronary syndrome.</p><p><b>METHOD</b>63 cases were divided by randomized, contrastive assigned to XMT group (n = 31) and control group (n = 32). The serum levels of MMP-9 and hs-CRP before and after treatment in 12 weeks were detected.</p><p><b>RESULT</b>After treatment, the serum levels of MMP-9 in control group had no changed and the levels of hs-CRP reduced. The serum levels of MMP-9 and hs-CRP in XMT group had significantly decreased. The serum levels of MMP-9 and hs-CRP had positive correlation, but had no correlation to levels of serum lipids.</p><p><b>CONCLUSION</b>XMT decreased breakdown of matrix collagen, and inflammatory reaction in the patients of ACS, which may have effect on plaque stabilization.</p>

Fluid shear stress upregulated endothelial nitric oxide synthase gene expression and nitric oxide formation in human endothelial progenitor cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of fluid shear stress on the eNOS gene expression and NO production in endothelial progenitor cells (EPCs).</p><p><b>METHODS</b>The peripheral blood mononuclear cells from healthy volunteers were inducted into EPCs and divided into stationary group (0 dyn/cm(2), 1 dyn/cm(2) = 0.1 Pa), low-flow shear stress group (5 dyn/cm(2)), medium-flow shear stress group (15 dyn/cm(2)) and high-flow shear stress group (25 dyn/cm(2)). The effects of shear stress on the endothelial nitric oxide synthase (eNOS) gene expression and nitric oxide (NO) production in human EPCs were measured.</p><p><b>RESULTS</b>Typical "spindle-shaped" appearance was shown in EPCs derived from peripheral blood mononuclear cells and were positively labeled by acetylated-LDL, lectin, FLK-1 and vWF. After 4 hours treatment with various shear stresses, the ratio of eNOS/beta-actin mRNA expression by human EPCs in low, medium and high-flow shear stress group was 0.364, 0.505 and 0.548 respectively, which was significantly higher than that in stationary group (0.183, all P < 0.05) and the NO secretion in human EPCs in low, medium and high-flow shear stress group was also significantly higher than that in stationary group (all P < 0.05).</p><p><b>CONCLUSION</b>Fluid shear stress enhances the eNOS mRNA expression and NO secretion in human EPCs, therefore, shear stress could potentiate the repair efficacy of EPCs for endothelial injury.</p>

Study on influence of buffer system on separate capacity of macroporous resin on ferulic liposome / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of buffer on separate capacity of macroporous resin. To evaluate the quality of ferulic acid liposome and determine its entrapment efficiency.</p><p><b>METHOD</b>Different type of macroporous resin counterpoised by buffer system of Na2 HPO3-NaH2, PO3 was used to separate the free ferulic acid from the preparation and HPLC was used to determine the concentration of the ferulic acid to calculate the entrapment efficiency.</p><p><b>RESULT</b>This method had good linearity in the range of 0.56 - 2.8 g x mL(-1) (r = 0.999 6). The precision RSD was less than 1.1%. The adsorption effect of macroporous resin on liposome was reduced while it had no effect on the absorption ability of macroporous resin on the ferulic acid by the usage of buffer. The recovery of HPD450 resin on blank liposome was between 97.2% - 100.8%, while the average recovery is 98.1%.</p><p><b>CONCLUSION</b>Buffer system can enhance the separate ability of macroporous resin on liposome and free drug.</p>

An investigation on nosocomial infection with severe acute respiratory syndrome in health-care workers at 13 key hospitals in Guangdong Province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To analysis the risk factors influencing nosocomial infection of severe acute respiratory syndrome (SARS) in health-care workers and to evaluate effectiveness of its control and preventive measures in 13 key hospitals caring for SARS patients.</p><p><b>METHODS</b>Number of SARS patients, clinical conditions of them, its attack rate in health-care workers, and characteristics of hospitals, including their environment, isolating measures, etc. were investigated at the 13 hospital in Guangzhou to analyze the risk factors influencing nosocomial infection of SARS and its attack rates in health-care workers before and after implementation of preventive measures and to evaluate their effectiveness.</p><p><b>RESULTS</b>Totally, 841 patients with SARS were treated at the 13 hospitals in Guangzhou and 285 health-care workers caring for them infected nosocomially. Attack rate in health-care workers was higher at general hospitals, hospital accepting more cases in critical conditions and hospitals with poor precautious measures, and lower in hospitals with isolated wards or areas, or department of infection, specially caring for SARS patients, and those with effective intervention measures to prevent secondary infection.</p><p><b>CONCLUSION</b>Nosocomial infection of SARS in health-care workers was affected by clinical condition of SARS patients, characteristics and environment of hospitals and their personal protective measures adopted.</p>

Efficacy and restenosis of cypher stent in elderly patients with coronary heart disease / 中华老年医学杂志

Objective To investigate the efficacy and security of cypher stent(sirolimus-eluting stent)in the treatment of old patients with coronary heart disease(CHD).Methods From November 2002 to May 2005,328 elderly CHD cases(age:60-86 years)were treated with 415 Cypher stents.Among the 328 patients,66 had ST-segment elevation of myocardial infarction,21 had non ST-segment elevation of myocardial infarction,149 had unstable angina and 92 had stable angina.As for lesion characteristics,diffuse disease was found in 91 case(26.1%),bifurcation lesions in 68 cases(19.6%),chronic total occlusion lesions in 56 cases(16.0%),in-stent restenosis in 14 cases and ostial lesions in 15 case.The immediate angiographic outcome,major cardiac event(MACE) and angiographic follow-up at 6 months were assessed.Results Stent implantation was successfully achieved in 99% patients with CHD.Acute and sub-acute stent thrombosis occurred in 2 patients,late stent thrombosis with AMI occurred in 2 patients,1 died during the 6 months follow-up.The MACE rate during hospitalization was 0.6% and 3.6% during 6 months follow-up.Angiographic follow-up in 84 patients at 6 months showed that in-stent restenosis rate(ISR)was 8.3%(restenosis within the stents was 2.4%).The target vessel revascularization(TLR)rate was 5.9%.Conclusions Cypher stent implantation in CHD is safe and effective,the ISR rate and TLR rate are significantly lower than those of bare metal stents.