Study on the status quo and correlation between body image and stigma of drug-resistant tuberculosis patients treated with Clofazimine / 中国实用护理杂志

Objective:To investigate the current situation of body image and stigma of drug-resistant tuberculosis patients treated with Clofazimine, and analyze the correlation between them.Methods:A cross-sectional study was conducted using convenience sampling method to investigate 150 patients with drug-resistant tuberculosis treated with Clofazimine in tuberculosis ward of Chengdu Public Health Clinical Medical Center from October 2020 to October 2021. The general questionnaire, Body Image Scale (BIS) and Tuberculosis Related Stigma Scale were used to conduct a questionnaire survey.Results:A total of 130 questionnaires were effectively collected. The body image score of 130 patients with drug-resistant tuberculosis treated with Clofazimine was (20.51 ± 6.80) points; the score of stigma was (17.78 ± 6.92) points. There was a positive correlation between the total score of disease shame and the total score of body image ( r=0.544, P<0.05). Conclusions:Patients with drug-resistant tuberculosis treated with Clofazimine have body image disorder and stigma, and the two are positively correlated. Caregivers should carry out psychological assessment and intervention at an early stage to improve the patient′s mental health level.

Progress of venetoclax in treatment of hematologic malignancies / 白血病·淋巴瘤

The anti-apoptotic protein bcl-2, a key regulator of the intrinsic apoptotic pathway, is frequently overexpressed in cells of hematologic malignancies, and the small molecule inhibitor venetoclax that targets this apoptotic pathway has shown promising efficacy in the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma. The survival and prognosis of patients with acute myeloid leukemia who are of advanced age or who are unsuitable for strong induction chemotherapy because of comorbidities also have significantly improved, but some patients develop progressive drug resistance during the course of venetoclax treatment, which affects the efficacy of medical therapy. This article reviews the action mechanism, therapeutic progress and resistance mechanism of venetoclax in hematologic malignancies.

Effect of apatinib combined with fluzoparib on proliferation ability of human ovarian cancer cisplatin-resistant cells / 肿瘤研究与临床

Objective:To investigate the effect of apatinib and fluzoparib on the proliferation ability of cisplatin-resistant human ovarian cancer cells.Methods:Human ovarian cancer cells SKOV3 and cisplatin-resistant SKOV3/DDP cells of human ovarian cancer were treated with different concentrations of 1, 2, 4, 8, 16, 32, 64,128 μg/ml cisplatin at different times; CCK-8 method was used to detect the proliferation rate and half-inhibitory concentration ( IC50) of SKOV3 and SKOV3/DDP cells, and the drug-resistance fold of SKOV3/DDP cell was also calculated. SKOV3/DDP cells were treated with different concentrations of apatinib (4, 8, 16, 32, 64 μmol/L) and fluzoparib (148.15, 222.22, 333.33, 500.00, 750.00 μmol/L) for 24 h, 48 h and 72 h, respectively; the cell proliferation rate was determined by using CCK-8 method and IC50 was calculated. SKOV3/DDP cells were divided into the blank control group (cells untreated with drugs), cisplatin group, cisplatin + apatinib group, cisplatin + fluzoparib group, cisplatin + fluzoparib + apatinib group, and drug intervention was given in each group; the inhibition rate of cells in each group was detected by using CCK8 method. Results:The proliferation rate of SKOV3 cells treated with the same concentration of cisplatin for the same time was lower than that of SKOV3/DDP cells, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 4, 8, 16, 32, 64 μmol/L apatinib was 742.1μmol/L at 24 h, 156.8 μmol/L at 48 h, and 77.5 μmol/L at 72 h. Compared with the control group, the proliferation rate of SKOV3/DDP cells treated with apatinib at an effective concentration greater than 32 μmol/L was significantly decreased, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 148.15, 222.22, 333.33, 500.00, 750.00 μmol/L fluzoparib was 878.5 μmol/L at 24 h, 406.7 μmol/L at 48 h, and 283.3μmol/L at 72 h. When the effective concentration of fluzoparib was more than 333.33 μmol/L for 24 h, the proliferation rate of SKOV3/DDP cells was lower than that of the control group, and the differences were statistically significant (all P < 0.05). Compared with the control group, the proliferation rate of SKOV3/DDP cells was decreased when the effective concentration was more than 148.15 μmol/L at 48 h and 72 h, and the differences were statistically significant (all P < 0.05). The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib group was lower than that of 5 μg/ml cisplatin group [(40.4±1.4)% vs. (62.7±1.4)%, t = 20.22, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(5.2±0.4)% vs. (62.7±1.4)%, t = 52.04, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(0.3±0.8)% vs. (62.7±1.4)%, t = 53.98, P < 0.001]. The 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group had the lowest proliferation rate of SKOV3/DDP cells, which was lower than that of 5μg/ml cisplatin + 64 μmol/L apatinib group and 5 μg/ml cisplatin + 290 μmol/L fluzoparib group (all P < 0.001). Conclusions:Apatinib and fluzoparib can enhance the sensitivity of human ovarian cancer cisplatin-resistant cells SKOV3/DDP to cisplatin, and the combination of drugs can produce the stronger inhibitory effects and reverse cisplatin resistance of ovarian cancer.

Transmission risk and resistance characteristics of Streptococcus pneumoniae among preschool children in Foshan / 中国学校卫生

Objective@#To understand the homology and resistance characteristics of Streptococcus pneumoniae (S. pneumoniae) in healthy preschool children, so as to provide basis for disease transmission prevention and rational use of antibiotics.@*Methods@#Stratified cluster random sampling method was used to sample 1 829 healthy children from six kindergartens in Shunde District, Foshan City. Nasal swabs were taken and tested for S. pneumoniae. Multi locus sequence typing was used for homology analysis. The Chi squared test and random forest analysis were used to explore the resistance characteristics.@*Results@#The nasal carriage rate of S. pneumoniae and multidrug resistant S. pneumoniae (MDRSP) in children were 22.5%(412/1 829) and 21.3%(390/1 829), respectively. Homology analysis in sequence types showed that the total homology rates of 6 kindergartens were 93.5%(87/93), 91.1% (72/79), 89.2%(58/65), 88.9%(64/72), 86.2%(50/58), 77.8%(35/45), respectively. It was found that the highest homology rate was 82.8% (48/58) within class and 93.1% (81/87) between classes. S. pneumoniae was mainly resistant to azithromycin (97.1%, 400/412), erythromycin (92.0%, 379/412) and tetracycline (91.5%, 377/412). The dominant multidrug resistance pattern of MDRSP isolates was not sensitive to azithromycin, erythromycin, cotrimoxazole, tetracycline and clindamycin. Random forest analysis indicated that the important phenotypic markers associated with MDRSP were resistance to azithromycin, cotrimoxazole, tetracycline, clindamycin and erythromycin(MDG=8.94, 6.92, 5.80, 4.84, 2.58).@*Conclusion@#The risk of cross transmission of S. pneumoniae among preschool children is high, and direct contact is the main way of transmission. Consequently, kindergartens and health departments should take effective measures to effectively prevent and block the spread of Streptococcus pneumoniae.

Progress of new anti-seizure medications in elderly patients with epilepsy / 中华神经科杂志

With the rapid aging of the population, elderly epilepsy probably becomes one of the most common forms of epilepsy. Lacosamide, brivaracetam, eslicarbazepine acetate, and perampanel have been approved by the United States Food and Drug Administration and the European Medicines Agency for monotherapy and (or) adjunctive treatment of seizures in the last few years. This review summarizes the efficacy and tolerability of third-generation anti-seizure medications in elderly epilepsy patients and introduces the effects of anti-seizure medications on cognitive function and mood, as well as drug-drug interactions, aiming to provide a reliable basis for clinicians to choose third-generation anti-seizure medications.

Loss of tolerance 5 days after discontinuing sulphonamide introduced via desensitization in delayed reaction / Perda da tolerância 5 dias após suspensão de sulfonamida introduzida através de dessensibilização por reação tardia

ABSTRACT The fixed drug eruption is a non-immediate hypersensitivity reaction to drug, characterized by recurrent erythematous or violaceous, rounded, well-defined border plaques, which always appear in the same location every time the culprit drug is administered. The usual practice is to avoid the drug involved and to use a structurally different drug. However, there are situations in which there is no safe and effective therapy. In such situations, desensitization is the only option. We describe the case of a patient who presented fixed eruption due to sulfamethoxazole-trimethoprim, who underwent successful desensitization, but required a repeat procedure twice due to relapse after inadvertent full-dose reintroduction. In non-immediate hypersensitivity reaction to drug, the indication is controversial and there is no technical standardization. Furthermore, the time at which such tolerance is lost after discontinuing the drug involved is unknown. In severe non-immediate reactions of types II and III, desensitization is contraindicated. The patient underwent desensitisation to sulfamethoxazole-trimethoprim three times − the first with recurrence of lesions and the second and third without manifestations, all concluded successfully and with no premedication.

RESUMO A erupção fixa por drogas é uma reação de hipersensibilidade a medicamento não imediata, caracterizada por placas eritematosas ou violáceas, arredondadas, recorrentes, de bordas bem definidas e que aparecem sempre na mesma localização cada vez que o medicamento culpado é administrado. A prática habitual é evitar a droga envolvida e utilizar um medicamento estruturalmente diferente. Contudo, há situações em que não há terapêutica segura e eficaz. Em tais situações, a dessensibilização é a única opção. Descrevemos o caso de um paciente que apresentou erupção fixa por drogas por sulfametoxazol-trimetoprim, tendo sido submetido à dessensibilização com sucesso, mas necessitou repetição do procedimento duas vezes, por recidiva da reação após reintrodução inadvertida em dose plena. Em reação de hipersensibilidade a medicamento não imediata, a indicação é controversa e não há padronização técnica. Além disso, não se conhece o tempo durante o qual essa tolerância é perdida após a suspensão da droga envolvida. Nas reações não imediatas graves e dos tipos II e III, a dessensibilização está contraindicada. O paciente foi submetido a dessensibilização ao sulfametoxazol-trimetoprim por três vezes − a primeira com recorrência de lesões, e a segunda e terceira sem manifestações, sendo todas concluídas com sucesso e sem uso de pré-medicação.

Consideraciones acerca del reporte y la evaluación del fallo terapéutico en farmacovigilancia / Considerations regarding the reporting and evaluation of therapeutic failure in pharmacovigilance

Resumen Introducción. Los fallos terapéuticos representan un problema de salud pública. Aunque existe abundante información al respecto, se requiere una revisión crítica de las definiciones existentes. Objetivo. Realizar una revisión crítica del concepto actual de fallo terapéutico, su clasificación y su importancia en farmacovigilancia. Materiales y métodos. Dos revisores independientes realizaron una búsqueda sistemática de las definiciones de fallo terapéutico existentes en la literatura y de los sistemas de clasificación descritos. Con base en esta información, se realizó un análisis crítico y la proposición de una nueva definición consensuada de fallo terapéutico. Resultados. La concepción actual de fallo terapéutico es imperfecta, pues desconoce la disminución del efecto de un medicamento en el uso real en comparación con el periodo de precomercialización, donde la estimación de la eficacia se basa en ensayos clínicos controlados. Aunque la clasificación actual es adecuada, tanto el algoritmo de Vaca-González et al. como las otras herramientas empleadas para evaluar la causalidad en farmacovigilancia dependen de la calidad del reporte. Conclusiones. Es necesario ]perfeccionar las definiciones actuales de fallo terapéutico y mejorar la calidad del reporte para sacar el máximo provecho de los sistemas de clasificación. Se propone realizar estudios clínicos pragmáticos para los medicamentos comercializados recientemente con el fin de establecer su verdadero perfil de efectividad y seguridad.

Abstract Introduction: Therapeutic failure is a public health problem. Although there is abundant theory, a critical review of existing definitions is required. Objective: To critically review the current concept of therapeutic failure, its classification and importance in pharmacovigilance. Materials and methods: Two independent reviewers conducted a systematic search of the existing definitions of treatment failure, as well as the classification systems described in the relevant literature. Based on this information, a critical analysis was carried out and a new consensual definition of therapeutic failure was proposed. Results: The current understanding of therapeutic failure is defective as it does not consider the decrease in drug effect in real life use compared to the premarketing period, where the estimate of efficacy is based on controlled clinical trials. Although the current classification is adequate, both the algorithm of Vaca-González et al. and other tools used to assess pharmacovigilance causality depend on the quality of the report. Conclusions: It is necessary to improve the current definitions of therapeutic failure, as well as the quality of the reports to take full advantage of the classification systems. Pragmatic clinical studies for newly marketed drugs are proposed in order to establish their true effectiveness and safety profile.

Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Analysis of drug susceptibility and risk factors for drug resistance of Escherichia coli in elderly patients with urinary tract infection / 中华老年医学杂志

Objective@#To investigate the risk factors for drug resistance of urinary tract infections-causing Escherichia coli producing extended spectrum beta-Lactamases (ESBLs) in elderly people (≥65 years old), in order to provide evidence for rational use of antibiotics in clinic.@*Methods@#Clinical data of elderly patients diagnosed as urinary tract infections in Beijing Chao-Yang Hospital from January 2016 to December 2017 were retrospectively analyzed. According to whether ESBLs were produced by Escherichia coli isolated from urine samples, the patients were divided into the ESBLs-producing E. Coli group (ESBLs group) and the control group. Single factor analysis was performed by Chi-square test.Logistic regression analysis was used to analyze the risk factors for ESBLs-producing Escherichia coli infections in urinary tract on the basis of statistical significance.@*Results@#A total of 452 strains of Escherichia coli were isolated, including 253 strains (55.97%) producing ESBLs, and 199 strains (44.03%) not producing ESBLs. The ureteral calculi (OR=2.675, 95%CI: 1.129-6.341), urinary obstructive diseases (≥ 2 kinds) (OR=8.680, 95%CI: 2.508-30.040), indwelling catheters (OR=5.762, 95%CI: 2.698-12.155), antibiotic treatment more than 2 weeks for urinary tract infections within one year (OR=3.461, 95%CI: 1.766-6.784) were independent risk factors for ESBLs-producing Escherichia coli urinary tract infections. The incidence rate of Escherichia coli resistance to various antibiotics was higher in elderly patients with urinary tract infection than in non-elderly patients.@*Conclusions@#Escherichia coli producing ESBLs can be easily isolated from elderly patients with urinary tract obstructive diseases, indwelling catheters and repeated long-term administration of broad-spectrum antibiotics. The proportion of ESBLs Escherichia coli-caused urinary tract infections is higher in elderly patients. Thereby, carbapenems or piperacillin/tazobactam is the reasonable antibiotics. Ampicillin, piperacillin, levofloxacin and ciprofloxacin should not be the first choice for the treatment of urinary tract infections in the elderly.

Changes in sensitivity of clinical strains of Ureaplasma urealyticum from the urogenital tract to nine kinds of antibiotics from 2007 to 2018 / 中华皮肤科杂志

Objective@#To analyze changes in sensitivity of clinical strains of Ureaplasma urealyticum (Uu) to 9 kinds of common antibiotics from 2017 to 2018.@*Methods@#The results of drug sensitivity testing of clinical Uu strains, which were isolated from 19 431 patients in Laboratory of Sexually Transmitted Disease (STD) , Department of Dermatology and Venereology, The Third Affiliated Hospital, Sun Yat-Sen University from 2007 to 2018, were analyzed retrospectively. Of the 19 431 patients, 6 076 were males, and 13 355 were females. Their age ranged from 15 to 68 years. The tested antibiotics included minocycline, doxycycline, erythromycin, azithromycin, clarithromycin, roxithromycin, ciprofloxacin, sparfloxacin and levofloxacin.@*Results@#Resistance rates of clinical Uu strains to minocycline and doxycycline gradually decreased from 10.08% and 10.42% in 2007 to 1.15% and 2.61% in 2018, respectively, while sensitivity rates to minocycline and doxycycline gradually increased from 85.88% and 87.56% in 2007 to 97.02% and 96.42% in 2018, respectively. The resistance rate and sensitivity rate of clinical Uu strains to erythromycin fluctuated greatly during 2014—2017, with the resistance rate fluctuating around 20%, and the sensitivity rate fluctuating around 50%. The resistance rate of clinical Uu strains to azithromycin dropped rapidly from 42.02% in 2007 to 8.39% in 2011, and then fluctuated slightly around 10%. However, the sensitivity rate to azithromycin increased from 8.40% in 2007 to 86.05% in2011, and remained above 80% from then on to 2018. During 2007—2018, Uu strains showed low resistance rates (10%-20%) and high sensitivity rates to clarithromycin (80%-90%) , and the resistance and sensitivity rates to roxithromycin were similar to those to erythromycin. Uu strains showed constantly high resistance to ciprofloxacin (more than 80% after 2013) and low sensitivity (persistently less than 10%) . The sensitivity rate of clinical Uu strains to sparfloxacin fluctuated around 40%, while the resistance rate was maintained below 10% after 2011. The resistance and sensitivity rates of Uu strains to levofloxacin were similar to sparfloxacin, but the sensitivity rate to levofloxacin was relatively lower, which had been maintained at about 30%.@*Conclusion@#From 2007 to 2018, clinical Uu strains maintained a relatively stable low resistance rate and a high sensitivity rate to minocycline, doxycycline and clarithromycin, a high resistance rate and low sensitivity rate to ciprofloxacin, and a low resistance rate and sensitivity rate to sparfloxacin and levofloxacin; a relatively stable low resistance rate and a high sensitivity rate to azithromycin were achieved only after 2011; the resistance rate and sensitivity rate to erythromycin and roxithromycin fluctuated greatly.

Changes in sensitivity of clinical strains of Ureaplasma urealyticum from the urogenital tract to nine kinds of antibiotics from 2007 to 2018 / 中华皮肤科杂志

Objective To analyze changes in sensitivity of clinical strains of Ureaplasma urealyticum (Uu) to 9 kinds of common antibiotics from 2017 to 2018.Methods The results of drug sensitivity testing of clinical Uu strains,which were isolated from 19 431 patients in Laboratory of Sexually Transmitted Disease (STD),Department of Dermatology and Venereology,The Third Affiliated Hospital,Sun Yat-Sen University from 2007 to 2018,were analyzed retrospectively.Of the 19 431 patients,6 076 were males,and 13 355 were females.Their age ranged from 15 to 68 years.The tested antibiotics included minocycline,doxycycline,erythromycin,azithromycin,clarithromycin,roxithromycin,ciprofloxacin,sparfloxacin and levofloxacin.Results Resistance rates of clinical Uu strains to minocycline and doxycycline gradually decreased from 10.08％ and 10.42％ in 2007 to 1.15％ and 2.61％ in 2018,respectively,while sensitivity rates to minocycline and doxycycline gradually increased from 85.88％ and 87.56％ in 2007 to 97.02％ and 96.42％ in 2018,respectively.The resistance rate and sensitivity rate of clinical Uu strains to erythromycin fluctuated greatly during 2014-2017,with the resistance rate fluctuating around 20％,and the sensitivity rate fluctuating around 50％.The resistance rate of clinical Uu strains to azithromycin dropped rapidly from 42.02％ in 2007 to 8.39％ in 2011,and then fluctuated slightly around 10％.However,the sensitivity rate to azithromycin increased from 8.40％ in 2007 to 86.05％ in 2011,and remained above 80％ from then on to 2018.During 2007-2018,Uu strains showed low resistance rates (10％-20％) and high sensitivity rates to clarithromycin (80％-90％),and the resistance and sensitivity rates to roxithromycin were similar to those to erythromycin.Uu strains showed constantly high resistance to ciprofloxacin (more than 80％ after 2013) and low sensitivity (persistently less than 10％).The sensitivity rate of clinical Uu strains to sparfloxacin fluctuated around 40％,while the resistance rate was maintained below 10％ after 2011.The resistance and sensitivity rates of Uu strains to levofloxacin were similar to sparfloxacin,but the sensitivity rate to levofloxacin was relatively lower,which had been maintained at about 30％.Conclusion From 2007 to 2018,clinical Uu strains maintained a relatively stable low resistance rate and a high sensitivity rate to minocycline,doxycycline and clarithromycin,a high resistance rate and low sensitivity rate to ciprofloxacin,and a low resistance rate and sensitivity rate to sparfloxacin and levofloxacin;a relatively stable low resistance rate and a high sensitivity rate to azithromycin were achieved only after 2011;the resistance rate and sensitivity rate to erythromycin and roxithromycin fluctuated greatly.

Analysis of drug susceptibility and risk factors for drug resistance of Escherichia coli in elderly patients with urinary tract infection / 中华老年医学杂志

Objective To investigate the risk factors for drug resistance of urinary tract infections-causing Escherichia coli producing extended spectrum beta-Lactamases (ESBLs) in elderly people (≥65 years old),in order to provide evidence for rational use of antibiotics in clinic.Methods Clinical data of elderly patients diagnosed as urinary tract infections in Beijing Chao-Yang Hospital from January 2016 to December 2017 were retrospectively analyzed.According to whether ESBLs were produced by Escherichia coli isolated from urine samples,the patients were divided into the ESBLs-producing E.Coli group (ESBLs group) and the control group.Single factor analysis was performed by Chi-square test.Logistic regression analysis was used to analyze the risk factors for ESBLs-producing Escherichia coli infections in urinary tract on the basis of statistical significance.Results A total of 452 strains of Escherichia coli were isolated,including 253 strains (55.97％)producing ESBLs,and 199 strains (44.03％) not producing ESBLs.The ureteral calculi (OR =2.675,95％CI:1.129-6.341),urinary obstructive diseases (≥ 2 kinds) (OR =8.680,95％CI:2.508-30.040),indwelling catheters (OR =5.762,95％ CI:2.698-12.155),antibiotic treatment more than 2 weeks for urinary tract infections within one year (OR =3.461,95％CI:1.766-6.784)were independent risk factors for ESBLs-producing Escherichia coli urinary tract infections.The incidence rate of Escherichia coli resistance to various antibiotics was higher in elderly patients with urinary tract infection than in non-elderly patients.Conclusions Escherichia coli producing ESBLs can be easily isolated from elderly patients with urinary tract obstructive diseases,indwelling catheters and repeated long-term administration of broad-spectrum antibiotics.The proportion of ESBLs Escherichia coli-caused urinary tract infections is higher in elderly patients.Thereby,carbapenems or piperacillin/tazobactam is the reasonable antibiotics.Ampicillin,piperacillin,levofloxacin and ciprofloxacin should not be the first choice for the treatment of urinary tract infections in the elderly.

Drug sensitivity test of human derived Brucella / 中华地方病学杂志

Objective To screen the most suitable medium for Brucella drug susceptibility test, and observe the resistance of human derived Brucella to different antibiotics. Methods Totally 180 strains of Brucella isolated from 25 provinces (municipalities, autonomous regions) in recent years were taken as observation objects. Mueller-Hinton ( MH ) agar , MH blood agar and Brinell agar were used to carried out the drug susceptibility test in vitro, and to compare the results of drug susceptibility test of different medium; the most suitable Brucella drug susceptibility test medium was used to detect the resistance of human derived Brucella to Doxycycline, Rifampicin, Streptomycin, Levofloxacin, Moxifloxacin, Ceftriaxone sodium, Co-trimoxazole and Amoxicillin/Clavulanic acid by K-B drug sensitive paper, and to observe the formation of antibacterial ring around the drug sensitive paper. Results The growth of Brucella on the MH agar and MH blood agar were slower than that on the Brinell agar, and the antibacterial rings were not obvious. All the 180 strains of Brucella were sensitive to seven antibiotics such as Doxycycline, Rifampicin, Streptomycin, Levofloxacin, Moxifloxacin, Ceftriaxone sodium, and Amoxicillin/Clavulanic acid; and 70 strains of Brucella were resistant to Co-trimoxazole, accounting for 39％ (70/180); Brucella strains resistant to Co-trimoxazole were found in 21 provinces. Conclusions Brinell agar is the most suitable medium for Brucella susceptibility test. The human derived Brucella is resistant to Co-trimoxazole; the resistant strains are distributed in 21 provinces ( municipalities , autonomous regions ) . It is recommended that relevant departm ents of the province ( municipalities , autonomous regions ) carry out epidemiological investigations on the resistance of Brucella, and strengthen the monitoring of drug resistance in clinical drugs of brucellosis patients.

Survival analysis of preoperative involved-field irradiation with concurrent chemotherapy for patients with Siewert's type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction / 中华放射肿瘤学杂志

Objective To analyze the clinical efficacy,toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy ( a total of 45 Gy in 25 fractions,5 times weekly). After 6-8 weeks,they underwent surgical resection. After the surgery,patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status,TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia,thrombocytopenia and neutropenia was 78%,47% and 44%,respectively. In terms of gastrointestinal reactions,the incidence of nausea,vomiting and loss of appetite was 62%,24% and 71%,respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer,1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-,2-and 3-year progression-free survival (PFS) rates were 90%,70% and 67%,respectively. The 1-,2-and 3-year overall survival rates were 95%,80% and 75%,respectively. The 1-,2-and 3-year local control rates were 95%,84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert typeⅡandⅢlocally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery.

Etiology, drug resistance and disinfectant resistance of Yersinia pestis in Hainan, Qinghai Province / 中华地方病学杂志

Objective To investigate the etiology and the epidemiologic features of drug resistance and disinfectant resistance of Yersinia pestis in Hainan,Qinghai Province,in order to provide a scientific basis for prevention and control of the plague in this area.Methods Totally 75 strains were isolated from vary kinds of host in Hainan from 1960 to 2009,and biochemical test,virulence factors evaluation [Fra1 (F1),pesticin Ⅰ (Pst Ⅰ),virulence antigen (VW),pigmentation (Pgm)],plasmid analysis,different region (DFR) genotyping,drug resistance and disinfectant resistance gene test were carried out.Forty-five strains of Yersinia pestis were selected to determine their toxicity in mice,median lethal dose (LD50) was calculated,and LD50 ＜ 1 000 was defined as strongly toxic.Results Sixty of the 75 strains were Qing-Tibet Plateau ecotype,7 strains were Qilian Mountain ecotype,and the remaining 8 were different ecotypes from the plague foci in Qinghai Plateau.Eighty percent (60/75) contained all the four virulence factors;and 97.78％ (44/45) of the strains were velogenic strains;96.00％ (72/75) of the strains contained 3 kinds of plasmids (Mr:6 × 106,45 × 106 and 52 × 106);the DFR strains had 3 genomovars,which were genomovar 8 (65 strains),genomovar 5 (8 strains) and genomovar 21 (2 strains).No strains related to streptomycin,sulfonamides,β-lactam antibiotics and disinfectants had been found in the 75 strains of Yersinia pestis.Conclusions The strains isolated in Hainan have the characteristics of Qinghai-Tibet Plateau plague's pathogen,and they have strong toxicity.In view of high mortality of plague,drug resistance and disinfectant resistance gene test should be put into routine monitoring of the plague.

The progresses and perspectives of the control and eradication of persistent bacteria / 医学研究生学报

Persistent bacteria is a microbial subpopulation which can survive from lethal concentration of antimicrobial agents. Unlike the resistant bacteria which usually acquire the resistance from heritable gene mutations, persisters are genetically identical to regular cells in genome but show a distinct antibiotic tolerant phenotype through a state of dormancy. Once the antimicrobial therapy is removed,the persisters can regrow to a new population and cause the recurrent infectious diseases. The increased threats due to the in-fections and drug tolerance caused by persistent bacteria promote the interests of preventing bacterial persistence. This review discusses the harmfulness of persistent infections, the mechanisms of bacterial persistence and summarizes the different control and eradication strategies,aiming to provide ideas and references for further research.

Effects of intrathecal administration of dexmedetomidine on morphine tolerance and inflammatory response in rats / 重庆医学

Objective To investigate the effects of intrathecal dexmedetomidine administration on the development of morphine tolerance and spinal inflammatory responses.Methods Thirty-three male SD rats weighing 180～200 g were randomly divided into 3 groups (n=11):Saline group (group NS),Morphine group (group M) and Dexmedetomidine group (group Dex).Animals of group NS were intrathecally injected with 10 tμL of saline daily for seven days;Animals in group M were intrathecally injected with 15 μg of morphine daily for seven days;Animals in group Dex were intrathecally injected with a mixture of 15μg morphine and 1.5 μg dexmedetomidine daily for seven days.At 1,3,5 and 7 day of intrathecal injection,hot water tail-flick test were used to evaluate analgesic response to thermal stimuli.After the last episode of behavioral test,Western blot analysis was applied to determine the protein levels of Iba-1 (microglial marker),IL-1β,TNF-a and phospho-p38MAPK (p-p38) in the spinal cord.In addition,microglia in the spinal cord was immuno-stained with anti-Iba-1 antibody and the densities of microglia were calculated.Results In group M and Dex,the values of maximal possible effect (MPE) in tail-flick test decreased gradually along with repeated morphine administration (P＜0.05).Compared with group NS,the values of MPE in tail-flick test at 1,3,5 and 7 day of morphine tolerance were higher in group M (P＜0.05).Compared with group M,the values of MPE in tail-flick test at 3,5 and 7 day of morphine tolerance were higher in group Dex (P＜0.05).Compared with group NS,the spinal protein levels of Iba-1,IL-1L TNF-α and p-p38 as well as the density of Iba-1 positive cells in group M were increased (P＜0.05).However,Compared with group M,the of Iba-1,IL-1β,TNF-α and p-p38 as well as the density of Iba-1 positive cells were decreased(P＜0.05).Conclusion Intrathecal dexmedetomidine administration can attenuate morphine tolerance by inhibiting microglia-mediated inflammatory responses in the spinal cord.

The function and mechanism of ErbB3 and IGF1R in breast cancer with Herceptin resistance / 中国医师杂志

Objective To investigate the role of epidermal growth factor receptor 3 (ErbB3) and insulin-like growth factor-1 receptor (IGF1R) in enhancing the resistance of Herceptin in human breast cancer.Methods HRG (Heregulin,the ligand of ErbB3) or IGF2 (insulin-like growth factor2,the ligand of IGF1R) was correspondingly added into breast cancer cells SKBR3 and BT474,and then 3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and were performed in these cells to evaluate the sensitivity of these cells to Herceptin.Furthermore,we used HRG or IGF2 antibodies to inhibit their joint receptors in Herceptin-resistant breast cancer cells SKBR3/POOL2 and BT474/HR20.Finally,the sensitivity of these treated cells to Herceptin was detected via MTS assay.HRG or IGF2 was added into breast cancer cell BT474,and co-IP assay was used to detect the expressions of ErbB3 and IGF1R which combined with ErbB2.Results The treatment groups used HRG or IGF2 enhanced the resistance of Herceptin in Herceptin-sensitive breast cancer cells.On the other hand,we used antibodies of HRG and IGF2 to block their combining with their receptors in Herceptin-resistant breast cancer cells,the cells became more sensitive to Herceptin.BT474 cell was treated with HRG or IGF2.The expressions of ErbB3 and IGF1R which combined with ErbB2 were increased.Conclusions The formation of heterodimers ErbB2/ErbB3 and ErbB2/IGF1R might enhance the resistance of Herceptin in ErbB2-overexpression human breast cancers.

Role of sonic hedgehog signaling pathway in spinal neurons in morphine tolerance in mice / 中华麻醉学杂志

Objective To evaluate the role of sonic hedgehog (SHH) signaling pathway in spinal neurons in morphine tolerance (MT) in mice.Methods Pathogen-free healthy female Kunming mice,weighing 20-25 g,aged 8-10 weeks,were used in the study.MT was induced with morphine 10 mg/kg injected subcutaneously twice a day for 7 consecutive days.The experiment was performed in two parts.Experiment Ⅰ Forty-eight mice were randomly assigned into 2 groups:control group (group C,n =8) and MT group (group M,n=40).The thermal pain threshold (TPT) was measured at 1 day before morphine injection and 1,3,5,7 and 14 days after the end of injection.Eight mice in each group were sacrificed at 2 h after measurement of TPT at each time point after the end of injection in group M or at 2 h after the last measurement of TPT in group C,and the lumbar segment (L4-6) of the spinal cord was removed.Experiment Ⅱ Forty-eight mice were randomly assigned into 6 groups (n=8 each):SHH inhibitor cyclopamine plus MT group (group CP+M),cyclopamine solvent plus MT group (group D1 +M),SHH agonist SAG plus MT group (group SAG+M),SAG solvent plus MT group (group D2+M),MT plus cyclopamine group (group M+CP) and morphine plus cyelopamine solvent group (group M+D1).At 15 min before morphine injection,cyclopamine 10 mg/kg was injected subcutaneously in group CP+M,and SAG 5 mg/kg was injected subcutaneously in group SAG+M.Cyclopamine 10 mg/kg was injected subcutaneously once a day during the 1-3 days after the end of morphine injection in group M+CP.The TPT was measured before injection of morphine,at 30 min after the first injection of morphine every day and at 1-3 days after the end of morphine injection.The animals were sacrificed at 2 h after the last measurement of TPT,and the lumbar segment (L4-6) of the spinal cord was removed for determination of the expression of SHH signaling pathway-related proteins SHH,ptch1,smo,gli1 and gli3 using Western blot.Results Experiment Ⅰ Compared with group C,the TPT was significantly decreased at 1 and 3 days after the end of morphine injection (P＜0.05),no significant change was found in TPT at 5-14 days after the end of morphine injection (P＞0.05),and the expression of SHH,smo and glil at 1-5 days after the end of morphine injection,of ptchl at 1 and 3 days after the end of morphine injection and of gli3 at 7 days after the end of morphine injection was up-regulated in group M (P＜0.05).Experiment Ⅱ Compared with group D1+M,the TPT was significantly increased,the expression of SHH,ptchl,smo and glil was down-regulated,and gli3 expression was up-regulated in group C P+M (P＜0.05).Compared with group D2+M,the TPT was significantly decreased,the expression of SHH,ptch1,smo and glil was up-regulated,and gli3 expression was down-regulated in group SAG+M (P＜0.05).There was no significant difference in the parameters mentioned above between group M+CP and group M+D1 (P＞0.05).The TPT was significantly lower on 3rd-7th days after beginning of morphine injection and 1-3 days after the end of morphine injection than at 30 min after the first injection of morphine in group CP+M (P＜0.05).Conclusion The mechanism underlying the development of MT is partially related to activation of SHH signaling pathway in spinal neurons of mice,however,the maintenance mechanism has no marked relationship with it.

Comparative analysis of pathogenic bacteria distribution and drug resistance from NICU blood culture at different altitudes / 重庆医学

Objective To compare and analyze the influencing factors of the distribution and drug resistance of blood culture positive pathogens in neonatal intensive care unit (NICU) at different altitude areas.Methods The distribution of blood culture positive pathogens and clinical susceptibility of children in NICU of two different altitude hospitals in 2015 were retrospectively analyzed.Results In 2015,children in NICU in upper elevation district hospital mainly infected with 19 strains(18.4％) of epidermis staphylococcus,18 strains(17.5 ％) of Escherichia coli,14 strains(13.6 ％) of Klebsiella pneumoniae,14 strains(13.6 ％) of Hemolysis staphylococcus,12 strains(11.7 ％) of Stenotrophomonas maltophilia;Children in NICU at low altitude hospital mainly infected with 31 strains(19.7％) of epidermis staphylococcus,27 strains(17.2％) of Achromobacter xylosoxidans,18 strains(11.5％) of Hemolysis staphylococcus,14 strains(8.9 ％) of Klebsiella pneumoniae,14 strains (8.9 ％) of Acinetobacter baumannii.The detection rate of Gram-negative bacilli in high altitude hospital was higher,and the detection rate of Gram positive cocci in low altitude hospital was higher.In high-altitude district hospital,the detection rate of methicillin-resistant coagulase negative staphylococci (MRCNS) extended-spectrum β-lactamase (ESBLs),and multidrug-resistant Acinetobacter baumannii(MDRAB) were than low altitude hospital.Conclusion Escherichia coli and Stenotrophomonas maltophilia detection rate and common antibiotics sensitive rate are relatively high at upper elevation areas;Detection rate of coagulase negative Staphylococcus aureus and common antibiotics resistance rate are high in low altitude.Different altitudes environmental factors may play an important role in pathogens distribution and drug resistance from NICU blood culture.