β-CTX、t-P1NP及N-MID-OT在绝经后女性骨质疏松性骨折风险评估中的应用

目的探讨β胶原特殊序列(β-crosslaps,β-CTX)、总1型胶原氨基端延长肽(t-P1NP)及N端中段骨钙素(N-MID-OT)在绝经后女性骨质疏松性骨折风险评估中的应用价值。方法回顾性分析2020年2月至2022年12月解放军总医院第六医学中心收治的102例绝经后骨质疏松(postmenopausal osteoporosis,PMOP)患者的临床资料,将其作为研究组,并根据是否发生骨折将其分为PMOP骨折组(39例)与PMOP未骨折组(63例),另选100名健康体检者作为对照组。记录所有研究对象的β-CTX、t-P1NP及N-MID-OT水平并进行比较,用ROC曲线评价β-CTX、t-P1NP及N-MID-OT在绝经后女性骨质疏松性骨折风险评估中的应用价值。结果研究组的平均体重、体质量指数、股骨颈骨密度(bone mineral density,BMD)、左髋总和BMD及L 1~4总和BMD均明显低于对照组(P<0.05);而两组研究对象的平均年龄、平均身高及绝经年龄等比较差异均无统计学意义(P>0.05)。研究组的β-CTX、t-P1NP及N-MID-OT均明显高于对照组(t值依次为12.688、37.430、26.599,P<0.05)。β-CTX+t-P1NP+N-MID-OT联合检测用于预测PMOP的AUC值为0.978,敏感度为98.04%,特异度为97.00%,表明β-CTX+t-P1NP+N-MID-OT三指标联合检测用于预测PMOP的效能更高。PMOP骨折组的β-CTX、t-P1NP及N-MID-OT均明显高于PMOP未骨折组(t值依次为6.078、16.363、12.227,P<0.05)。β-CTX+t-P1NP+N-MID-OT联合检测用于评估PMOP骨折风险的AUC值为0.939,敏感度为94.87%,特异度为95.24%,表明β-CTX+t-P1NP+N-MID-OT联合检测用于评估PMOP骨折风险的效能更高。结论PMOP患者β-CTX、t-P1NP及N-MID-OT水平均明显升高,而PMOP骨折患者β-CTX、t-P1NP及N-MID-OT水平升高更为明显,且β-CTX+t-P1NP+N-MID-OT联合检测可显著提高对PMOP预测及骨折风险评估效能,值得借鉴。

血液高RDW和高N-MID OC/β-CTX比值在老年女性椎体骨折中的诊断价值

目的 探讨血液红细胞分布宽度(RDW)及骨钙素N段中分子片段(N-MID OC)/Ⅰ型胶原羧基端肽β特殊序列(β-CTX)比值联合检测对老年女性骨质疏松椎体骨折(OPVF)的诊断价值。方法 纳入2021年1月—2021年12月我院≥60岁女性骨质疏松住院患者786例,分为无骨折组(A组,378例)和OPVF组(B组,388例)。N-MID OC、β-CTX、NMID-OC/β-CTX比值、红细胞计数(RBC)、红细胞压积(HCT)、血红蛋白(Hb)、红细胞平均体积(MCV)、平均血红蛋白浓度(MCHC)、平均血红蛋白量(MCH)、红细胞分布宽度(RDW-CV)、钙(Ca)、磷(P)及镁(Mg)。结果 与A组相比,B组Ca、P、Hb、HCT、MCV、MCH、MCHC含量降低,RDW-CV、N-MID OC/β-CTX含量增加,差异有统计学意义(均P<0.05)。OPVF与β-CTX、Ca、P呈负相关,与RDW-CV、N-MID OC/β-CTX呈正相关(均P<0.05)。骨折患者RDW与N-MID OC、β-CTX、Ca、P、Mg呈负相关(均P<0.05)。RDW、N-MID-OC/β-CTX为OPVF的风险因素(均P<0.05),OR分别为1.38、1.005。二者含量越高,椎体骨折风险越高,最高层是最低层的约3倍和2倍,OR为2.818,1.734。二者联合检测可提高对OPVF的诊断性能,其AUC敏感性、特异性、阳性预示值、阴性预示值分别为0.64、42.78%、82.01%、70.9%、58.3%。结论 血液高RDW和高N-MID OC/β-CTX比值与老年女性骨质疏松性椎体骨折明显相关,是其危险因素,可用于辅助诊断及预测其发生。

广东省腹泻仔猪大肠杆菌blaCTX-M-65与mcr-1基因共传播特征

【目的】调查分析广东省某生猪养殖场腹泻仔猪的大肠杆菌耐药情况以及同时携带blaCTX-M-65与mcr-1两种耐药基因的阳性大肠杆菌的分子特征与其共同传播特征,为耐药性监测及风险防控提供科学依据。【方法】从广东省肇庆市某生猪养殖场采集腹泻仔猪直肠棉拭子样品90份,并进行大肠杆菌分离鉴定;采用PCR方法检测产超广谱β-内酰胺酶(ESBLs)与mcr-1基因,通过测序确定CTX-M亚型;采用琼脂二倍稀释法和微量肉汤稀释法测定分离菌对12种抗菌药物的最小抑菌浓度(MIC);使用脉冲场凝胶电泳(PFGE)及多位点序列分型(MLST)分析菌株间的遗传背景;通过接合转移方法确定质粒水平转移的能力;使用复制子分型、S1-PFGE、Southern blotting方法检测质粒类型、耐药基因的定位及定位质粒的大小;通过三代测序及序列分析确定质粒的重组过程。【结果】共分离鉴定86株大肠杆菌,检测到44株携带CTX-M型ESBLs基因,其中blaCTX-M-55基因最流行(n=16,36.4%),其次是blaCTX-M-65(n=10,22.7%)、blaCTX-M-27(n=8,18.2%)、blaCTX-M-15(n=5,11.4%),还检测出blaCTX-M-79(n=2,4.5%)、blaCTX-M-14(n=2,4.5%)和blaCTX-M-24(n=1,2.3%)。10株blaCTX-M-65基因阳性菌有8株同时携带mcr-1基因。这8株大肠杆菌均表现为多药耐药,包括氨苄西林、阿莫西林、头孢噻呋、头孢喹肟、黏菌素等多种抗生素。8株菌共分为6种ST型、7个PFGE谱型。接合转移试验发现,有6株菌的blaCTX-M-65和mcr-1基因发生了共转移,且blaCTX-M-65与mcr-1基因均位于IncHI2型(253 kb)质粒上。其中1株菌在接合转移的过程中,其所携带的一个253 kb IncHI2质粒与一个69 kb IncFⅡ质粒发生融合,形成一个大小323 kb的融合质粒。对融合质粒进行三代测序解析,结果表明,在接合转移的过程中IS26介导了两个不同大小质粒的重组。【结论】IncHI2质粒是介导blaCTX-M-65和mcr-1基因共同传播的主要媒介,IS26通过与靶位点GTTTCACT的整合导致IncHI2质粒与IncFⅡ质粒融合。质粒重组扩大了大肠杆菌的耐药谱,加速了耐药基因的传播,促使多药耐药现象更严重,对公共卫生安全构成威胁,本研究为阐明多重耐药大肠杆菌的传播机制提供了参考依据。

新疆维吾尔自治区塔额垦区牛源大肠杆菌耐药性、CTX-M基因携带情况与毒力基因检测

[目的]了解新疆维吾尔自治区塔额垦区牛源大肠杆菌耐药性及CTX-M基因和毒力基因携带情况。[方法]从塔额垦区某牛场采集16份牛腹泻粪样,通过选择性培养、革兰染色镜检、16S rDNA PCR扩增及测序进行大肠杆菌分离鉴定。利用PCR法对牛源大肠杆菌分离株进行分子分型(系统发育群和脂多糖核心型)以及耐药基因、CTX-M基因亚型、毒力基因检测;分别使用K-B纸片法、CTX与TCL双纸片法进行药物敏感性试验和产ESBLs大肠杆菌鉴定;采用结晶紫染色法半定量检测菌株的生物被膜形成能力。[结果]根据菌落生长特征、革兰染色特性及16S rDNA测序结果,从16份牛腹泻粪样中分离鉴定出16株大肠杆菌,分离率为100%;系统发育群主要为B1群(14/16,87.50%),脂多糖核心型多为R1型(15/16,93.75%)。分离菌株对青霉素、利福平、复方新诺明表现出较强耐药性,耐药率分别为100%、68.75%、68.75%;对多黏菌素、替加环素、美罗培南敏感,耐药率均为0;有12株(75.00%)具有多重耐药表型;有11株(68.75%)产ESBLs;有15株(93.75%)可形成生物被膜。16株大肠杆菌中共检出17种耐药基因,CTX-M、ant(6′)、sul1等8种耐药基因的检出率为100%;有14株(87.50%)为CTX-M-1G基因亚型;共检出12种毒力基因,iroN、ompA、yijP等5种毒力基因的检出率为100%。[结论]新疆维吾尔自治区塔额垦区牛源大肠杆菌CTX-M基因检出率较高,携带多种耐药基因和毒力基因,耐药性较强,对该地区牛健康养殖存在潜在威胁,应加强该地区CTX-M型大肠杆菌的流行情况监控。

Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

Moxibustion at ST36 activates peritoneal macrophages in CTX-induced immunosuppression in mouse model via IFN-γ

Background:To explored whether moxa cone moxibustion can reduce peritoneal inflammation by increasing the content of peritoneal macrophages and B cells via interferon-gamma.Methods:The mice were randomly divided into three groups with six mice in each group:the control group,model group,and moxibustion group,and the model was established in mice using cyclophosphamide.In the moxibustion group,the mice received moxa cone moxibustion at Zusanli(ST36)for 7 days.Analysis of Peritoneal cell were detected by flow cytometry and immunofluorescence,the protein expression level in the peritoneal fluid were measured with mouse cytokine antibody arrays and verified by enzyme linked immuno sorbent assay test,and RNA-Sequencing was used for peritoneal cell RNA analysis.Results:Our results showed that moxa cone moxibustion could reduce the loss of large peritoneal macrophages and B1 cells(P<0.05).With the cytokine array analysis and enzyme linked immuno sorbent assay test of peritoneal fluid,we found that IFN‐γwas up-regulated in moxibustion group(P<0.05).There were 169 genes were down-regulated in the model group and up-regulated in the moxibustion group while 19 genes that were up-regulated in the model group and down-regulated in the moxibustion group via RNA-sequencing.Kyoto Encyclopedia of Genes and Genomes pathway analysis of 188 intersect differentially expressed genes were found that the top 3 pathways with the highest enrichment of up-regulated genes included Hematopoietic cell lineage,Inflammatory bowel disease and Malaria.The differentially expressed genes visualization protein-protein interaction network shows the top 10 genes including Ifng,Grb2,CCR7,CTLA4,CXCR5,Foxp3,kit,PRF1,CD5 and klrg1.Conclusion:These findings showed that moxa cone moxibustion can alleviate chemotherapy-induced diarrhea by reducing the loss of large peritoneal macrophages and B1 cells in the peritoneal cavity,possibly through up-regulating inflammatory bowel disease signaling pathway via interferon-gamma to regulate the survival and function of large peritoneal macrophages and B1 cells.

经皮椎体后凸成形术治疗椎体压缩性骨折瘦素、脂联素及CTX-Ⅰ水平分析

目的 探讨经皮椎体后凸成形术(PKP)治疗椎体压缩性骨折瘦素、脂联素及Ⅰ型胶原蛋白C末端异物肽(CTX-Ⅰ)水平。方法 选取2019年6月至2022年5月南京中医药大学附属南京市中西医结合医院收治的92例椎体压缩性骨折患者为研究对象,根据治疗方式的不同分为对照组45例[予经皮椎弓根螺钉内固定术(PPSF)]、观察组47例(予PKP治疗);比较两组瘦素、脂联素和CTX-Ⅰ水平、分析观察组不同临床特征与病理特征的瘦素、脂联素和CTX-Ⅰ水平、采用多元Logistic回归分析影响观察组瘦素、脂联素和CTX-Ⅰ水平的危险因素,比较两组临床疗效及并发症情况。结果 观察组血清瘦素水平高于对照组,脂联素和CTX-Ⅰ水平均低于对照组,差异具有统计学意义(P<0.05);观察组不同年龄段、有无骨折病史、术前骨折椎体数和术中骨水泥量之间瘦素水平比较差异有统计学意义(P<0.05);不同性别、不同年龄段、有无骨折病史和术中骨水泥量之间脂联素水平比较差异有统计学意义(P<0.05);不同性别、不同年龄段、有无骨折病史和术中骨水泥量之间CTX-Ⅰ水平比较差异有统计学意义(P<0.05);经多元Logistic回归分析可知,女性、年龄>62岁、有骨折病史、术前骨折椎体数≥2个及术中骨水泥量使用1~5 mL为影响瘦素、脂联素和CTX-Ⅰ水平的危险因素(P<0.05);观察组临床总有效率(95.74%)高于对照组(82.22%),差异具有统计学意义(P<0.05);观察组并发症总发生率(2.13%)比对照组(13.33%)低,差异具有统计学意义(P<0.05)。结论 经PKP治疗能有效提高椎体压缩性骨折患者的临床疗效,有效改善患者血清瘦素、脂联素及CTX-Ⅰ水平,通过检测上述三指标水平可对PKP术后治疗提供参考依据。

新疆部分地区动物源CTX-M大肠埃希氏菌的多重耐药性分析

为了解新疆动物源产CTX-M大肠埃希氏菌携带的CTX-M基因亚型和多重耐药性的特点,采用PCR方法检测新疆猪、牛、羊、骆驼、马、鸡、鹅、鸽、犬和猫源产CTX-M大肠埃希氏菌的CTX-M基因亚型(bla_(CTX-M-1)、bla_(CTX-M-2)和bla_(CTX-M-9)亚群),利用K-B纸片法对产CTX-M大肠埃希氏菌进行药物敏感性检测。结果显示,在148株产CTX-M大肠埃希氏菌中,bla_(CTX-M-1)亚群的检出率最高为76.35%(113/148),bla_(CTX-M-9)亚群次之为20.27%(30/148),2.70%(4/148)的菌株同时携带bla_(CTX-M-1)和bla_(CTX-M-9)亚群,0.68%(1/148)不可分型,未检出bla_(CTX-M-2)亚群。药敏试验结果显示,148株产CTX-M大肠埃希氏菌中对氨苄西林、复方新诺明、阿莫西林、四环素、头孢噻肟和头孢曲松的耐药率在93.24%~99.32%,对环丙沙星、庆大霉素、左氧氟沙星、头孢他啶和多黏菌素B的耐药率在27.03%~50.00%,对氨苄西林-舒巴坦、哌拉西林-他唑巴坦和亚胺培南的耐药率为1.35%~10.14%,98.65%呈多重耐药(146/148),其中以5重耐药菌株为主(45.95%,68/148)。结果表明,新疆动物源产CTX-M大肠埃希氏菌以bla_(CTX-M-1)亚群为主,bla_(CTX-M-9)亚群次之,多重耐药情况严重。

UPLC-Q-TOF/MS-based metabolomics reveals modulatory effects of Mesona chinensis Benth polysaccharide in liver injury mice induced by cyclophosphamide

The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.

扬州某社区健康人源大肠杆菌bla_(CTX-M)的流行特征

目的为调查扬州某社区健康人源大肠杆菌的耐药状况以及超广谱β-内酰胺酶基因bla_(CTX-M)的流行特征。方法2021年从扬州某社区健康人群中采集鼻拭子样品58份和粪便样品37份,通过麦康凯琼脂、PCR等方法进行大肠杆菌的分离和鉴定,采用琼脂稀释法或微量稀释法测定药物敏感性,通过PCR扩增和测序检测bla_(CTX-M)基因,同时对bla_(CTX-M)阳性大肠杆菌进行全基因组测序。结果从95份样品中分离获得35株大肠杆菌。大肠杆菌对四环素耐药率最高为35.3%,其次为氨苄西林(30.6%)和萘啶酸(27.8%),对头孢他啶、头孢噻肟、庆大霉素、链霉素、复方新诺明的耐药率在10%~20%,对氯霉素、氟苯尼考、环丙沙星、磷霉素耐药率均在10%以下。4株(11.4%)对头孢噻肟耐药的菌株携带bla_(CTX-M)-1G基因,包括bla_(CTX-M)-55(n=3)和bla_(CTX-M)-15(n=1),其中1株可将bla_(CTX-M)接合转移至大肠杆菌C600。在bla_(CTX-M)基因的上游均存在1个拷贝的插入序列ISEcp 1或被IS 26截断的ISEcp 1。结论bla_(CTX-M)基因在扬州某社区健康人源大肠杆菌携带率低,其传播可能与ISEcp 1有关。

地舒单抗治疗绝经后骨质疏松症的疗效观察及对PINP、β-CTX的影响

目的观察地舒单抗治疗绝经后骨质疏松症的疗效及对血清PINP、β-CTX含量的影响。方法选取自2021年5月~2022年1月就诊的绝经后骨质疏松症患者80例,给予地舒单抗60 mg治疗,同时给予维D钙咀嚼片。比较治疗前及治疗6个月后患者腰椎骨密度、疼痛数字评定量表(NRS)评分、Oswestry功能障碍指数(ODI)评分变化情况及对血清Ⅰ型前胶原氨基端前肽(PINP)、Ⅰ型胶原羧基端肽β特殊序列(β-CTX)水平的影响。结果治疗6个月后,患者腰椎骨密度增加,差异有统计学意义(P<0.05);NRS评分以及ODI指数较治疗前均降低,差异有统计学意义(P<0.05);血清PINP、β-CTX水平较治疗前均下降,差异有统计学意义(P<0.05)。结论地舒单抗联合钙制剂的治疗可以明显改善绝经后骨质疏松患者的骨痛症状,提升骨密度,调节骨代谢生化等指标。

Treatment outcome analysis of bevacizumab combined with cyclophosphamide and oxaliplatin in advanced pseudomyxoma peritonei

BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.

Prevalence and Resistance Profile of Muenchen Cefotaximase (CTX-M) Group 1 Extended Spectrum Beta-Lactamase (ESBL)-Producing Uropathogenic Escherichia coli Strains in Dakar, Senegal

Background: Extended-spectrum beta-lactamase (ESBL) producing bacteria are a real public health problem, particularly in Africa. Among these ESBLs, there are the Muenchen Cefotaximase (CTX-M) described all over the world of which the most frequent is the CTX-M of group 1 particularly the CTX-M-15 variant. The objective of this study was to determine the prevalence of CTX-M group 1 ESBL-producing Escherichia coli strains and to test their antibiotics susceptibility profile. Methodology: A retrospective cross-sectional descriptive study was conducted to detect ESBL-secreting Escherichia coli strains by the synergy test. Identification of CTX-M type ESBL from group 1 was performed using the NG-Test CTX-M rapid diagnostic test (NG-Biotech®). Antibiotic susceptibility profile was determined using CA-SFM/EUCAST guidelines 2019. Data entry and statistical analysis were performed with Excel version 2010 and SPSS 20.0 respectively. Results: Eighty-two ESBL-producing Escherichia coli strains were tested. A group 1 CTX-M ESBL was detected in 75.6% of the strains (n = 62). These strains were highly resistant to cefotaxim (100%), aztreonam (100%), ceftazidim (85.4%) and cefepim (66.1%). They were also resistant to quinolones, gentamycin and sulfadoxine-trimethoprim combination. However, these strains showed sensitivity to ertapenem (100%), cefoxitin (69.3%), tigecyclin (66%), and amikacin (66.1%). The combination of piperacillin and tazobactam was active on 30.6% of the strains against 6.4% for the combination of amoxicillin and clavulanic acid. Conclusion: The CTX-M type ESBL of group 1 was present in the majority of ESBL-producing Escherichia colis trains. Despite the production of this enzyme conferring resistance to most beta-lactam antibiotics, some antibiotics remain active to treat infections caused by these germs.

miR-7抑制剂治疗MRL/lpr小鼠的实验性研究

目的:探讨miR-7抑制剂治疗MRL/lpr小鼠的疗效。方法:选取30只MRL/lpr小鼠,随机分为miR-7抑制剂(miR-7 antagomir)组、环磷酰胺(CTX)组和生理盐水(Saline)对照组,10只/组。MRL/lpr小鼠13周时开始治疗,以上药物分别连续给药5周。每周观察各组小鼠一般状况并称重,留取血清和尿液标本。ELISA检测13~17周三组小鼠血清ANA、抗ds-DNA抗体、C3水平,并检测上述各周三组小鼠尿蛋白水平。流式细胞术检测三组小鼠Tfh细胞比例变化。RT-PCR检测三组小鼠脾脏和淋巴结miR-7和PTEN mRNA表达水平。HE、PAS、PASM染色观察光镜下三组小鼠的肾脏病理情况。结果:治疗5周后,形态学方面:与Saline组相比,miR-7 antagomir组和CTX组小鼠一般状况良好,体质量随周龄增加而增加。血清学方面:miR-7 antagomir组和CTX组血清ANA和抗ds-DNA抗体较Saline组明显下降,补体C3水平明显上升,但两治疗组间上述指标差异均无统计学意义。细胞学方面:miR-7 antagomir组小鼠脾脏Tfh细胞比例明显低于Saline组。与Saline组比较,miR-7 antagomir组小鼠脾B细胞miR-7表达水平降低,PTEN mRNA表达水平升高。此外,miR-7 antagomir组和CTX组小鼠光镜下肾脏病理改变均较Saline组有所好转,但该两组间肾脏病理改变无明显差异。结论:miR-7可作为系统性红斑狼疮的潜在治疗靶点,miR-7 antagomir能够显示出与经典免疫抑制剂CTX相近的治疗效果,有效地改善了MRL/lpr小鼠的狼疮样疾病表现,延缓了病情进展。

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

补骨脂素对环磷酰胺抑制小鼠骨髓间充质干细胞成骨分化的恢复作用

背景:补骨脂素具有很强的抗骨质疏松活性,可能对化疗导致的骨质疏松具有恢复作用。目的:探讨补骨脂素对环磷酰胺抑制小鼠骨髓间充质干细胞成骨分化的恢复作用及机制。方法:分离培养C57BL/6小鼠骨髓间充质干细胞,以MTT法检测补骨脂素对骨髓间充质干细胞活力的影响,以成骨诱导结合碱性磷酸酶染色确定补骨脂素对环磷酰胺抑制骨髓间充质干细胞成骨分化恢复作用的最佳剂量。采用RT-qPCR法检测补骨脂素干预不同时间点成骨分化标志基因Runx2、ALP、Osteocalcin、骨保护素及Wnt/β-catenin信号通路相关基因Wnt1、Wnt4、Wnt10b、β-catenin、c-MYC的mRNA表达;采用Western blot法检测补骨脂素干预不同时间点成骨特异性转录因子Runx2及Wnt/β-catenin信号通路相关基因Activeβ-catenin、DKK1、c-MYC、Cyclin D1的蛋白表达。结果与结论:(1)不同浓度补骨脂素对骨髓间充质干细胞活力没有显著影响;200μmol/L补骨脂素干预后对环磷酰胺诱导骨髓间充质干细胞成骨分化抑制的恢复作用最佳;(2)补骨脂素可以逆转环磷酰胺条件培养基导致的骨髓间充质干细胞成骨标志基因Runx2、ALP、Osteocalcin、骨保护素mRNA表达和Runx2蛋白表达的降低;(3)补骨脂素可以逆转环磷酰胺条件培养基导致的骨髓间充质干细胞Wnt/β-catenin通路相关基因Wnt4、β-catenin、c-MYC mRNA表达和Activeβ-catenin、c-MYC、Cyclin D1蛋白表达的降低以及DKK1蛋白表达的升高;(4)结果表明,环磷酰胺能抑制小鼠骨髓间充质干细胞成骨分化,补骨脂素对其具有恢复作用,且200μmol/L补骨脂素干预效果最佳,而这种保护作用可能与补骨脂素激活Wnt4/β-catenin信号通路有关。

来氟米特联合环磷酰胺对狼疮性肾炎患者血清白蛋白及补体C3水平的影响

目的探讨狼疮性肾炎(LN)患者应用来氟米特联合环磷酰胺治疗的临床效果。方法选择2019年4月至2021年4月九江市第一人民医院收治的84例LN患者作为研究对象,采用随机数字表法将其分为观察组(42例)及对照组(42例)。两组均予以泼尼松治疗,观察组同时给予环磷酰胺加用来氟米特治疗,对照组同时给予环磷酰胺治疗。两组均持续用药6个月。比较两组的临床疗效、肾功能指标、血清白蛋白和补体C3水平,并记录不良反应发生情况。结果观察组的治疗总有效率高于对照组,差异有统计学意义(P<0.05);观察组治疗后的血尿素氮(BUN)、血肌酐(SCr)、24 h尿蛋白量水平均低于对照组,血清白蛋白、补体C3水平均高于对照组,差异有统计学意义(P<0.05);两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论来氟米特联合环磷酰胺治疗LN效果显著,可有效提高血清白蛋白和补体C3水平,促进肾功能恢复,减轻肾功能损害,缓解临床症状,稳定病情,值得推广应用。

毫针和火针疗法治疗骨髓抑制大鼠模型的分子作用机制

目的探讨毫针和火针治疗大鼠骨髓抑制模型的分子作用机制。方法研究时间2022年3月至9月。采用随机数字表法将购于北京维通利华实验动物技术有限公司的96只4~6周龄、体质量为250~300 g的SD大鼠分为对照组、模型组、火针组和毫针组,各24只。除对照组外,其余各组大鼠用环磷酰胺诱导建立大鼠骨髓抑制模型,造模成功后,对照组和模型组大鼠每天陪同抓取、固定,但是不进行治疗;火针组大鼠根据编号依次将大鼠俯卧固定于鼠板上,选取双侧足三里穴于造模后第1天、第3天、第5天、第7天,采用火针点刺法治疗,火针垂直刺入3 mm,不留针,隔日1次,连续7 d;毫针组大鼠根据编号依次将大鼠俯卧固定于鼠板上,针具、选穴同火针组,垂直刺入3 mm,留针6 min,于造模后第1天开始,每天1次,连续7 d。分别于干预1~7 d取大鼠尾静脉血10μl测定白细胞数量、红细胞数量、血红蛋白含量和血小板数量等血常规指标;制作骨髓组织切片,进行瑞氏吉姆沙染色;流式细胞术检测骨髓单核成纤维细胞周期;免疫印迹法检测骨髓单核成纤维细胞周期相关蛋白的表达。采用LSD-t检验、单因素方差分析和Kruskal-Wallis检验。结果模型组大鼠白细胞数量和血小板数量均低于对照组(均P<0.05),红细胞数量、血红蛋白含量高于对照组(均P<0.05)。治疗后3、5、7 d,火针组和毫针组白细胞数量[(3.53±0.19)×10^(9)/L、(3.42±0.22)×10^(9)/L比(3.12±0.10)×10^(9)/L;(3.78±0.23)×10^(9)/L、(3.65±0.29)×10^(9)/L比(2.88±0.24)×10^(9)/L;(4.08±0.43)×10^(9)/L、(3.70±0.17)×10^(9)/L比(2.27±0.12)×10^(9)/L]和血小板数量[(79.72±3.89)×10^(9)/L、(79.15±5.22)×10^(9)/L比(70.17±2.20)×10^(9)/L;(85.18±3.40)×10^(9)/L、(81.88±4.97)×10^(9)/L比(62.73±3.80)×10^(9)/L;(92.18±7.64)×10^(9)/L、(83.45±4.29)×10^(9)/L比(51.92±1.64)×10^(9)/L]高于模型组(均P<0.05),红细胞数量[(1.36±0.03)×10^(12)/L、(1.37±0.03)×10^(12)/L比(1.52±0.03)×10^(12)/L;(1.32±0.03)×10^(12)/L、(1.34±0.02)×10^(12)/L比(1.59±0.02)×10^(12)/L;(1.24±0.07)×10^(12)/L、(1.32±0.05)×10^(12)/L比(1.68±0.03)×10^(12)/L]和血红蛋白含量[(84.00±1.67)g/L、(84.33±1.86)g/L比(94.00±1.26)g/L;(82.00±2.68)g/L、(83.50±0.84)g/L比(97.83±1.17)g/L;(76.67±5.32)g/L、(81.83±3.43)g/L比(104.17±2.04)g/L]低于模型组(均P<0.05);毫针组和火针组中骨髓原始细胞数量高于模型组,且可见杆状核细胞的出现;火针组和毫针组G0/G1期骨髓单核成纤维细胞百分率始终低于模型组(均P<0.05),其中火针组变化较毫针组更显著,并且S期和G2/M期骨髓单核成纤维细胞百分率始终高于模型组(均P<0.05)。毫针组和火针组治疗后3、7 d大鼠骨髓单核成纤维细胞中CD4、CD6、Cylcin D1和E2F1蛋白相对表达量明显上调(均P<0.05)。火针组细胞周期相关蛋白CD4、CD6、Cylcin D1和E2F1的表达上调更显著。结论毫针和火针治疗均可以改善环磷酰胺诱导的大鼠骨髓抑制,其分子机制可能与上调大鼠骨髓单核成纤维细胞中细胞周期相关蛋白CD4、CD6、Cylcin D1和E2F1表达有关,从而恢复骨髓基质细胞增殖和休眠的代谢平衡。

他克莫司联合糖皮质激素治疗Ⅱ~Ⅲ期特发性膜性肾病患者的效果

目的:观察他克莫司联合糖皮质激素治疗Ⅱ~Ⅲ期特发性膜性肾病(IMN)患者的效果。方法:选取2019年6月至2022年9月该院收治的84例Ⅱ~Ⅲ期IMN患者进行前瞻性研究,采用单双号法将其分为对照组和研究组各42例。对照组给予环磷酰胺联合糖皮质激素治疗,研究组给予他克莫司联合糖皮质激素治疗,比较两组临床疗效,治疗前后24 h蛋白尿定量、血清总蛋白(ALB)水平,肾功能指标[血肌酐(Scr)、内生肌酐清除率(Ccr)]水平,以及治疗期间不良反应发生率。结果:研究组治疗总有效率为97.62%(41/42),高于对照组的80.95%(34/42),差异有统计学意义(P<0.05);治疗后,研究组24 h尿蛋白定量和Scr水平均低于对照组,血清ALB、Ccr水平均高于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:他克莫司联合糖皮质激素治疗Ⅱ~Ⅲ期IMN患者可提高治疗总有效率和ALB水平,改善肾功能指标水平,降低24 h尿蛋白定量,效果优于环磷酰胺联合糖皮质激素治疗。

鸡猪源大肠杆菌CTX-M型ESBLs的分子检测

为了解河南地区鸡猪源CTX-M型超广谱β-内酰胺酶(ESBLs)的流行情况,并进行基因型分析,通过表型确证试验检测产ESBLs大肠杆菌,分别用5组CTX-M型引物对其进行聚合酶链式反应扩增。表型确证试验检测结果显示,鸡、猪源大肠杆菌中产ESBLs菌株检出率分别为62.8%(59/94)和78.3%(36/46)。PCR扩增结果进一步显示,鸡源大肠杆菌中CTX-M型ESBLs阳性率为89.8%(53/59),其中CTX-M-2组型14株,CTX-M-9组型26株,CTX-M-2和CTX-M-9组型13株;猪源大肠杆菌CTX-M型ESBLs的阳性检出率为69.4%(25/36),其中,CTX-M-2组型7株,CTX-M-9组型17株,CTX-M-2和CTX-M-9组型1株。河南地区鸡、猪源大肠杆菌CTX-M型ESBLs的产生率较高,而以CTX-M-2组型和CTX-M-9组型为主。