Antibacterial resistance patterns in Streptococcus pneumoniae isolated from elderly patients: PROTEKT years 1-5 (1999-2004)

The antibacterial susceptibilities of 6646 Streptococcus pneumoniae isolates collected in 38 countries from patients ≥65 years of age with community-acquired respiratory tract infections (RTIs) during years 1–5 of the PROTEKT study (1999–2004) were analysed. Rates of erythromycin resistance (36.0%), penicillin non-susceptibility (31.3%; 20.2% resistant plus 11.1% intermediately susceptible) and resistance to multiple antibacterials (37.2%) were stable over the 5 years. The most common macrolide resistance mechanism was erm(B) (61.4%); erm(B) + mef(A) strains increased from 5.4% (year 1) to 7.4% (year 5) (P = 0.037). Overall, 37.2% of isolates exhibited resistance to two or more antibacterials, including 15.9% resistant to both penicillin and erythromycin. Antibacterial resistance was highest in the Far East. Telithromycin resistance was rare (0.12%). Appropriate alternative empirical first-line therapies may be required for treating community-acquired RTIs in the elderly.     

Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and telithromycin (PROTEKT 1999-2003)

Isolates of Streptococcus pneumoniae collected over the first 4 years of the PROTEKT study were tested for susceptibility to penicillin, azithromycin and telithromycin. A total of 20 750 isolates were collected from 39 countries. Penicillin non-susceptibility rates were stable over the study period; overall, 21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin varied between countries and were highest in France, Spain, South Africa, USA and the Far East. Multidrug resistance in S. pneumoniae did not change significantly over the 4 years, with an overall rate of 38.6%. Telithromycin retained good activity against S. pneumoniae (0.1% of isolates resistant), including multidrug-resistant isolates.     

2004～2009年临床分离肺炎链球菌的血清型/群分布及耐药性监测

目的：了解当前本院临床分离肺炎链球菌的血清型/群分布及耐药趋势,为临床合理使用抗生素提供参考。方法：以2004～2009年临床分离的822株肺炎链球菌为研究对象,采用荚膜肿胀试验进行血清分型/群,E-test检测菌种对青霉素、头孢呋辛、头孢地尼、头孢克罗、红霉素、四环素、左氧氟沙星、万古霉素等8种抗生素的敏感性。结果：2004年青霉素不敏感肺炎链球菌（PNSP）的分离率为49.4%,并呈逐年上升趋势,至2006年PNSP分离率高达67.8%,2009年下降至51.0%。822株肺炎链球菌最常见的型/群是19群,其次是23、6、14、3、其他。PNSP在6种血清型/群中所占的比例在2004～2009年期间无显著性变化（P〉0.05）。肺炎链球菌对其他β内酰胺类抗生素的非敏感趋势类似青霉素,对红霉素、四环素的非敏感率始终在60%以上,其中青霉素耐药肺炎链球菌（PRSP）对红霉素和四环素几乎100%耐药,对左氧氟沙星、万古霉素的非敏感率均〈3%。结论：临床分离肺炎链球菌以19群、23群、6群、14群、3群常见;对β内酰胺类抗生素的非敏感率自2007年呈下降趋势,且对左氧氟沙星、万古霉素始终具有较高的敏感性。     

抗生素诱导的细胞感受态与肺炎链球菌的耐药性

针对环境中的压力,细菌会采取不同的响应以维持自身的稳定。某些抗生素能够诱导肺炎链球菌转变为感受态细胞,提高细胞转化率,从而产生更适宜生存的耐药突变株。本文根据近年来有关感受态的研究,重点阐述肺炎链球菌中抗生素诱导的感受态与耐药性之间的关系。     

广东东莞地区儿童肺炎链球菌和流感嗜血菌携带和耐药性研究

目的总结和分析东莞地区学龄前健康儿童鼻咽部携带肺炎链球菌和流感嗜血菌情况和对常用抗生素耐药特点，为预防儿童肺炎链球菌和流感嗜血菌感染和合理利用抗生素提供参考。方法采用专用巧克力和血平板培养基对采集的400名3～5岁儿童鼻咽分泌物培养并鉴定，对鉴定明确的肺炎链球菌和流感嗜血菌进行不同抗生素检测。结果该地区儿童肺炎链球菌和流感嗜血菌携带率分别是34．5％和26．8％；药敏检测显示，肺炎链球菌对万古霉素、左氧氟沙星、氯霉素、复方磺胺甲晤唑、苯唑西林、四环素、红霉索耐药率分别为0、2％、24％、42％、64％、74％和78％；流感嗜血菌对头孢噻肟、环丙沙星、左氧氟沙星耐药率均为2％，氨苄西林和四环素耐药率均为8％，亚胺培南为10％。复方磺胺甲略唑耐药率为12％。氯霉索和氨曲南耐药率均为28％。利福平为90％，对头孢呋辛和头孢克洛敏感。结论本地区健康学龄前儿童鼻咽部肺炎链球菌和流感嗜血菌携带率高于国内许多地区，对常用抗生索耐药性严重。并存在多重耐药现象。     

Drug-resistant Streptococcus pneumoniae in the Lebanon: implications for presumptive therapy.

A total of 50 consecutive clinical isolates of Streptococcus pneumoniae, collected between 1996 and 1998, were tested against six antimicrobial agents using the E-test. The percentages of fully resistant (R) and intermediately-R strains, respectively, were: benzyl penicillin 18 and 38%, amoxycillin-clavulanate 6 and 12%, cefuroxime 22 and 16%, ceftriaxone 2 and 16%, and clarithromycin 10%. Fully and or intermediately multidrug-resistance (two or more drugs) was seen in 44% of the isolates, 18% being fully resistant. The MIC breakpoint for cefaclor is not defined by the National Committee for Clinical Laboratory Standards (NCCLS) but MICs showed that: 76% of the isolates had an MIC of ≤8 mg/l, 4% had an MIC of 16 mg/l and 20% had an MIC of ≥32 mg/l. There was agreement between the E-test Pen MIC results and the 1 μg oxacillin (oxa) disk diffusion screen test for the 22 susceptible and the nine fully R strains but not for the 19 strains with Pen MICs between 0.1 and 1 mg/l; this shows the importance of MIC determination in such isolates. Penicillin and multiply antibiotic-resistant pneumococci are spreading in Lebanon, emphasizing the necessity to reconsider current treatment regimens in this country.     

Distribution and antibacterial susceptibility of macrolide resistance genotypes in Streptococcus pneumoniae: PROTEKT Year 5 (2003-2004)

The distribution and antibacterial susceptibility of macrolide resistance genotypes among 7083 Streptococcus pneumoniae isolates collected worldwide during 2003-2004 from patients with community-acquired respiratory tract infections, including patients within 48h of admission to hospital, were analysed. The overall rate of erythromycin resistance was 37.2% (intercountry range <10% to >50%). The most common resistance mechanism globally was erm(B) (55.0% of erythromycin-resistant S. pneumoniae (ERSP)), followed by mef(A) (30.6%) and erm(B)+mef(A) (12.0%). Genotype distribution varied by age group (P<0.0001); erm(B)+mef(A) was more prevalent (21.8% of isolates) among patients 0-2 years of age than among other age groups (P<0.001). The prevalence of tetracycline resistance among mef(A) isolates varied between different countries. Of the erm(B)+mef(A) strains, 43.5% were resistant to amoxicillin/clavulanic acid. Most ERSP isolates were susceptible to levofloxacin (98.3%) and telithromycin (99.4%).     

上海地区儿童肺炎链球菌耐药性研究

目的 了解上海地区2001年小儿社区获得性呼吸道感染息儿肺炎链球菌(SP)耐药情况，以指导临床抗生素合理使用。方法 用Kirby—Bauer法和E—test法检测100株SP对青霉素等10种抗菌药物敏感性。结果 SP总分离率29．1％；SP对青霉素耐药率55％，最低抑菌浓度(MIC90)0．75mg/L，MIC均值0．06mg/L；对阿莫西林、阿莫西林/克拉维酸和头孢曲松呈低耐药率，分别为3％、3％和6％；对头孢克洛耐率15％；对头孢映辛29％。SP对氯霉素耐药34％，而对磺胺甲恶唑／甲氧苄啶、红霉素和四环素均呈高度耐药，达80％～82％。结论 小儿SP耐药率远远高于成人，但阿莫西林和头孢曲松依然敏感，抗生素合理使用是重要的。     

Role of efflux mechanisms on fluoroquinolone resistance in Streptococcus pneumoniae and Pseudomonas aeruginosa

Prokaryotic efflux mechanisms can effectively increase the intrinsic resistance of bacteria by actively transporting antibiotics out of cells, thus reducing the effective concentration of these agents. The fluoroquinolones, similar to most other antimicrobial classes, are susceptible to efflux mechanisms, particularly in Gram-negative organisms, such as Pseudomonas aeruginosa. Resistant P. aeruginosa clones isolated after fluoroquinolone therapy frequently over express at least one of the multiple efflux pump mechanisms found in this organism. Gram-positive bacteria, such as Streptococcus pneumoniae, also possess efflux mechanisms, though their effect on fluoroquinolone resistance seems to be more limited and selective. In the future, efflux pump inhibitors may offer effective adjunctive therapy to antibiotics for the treatment of difficult infections by efflux mutants. In the meantime, appropriate antibiotic selection and optimal dosing strategies should aim to eradicate the causative pathogen before a resistant efflux mutant can emerge.     

呼和浩特市89株肺炎链球菌携带耐药及毒力基因特征分析

目的 探究呼和浩特地区住院患者分离肺炎链球菌抗生素耐药基因及携带毒力基因分布情况,了解儿童株和成人株之间的差异。方法 收集内蒙古医科大学附属医院2010年10月-2016年4月临床患者分离89株肺炎链球菌,采用PCR技术检测其携带耐药和毒力基因表达情况,分别统计分析其在儿童及成人分布不同。结果 89株肺炎链球菌耐药基因pbp2a、pacE阳性率为100%;pbp2b、pbp3、teM、ermB、gyrB和parC阳性率在90%以上;tetM、teO基因阳性率分别为51.7%、36.0%。pbp1a和tet基因在儿童分离株和成人分离株之间有差异(χ2=5.107和22.984, P=0.01)。毒力基因stkP、nanA和piaA阳性率为100%;pcsB、phtD、pneumolysin、lytA、pspA和psaA基因阳性率均在90%以上;bacteriocin和clpP基因检测率较低,分别为79.8%和68.5%;cps2A基因在儿童株和成人株之间有差异(P=0.031)。结论 肺炎链球菌儿童分离株耐药基因携带率低于成人分离株,但毒力基因携带率明显高于成人分离株,不同人群肺炎链球菌菌分离株的生物学特征差异及其机制有待进一步研究。     

社区呼吸道感染中肺炎链球菌对常用抗菌药物敏感性

目的了解社区获得性呼吸道感染中肺炎链球菌对常用抗菌药物的体外抗菌活性。方法先用做肺炎链球菌鉴定粗筛,后用全自动细菌分析系统的革兰阳性菌鉴定卡和单克隆乳胶试剂做肺炎链球菌的最终鉴定,药物敏感性试验用微量稀释方法测定其最低抑菌浓度。结果在1997-11~1998-04,1999-11~2000-04和2001-11~2002-04 3个阶段共收集肺炎链球菌271株。在这3个阶段,肺炎链球菌分别为83,101,87株;对青霉素不敏感率分别为9.6%,8.9%和16%,对青霉素耐药率分别为1.2%,2%和8%;对大环类脂类抗生素的敏感性分别为28.9%,39.6%和18.4%。肺炎链球菌对克拉霉素显示高水平耐药。阿其霉素和克拉霉素的交叉耐药率可达98.4%。对左氧氟沙星的耐药率分别为1.2%,6.9%和1.2%; 对复方新诺明的耐药率分别为30.1%,62.4%和66.7%;多重耐药的肺炎链球菌分别为2.4%,3.0%和6.9%。在多重耐药的肺炎链球菌中,以阿齐霉素、复方新诺明和青霉素模式为主,占72.7%(8/11),同时有80%(8/10)对青霉素耐药的肺炎链球菌发生多重耐药;肺炎链球菌对万古霉素未见有耐药株。结论对青霉素耐药的肺炎链球菌有逐年上升的趋势,定期进行细菌耐药性的监测,有助于合理应用抗菌药物。     

The medicinal chemistry of multidrug resistance (MDR) reversing drugs

Multidrug resistance (MDR) is a kind of resistance of cancer cells to multiple classes of chemotherapic drugs that can be structurally and mechanistically unrelated. Classical MDR regards altered membrane transport that results in lower cell concentrations of cytotoxic drug and is related to the over expression of a variety of proteins that act as ATP-dependent extrusion pumps. P-glycoprotein (Pgp) and multidrug resistance protein (MRP1) are the most important and widely studied members of the family that belongs to the ABC superfamily of transporters. It is apparent that, besides their role in cancer cell resistance, these proteins have multiple physiological functions as well, since they are expressed also in many important non-tumoural tissues and are largely present in prokaryotic organisms. A number of drugs have been identified which are able to reverse the effects of Pgp, MRPI and sister proteins, on multidrug resistance. The first MDR modulators discovered and studied in clinical trials were endowed with definite pharmacological actions so that the doses required to overcome MDR were associated with unacceptably high side effects. As a consequence, much attention has been focused on developing more potent and selective modulators with proper potency, selectivity and pharmacokinetics that can be used at lower doses. Several novel MDR reversing agents (also known as chemosensitisers) are currently undergoing clinical evaluation for the treatment of resistant tumours. This review is concerned with the medicinal chemistry of MDR reversers, with particular attention to the drugs that are presently in development.     

肺炎链球菌鼻咽部定植及胞内感染的致病机制研究进展

肺炎链球菌是人上呼吸道常见定植菌,但在免疫力低下人群中可引起致死性疾病,如肺炎、菌血症、脑膜炎等。过去,肺炎链球菌常常被认为是一个胞外感染菌,但近年来研究显示其也可以在各种毒力因子相互作用下逃避宿主的免疫反应,在细胞内存活。本文综述了肺炎链球菌从鼻咽部定植发展为在不同器官组织内发生胞内感染的致病机制研究进展。     

Levofloxacin for the treatment of pneumonia caused by Streptococcus pneumoniae including multidrug-resistant strains: pooled analysis

ABSTRACT

Objective: To determine the clinical and microbiologic efficacy of levofloxacin for the treatment of subjects with pneumonia caused by multidrug-resistant (MDR) Streptococcus pneumoniae (MDRSP) and non-MDRSP strains.

Research design and methods: A pooled analysis was conducted using data from ten clinical studies in pneumonia: five comparative studies and five noncomparative studies conducted from 1992 to 2002. This analysis included data from levofloxacin-treated subjects with S.?pneumoniae isolated at study entry. Susceptibility of S.?pneumoniae isolated from subjects at study entry was determined against representative agents from five antimicrobial classes: tetracyclines, sulfonamides, second-generation cephalosporins, penicillins, and macrolides. Isolates were classified as MDRSP (based on resistance to two or more antimicrobial classes) or non-MDRSP (intermediate resistance or susceptible to all classes or resistant to 1 antimicrobial class). Clinical and microbiologic efficacy of levofloxacin (i.v., p.o., or i.v./p.o. for 5 to 14 days) in the microbiologically evaluable population was determined at post-therapy; a test for homogeneity of the odds ratio of the difference in clinical success for comparative versus noncomparative studies was performed.

Main outcome measures and results: The main outcome measures were clinical success rates and microbiologic eradication rates of 419 microbiologically evaluable levofloxacin-treated subjects with MDRSP or non-MDRSP. Clinical success rates were 96.3% (52/54) and 95.1% (347/365), respectively (difference ?1.2; 95% confidence interval [CI]: ?6.7, 4.3). Similarly, per pathogen microbiologic eradication rates for MDRSP and non-MDRSP were 96.3% (52/54) and 95.6% (350/366), respectively (difference ?0.7; 95%?CI: ?6.1, 4.8). Study limitations include the use of data from comparative and noncomparative studies. A test for homogeneity of the odds ratios for clinical success in comparative versus noncomparative studies showed no significant difference (p?=?0.27).

Conclusions: These data support the use of levofloxacin for patients with community-acquired pneumonia caused by S.?pneumoniae, including MDR strains.     

On the spread and control of MDR-TB epidemics: An examination of trends in anti-tuberculosis drug resistance surveillance data

BackgroundMultidrug resistant tuberculosis (MDR-TB) poses serious challenges for tuberculosis control in many settings, but trends of MDR-TB have been difficult to measure.MethodsWe analyzed surveillance and population-representative survey data collected worldwide by the World Health Organization between 1993 and 2012. We examined setting-specific patterns associated with linear trends in the estimated per capita rate of MDR-TB among new notified TB cases to generate hypotheses about factors associated with trends in the transmission of highly drug resistant tuberculosis.Results59 countries and 39 sub-national settings had at least three years of data, but less than 10% of the population in the WHO-designated 27-high MDR-TB burden settings were in areas with sufficient data to track trends. Among settings in which the majority of MDR-TB was autochthonous, we found 10 settings with statistically significant linear trends in per capita rates of MDR-TB among new notified TB cases. Five of these settings had declining trends (Estonia, Latvia, Macao, Hong Kong, and Portugal) ranging from decreases of 3% to 14% annually, while five had increasing trends (four individual oblasts of the Russian Federation and Botswana) ranging from 14% to 20% annually. In unadjusted analysis, better surveillance indicators and higher GDP per capita were associated with declining MDR-TB, while a higher existing absolute burden of MDR-TB was associated with an increasing trend.ConclusionsOnly a small fraction of countries in which the burden of MDR-TB is concentrated currently have sufficient surveillance data to estimate trends in drug-resistant TB. Where trend analysis was possible, smaller absolute burdens of MDR-TB and more robust surveillance systems were associated with declining per capita rates of MDR-TB among new notified cases.     

湘潭市中心医院社区获得性肺炎住院患儿肺炎链球菌的耐药性研究

目的了解湘潭市中心医院因社区获得性肺炎住院的患儿肺炎链球菌(SP)的耐药情况。方法对本院2010-2011年住院患儿分离的115株SP进行分析,采用K-B纸片琼脂扩散法及浓度梯度法(E测试)检测SP对青霉素、头孢曲松、红霉素、克林霉素、左氧氟沙星、万古霉素、利奈唑胺、复方磺胺甲噁唑的耐药性。结果 115株SP中青霉素敏感肺炎链球菌(PSSP)占86.1%,青霉素中介肺炎链球菌(PISP)占7.8%,青霉素耐药肺炎链球菌(PRSP)占6.1%。SP对红霉素、克林霉素及复方磺胺甲噁唑的耐药率分别为95.6%、94.8%和73.9%,左氧氟沙星的耐药率为1.7%,头孢曲松的耐药率为6.9%,未发现对万古霉素及利奈唑胺耐药的SP菌株。结论本院分离的SP对儿科常用抗生素青霉素及头孢曲松钠仍高度敏感,但对大环内酯类抗生素红霉素、林可酰胺类抗生素克林霉素耐药情况严重。     

Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibiotics in Gifu prefecture (2004)

We analyzed Streptococcus pneumoniae isolates in Gifu prefecture between November 2004 and December 2004. We analyzed isolates of 160 strains from 8 medical facilities to determine antibiotic susceptibility, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes of penicillin-resistant S. pneumoniae (PRSP). When referred to the classification in CLSI (formerly NCCLS), the overall incidence of penicillin-susceptible (PSSP), penicillin-intermediate (PISP) and penicillin-resistant (PRSP) were 48 (30.0%), 81 (50.6%) and 31 (19.4%) strains, respectively, and the susceptibility distribution to benzylpenicillin showed triplet peaks. The incidence of PISP and PRSP was higher in the material of throat and nasal cavity, and area of Chuno and Gifu district. The sum of the incidence of PISP and PRSP was slightly higher in inpatient-derived stains than outpatient-derived strains. The incidence that didn't possess mutations in PBP genes and macrolide-resistant genes was 6 (3.75%) and the others 154 strain (96.25%) had abnormal PBP genes or macrolide-resistant genes. The 90% of pneumococcal serotypes of PRSP 31 strains were serotype 6 (14 strains, 45.2%), 19 (7 strains, 22.6%) and 23 (7 strains, 22.6%). The MIC90 of each antibiotics was as follows; 0.1 microg/mL for panipenem, 0.2 microg/mL for imipenem and tosufloxacin, 0.39 microg/mL for meropenem and gatifloxacin, 0.78 microg/mL for amoxicillin, cefteram and cefditoren, 1.56 microg/mL for piperacillin, cefcapene and levofloxacin, 3.13 microg/mL for flomoxef, 6.25 microg/mL for cefdinir and cefotiam, 12.5 microg/mL for norfloxacin and minocycline, 25 microg/mL for cefixime, and 100 microg/mL for clarithromycin.     

急性白血病患者多药耐药基因表达的检测及意义

为研究急性白血病患者多药耐药基因（ＭＤＲ１）民临床耐药、预后判断等关系，应用逆转录酶／多聚酶链反应（ＲＴ－ＰＣＲ）检测了３６例急性白血病及１０例正常人骨ＭＤＲ１基因的表达，并以ＭＤＲ１／β２ＭＧ≥０．２定为ＭＤＲ１ｍＲＮＡ阳性。结果显示，１０便正常人ＭＤＲ１ｍＲＮＡ表达均阴性。初治患者中ＭＤＲ１ｍＲＮＡ阳性率为２５％，而复发和未缓解患者则达８０％。化疗缓解率在ＭＤＲ１ｍＲＮＡ阴性及阳性的急性白血病     

1,25(OH)2D3对肺炎链球菌感染的肺泡上皮细胞功能的影响

目的观察1,25-双羟维生素D3(1,25(OH)2D3)通过miR-124-3p调控磷脂酰肌醇3激酶/蛋白质丝氨酸苏氨酸激酶(PI3K/AKT)通路对肺炎链球菌(SP)感染的肺泡上皮细胞功能的影响,探讨其作用机制。方法体外培养肺泡上皮细胞A549,肺炎链球菌刺激后,随机分为10,20,40,80,160 ng·mL^-11,25(OH)2D3组、Control组、1,25(OH)2D3组、1,25(OH)2D3+anti-miR-NC组、1,25(OH)2D3+anti-miR-124-3p组和1,25(OH)2D3+anti-miR-124-3p+LY294002组。以细胞计数(CCK-8)法试剂盒法、流式细胞仪检测各组细胞增殖、凋亡,以蛋白质印迹(WB)法检测细胞周期蛋白D1(CyclinD1)、B细胞淋巴瘤/白血病-2(Bcl-2)、PI3K/AKT通路的相关蛋白表达,以反转录-聚合酶链反应(RT-PCR)法检测miR-124-3p的表达。结果10,20,40,80,160 ng·mL^-11,25(OH)2D3处理A549细胞72 h,细胞活力分别为(83.20±1.92)%,(75.73±3.70)%,(64.40±5.10)%,(47.13±3.56)%,(33.93±5.27)%;细胞凋亡率分别为(8.14±0.96)%,(12.26±1.00)%,(14.37±0.88)%,(16.44±0.96)%,(18.12±1.15)%,最终选择160 ng·mL^-11,25(OH)2D3进行后续实验。Control组、1,25(OH)2D3组、1,25(OH)2D3+anti-miR-NC和1,25(OH)2D3+anti-miR-124-3p组的miR-124-3p相对表达量为1.00±0.11,1.69±0.05,1.71±0.13,1.12±0.09,细胞活力分别为(100.00±9.67)%,(34.83±2.44)%,(37.70±1.50)%,(68.80±2.45)%,细胞凋亡率分别为(7.20±0.85)%,(18.59±0.82)%,(19.06±0.60)%,(13.44±2.15)%。与Control组对比,其他组miR-124-3p、细胞活力和细胞凋亡率均有统计学意义,CyclinD1、Bcl-2、p-PI3K、p-AKT蛋白表达降低,差异均有统计学意义(均P<0.05)。Control组、1,25(OH)2D3组、1,25(OH)2D3+anti-miR-124-3p组和1,25(OH)2D3+anti-miR-124-3p+LY294002的细胞活力分别为(100.00±9.64)%,(40.13±7.13)%,(74.40±6.54)%,(42.93±1.82)%,细胞凋亡率分别为(5.51±1.11)%,(15.90±0.24)%,(9.35±0.86)%,(14.24±0.84)%,与Control组相比,1,25(OH)2D3对肺泡上皮细胞A549的增殖、凋亡及CyclinD1、Bcl-2、p-PI3K、p-AKT蛋白表达的作用,以及抑制下游PI3K/AKT通路的作用,差异均有统计学意义(均P<0.05)。结论1,25(OH)2D3通过抑制miR-124-3p负向调控PI3K/AKT通路,促进肺泡上皮细胞的增殖,并诱导凋亡。