P2Y1 receptor in Alzheimer’s disease

Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last decades.However,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic strategies.Increasing evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s disease.These receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s disease.This review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.

Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC.Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups.Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.

The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity:A Meta-Analysis

Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity.Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixedeffects model.Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed.Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Leukocyte immunoglobulin-like receptor B2:A promising biomarker for colorectal cancer

According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

A Retrospective Analysis of Glucagon-Like Peptide 1 Receptor Agonists in Treating Type 2 Diabetes Mellitus Complicated by Nonalcoholic Fatty Liver Disease

Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer

BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

高良姜素调节CCL2/CCR2信号轴对自身免疫性甲状腺炎大鼠炎症反应的影响

目的:探讨高良姜素调节趋化因子配体2(CCL2)/趋化因子受体2(CCR2)通路对自身免疫性甲状腺炎(AIT)大鼠炎症反应的影响。方法:84只大鼠随机分为对照组、模型组、高良姜素低剂量组、高良姜素中剂量组、高良姜素高剂量组、硒酵母片组、高良姜素高剂量+大鼠CCL2重组蛋白(rCCL2)组,每组12只。除对照组外,其他组大鼠均构建AIT模型,造模成功后给药,1次/d,持续8周。ELISA检测大鼠血清中甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)水平及甲状腺组织TNF-α、IL-6、IL-1β水平;HE染色检测大鼠甲状腺组织病理变化并对甲状腺组织进行炎症评分;qRT-PCR检测大鼠甲状腺组织CCL2、CCR2 mRNA表达;Western blot检测大鼠甲状腺组织CCL2、CCR2蛋白表达。结果:与对照组比较,模型组大鼠甲状腺组织病理损伤严重,炎症评分、TGAb、TPOAb、FT4、FT3、TNF-α、IL-6、IL-1β水平、CCL2、CCR2 mRNA及蛋白表达升高(P<0.05);与模型组比较,高良姜素低剂量组、高良姜素中剂量组、高良姜素高剂量组、硒酵母片组大鼠甲状腺组织病理损伤减轻,炎症评分、TGAb、TPOAb、FT4、FT3、TNF-α、IL-6、IL-1β水平、CCL2、CCR2 mRNA及蛋白表达降低(P<0.05);与高良姜素高剂量组比较,高良姜素高剂量+rCCL2组大鼠甲状腺组织病理损伤加剧,炎症评分、TGAb、TPOAb、FT4、FT3、TNF-α、IL-6、IL-1β水平、CCL2、CCR2 mRNA及蛋白表达升高(P<0.05)。结论:高良姜素可能通过抑制CCL2/CCR2信号通路抑制AIT大鼠炎症反应。

电针对脑出血后偏瘫痉挛大鼠脊髓颈膨大处GluR2表达的影响

目的研究电针经穴对脑出血后偏瘫痉挛大鼠脊髓颈膨大处谷氨酸受体2(GluR2)表达的影响,探讨电针缓解脑出血后偏瘫痉挛症状的机制。方法将45只健康SD大鼠随机分为假手术组9只、模型组18只、电针组18只。模型组和电针组大鼠采用立体定向在右侧内囊注入自体尾血方法建立脑出血模型,假手术组大鼠不注射自体尾血。造模后电针组采用电针刺激大鼠曲池与足三里穴,假手术组与模型组不给予任何干预。术后第3天、第7天对大鼠分别进行行为学检测[神经功能状态(采用Zea-longa评分评定)、肌张力(采用改良的Ashworth分级评分测定)、旷场实验],并采用Western blot法和免疫组化法检测脊髓颈膨大处GluR2表达情况。结果术后第3天、第7天与假手术组比较,模型组大鼠的Zea-longa评分和左前肢、左后肢的改良Ashworth评分均明显增高(P均<0.05),运动总路程明显缩短(P均<0.05),平均速度明显减慢(P均<0.05),静止时间明显延长(P均<0.05),脊髓颈膨大处GluR2蛋白相对表达量和阳性表达平均光密度值均明显降低(P均<0.05)。与模型组比较,电针组大鼠的Zea-longa评分和左前肢、左后肢的改良Ashworth评分均明显降低(P均<0.05),运动总路程明显延长(P均<0.05),平均速度明显加快(P均<0.05),静止时间明显缩短(P均<0.05),脊髓颈膨大处GluR2蛋白相对表达量和阳性表达平均光密度值均明显增高(P均<0.05)。结论电针刺激曲池和足三里穴可以显著改善脑出血大鼠痉挛性瘫痪症状,缓解肌张力增高,上调脊髓颈膨大处GluR2表达可能是电针治疗缓解脑出血后肢体痉挛的机制之一。

PCNA、Bcl-2及EGFR在喉癌组织中的表达及与临床病理特征、生存的关系

目的探讨增殖细胞核抗原(PCNA)、B淋巴细胞瘤-2(Bcl-2)及表皮生长因子受体(EGFR)在喉癌组织中的表达及与临床病理特征、生存的关系。方法选取2017年3月—2020年1月在苏州大学附属第一医院因喉癌行手术治疗的92例患者的喉癌组织及对应癌旁组织标本。检测癌组织与癌旁组织PCNA mRNA、Bcl-2mRNA、EGFR mRNA相对表达量,多元线性回归分析其癌组织表达与临床病理特征的关系。随访3年,采用Kaplain-Maier曲线分析不同PCNA、Bcl-2、EGFR表达水平患者生存情况差异。结果癌组织PCNA mRNA、Bcl-2 mRNA、EGFR mRNA相对表达量高于癌旁组织(P<0.05)。不同年龄、肿瘤部位患者PCNA mRNA、Bcl-2 mRNA、EGFR mRNA相对表达量比较,差异无统计学意义(P>0.05);低分化,临床分期Ⅲ、Ⅳ期及淋巴结转移患者PCNA mRNA、Bcl-2 mRNA、EGFR mRNA相对表达量分别高于中、高分化,临床分期Ⅰ、Ⅱ期,无淋巴结转移患者(P<0.05)。多元线性回归分析结果显示,肿瘤分化程度、临床分期、淋巴结转移是喉癌组织PCNA mRNA、Bcl-2 mRNA、EGFR mRNA表达的影响因素。Kaplain-Maier曲线分析结果显示,PCNA mRNA高表达患者3年无进展生存率、总生存率分别为59.57%和70.21%,低于低表达患者的80.00%和88.89%(P<0.05);Bcl-2 mRNA高表达患者3年无进展生存率、总生存率分别为60.78%和70.59%,低于低表达患者的80.49%和90.24%(P<0.05);EGFR mRNA高表达患者3年无进展生存率、总生存率分别为59.09%和70.45%,低于低表达患者的79.17%、87.50%(P<0.05)。结论喉癌组织PCNA、Bcl-2、EGFR呈高表达,且其高表达状态与肿瘤分期高、分化程度低、淋巴结转移有关,PCNA、Bcl-2、EGFR表达水平可在一定程度上反映患者预后。

伊尼妥单抗治疗人表皮生长因子受体2阳性转移性乳腺癌伴胃肠功能紊乱1例

乳腺癌是女性常见的肿瘤,如今乳腺癌实体肿瘤通过相应的治疗可取得较好的疗效,但人表皮生长因子受体2(HER2)阳性乳腺癌侵袭性较强、恶性程度高,需引起患者及医务人员的重视。本文回顾性分析1例激素受体阴性、HER2阳性伴胃肠功能紊乱的乳腺癌患者诊治经过。患者初诊为局部晚期炎症乳腺癌伴腋窝淋巴结转移,给予新辅助化疗及手术治疗。术后3年后病情进展,予以伊尼妥单抗联合白蛋白紫杉醇,后续伊尼妥单抗单独靶向治疗,病情持续缓解。提示对于HER2阳性晚期乳腺癌,伊尼妥单抗是个很好的单抗类药物选择。

外周血sIL-2R、CD4^(+)/CD8^(+)、TNF-α对初治活动性肺结核老年患者化疗疗效的评估价值

目的探讨外周血可溶性白细胞介素2受体(sIL-2R)、CD4^(+)淋巴细胞百分比/CD8^(+)淋巴细胞百分比比值(下称CD4^(+)/CD8^(+))、肿瘤坏死因子-α(TNF-α)对初治活动性肺结核老年患者化疗疗效的评估价值。方法将2019年12月至2022年12月该院收治的102例初治活动性肺结核老年患者纳入研究作为观察组,另选取102例年龄≥60岁且同期于该院体检的健康者作为对照组。比较两组外周血sIL-2R、TNF-α、CD4^(+)/CD8^(+)水平并分析sIL-2R、TNF-α、CD4^(+)/CD8^(+)间的相关性。观察组均采用2HRZE/4HR抗结核治疗方案,比较观察组治疗前、治疗1个月、治疗6个月时不同疗效患者外周血sIL-2R、TNF-α、CD4^(+)/CD8^(+);分析sIL-2R、CD4^(+)/CD8^(+)、TNF-α水平与疗效的相关性;采用受试者工作特征(ROC)曲线分析各指标用于老年患者化疗疗效评估的效能。结果观察组sIL-2R、TNF-α水平高于对照组,而CD4^(+)/CD8^(+)低于对照组,差异均有统计学意义(P<0.05)。观察组sIL-2R、TNF-α与CD4^(+)/CD8^(+)呈负相关(P<0.05),sIL-2R与TNF-α呈正相关(P<0.05)。治疗1个月、治疗6个月时显效患者sIL-2R、TNF-α水平低于有效患者,而后者又低于无效患者,显效患者CD4^(+)/CD8^(+)高于有效患者,而后者又高于无效患者,差异均有统计学意义(P<0.05)。sIL-2R、TNF-α水平与疗效呈负相关(P<0.05),CD4^(+)/CD8^(+)与疗效呈正相关(P<0.05)。ROC曲线分析显示,治疗1个月、6个月时sIL-2R、CD4^(+)/CD8^(+)、TNF-α联合用于评估疗效的曲线下面积(AUC)明显大于各时间点单项指标用于评估的AUC(P<0.05),而且治疗6个月时各指标联合评估的AUC大于治疗1个月(P<0.05)。结论初治活动性肺结核老年患者sIL-2R、CD4^(+)/CD8^(+)、TNF-α水平与患者疗效密切相关,将以上指标联合用于评估患者化疗疗效具有一定参考价值。

肺腺癌组织中前列腺素内过氧化物合酶2表达水平与表皮生长因子受体基因突变的相关性分析

目的 分析肺腺癌组织中前列腺素内过氧化物合酶2(PTGS2)表达水平与表皮生长因子受体(EGFR)基因突变的相关性。方法 选取57例肺腺癌患者为研究对象,收集肺腺癌组织及其相应癌旁组织。采用实时荧光定量PCR(RT-PCR)法检测癌组织及癌旁组织中PTGS2 mRNA表达水平;采用免疫组织化学法分析PTGS2蛋白表达;采用RT-PCR法检测癌组织及癌旁组织EGFR基因突变情况。分析肺腺癌患者临床病理参数与PTGS2 mRNA水平、EGFR基因突变情况的关系。采用Spearman秩相关分析探讨肺腺癌患者EGFR基因突变情况与PTGS2 mRNA水平的相关性。结果 57例肺腺癌患者中,5例癌旁组织EGFR基因突变型患者,其对应癌组织也均发生突变,且为同一突变类型。26例(45.61%)癌组织EGFR基因突变型患者,未发现双重突变,其中19外显子突变17例(29.82%),均为缺失突变;21外显子突变9例(15.79%),均为L858R点突变。癌组织中PTGS2mRNA表达水平、PTGS2蛋白阳性率及EGFR基因突变型比例高于癌旁组织,EGFR基因野生型比例低于癌旁组织(P<0.01)。肺腺癌患者性别、TNM分期、吸烟与PTGS2 mRNA表达水平、EGFR基因突变情况有关(P<0.05或0.01)。EGFR基因突变型PTGS2 mRNA表达水平高于EGFR基因野生型(P<0.01)。肺腺癌患者EGFR基因突变与PTGS2 mRNA表达水平呈正相关(r=0.512,P<0.01)。结论 肺腺癌患者癌组织中PTGS2mRNA表达水平及PTGS2蛋白阳性率升高,且与EGFR基因突变关系密切,二者可能共同影响疾病进程。

达格列净联合胰高血糖素样肽-1受体激动剂对2型糖尿病的疗效研究

目的探讨达格列净联合胰高血糖素样肽-1受体激动剂(GLP-1 RAs)对2型糖尿病患者血液流变学及胰岛素抵抗的影响。方法将2020年11月—2022年10月泉州市中医院收治的102例2型糖尿病患者随机分为2组,每组51例。对照组给予达格列净治疗,研究组采用达格列净联合GLP-1 RAs(利拉鲁肽)的治疗方案。比较2组临床疗效、血糖指标[空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)]、空腹胰岛素(FINS)及胰岛素抵抗[胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)]、血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、血液流变学指标[红细胞聚集指数(EAI)、红细胞压积(HCT)、红细胞变形指数(EDI)、血浆黏度(PV)]和不良反应。结果研究组总有效率为94.12%,高于对照组的80.39%,差异有统计学意义(P<0.05)。研究组和对照组治疗后FBG、2 hPG、HbAlc、BMI均低于治疗前,且研究组治疗后FBG、2 hPG、HbAlc水平低于对照组,差异有统计学意义(P<0.05)。治疗后,研究组FINS、HOMA-β水平高于对照组,HOMA-IR水平低于对照组,差异有统计学意义(P<0.05)。研究组和对照组治疗后HDL-C均高于治疗前,TC、TG、LDL-C水平均低于治疗前;研究组治疗后HDL-C水平高于对照组,TC、TG、LDL-C水平低于对照组,差异均有统计学意义(P<0.05)。治疗后,研究组和对照组EAI、HCT、EDI、PV水平均低于治疗前,且研究组EAI、HCT、EDI、PV水平低于对照组,差异均有统计学意义(P<0.05)。研究组不良反应总发生率为11.76%,与对照组的9.80%比较,差异无统计学意义(P>0.05)。结论达格列净联合GLP-1 RAs(利拉鲁肽)治疗2型糖尿病的疗效确切,可有效调节患者血糖及血脂水平,缓解胰岛素抵抗,改善血液流变学指标。

miRNA-27a与TOP2A蛋白在乳腺癌化疗中的表达水平及效能评估

目的探析微核糖核酸-27a(microRNA-27a,miRNA-27a)与DNA拓扑异构酶Ⅱα(TopoisomeraseⅡ-Alpha,TOP2A)蛋白在乳腺癌化疗中的表达水平及预测效能。方法回顾性分析2020年1月至2022年1月聊城市人民医院乳甲外科收治的47例乳腺癌患者的病案资料,均接受化疗治疗。用实时荧光定量PCR法进行血浆miRNA-27a表达水平的检测,用免疫组织化学法进行TOP2A蛋白表达情况的检测。比较乳腺癌患者化疗前后的miRNA-27a、TOP2A蛋白表达水平差异,采用Logistic回归分析法探析miRNA-27a、TOP2A蛋白与乳腺癌化疗预后不良的关系,绘制受试者工作特征(Receiver Operating Characteristic,ROC)曲线分析miRNA-27a、TOP2A蛋白在乳腺癌化疗疗效预测中的应用价值。结果47例患者开始化疗后第4个月的miRNA-27a、TOP2A蛋白检测值显著低于化疗前(入院时)(P<0.05)。开始化疗后第4个月,预后良好35例(74.47%),预后不良12例(25.53%),预后良好组的miRNA-27a、TOP2A蛋白检测值低于预后不良组。Logistic分析结果显示,miRNA-27a、TOP2A蛋白高表达是乳腺癌化疗预后不良的危险因素(P<0.05)。ROC曲线结果显示,miRNA-27a、TOP2A蛋白联合预测乳腺癌化疗预后不良的曲线下面积(0.875,95%CI:0.798~0.952)最大,敏感度、特异性分别为91.67%、94.29%(P<0.05)。结论miRNA-27a、TOP2A蛋白在乳腺癌化疗预后不良中呈高表达,若乳腺癌化疗患者miRNA-27a、TOP2A蛋白表达水平显著上升,侧面说明患者病情可能有恶化风险,化疗疗效有限。

单核细胞Toll样受体和核因子-κB水平与2型糖尿病患者自主神经病变的相关性

目的探讨单核细胞中Toll样受体(TLR)、核因子-κB(NF-κB)表达水平与2型糖尿病(T2DM)患者自主神经病变的相关性。方法选择2021年4月至2022年12月濮阳市人民医院收治的112例T2DM患者为观察组,另选择同期在本院进行体检的50例健康志愿者为对照组。采用反转录聚合酶链反应检测2组受试者血浆单核细胞中TLR2、TLR4、NF-κB表达水平。根据是否并发有自主神经病变将观察组患者分为自主神经病变组(n=46)和无自主神经病变组(n=66),比较2组患者的临床资料,将差异有统计学意义的指标进一步行多因素logistic回归来分析T2DM患者发生自主神经病变的危险因素;采用Spearman相关分析TLR2、TLR4、NF-κB表达水平与T2DM患者发生自主神经病变的相关性。结果观察组患者单核细胞中TLR2、TLR4、NF-κB水平显著高于对照组(P<0.05)。单因素分析结果显示,自主神经病变组与无自主神经病变组患者的年龄、单核细胞/高密度脂蛋白比值(MHR)及胱抑素C、TLR2、TLR4、NF-κB水平比较差异有统计学意义(P<0.05)。多因素logistic回归分析结果显示,MHR、TLR2、TLR4、NF-κB是T2DM患者发生自主神经病变的危险因素(P<0.05)。Spearman相关分析结果显示,TLR2、TLR4、NF-κB水平与T2DM患者发生自主神经病变呈正相关(r=0.825、0.822、0.819,P<0.05)。结论TLR2、TLR4、NF-κB在T2DM患者中表达上调,TLR2、TLR4、NF-κB表达水平与T2DM患者自主神经病变有关。