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.

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.

C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

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.

Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections

BACKGROUND Mycoplasma pneumoniae(MP)frequently causes respiratory infections in children,whereas Epstein-Barr virus(EBV)typically presents subclinical manifestations in immunocompetent pediatric populations.The incidence of MP and EBV coinfections is often overlooked clinically,with the contributory role of EBV in pulmonary infections alongside MP remaining unclear.AIM To evaluate the serum concentrations of interleukin-2(IL-2)and interleukin-12(IL-12)in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications.METHODS We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection,isolated MP infection,and a control group of healthy children,spanning from January 1,2018 to December 31,2021.Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay.Logistic regression was employed to identify factors influencing poor prognosis,while receiver operating characteristic(ROC)curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients.RESULTS The co-infection group exhibited elevated serum IL-2 and C-reactive protein(CRP)levels compared to both the MP-only and control groups,with a reverse trend observed for IL-12(P<0.05).In the poor prognosis cohort,elevated CRP and IL-2 levels,alongside prolonged fever duration,contrasted with reduced IL-12 levels(P<0.05).Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes(P<0.05).ROC analysis indicated that the area under the curves for IL-2,IL-12,and their combination in predicting poor prognosis were 0.815,0.895,and 0.915,respectively.CONCLUSION Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis,with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.

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.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

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.

N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats:Focus on oxidative and sex hormone receptors mechanisms

Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor activity.Methods:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control group.Group 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),respectively.All treatments lasted for 21 days.Samples were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay.The amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies.Results:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and testes.NAC or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and testes.The combination of both treatments appeared to be more effective.The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to androgen.However,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to DEHP.Conclusions:The possibility that NAC and ZnSO_(4) could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

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.

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.

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。

炎性因子IL-8、PCT、IL-2R与严重细菌性颅内感染GCS评分的关系及预测预后的价值

目的分析严重细菌性颅内感染患者炎性因子白介素-8(IL-8)、降钙素原(PCT)、白介素-2受体(IL-2R)与格拉斯哥昏迷量表(GCS)评分的关系,并探讨其预测预后的价值。方法前瞻性选取2020年1月至2023年1月平顶山市第一人民医院收治的80例严重颅内感染患者作为研究对象,根据GCS评分分为轻中度组(9~14分)32例和重度组(≤8分)48例。比较两组患者的GCS评分和血清IL-8、PCT、IL-2R水平,采用Pearson相关系数分析血清IL-8、PCT、IL-2R水平与GCS评分的相关性,并以格拉斯哥预后量表(GOS)评估预后情况,比较预后良好、预后不良患者的临床资料和血清IL-8、PCT、IL-2R水平,通过Lasso回归筛选预后不良的预测因素,采用受试者工作特征(ROC)曲线分析血清IL-8、PCT、IL-2R预测预后不良的价值,并比较含与不含血清IL-8、PCT、IL-2R预测方案对预后不良的预测能力。结果重度组患者入院时血清IL-8、PCT、IL-2R水平分别为(35.12±4.26)pg/mL、(11.83±2.26)pg/mL、(912.35±105.83)U/m L,明显高于轻中度组的(26.74±3.81)pg/m L、(8.49±2.03)pg/m L、(749.21±92.56)U/m L,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,严重细菌性颅内感染患者入院时的血清IL-8、PCT、IL-2R水平与GCS评分呈负相关(P<0.05);预后不良患者的年龄、机械通气占比、糖尿病占比、感染至入院时间、入院时血清IL-8、PCT、IL-2R水平分别为(65.13±7.26)岁、67.57%、27.03%、(38.05±4.17)h、(40.12±4.81)pg/m L、(12.67±2.59)pg/m L、(951.46±121.49)U/mL,明显高于预后良好患者的(56.39±6.41)岁、41.86%、9.30%、(26.92±3.46)h、(24.59±3.95)pg/mL、(8.61±2.24)pg/mL、(757.28±97.28)U/mL,入院时GCS评分为(6.72±0.39)分,明显低于预后良好患者的(10.81±0.82)分,差异均有统计学意义(P<0.05);经Lasso回归分析结果显示,年龄、感染至入院时间、GCS评分、血清IL-8、PCT、IL-2R水平均为预后不良的预测因素(P<0.05);经ROC分析结果显示,血清IL-8、PCT、IL-2R预测预后不良的曲线下面积(AUC)分别为0.729、0.717、0.719;含炎性因子预测方案的AUC为0.933,不含炎性因子预测方案的AUC为0.811;经DeLong检验结果显示,与不含炎性因子预测方案比较,含炎性因子预测方案的AUC明显增大(P<0.05),净重新分类指数(NRI)、综合判别改善指数(IDI)均>0(P<0.05)。结论严重细菌性颅内感染患者血清IL-8、PCT、IL-2R水平与GCS评分存在明显负相关,且与预后转归密切相关,可为临床预测预后提供参考。

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。