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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China shandong provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease Jinan 250033China department of pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China department of pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is ***: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

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Changes in posterior corneal elevation after small incision lenticule extraction for different myopic diopters

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 491-498页

作者： Xiao-Tong Sun Yang Zhang Xiao-Kun Mei Nan-Nan Zheng Ling-Zhi Niu Xiao-Li Qu Ai-Ping Song Jian Zhuo department of Ophthalmology the First Affiliated Hospital of Shandong First Medical UniversityShandong Provincial Qianfoshan HospitalJinan 250014Shandong ProvinceChina

●AIM:To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction(SMILE)with different myopic diopters.●METHODS:Ninety eyes of 90 patients who underwent SMILE were included in this retrospective *** were allocated into three groups based on the preoperative spherical equivalent(SE):low myopia(SE≥-3.00 D),moderate myopia(-3.00 D>SE>-6.00 D)and high myopia(SE≤-6.00 D).Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times(1wk,1,3,6mo,and 1y).Posterior mean elevation(PME)at 25 predetermined points of 3 concentric circles(2-,4-,and 6-mm diameter)above the best fit sphere was analyzed.●RESULTS:All surgeries were completed uneventfully and no ectasia was found through the *** difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively(1mo:P=0.017;3mo:P=0.018).The effect of time onΔPME was statistically significant(2-mm ring:P=0.001;4-mm ring:P<0.001;6-mm ring:P<0.001).The effect of different corneal locations onΔPME was significant except 1wk postoperatively(1mo:P=0.000;3mo:P=0.000;6mo:P=0.001;1y:P=0.001).Posterior corneal stability was linearly correlated with SE,central corneal thickness,ablation depth,residual bed thickness,percent ablation depth and percent stromal bed thickness.●CONCLUSION:The posterior corneal surface changes dynamically after *** protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after *** has good stability,accuracy,safety and predictability.

关键词： myopia posterior corneal elevation corneal ectasia small incision lenticule extraction

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Hem-o-lok clip migration to duodenal bulb post-cholecystectomy:A case report

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1461-1466页

作者： Hong-Yan Liu Ai-Hong Yin Zhi Wei department of Gastroenterology Shandong Second Provincial General HospitalJinan 250022Shandong ProvinceChina

BACKGROUND Hem-o-lok clips are typically used to control the cystic duct and vessels during laparoscopic cholecystectomy(LC)and common bile duct exploration for stones in the bile duct and ***,we report a unique example of Hem-o-lok clip movement towards the duodenal bulb after LC,appearing as a submucosal tumor(SMT).Additionally,we provide initial evidence of gradual and evolving endoscopic manifestations of Hem-o-lok clip migration to the duodenal bulb wall and review the available *** SUMMARY A 72-year-old man underwent LC for gallstones,and Hem-o-lok clips were used to ligate both the cystic duct and cystic ***(EGD)2 years later revealed an SMT-like lesion in the duodenal *** to the symptomatology,the clinical examination did not reveal any major abnormalities,and the patient was followed up as an outpatient.A repeat EGD performed 5 months later revealed an SMT-like lesion in the duodenal bulb with raised edges and a central depression.A third EGD was conducted,during which a Hem-o-lok clip was discovered connected to the front side of the *** clip was extracted easily using biopsy forceps,and no complications *** months after the fourth EGD,the scar was surrounded by normal *** Clinicians should be aware of potential post-LC ***-o-lok clips should be removed if symptomatic.

关键词： Hem-o-lok clip Migration Duodenum Laparoscopic cholecystectomy Laparoscopic common bile duct exploration Case report

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Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

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Asian Journal of Andrology 2024年第1期26卷 57-66页

作者： Chang-Bo Zhao Wei-Bo Chen Wen-Zhen Wang Fang-Xin Gong Cui-Qin Fan Ye Li Tian Lan Wen-Jing Wang Ming-Zhen Yuan department of Urology Shandong Provincial HospitalShandong UniversityJinan 250012China department of Andrology Liaocheng People's HospitalShandong UniversityLiaocheng 252000China department of Urology The Second Hospital of Shandong UniversityJinan 250012China department of Physiology School of Basic Medical SciencesShandong UniversityJinan 250012China

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging *** factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this ***,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of *** results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control ***,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile *** expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED *** expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED ***,the cell morphology in the cavernous tissue of the DMED group also changed ***,-OA treatment significantly reversed all these changes observed in the DMED *** conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.

关键词： apoptosis diabetic mellitus erectile dysfunction nitro-oleic acid NO/cGMP pathway oxidative stress

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Identification of risk factors and construction of a nomogram predictive model for post-stroke infection in patients with acute ischemic stroke

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World Journal of Clinical Cases 2024年第20期12卷 4048-4056页

作者： Xiao-Chen Liu Xiao-Jie Chang Si-Ren Zhao Shan-Shan Zhu Yan-Yan Tian Jing Zhang Xin-Yue Li department of Neurosurgery Shandong Provincial Third HospitalJinan 250031Shandong ProvinceChina department of Neurology Shandong Provincial Third HospitalJinan 250031Shandong ProvinceChina

BACKGROUND Post-stroke infection is the most common complication of stroke and poses a huge threat to *** addition to prolonging the hospitalization time and increasing the medical burden,post-stroke infection also significantly increases the risk of disease and *** the risk factors for post-stroke infection in patients with acute ischemic stroke(AIS)is of great *** can guide clinical practice to perform corresponding prevention and control work early,minimizing the risk of stroke-related infections and ensuring favorable disease *** To explore the risk factors for post-stroke infection in patients with AIS and to construct a nomogram predictive *** The clinical data of 206 patients with AIS admitted to our hospital between April 2020 and April 2023 were retrospectively *** data and post-stroke infection status of all study subjects were assessed,and the risk factors for poststroke infection in patients with AIS were *** Totally,48 patients with AIS developed stroke,with an infection rate of 23.3%.Age,diabetes,disturbance of consciousness,high National Institutes of Health Stroke Scale(NIHSS)score at admission,invasive operation,and chronic obstructive pulmonary disease(COPD)were risk factors for post-stroke infection in patients with AIS(P<0.05).A nomogram prediction model was constructed with a C-index of 0.891,reflecting the good potential clinical efficacy of the nomogram prediction *** calibration curve also showed good consistency between the actual observations and nomogram *** area under the receiver operating characteristic curve was 0.891(95%confidence interval:0.839–0.942),showing predictive value for post-stroke *** the optimal cutoff value was selected,the sensitivity and specificity were 87.5%and 79.7%,*** Age,diabetes,disturbance of consciousness,NIHSS score at admission,invasive surgery,and COPD are risk factors for post-st

关键词： Acute ischemic stroke Infection Risk factors Nomogram prediction model Chronic obstructive pulmonary disease

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Establishment and Validation of a Four-stress Granule-related Gene Signature in Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 1-14页

作者： Mengzhu Li Xiude Fan Jiajun Zhao Dawei Wang department of Endocrinology Shandong Provincial HospitalShandong UniversityJinanShandongChina Key Laboratory of Endocrine Glucose&Lipids Metabolism and Brain Aging Ministry of EducationDepartment of EndocrinologyShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina shandong Key Laboratory of Endocrinology and Lipid Metabolism JinanShandongChina shandong Institute of Endocrine and Metabolic Diseases JinanShandongChina

Background and Aims:Stress granules(SGs)as membrane-less cytoplasmic foci formed in response to unfavorable external stimuli could promote cancer cells to adapt to hostile *** carcinoma(HCC)is prone to be highly aggressive once diagnosed,which markedly reduces patient survival ***,it is crucial to develop valid diagnostic markers to prognosticate HCC patient prognosis,which promotes individualized precision therapeutics in *** the pro-tumorigenic activity of SGs,it is of great potential value to construct a prognostic tool for HCC based on the expression profiles of SG-related genes(SGGs).Methods:Bioinformatic analysis was employed to establish an SGG-based prognostic *** blotting and realtime polymerase chain reaction assays were used to assess the expression patterns of the related ***-of-function experiments were performed to analyze the effect of the SGGs on SG formation and cell ***:A four-SGG signature(KPNA2,MEX3A,WDR62,and SFN)targeting HCC was established and validated to exhibit a robust performance in predicting HCC ***,all four genes were further found to be highly expressed in human HCC *** important,we demonstrated that individually knocking down the four SGGs significantly reduced HCC cell proliferation and metastasis by compromising the SG formation ***:We developed an SGG-based predictive signature that can be used as an independent prognostic tool for *** strong predictive power of this signature was further elucidated by the carcinogenic activity of KPNA2,MEX3A,WDR62,and SFN in HCC cells by regulating SG formation.

关键词： Hepatocellular carcinoma Stress granules Prognostic factor G3BP1

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Hemoglobin loss method calculates blood loss during pancreaticoduodenectomy and predicts bleeding-related risk factors

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 419-428页

作者： Chao Yu Yi-Min Lin Guo-Zhe Xian department of Hepatobiliary Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina

BACKGROUND The common clinical method to evaluate blood loss during pancreaticoduoden-ectomy(PD)is visual inspection,but most scholars believe that this method is extremely subjective and ***,there is no accurate,objective me-thod to evaluate the amount of blood loss in PD *** retrospectively analyzed the clinical data of 341 patients who underwent PD in shandong provincial hospital from March 2017 to February *** to different surgical methods,they were divided into an open PD(OPD)group and a laparoscopic PD(LPD)*** differences and correlations between the in-traoperative estimation of blood loss(IEBL)obtained by visual inspection and the intraoperative calculation of blood loss(ICBL)obtained using the Hb loss method were ***,IEBL and perioperative calculation of blood loss(PCBL)were compared between the two groups,and single-factor regression analysis was *** There was no statistically significant difference in the preoperative general patient information between the two groups(P>0.05).PD had an ICBL of 743.2(393.0,1173.1)mL and an IEBL of 100.0(50.0,300.0)mL(P200μmol/L(95%CI:7.09-644.26;P=0.045)were independent risk factors for *** ICBLs of the LPD group and OPD group were 767.7(435.4,1249.0)mL and 663.8(347.7,1138.2)mL,respectively(P>0.05).The IEBL of the LPD group 200.0(50.0,200.0)mL was slightly greater than that of the OPD group 100.0(50.0,300.0)mL(P>0.05).PCBL was greater in the LPD group than the OPD group[1061.6(612.3,1632.3)mL vs 806.1(375.9,1347.6)mL](P<0.05).CONCLUSION The ICBL in patients who underwent PD was greater than

关键词： Pancreaticoduodenectomy Hemoglobin loss Calculated blood loss Estimated blood loss

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Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infltration

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Oncology Research 2024年第3期32卷 545-561页

作者： JIECHUAN QIU TIANMIN YANG YANNING SUN KAI SUN YINGKUN XU QINGHUA XIA department of Urology Shandong Provincial Hospital A fliated to Shandong First Medical UniversityJinan250021China Depatment of Urology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinan250021China Depatment of Breast and Thyroid Surgery The First Afiliated Hospital of Chongqing Medical UniversityChongqing400042China

This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key *** rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer *** logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical *** diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)*** co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were *** correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing *** differential analysis and intersection,we identifed six hub genes,induding *** found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse *** to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune ***,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC *** conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor *** results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.

关键词： Kidney renal clear cell carcinoma Acyl CoA dehydrogenase medium chain Immune infiltration Fatty acid oxidation Prognosis

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Characteristics and risk factor analyses of high-grade intraepithelial neoplasia in older patients with colorectal polyps

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4129-4137页

作者： Xin Zhang Ying Wang Tong Zhu Jian Ge Jun-Hua Yuan department of Geriatric Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021Shandong ProvinceChina

BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Currently,it is difficult to accurately diagnose LGIN and HGIN through imaging,and clinical diagnosis depends on postoperative histopathological diagnosis.A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal *** To explore the characteristics and risk factors of HGIN in older patients with colorectal *** We selected 84 older patients diagnosed with HGIN as the HGIN group(n=95 colonic polyps)and 112 older patients diagnosed with LGIN as the LGIN group(n=132 colonic polyps)from shandong provincial hospital Affiliated to shandong First Medical *** endoscopic features,demographic characteristics,and clinical manifestations of the two patient groups were compared,and a logistic regression model was used to analyze the risk factors for HGIN in these *** The HGIN group was older and had a higher number of sigmoid colon polyps,rectal polyps,pedunculated polyps,polyps≥1.0 cm in size,polyps with surface congestion,polyps with surface depression,and polyps with villous/tubular adenomas,a higher proportion of patients with diabetes and a family history of colorectal cancer,patients who experienced rectal bleeding or occult blood,patients with elevated carcinoembryonic antigen(CEA)and cancer antigen 199(CA199),and lower nutritional levels and higher frailty *** polyp location(in the sigmoid colon or rectum),polyp diameter(≥1.0 cm),pathological diagnosis of(villous/tubular adenoma),family history of colorectal cancer,rectal bleeding or occult blood,elevated serum CEA and CA199 levels,lower nutritional levels and higher frailty levels also are independent risk factors for *** The occurrence of high-grade neoplastic transformat

关键词： Elderly Colorectal polyps High-grade intraepithelial neoplasia Low-grade intraepithelial neoplasia Risk factors

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Tumor-associated telocytes

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Chinese Medical Journal 2024年第4期137卷 490-492页

作者： Jinqing Zhang Ying Xu department of General Surgery Shandong Provincial Third HospitalShandong UniversityJinanShandong 250117China

To the Editor:It has been eighteen years since telocytes(TCs)were first categorized by Popescu et al^([1])in *** were classified into interstitial cells of the Cajal(ICC)type based on their ultrastructure and immunohistochemical features,which are similar to mesenchymal cells.^([2])In the following ten years,TCs were found to have their own distinctive characteristics in terms of three-dimensional structure,immunological biomarkers,genomics,and multiple ***,TCs are definitely distinct from fibroblasts,mesenchymal stem cells,and endothelial cells in multiple organs of human beings and animals.^([3])

关键词： cytes organs definitely

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