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Clinicopathological features,psychological status,and prognosis of 33 patients with occult breast cancer

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World Journal of Psychiatry 2024年第1期14卷 76-87页

作者： Hong-Mei Wang Ao-Yang Yu Lin-Lin Li Lu-Yao Ma Meng-Han Cao Yu-Le Yang Xiao-Bing Qin Juan-JuanTang Zheng-Xiang Han Department of Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina Graduate School Xuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of Pathology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

BACKGROUND Occult breast cancer(OBC)has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer.Due to the small number of cases and limited clinical experience,treatments vary greatly around the world and no standardized treatment has yet been established.AIM To investigate the clinicopathological features,psychological status and prognostic features of patients with OBC.METHODS The clinicopathological data of 33 OBC patients diagnosed and treated in the affiliated hospital of xuzhou medical university and xuzhou Central hospital from November 2015 to November 2022 were retrospectively analyzed.The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale.Patients’emotions,stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule,the Chinese Perceived Stress Scale,and the Connor-Davidson Resilience Scale(CD-RISC),respectively.Patient survival was calculated using the Kaplan-Meier method,and survival curves were plotted for analysis with the log-rank test.Univariate and multivariate survival analyses were performed using the Cox regression model.RESULTS The 33 OBC patients included 32 females and 1 male.Of the 33 patients,30(91%)had axillary tumors,3(9%)had a neck mass as the primary symptom;18(54.5%)had estrogen receptor-positive tumors,17(51.5%)had progesterone receptor-positive tumors,and 18(54.5%)had Her-2-positive tumors;24(72.7%)received surgical treatment,including 18 patients who underwent modified radical mastectomy,1 patient who underwent breast-conserving surgery plus axillary lymph node dissection(ALND),and 5 patients who underwent ALND alone;12 patients received preoperative neoadjuvant therapy.All 30 patients developed anxiety and depression,with low positive affect scores and high negative affect scores,accompanied by a high stress level and poor psychological resilience.There were no differences in

关键词： Occult breast cancer Breast cancer Perceived Stress Scale Axillary lymph node dissection

Efficacy of scleral buckling for the treatment of rhegmatogenous retinal detachment using a novel foldable capsular buckle

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 558-563页

作者： Fang-Fang Fan Chang Xiao Liang Wang Xin-Ting Wang Dan-Dan Liu Xing Ge Ya-Lu Liu Su-Yan Li The affiliated xuzhou Municipal hospital of xuzhou medical university Xuzhou 221000Jiangsu ProvinceChina Department of Ophthalmology Xuzhou First People’s HospitalXuzhou 221116Jiangsu ProvinceChina Eye Disease Prevention and Treatment Institute of xuzhou Xuzhou 221116Jiangsu ProvinceChina The affiliated Shuyang hospital of xuzhou medical university Shuyang 223600Jiangsu ProvinceChina

●AIM:To evaluate the effectiveness and safety of scleral buckling for the treatment of rhegmatogenous retinal detachment(RRD)using a novel foldable capsular buckle(FCB).●METHODS:This was a series of case observation studies.Eighteen patients(18 eyes)who visited our ophthalmology department between August 2020 and August 2022 and were treated for RRD with scleral buckling using FCB were included.The procedure was similar to conventional scleral buckling,while a balloon-like FCB was placed onto the retinal break with balanced salt solution filling for a broad,external indentation instead of the silicone buckle.The retinal reattachment rate,best corrected visual acuity(BCVA),intraocular pressure(IOP),refractive dioptre and astigmatism degree,and complications were evaluated and recorded.●RESULTS:There were 7 males and 11 females aged 19-58y.The average time course of RRD was 12d,ranging from 7-20d.The retinal break was located in the superior quadrants in 8 eyes and in the inferior quadrants in 10 eyes,with macula-off detachments in 12 eyes.The patients were followed-up for at least 6mo.The final retinal reattachment rate was 100%.The BCVA was significantly improved compared with the baseline(P0.05).Three patients had transiently high IOPs within one week after surgery.Mild diplopia occurred in 5 patients after surgery and then disappeared after the balloon fluid was removed.●CONCLUSION:The success rate of FCB scleral buckling for RRD is satisfactory.This procedure can be expected to be applied in new,uncomplicated cases of RRD.

关键词： rhegmatogenous retinal detachment scleral buckling foldable capsular buckle

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

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World Journal of Emergency Medicine 2024年第2期15卷 111-120页

作者： Weichao Ding Wei Zhang Juan Chen Mengmeng Wang Yi Ren Jing Feng Xiaoqin Han Xiaohang Ji Shinan Nie Zhaorui Sun Department of Emergency Medicine Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210002China Department of Emergency Medicine Jinling Clinical Medical College of Nanjing University of Chinese MedicineNanjing 210002China Department of Emergency Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002China Department of Emergency Medicine Xuzhou Municipal Hospital Affiliated to Xuzhou Medical UniversityXuzhou 221000China

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

关键词： Quercetin Sepsis-related acute respiratory distress syndrome Network pharmacology

Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice

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Chinese Journal of Natural Medicines 2024年第2期22卷 137-145页

作者： LIU Mingming GUO Jiatian ZHAO Jing LI Hongye FENG Xiaoxiao LIU Haojun ZHANG Hao JIA Xuejun WEI Rushuai LI Fang CHEN Chong HOU Mingzhuang LV Nanning XU Haiyan Department of human anatomy Xuzhou Medical UniversityXuzhou 221004China Department of Orthopedic Surgery The Affiliated Lianyungang Clinical College of Xuzhou Medical University(The Second People’s Hospital of Lianyungang)Lianyungang 222003China Department of Orthopaedics The First Afliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Institute of Hematology Xuzhou Medical UniversityXuzhou 221004China

Excessive oxidative stress impairs cartilage matrix metabolism balance,significantly contributing to osteoarthritis(OA)development.Celastrol(CSL),a drug derived from Tripterygium wilfordii,has recognized applications in the treatment of cancer and immune system disorders,yet its antioxidative stress mechanisms in OA remain underexplored.This study aimed to substantiate CSL’s chondroprotective effects and unravel its underlying mechanisms.We investigated CSL’s impact on chondrocytes under both normal and inflammatory conditions.In vitro,CSL mitigated interleukin(IL)-1β-induced activation of proteinases and promoted cartilage extracellular matrix(ECM)synthesis.In vivo,intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA mice.Mechanistically,it was found that inhibiting nuclear factor erythroid 2-related factor 2(NRF2)abrogated CSL-mediated antioxidative functions and exacerbated the progression of OA.This study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2,offering a novel therapeutic avenue for arthritis therapy.

关键词： Osteoarthritis Celastrol Articular cartilage Extracellular matrix NRF2

TREM-1 mediates interaction between substantia nigra microglia and peripheral neutrophils

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Neural Regeneration Research 2024年第6期19卷 1375-1384页

作者： Tong Shen Guiyun Cui Hao Chen Long Huang Wei Song Jie Zu Wei Zhang Chuanying Xu Liguo Dong Yongmei Zhang Jiangsu Province Key Laboratory of Anesthesiology Xuzhou Medical University Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology Xuzhou Medical University NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs Department of Neurology The Affiliated Hospital of Xuzhou Medical University

Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson’s disease. Triggering receptor expressed on myeloid cell-1(TREM-1) can amplify the inherent immune response, and crucially, regulate inflammation. In this study, we found marked elevation of serum soluble TREM-1 in patients with Parkinson’s disease that positively correlated with Parkinson’s disease severity and dyskinesia. In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease, we found that microglial TREM-1 expression also increased in the substantia nigra. Further, TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson’s disease and reduced dopaminergic neuronal injury. Meanwhile, TREM-1 knockout attenuated the neuroinflammatory response, dopaminergic neuronal injury, and neutrophil migration. Next, we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson’s disease and treated the cells with the TREM-1 inhibitory peptide LP17. We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration. Moreover, inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide. TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK. These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson’s disease by regulating the interaction between microglia and peripheral neutrophils.

关键词： 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-methyl-4-phenylpyridiniumion dopaminergic neurons infiltration microglia neuroinflammation neutrophils Parkinson’s disease SYK TREM-1

Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2504-2519页

作者： Di Pan Hao-Nan Liu Zhi-Yuan Yao Xiao-Xiao Chen Yu-Qi Li Jing-Jing Zhu Zheng-Xiang Han Xiao-Bing Qin Department of Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(HBV)-DNA levels on the clinical efficacy of this regimen is still limited.AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts:HBV-DNA≤2000(n=66)and HBV-DNA>2000(n=54).The main outcomes measured were overall survival(OS)and progression-free survival(PFS),while additional outcomes included the rate of objective response rate(ORR),disease control rate(DCR),and any negative events.Cox proportional hazards regression analysis revealed independent predictors of OS,leading to the creation of a nomogram incorporating these variables.RESULTS The median PFS was 8.32 months for the HBV-DNA≤2000 group,which was similar to the 7.80 months observed for the HBV DNA>2000 group(P=0.88).Likewise,there was no notable variation in the median OS between the two groups,with durations of 13.30 and 14.20 months respectively(P=0.14).The ORR and DCR were compared between the two groups,showing ORR of 19.70%vs 33.33%(P=0.09)and DCR of 72.73%vs 74.07%(P=0.87).The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results,with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

关键词： Hepatitis B virus Hepatocellular carcinoma Camrelizumab Lenvatinib Efficacy

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2024年第9期19卷 2081-2088页

作者： Xiaoli Fang Sha Liu Bilal Muhammad Mingxuan Zheng Xing Ge Yan Xu Shu Kan Yang Zhang Yinghua Yu Kuiyang Zheng Deqin Geng Chun-Feng Liu Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Xuzhou Central HospitalXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of Neuropsychiatric Disease and Institute of Neuroscience Soochow UniversitySuzhouJiangsu ProvinceChina

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor de

关键词： C/EBP/AEP signaling pathway endotoxemia fecal microbiota transplantation intestinal barrier intestinal inflammation microbiota-gut-brain axis Parkinson’s disease

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua Qian-Qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi Yu Man Liu Zheng-Rui Bian Bei-Bei Zhang Qian Yu Yin-Hai Xu Ren-Xian Tang Kui-Yang Zheng Chao Yan Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation