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Phenotypic research on senile osteoporosis caused by SIRT6 deficiency

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International Journal of Oral Science 2016年第2期8卷 84-92页

作者： De-Mao Zhang Di-Xin Cui ruo-shi xu Ya-Chuan Zhou Li-Wei Zheng Peng Liu xue-Dong Zhou State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University

Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out （KO） in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b （TRAP5b） concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption.

关键词： ageing osteoclastogenesis osteogenesis osteoporosis

Spatial signalling mediated by the transforming growth factor-β signalling pathway during tooth formation

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International Journal of Oral Science 2016年第4期8卷 199-204页

作者： Xin-Yu He Ke Sun ruo-shi xu Jia-Li Tan Cai-Xia Pi Mian Wan Yi-Ran Peng Ling Ye Li-Wei Zheng xue-Dong Zhou State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University West China School of Stomatology Sichuan University Guanghua School of Stomatology Hospital of Stomatology Department of Endodontics Guangdong Provincial Key Laboratory of Stomatology Sun Yat-sen University

Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pathways. It is well known that suspensions of tooth germ cells can form tooth-like structures after losing the positional information provided by the epithelial and mesenchymal tissues. However, the particular stage in which the tooth germ cells start to form tooth-like structures after losing their positional information remains unclear. In this study, we investigated the reassociation of tooth germ cells suspension from different morphological stages during tooth development and the phosphorylation of Smad2/3 in this process. Four tooth morphological stages were designed in this study. The results showed that tooth germ cells formed odontogenic tissue at embryonic day （E） 14.5, which is referred to as the cap stage, and they formed tooth-like structures at E16.5, which is referred to as the early bell stage, and E18.5, which is referred to as the late bell stage. Moreover, the transforming growth factor-β signalling pathway might play a role in this process.

关键词： positional information transforming growth factor-13 signalling pathway tooth development

Sorafenib in treatment of patients with advanced hepatocellular carcinoma:a systematic review

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Hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 458-466页

作者： Xin Zhang, Xin-Rong Yang, Xiao-Wu Huang, Wei-Min Wang, ruo-Yu shi, Yang xu, Zheng Wang, Shuang-Jian Qiu, Jia Fan ,Jian Zhou Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory for Organ Transplantation, Shanghai 200032, China,Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China [a] Liver Cancer Institute Zhongshan Hospital Fudan University and Shanghai Key Laboratory for Organ Transplantation Shanghai 200032 Shanghai China [b] Institute of Biomedical Sciences Fudan University Shanghai 200032 Shanghai China

BACKGROUND: Sorafenib has become the standard first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of sorafenib in advanced HCC patients and explore its true value for specific subgroups. DATA SOURCES: A computer-based systematic search from January 2005 to June 2011 with 'sorafenib' and 'advanced hepatocellular carcinoma' as search terms was performed for possible clinical trials. Hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival (OS) and time to progression (TTP), rates of partial response (PR), rates of toxicity effects, and details of subgroup analysis were extracted. Meta-analyses were done using the software Review Manager (version 5.0). RESULTS: Six trials with 1164 patients were included. Based on three randomized controlled trials, the pooled HR (sorafenib/ placebo) was 0.66 for OS (95% CI: 0.56-0.78; P<0.00001) and 0.57 for TTP (95% CI: 0.47-0.68; P<0.00001). The pooled odds ratio (OR) for PR was 2.96 (95% CI: 0.96-9.15; P=0.06). For three single-arm trials, the pooled HR was 0.69 for OS (95% CI: 0.56-0.84; P=0.0002) and 0.64 for TTP (95% CI: 0.52-0.78; P<0.00001). The pooled OR for PR in three single-arm trials was 3.56 (95% CI: 1.22-10.39; P=0.02). Subgroup analysis indicated that sorafenib was less effective in patients with extrahepatic spread (with: P=0.13 vs without: P<0.0001), with normal alpha-fetoprotein level (AFP) (P=0.15 vs elevated: P=0.0006), and with elevated level of serum bilirubin (P=0.06 vs normal: P=0.0009). Sorafenib-based therapy significantly increased the risk of grade 3/4 hand-foot skin reaction, diarrhea, fatigue, and rash/***: Sorafenib-based therapy benefits advanced HCC patients. Meanwhile, sorafenib is less effective for patients with extrahepatic spread, with normal AFP level and with elevated level of bilirubin.

关键词： advanced hepatocellular carcinoma sorafenib systematic review

Complete response of gallbladder cancer treated with gemcitabine and cisplatin chemotherapy combined with durvalumab:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 226-232页

作者： Kai Chen xu Feng Yuan shi Xin-Lin Li Zheng-Rong shi Xiang Lan Department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced ***,the efficacy of this treatment for GBC remains *** SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative *** three cycles of therapy,a partial response was *** one year of combined therapy,a clinical complete response was successfully *** maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the *** patient experienced tolerable toxicities of reversible grade 2 nausea and *** adverse events were observed in the patient throughout the entirety of the *** The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse *** research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.

关键词： Gallbladder cancer Chemotherapy Immunotherapy Durvalumab Complete response Case report

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

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Neural Regeneration Research 2025年第7期20卷 1829-1848页

作者： Wenjing Ning shi Lv Qian Wang Yuzhen xu Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina Department of Central Laboratory The Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong ProvinceChina

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter ***,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective *** evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid ***,microglia play certain neuroprotective roles in the recovery phase of subarachnoid *** approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage *** provides new targets and ideas for the treatment of subarachnoid ***,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still *** review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter *** also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid ***,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese ***,most of these are still being evaluated at the laboratory *** clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemor

关键词： apoptosis blood–brain barrier brain edema microglia neuroinflammation neuron neuroprotection subarachnoid hemorrhage vasoconstriction white matter injury

Development of a nomogram for overall survival in patients with esophageal carcinoma:A prospective cohort study in China

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 158-168页

作者： shi-shi Yu Xi Zheng Xiao-Sheng Li Qian-Jie xu Wei Zhang Zhong-Li Liao Hai-Ke Lei Department of Gastroenterology Chongqing University Cancer HospitalChongqing 400030China Chongqing Cancer Multi-omics Big Data Application Engineering Research Center Chongqing University Cancer HospitalChongqing 400030China Department of Health Statistics School of Public HealthChongqing Medical UniversityChongqing 400016China

BACKGROUND Esophageal carcinoma(EC)presents a significant public health issue in China,with its prognosis impacted by myriad *** creation of a reliable prog-nostic model for the overall survival(OS)of EC patients promises to greatly advance the customization of treatment *** To create a more systematic and practical model that incorporates clinically significant indicators to support decision-making in clinical *** This study utilized data from a prospective longitudinal cohort of 3127 EC patients treated at Chongqing University Cancer Hospital between January 1,2018,and December 12,*** the least absolute shrinkage and selection operator regression alongside multivariate Cox regression analyses helped pinpoint pertinent variables for constructing the *** efficacy was assessed by concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA).RESULTS Nine variables were determined to be significant predictors of OS in EC patients:Body mass index(BMI),Karnofsky performance status,TNM stage,surgery,radiotherapy,chemotherapy,immunotherapy,platelet-to-lymphocyte ratio,and albumin-to-globulin ratio(ALB/GLB).The model demonstrated a C-index of 0.715(95%CI:0.701-0.729)in the training cohort and 0.711(95%CI:0.689-0.732)in the validation *** the training cohort,AUCs for 1-year,3-year,and 5-year OS predictions were 0.773,0.787,and 0.750,respectively;in the validation cohort,they were 0.772,0.768,and 0.723,respectively,illustrating the model's *** curves and DCA verified the model's predictive accuracy and net *** A novel prognostic model for determining the OS of EC patients was successfully developed and validated to help clinicians in devising individualized treatment schemes for EC patients.

关键词： Esophageal carcinoma High-risk factors Prognosis Overall survival Prediction model

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不确定条件下三级供应链收益共享契约研究

工业工程与管理 2016年第5期21卷 69-75页

作者：朱宝琳戚亚萍戢守峰邱若臻崔世旭东北大学工商管理学院辽宁沈阳110819

探讨了不确定环境下单一供应商、制造商和零售商组成的三级供应链契约协调问题。分别建立了供应链集中、分散和契约协调最优决策模型。分析了基于收益共享契约的分散无协调和集中决策下供应链的期望利润。证明了通过收益共享和批发价格... 详细信息

探讨了不确定环境下单一供应商、制造商和零售商组成的三级供应链契约协调问题。分别建立了供应链集中、分散和契约协调最优决策模型。分析了基于收益共享契约的分散无协调和集中决策下供应链的期望利润。证明了通过收益共享和批发价格的组合契约可以使供应链实现帕累托改进。数值算例说明了契约协调的有效性。

关键词：供应链协调收益共享契约产需不确定收益共享因子

Molecular mechanism and research progress of traditional Chinese medicine in the treatment of prostate cancer

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Traditional Medicine Research 2025年第1期10卷 62-72页

作者： Hai-Luo Wang ruo-Ran Zhang Hao Wang Peng xu Jing-Kai Wang Bo Chen Hao xu Deng Pan Yu-Yang Ma Kun Pang Department of Urology Xuzhou Central HospitalXuzhou Clinical School of Xuzhou Medical CollegeXuzhou 221009China Graduate School Jiangsu UniversityZhenjiang 212013China Graduate School Bengbu Medical UniversityBengbu 233040China Department of Urology The Peixian People’s HospitalXuzhou 221699China.

Prostate cancer(PCa)is one of the most common malignant tumors in the male genitourinary system,ranking second in incidence *** Chinese medicine(TCM),as an important component of complementary and alternative medicine,shows unique advantages in cancer *** herbal medicine is usually composed of multiple ingredients and involves multiple signaling pathways,which showed function of inducing apoptosis of cancer cells,arresting the cell cycle,inhibiting invasion and metastasis,reducing drug resistance,and regulating immune *** therapy is also an important treatment of ***,Physical therapy such as acupuncture or Tai Chi and Qigong are gaining increased recognition in the management of PCa,particularly in addressing issues like urinary incontinence and bone metastasis-related *** article reviews the TCM treatment and therapy of PCa,in order to provide new research avenues and treatment options for the treatment of PCa with TCM and improve the quality of life of patients.

关键词： traditional Chinese medicine prostate cancer Chinese herbal medicine physical therapy

Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling shi Quan-Hong Ma Department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response