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Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

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Chinese Journal of Cancer Research 2024年第2期36卷 114-123页

作者： Yupeng Ren Yuxuan Li Mingbo Cao Yongchang Tang Feng Yuan Gaoyuan Yang Zhiwei He Zheng Shi Xiaorui Su Zhicheng Yao Meihai Deng Department of Hepatobiliary Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of general Surgery Qilu HospitalShandong UniversityJinan 250012China Department of Hepatobiliary Surgery the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Hepatobiliary and Pancreatic Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of ***: From February 2.2. to November 2.2., a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2.[95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) *** OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 2.(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(2..4%), hypertension(2..6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher ***: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

关键词： Hepatocellular carcinoma lenvatinib low-dose cyclophosphamide pembrolizumab transarterial chemoembolization

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Polydopamine-modified metal-organic frameworks nanoparticles enhance the corrosion resistance and bioactivity of polycaprolactone coating on high-purity magnesium

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Journal of Magnesium and Alloys 2024年第5期12卷 2070-2089页

作者： Qingyun Fu Shaojie He Junjie Yang Ziyu Su Ping Li Xincheng Yu Weihong Jin Shulan Xu Zhentao Yu Dingsheng Zha Center of Oral Implantology Stomatological HospitalSouthern Medical UniversityGuangzhouChina Panyu hospital of Chinese Medicine Guangzhou 511400China Institute of Advanced Wear&Corrosion Resistant and Functional Materials Jinan UniversityGuangzhou 510632China First Affiliated hospital of Jinan University Guangzhou 510630China

Biodegradable magnesium(Mg)and its alloys exhibit excellent biocompatibility and mechanical compatibility,demonstrating tremendous potential for applications in ***,the rapid degradation rate has limited their clinical ***(PCL)is commonly employed as a polymer coating to impede the rapid degradation of ***,its long-term anti-corrosion capability and bioactivity are *** address these issues,polydopamine(PDA)-modified zeolitic imidazolate framework-8(PZIF-8)bioactive nanoparticles are fabricated and incorporated into the PCL *** PZIF-8 particles,featuring catechol motifs,can enhance the compactness of the PCL coating,reduce its defects,and possess biomineralization ability,thereby effectively improving its anti-corrosive and bioactive ***,the active substances released from the degradation of the PZIF-8 particles such as Zn^(2.)and PDA are beneficial for *** corrosion tests indicate that the corrosion current density of PCL-treated sample decreases by more than one order of magnitude and the amount of H_(2.released decreases from 0.2.±0.12.to 0.08±0.08 ml cm^(-2.after doping with the ***,the improved corrosion resistance and released PDA and Zn^(2.)from the coating can promote osteogenic differentiation by up-regulating the expression of alkaline phosphatase activity,related osteogenic genes,and *** addition,in vivo implantation experiments in rabbit femur defects further offer strong evidence that the doping of PZIF-8 nanoparticles accelerates bone reconstruction of the PCL *** summary,this work implies a new strategy to fabricate a PCL-based coating on Mg-based implants by introducing the PZIF-8 particles for orthopedic applications.

关键词： Polydopamine ZIF-8 High-purity magnesium Polycaprolactone coating Anticorrosion Bone regeneration

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Assessment of the Respiratory Disease Mortality Risk from Single and Composite Exposures to PM_(2.5)and Ozone—guangzhou City,Guangdong Province,China,2.18-2.2.

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China CDC weekly 2024年第34期6卷 857-861,I0001-I0006页

作者： Hongwei Tu Yijun Hu Keqi Hu Peipei Dong Yue Wen Jing Jiang Xuedan Xu Jinxu Huang Jiemin Zhu Changyun He Qiuxia Chen Yongying Liu Guangdong Provincial Center for Disease Control and Prevention Guangzhou CityGuangdong ProvinceChina Jinan University Guangzhou CityGuangdong ProvinceChina Department of Science and Education Guangdong Second Provincial General HospitalGuangzhou CityGuangdong ProvinceChina Sun Yat-sen University Guangzhou CityGuangdong ProvinceChina

Summary What is already known about this topic?Fine particulate matter(PM_(2.5))and ozone(O_(3))are prevalent pollutants in the atmosphere,which threaten human health,especially the respiratory ***,people are exposed to a mixture of various pollutants in the ***,the single and combined effects of both pollutants need to be investigated.

关键词： environment. ozone Guangdong

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Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity

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Chinese Journal of Integrative Medicine 2024年第2期30卷 143-151页

作者： HUANG Yong-quan LIU Jia-lin CHEN Geng-xin SHEN Dan-ting ZHU Wang CHEN Xin-lin LIU Feng-bin HOU Qiu-ke Graduate School Guangzhou University of Chinese MedicineGuangzhou(510405)China Department of Orthopedics the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Preventive Medicine and Health Statistics Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Gastroenterology the First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510405)China

Objective:To evaluate if berberine can act on vitamin D receptors(VDR)and thereby regulate the expression of tight junction proteins(TJPs)in irritable bowel syndrome-diarrhea-predominant(IBS-D)***:The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical *** modeling,the model was evaluated and rats were divided into the control group and berberine treatment groups(0.85,1.7 and 3.4 mg/kg,once a day for 2.weeks).The distal colon was obtained and colonic epithelial cells(CECs)were isolated and cultured after IBS-D model *** vitamin D receptor response element(VDRE)reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE *** overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair,and to determine which region of VDR plays a role in berberine-regulated intestinal ***:The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner(P<0.05).The activity of VDRE promoter was also effectively promoted by berberine(P<0.05).Berberine increased the expression of TJPs in IBS-D CECs(P<0.05).VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups(all P<0.05).RT-qPCR and Western blot results showed that compared with the blank group,expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups(all P<0.05).Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1(P<0.05).Conclusion:Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity,and the main site of action is the N-terminal region of VDR.

关键词： berberine Chinese medicine irritable bowel syndrome-diarrhea-predominant vitamin D receptors intestinal mucosal barrier tight junction proteins

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Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

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Current Medical Science 2024年第2期44卷 419-425页

作者： Jia-xun LI Ling-rui MENG Bao-ke HOU Xiao-lu HAO Da-jiang WANG Ling-hui QU Zhao-hui LI Lei ZHANG Xin JIN Department of Senior Ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China Department of Ophthalmology the 74th Army Group HospitalGuangzhou 510318China

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on *** potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2.-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and *** this study,the complete clinical characteristics of two Chinese ARB families were ***:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family ***:Two novel mutations,c.2.2.>C(chr11:6172.62.,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB *** novel missense mutation BEST1 c.2.2.>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2.of *** novel variant,BEST1 c.867+97G>A(chr11:6172.867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional ***:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific *** novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

关键词： autosomal recessive bestrophinopathy BEST1 gene third-generation sequencing mutation

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Chinese expert consensus on the clinical application of drugcoated balloon(2.(nd) Edition)

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Journal of Geriatric Cardiology 2024年第2期21卷 135-152页

作者： The Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon(2.(nd)Edition) Jun-Bo GE Yun-Dai CHEN 不详 Zhongshan hospital Fudan University Chinese PLA general hospital

Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary *** more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.

关键词： balloon drugs dealing

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CHCHD2.Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

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Neural Regeneration Research 2024年第1期19卷 196-204页

作者： Xiang Chen Yuwan Lin Zhiling Zhang Yuting Tang Panghai Ye Wei Dai Wenlong Zhang Hanqun Liu Guoyou Peng Shuxuan Huang Jiewen Qiu Wenyuan Guo Xiaoqin Zhu Zhuohua Wu Yaoyun Kuang Pingyi Xu Miaomiao Zhou Department of Neurology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology The People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2.CHCHD2.,a crucial mitochondrial protein,has been reported to cause Parkinson's ***-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy ***,the specific roles of wild-type(WT)CHCHD2.and T611-mutant CHCHD2.in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2.or CHCHD2.T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea ***,in this study,we expressed WT CHCHD2.and T61l-mutant CHCHD2.in an MPP^(+)-induced SH-SY5Y cell model of *** found that CHCHD2.protected mitochondria from developing MPP^(+)-induced *** normal conditions,ove rexpression of WT CHCHD2.promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2.appeared to have lost the ability to regulate F1FO-ATPase *** addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2.and *** weeks after transfection with AAV-CHCHD2.T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2.3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this *** findings suggest that WT CHCHD2.can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

关键词： ATP synthase(F1F0-ATPase) coiled-coil helix coiled-coil helix domain containing 2 dopaminergic neuron mitochondrial dysfunction neurodegeneration oligomycin sensitivity-conferring protein Parkinson's disease T61I mutation tyrosine hydroxylase

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Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis:A case report

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2219-2224页

作者： Wen-Tao Zhong Yuan Lv Qian-Yu Wang Ran An Gang Chen Jun-Feng Du The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of general Surgery The 7^(th)Medical Center of PLA General HospitalBeijing 100700China Department of Pathology The 7^(th)Medical Center of PLA General HospitalBeijing 100700China

BACKGROUND According to the latest report,colorectal cancer is still one of the most prevalent cancers,with the third highest incidence and mortality *** of advanced rectal cancer with distant metastases is usually unsatisfactory,especially for mismatch repair proficient(pMMR)rectal cancer,which leads to poor prognosis and *** SUMMARY We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes,including the left supraclavicular lymph node,before treatment in a 70-year-old *** received full courses of chemoradiotherapy(CRT)followed by 4 cycles of programmed death 1 inhibitor Tislelizumab,and a pathologic complete response(pCR)was achieved,and the lesion of the left supraclavicular lymph node also *** pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

关键词： Rectal cancer Metastasis Chemoradiotherapy Immunotherapy Prognosis Case report

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Intermittent melena and refractory anemia due to jejunal cavernous lymphangioma:A case report

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1208-1214页

作者： Kai-Rui Liu Sheng Zhang Wei-Run Chen You-Xing Huang Xu-Guang Li Department of Abdominal Surgery The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000Guangdong ProvinceChina Department of general Surgery The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and The Ministry of Education of China Guangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Lymphangiomas in the gastrointestinal tract are extremely rare in *** a benign lesion,small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive ***,lymphangiomas can give rise to complications such as abdominal pain,bleeding,volvulus,and ***,we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male *** SUMMARY A 66-year-old man presented with intermittent melena,fatigue and refractory anemia nine months *** and colonoscopy were performed many times and revealed no apparent *** management,including transfusion,hemostasis,gastric acid secretion inhibition and symptomatic treatment,was performed,but the lesions tended to recur shortly after ***,the patient underwent capsule endoscopy,which revealed a more than 10 cm lesion accompanied by active *** singleballoon enteroscopy and biopsy,a diagnosis of jejunal cavernous lymphangioma was confirmed,and the patient underwent surgical *** complications or recurrences were observed *** Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal *** endoscopy and single-balloon enteroscopy can facilitate *** resection is an effective management method.

关键词： Intermittent melena Refractory anemia Capsule endoscopy Single-balloon enteroscopy Jejunal cavernous lymphangioma Enterectomy Case report

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N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation

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Asian Journal of Andrology 2024年第1期26卷 99-106页

作者： Wei Ding Jun-Hong Fan Li-Ren Zhong Nan-Xiong Wang Lu-Hao Liu Hai-Bo Zhang Li Wang Ming-Qiang Wang Bing-Lin He An-Yang Wei Department of Urology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang 550002China Department of Urology Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510000China Department of Urology Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Department of Urology Shenzhen Immigration Inspection General Station HospitalShenzhen 518000China Department of Organ Transplantation The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510000China Department of Endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang 550002China

Hyperlipidemia is a major risk factor for erectile dysfunction(ED).Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells(CcSMCs)are the key pathological factors of ED.N-acetylcysteine(NAC)can inhibit oxidative stress;however,whether NAc can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear.A hyperlipidemia model was established using 2. eight-week-old male Sprague-Dawley(SD)rats fed a high-fat and high-cholesterol diet(hyperlipidemic rats,HR).In addition,9 male SD rats were fed a normal diet to serve as controls(NC).HR rats were divided into three groups:HR,HR+normal saline(NS),and HR+NAC(n=9 for each group;NS or NAc intraperitoneal injections were administered daily for 16 weeks).Subsequently,the lipid profiles,erectile function,oxidative stress,phenotypic modulation markers of ccsMCs,and tissue histology were *** experimental results revealed that erectile function was significantly impaired in the HR and HR+NS groups,but enhanced in the HR+NAC *** lipid levels,over-activated oxidative stress,and multi-organ lesions observed in the HR and HR+NS groups were improved in the HR+NAC ***,the HR group showed significant phenotypic modulation of CCSMCs,which was also inhibited by NAC *** report focuses on the therapeutic effect of NAc in restoring erectile function using a hyperlipidemic rat model by preventing CcSMC phenotypic modulationand attenuating oxidativestress.

关键词： erectile dysfunction hyperlipidemia N-acetylcysteine oxidative stress henotypic modulation

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