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Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits

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International Journal of Ophthalmology(English edition) 2023年第1期16卷 22-32页

作者： Yi-Ming Zhao Rong-Sha Sun fang Duan fang-yu wang yu-Jie Li Xiao-Bing Qian Jie-Ting Zeng Yao Yang Xiao-Feng Lin State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060Guangdong ProvinceChina Xi’an People’s Hospital(Xi’an Fourth Hospital) Shaanxi Eye HospitalXi’an 710004Shaanxi ProvinceChina

AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.METHODS:Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus,followed by treatment with a slow-release dexamethasone implant(Ozurdex)or sham injection.Left eyes were used as normal controls.The intraocular pressure(IOP)was monitored using an iCare tonometer.PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk;specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction,Western blot,protein chip analysis,or immunofluorescence staining.RESULTS:During the observation period,PVR severity gradually increased.Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group.Ozurdex significantly alleviated PVR development and Müller cell gliosis.Post-traumatic inflammation fluctuated and was persistent.The interleukin-1β(IL-1β)mRNA level was significantly upregulated,peaking on day 3 and increasing again on day 21 after injury.The expression of nod-like receptor family pyrin domain containing 3(NLRP3)showed a similar trend that began earlier than that of IL-1βexpression.Ozurdex suppressed the expression of IL-1β,NLRP3,and phosphorylated nuclear factor-kappa B(NF-κB).The average IOP after treatment was within normal limits.CONCLUSION:The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk.Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis,and thus alleviates PVR severity.This study highlights the important role of IL-1β,and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1βinflammatory axi

关键词： ocular trauma proliferative vitreoretinopathy gliosis Ozurdex inflammation rabbit

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Patient-specific ventricular puncture trajectory plane and puncture trajectory: a novel method of frontal ventricular puncture

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Chinese Medical Journal 2021年第19期134卷 2359-2361页

作者： Chen-yu Ding Jun-yu Lin yue Chen yue Pang Xiao-Yong Chen Wen-Hua fang fang-yu wang yuang-Xiang Lin De-Zhi Kang Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350001China Fujian Provincial Key Laboratory of Precision Medicine for Cancer FuzhouFujian 350001China Department of Clinical Medicine Fujian Medical UniversityFuzhouFujian 350001China

Ventricular puncture is a common neurosurgical procedure,which is usually performed freehand using body surface anatomic landmarks as targeting references.[1,2]However,it is reported that the failure rate of freehand lateral ventricle puncture could be as high as 43%in traumatic brain injury cases if body surface anatomic landmarks are used as targeting references,[3]and the occurrence of hemorrhages associated with ventricular puncture could reach 16.2%.[4]Classic puncture sites,such as Kocher point,are helpful in improving the success rate of ventricular puncture.However,it is still risky to perform freehand puncture with classic puncture sites.Several causes could lead to this issue,including the following:(1)Individual patients have different conditions;a puncture approach suitable for all patients might not be possible.(2)Selection of puncture approach is largely dependent on the judgment of the surgeon,because the puncture approach does not usually fall on the coronal,sagittal,or axial images of the regular computed tomography(CT)scan;surgeons need to use spatial imagination based on CT images to design the ventricular puncture trajectory(VPT),which could lead to errors.(3)In freehand puncture,directional deviations could occur easily without the guidance of a frame as a fixed space reference to the puncture path.

关键词： puncture ventricular plane

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Can admission lipoprotein-associated phospholipase A2 predict the symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage?

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Chinese Neurosurgical Journal 2020年第4期6卷 196-203页

作者： Chen-yu Ding fang-yu wang Han-Pei Cai Xiao-Yong Chen Shu-Fa Zheng Liang-Hong yu yuan-Xiang Lin Zhang-Ya Lin De-Zhi Kang Department of Neurosurgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujianPeople’s Republic of China

Background:Inflammation has been believed to be related to the development of cerebral vasospasm following aneurysmal subarachnoid hemorrhage(aSAH).A potential biomarker for vascular inflammation that is well recognized is the lipoprotein-associated phospholipase A2(Lp-PLA2).However,whether Lp-PLA2 can predict the occurrence of symptomatic cerebral vasospasm(SCV)in aSAH patients is still unknown.Thus,this study aimed to assess the value of Lp-PLA2 for predicting SCV in patients with aSAH.Methods:Between March 2017 and April 2018,we evaluated 128 consecutive aSAH patients who were admitted in the First Affiliated Hospital of Fujian Medical University.Their Lp-PLA2 level was obtained within 24 h of the initial bleeding.Factors might be related to SCV were analyzed.Results:Compared to patients without SCV,those with SCV(9.4%,12/128)had significantly higher Lp-PLA2 level.Multivariate logistic analysis revealed that worse modified Fisher grade(OR=10.08,95%CI=2.04–49.86,P=0.005)and higher Lp-PLA2 level(OR=6.66,95%CI=1.33–3.30,P=0.021)were significantly associated with SCV,even after adjustment for confounders.Based on the best threshold,Lp-PLA2 had a sensitivity of 83.3%and a specificity of 51.7%for predicting SCV,as shown by the receiver operating characteristic curve analysis.In the poor World Federation of Neurosurgical Societies grade patient sub-group,patients with Lp-PLA2>200μg/L had significantly higher SCV rate than that of patients having Lp-PLA2≤200μg/L.Conclusion:The admission Lp-PLA2 level might be a helpful predictor for SCV in aSAH.

关键词： Aneurysmal subarachnoid hemorrhage Vasospasm Biological markers

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Characteristic expression of γ-aminobutyric acid and glutamate decarboxylase in rat jejunum and its relation to differentiation of epithelial cells

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World Journal of Gastroenterology 2004年第24期10卷 3608-3611页

作者： fang-yu wang Masahito Watanabe Ren-Min Zhu Kentaro Maemura Department of Anatomy Osaka Medical CollegeOsaka 659-8686Japan

AIM: To investigate the expression between γ-aminobutyric acid (GABA) and glutamate decarboxylase and its relation with differentiation and maturation of jejunal epithelial cells in rat jejunum.METHODS: Immunohistochemical expression of GABA and glutamate decarboxylase (GAD, including two isoforms,GAD65 and GAD67) was investigated in rat jejunum.Meanwhile, double staining was performed with GAD65 immunohistochemistry, followed by lectin histochemistry of fluorescent wheat germ agglutinin. Furthermore,evaluation of cell kinetics in jejunum was conducted by ^3Hthymidine autoradiography and immunohistochemistry using a monoclonal antibody to proliferating cell nuclear antigen (PCNA).RESULTS: The cells showing positive immunoreactivity GABA and GAD65 were mainly distributed in the villi in rat jejunum, while jejunal epithelial cells were negative for GAD67. Positive GABA or GAD65 staining was mainly located in the cytoplasm and along the brush border of epithelial cells in the middle and upper portions. In addition, a few GABA and GAD65 strongly positive cells were scattered in the upper two thirds of jejunal villi. Double staining showed that GAD65 immunoreactivity was not found in goblet cells.^3H-thymidine-labeled nuclei were found in the lower and middle portions of jejunal crypts, which was consistent with PCNA staining. Therefore, GABA and GAD65 were expressed in a maturation or functional zone.CONCLUSION: The characteristic expression of GABA and GAD suggests that GABA might be involved in regulation of differentiation and maturation of epithelial cells in rat jejunum.

关键词：特性表达 γ-氨基丁酸谷氨酸脱羧酶老鼠空肠上皮细胞消化系统 GABA

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Unfavorable outcome of antiviral therapy in cytomegaloviruspositive ulcerative colitis may be due to inappropriate study inclusion in meta-analysis

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World Journal of Gastroenterology 2015年第5期21卷 1689-1690页

作者： Xiao-Wei Wu Miao-fang Yang Nan Li fang-yu wang Department of Gastroenterology and Hepatology Jinling HospitalMedical School of Nanjing University

Some previous articles reported that antiviral treatment was effective to reduce the colectomy rate in ulcerative colitis(UC) patients with cytomegalovirus(CMV) infection.Kopylov et al recently carried out a systematic review and meta-analysis to evaluate the impact of antiviral therapy on CMV-positive UC.The results showed that patients who received antiviral treatmenthad a higher risk of 30-d colectomy.We found that in this meta-analysis,some studies were inappropriately included,leading to an unfavorable outcome of antiCMV therapy in UC patients.

关键词： Ulcerative colitis Cytomegalovirus Antiviral thera

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Confusing untypical intestinal Behcet's disease:Skip ulcers with severe lower gastrointestinal hemorrhage

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World Journal of Gastrointestinal Endoscopy 2014年第1期6卷 27-31页

作者： Zhen-Kai wang Hui Shi Shao-Dong wang Jiong Liu Wei-Ming Zhu Miao-fang Yang Chan Liu Heng Lu fang-yu wang Department of Gastroenterology and Hepatology Jinling Hospital Department of General Surgery Jinling Hospital

Behcet's disease(BD) is a rare and life-long disorder characterized by inflammation of blood vessels throughout the body. BD was originally described in 1937 as a syndrome involving oral and genital ulceration in addition to ocular inflammation. Intestinal BD refers to colonic ulcerative lesions documented by objective measures in patients with BD. Many studies have shown that over 40% of BD patients have gastrointestinal complaints. Symptoms include abdominal pain, diarrhea, nausea, anorexia and abdominal distension. Although gastrointestinal symptoms are common, the demonstration of gastrointestinal ulcers is rare. This so-called intestinal BD accounts for approximately 1% of cases. There is no specific test for BD, and the diagnosis is based on clinical criteria. The manifestations of intestinal BD are similar to those of other colitis conditions such as Crohn's disease or intestinal tuberculosis, thus, it is challenging for gastroenterologists to accurately diagnose intestinal BD in patients with ileocolonic ulcers. However, giant ulcers distributed in the esophagus and ileocecal junction with gastrointestinal hemorrhage are rare in intestinal BD. Here, we present a case of untypical intestinal BD. The patient had recurrent aphthous ulceration of the oral mucosa, and esophageal and ileo-colonic ulceration, but no typical extra-intestinal symptoms. During examination, the patient had massive acute lower gastrointestinal bleeding. The patient underwent ileostomy after an emergency right hemicolectomy and partial ileectomy, and was subsequently diagnosed with incomplete-type intestinal BD by pathology. The literature on the evaluation and management of this condition is reviewed.

关键词： Intestinal Behcet’s disease Hemorrhage Skip ulcers

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Helicobacter pylori infection and inflammatory bowel disease in Asians:A meta-analysis

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World Journal of Gastroenterology 2015年第15期21卷 4750-4756页

作者： Xiao-Wei Wu Hong-Zan Ji Miao-fang Yang Lin Wu fang-yu wang Department of Gastroenterology and Hepatology Jinling Hospital Medical School of Nanjing University

AIM: To investigate the relationship between Helicobacter pylori infection and inflammatory bowel disease(IBD) in an Asian population.METHODS: The Pub Med, EMBASE, and CochraneLibrary databases were searched for observational studies published up until June 2014, without language restrictions. Additional references were obtained from reviewed articles. RESULTS: Ten studies involving 1299 IBD patients and 1817 controls were included in the meta-analysis(24.9% of IBD patients had H. pylori infection vs 48.3% of the controls). The pooled risk ratio for H. pylori infection in IBD patients compared with controls was 0.48(95%CI: 0.43-0.54; P < 0.001). There was no significant heterogeneity in the included studies(I2= 21%). Egger's linear regression indicated that there was no significant publication bias(P = 0.203).CONCLUSION: The H. pylori infection rate in Asian IBD patients is significantly lower than in non-IBD patients, indicating that infection protects against the development of IBD.

关键词： Asian population Crohn's disease Helicobacterpylori Inflammatory bowel disease Meta-analysis Ulcerative colitis

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Histopathological and genetic differences between polypoid and non-polypoid submucosal colorectal carcinoma

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World Journal of Gastroenterology 2007年第14期13卷 2048-2052页

作者： Ichiro Hirata fang-yu wang Mitsuyuki Murano Takuya Inoue Ken Toshina Takashi Nishikawa Kentaro Maemura Department of Gastroenterology Fujita Health University Japan Department of Gastroenterology Jinling Hospital Nanjing University School of Medicine Nanjing 210000 Jiangshu Province China Second Department of Internal medicine Osaka medical College Japan Department of Anatomy Osaka Medical College Japan

瞄准：调查水虫息似的生长(PG ) 和非水虫息似的生长(NPG ) 之间的组织病理学说、基因的差别粘膜下层的侵略肤色表面的癌(CRC ) 。方法：粘膜下层 CRC 的 96 个案例的一个总数根据他们的生长类型被划分成二个组；PG 的 60 个案例和 NPG ... 详细信息

瞄准：调查水虫息似的生长(PG ) 和非水虫息似的生长(NPG ) 之间的组织病理学说、基因的差别粘膜下层的侵略肤色表面的癌(CRC ) 。方法：粘膜下层 CRC 的 96 个案例的一个总数根据他们的生长类型被划分成二个组；PG 的 60 个案例和 NPG 的 36 个案例。尺寸，发育异常的组织学的度，粘膜下层侵略的深度和淋巴节点转移在二个组之间被比较。而且， p53 的表示被免疫检测组织化学的染色，并且 K 地岬基因变化被聚合酶链反应检验基于的单个海滨的符合构造多型性(SSCP ) 。结果：在 NPG 组的损害的平均尺寸是比在 PG 组的那些显著地小的(7.5 公里对 13.8 公里， P < 0.001 ) 。当粘膜下层的巨大的侵略和淋巴节点转移的发生比在 PG 组在 NPG 类型更高显著地是两个时，发育异常的组织学的度趋于在 NPG 组更严重(64.3% 对 43.3% ， P = 0.004；43% 对 7% ， P = 0.008，分别地) 。另外， K 地岬基因变化在 NPG 组在 PG 组，而是没有在 67% 损害被检测，当在组织化学的表示在二之间被发现的 p53 免疫的差别都不组织时。结论：与 PG 粘膜下层的 CRC 相比， NPG 类型表明更经常的粘膜下层的巨大的侵略，更多的淋巴节点转移和更高的度发育异常。遗传上， NPG 类型显示出更不经常的 K 地岬变化。

关键词：突出膨大型非突出膨大粘膜下结肠直肠癌组织病理遗传差异

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Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies

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Cancer Biology & Medicine 2024年第1期21卷 45-64页

作者： Jiawen Zhang Sihui yu Qiao Peng Ping wang Lan fang Tongji University Cancer Center Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China Reproductive Medicine Center Department of Obstetrics and GynecologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China Department of Obstetrics and Gynecology Zhongshan HospitalFudan UniversityShanghai 200032China

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.

关键词： cGAS-STING pathway type I interferon cyclic dinucleotide STING agonist cancer immunotherapy

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No Incidence of Liver Cancer Was Observed in A Retrospective Studyof Patients with Aristolochic Acid Nephropathy

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Chinese Journal of Integrative Medicine 2024年第2期30卷 99-106页

作者： SU Tao fang Zhi-e GUO yu-ming wang Chun-yu wang Jia-bo JI Dong BAI Zhao-fang YANG Li XiAO Xiao-he Renal Division Department of MedicinePeking University First HospitalBeijing(100034)China Department of Pharmacy Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Department of Hepatology Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Phase I Clinical Trials Unit Department of Medicine for Infectious DiseasesFifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Department of Pharmacy Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250000)China National Key Laboratory of Kidney Diseases Beijing(100039)China

Objective:To assess the risk of aristolochic acid(AA)-associated cancer in patients with AA nephropathy(AAN).Methods:A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014.Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer.The primary endpoint was the incidence of liver cancer,and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.Results:A total of 337 patients diagnosed with AAN were included in this study.From the initiation of taking AA to the termination of follow-up,39 patients were diagnosed with cancer.No cases of liver cancer were observed throughout the entire follow-up period,with urinary cancer being the predominant type(34/39,87.17%).Logistic regression analysis showed that age,follow-up period,and diabetes were potential risk factors,however,the dosage of the drug was not significantly associated with urinary cancer.Conclusions:No cases of liver cancer were observed at the end of follow-up.However,a high prevalence of urinary cancer was observed in AAN patients.Establishing a direct causality between AA and HCC is challenging.

关键词： aristolochic acid hepatocellular carcinoma urinary cancer drug safety retrospective study

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