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Delivery of nitric oxide-releasing silica nanoparticles for in vivo revascularization and functional recovery after acute peripheral nerve crush injury

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Neural Regeneration Research 2022年第9期17卷 2043-2049页

作者： jung il lee Ji Hun Park Yeong-Rim Kim Kihak Gwon Hae Won Hwang Gayoung jung Joo-Yup lee Jeong-Yun Sun Jong Woong Park Jae Ho Shin Myoung-Ryul Ok Department of Orthopedic Surgery College of MedicineKorea UniversitySeoulRepublic of Korea Medical Sensor Biomaterial Research Institute Kwangwoon UniversitySeoulRepublic of Korea Center for Biomaterials Korea Institute of Science&TechnologySeoulRepublic of Korea Department of Materials Science and Engineering Seoul National UniversitySeoulRepublic of Korea Department of Orthopedic Surgery College of MedicineCatholic UniversitySeoulRepublic of Korea Department of Chemistry Kwangwoon UniversitySeoulRepublic of Korea

Nitric oxide(NO)has been shown to promote revascularization and nerve regeneration after peripheral nerve injury.However,in vivo application of NO remains challenging due to the lack of stable carrier materials capable of storing large amounts of NO molecules and releasing them on a clinically meaningful time scale.Recently,a silica nanoparticle system capable of reversible NO storage and release at a controlled and sustained rate was introduced.In this study,NO-releasing silica nanoparticles(NO-SNs)were delivered to the peripheral nerves in rats after acute crush injury,mixed with natural hydrogel,to ensure the effective application of NO to the lesion.Microangiography using a polymer dye and immunohistochemical staining for the detection of CD34(a marker for revascularization)results showed that NO-releasing silica nanoparticles increased revascularization at the crush site of the sciatic nerve.The sciatic functional index revealed that there was a significant improvement in sciatic nerve function in NO-treated animals.Histological and anatomical analyses showed that the number of myelinated axons in the crushed sciatic nerve and wet muscle weight excised from NO-treated rats were increased.Moreover,muscle function recovery was improved in rats treated with NO-SNs.Taken together,our results suggest that NO delivered to the injured sciatic nerve triggers enhanced revascularization at the lesion in the early phase after crushing injury,thereby promoting axonal regeneration and improving functional recovery.

关键词： crush injury nerve injury,nerve regeneration nitric oxide peripheral nerve revascularization silica nanoparticles

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Value of controlled attenuation parameter in fibrosis prediction in nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2019年第33期25卷 4959-4969页

作者： jung il lee Hyun Woong lee Kwan Sik lee Department of Internal Medicine Gangnam Severance Hospital Yonsei University College of Medicine

BACKGROUND Liver stiffness measurement(LSM)tends to overestimate fibrosis stage in nonalcoholic fatty liver disease(NAFLD).Controlled attenuation parameter(CAP),provided by LSM device,has been introduced for noninvasive quantification of hepatic steatosis.AIM To determine the role of CAP values in predicting liver fibrosis stage by LSM in nonalcoholic steatohepatitis(NASH).METHODS One hundred eighty-four patients with biopsy proven NASH had LSM and CAP evaluated at baseline.Among them,130 patients had 1-year follow up LSM and analyzed for the changes of LSM after pioglitazone or ursodeoxycholic acid(UDCA)treatment.RESULTS In Kleiner fibrosis stage F0-1,LSM values increased at higher CAP tertile(P=0.001),and in F2,at middle and higher tertiles(P=0.027).No difference across CAP tertiles was noticed in F3-4(P=0.752).Receiver operating characteristic curve for LSM cutoff in diagnosis of F≥2 identified 8.05 kPa for lower CAP tertile,9.35 kPa for middle,and 10.55 kPa for high tertile.When changes in proportion of significant fibrosis(F≥2)were assessed among pioglitazone and UDCA treated patients considering CAP values,pioglitazone treated patients demonstrated decrease in proportion of high LSM.CONCLUSION In patient with NAFLD,interpretation of LSM in association with CAP scores may provide helpful information sparing unnecessary liver biopsy.

关键词： Fibroscan Controlled attenuation parameter Liver stiffness Nonalcoholic steatohepatitis Liver fibrosis

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Prognosis of hepatocellular carcinoma expressing cytokeratin 19:Comparison with other liver cancers

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World Journal of Gastroenterology 2012年第34期18卷 4751-4757页

作者： jung il lee Jin-Woo lee Joon Mee Kim Ja Kyung Kim Hyun jung Chung Young Soo Kim Department of Internal Medicine School of MedicineInha UniversityIncheon 400-711South Korea Department of Pathology School of MedicineInha UniversityIncheon 400-711South Korea Department of Internal Medicine Yonsei University College of MedicineGangnam Severance HospitalSeoul 135-720South Korea

AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively). Predictors of outcome after the surgery of prima

关键词： Cytokeratin 19 Hepatocellular 癌 Intrahepatic cholangiocarcinoma 肝癌症 Hepatectomy

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Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice:effects of 4-aminopyridine

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Neural Regeneration Research 2023年第2期18卷 439-444页

作者： jung il lee M A Hassan Talukder Zara Karuman Anagha A.Gurjar Prem Kumar Govindappa Jagadeeshaprasad M.Guddadarangaiah Kristen M.Manto Grant D.Wandling John P.Hegarty David L.Waning John C.Elfar Department of Orthopaedics and Rehabilitation Center for Orthopaedic Research and Translational ScienceThe Pennsylvania State University College of MedicineHersheyPAUSA Department of Orthopaedic Surgery Korea University Guro HospitalSeoulSouth Korea Department of Cellular and Molecular Physiology The Pennsylvania State University College of MedicineHersheyPAUSA

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine(4-AP),a potassium channel blocker,on functional recove ry and muscle atrophy after sciatic nerve crush injury in rodents.However,this effect of 4-AP is unknown in nerve transection,gap,and grafting models.To evaluate and compare the functional recovery,nerve morphology,and muscle atrophy,we used a novel stepwise nerve transection with gluing(STG),as well as 7-mm irreparable nerve gap(G-7/0)and 7-mm isografting in 5-mm gap(G-5/7)models in the absence and presence of 4-AP treatment.Following surgery,sciatic functional index was determined wee kly to evaluate the direct in vivo global motor functional recovery.After 12 weeks,nerves were processed for whole-mount immunofluorescence imaging,and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber crosssectional area and minimal Feret's diameter.Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model.4-AP did not affect the sciatic functional index recovery in any model.Compared to STG,nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting.While muscle weight,cross-sectional area,and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7,4-AP treatment significantly increased right TA muscle mass,cross-sectional area,and minimal Feret's diameter in G-7/0 model.These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap,and 4-AP exerts diffe rential effects on functional recove ry and muscle atrophy.

关键词： 4-aminopyridine functional recovery muscle atrophy nerve gap nerve grafting nerve imaging nerve transection

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Does the bile duct angulation affect recurrence of choledocholithiasis?

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World Journal of Gastroenterology 2011年第36期17卷 4118-4123页

作者： Dong Beom Seo Byoung Wook Bang Seok Jeong Don Haeng lee Shin Goo Park Yong Sun Jeon jung il lee Jin-Woo lee Division of Gastroenterology Department of Internal MedicineInha University School of MedicineIncheon 400-711South Korea Division of Gastroenterology Department of Internal Medicine and Center for Advanced Medical Education by BK21 ProjectInha University School of Medicineand Utah-Inha DDS and Advanced Therapeutics Research CenterIncheon 400-711South Korea Department of Occupational and Environmental Medicine Inha University School of MedicineIncheon 400-711South Korea Department of Radiology Inha University School of MedicineIncheon400-711South Korea

AIM:To investigate whether bile duct angulation and T-tube choledochostomy influence the recurrence of choledocholithiasis.METHODS:We conducted a retrospective study including 259 patients who underwent endoscopic sphincterotomy and cholecystectomy for choledocholithiasis between 2000 and 2007.The imaginary line was drawn along the center of the bile duct and each internal angle was measured at the two angulation sites ofthe bile duct respectively.The values of both angles were added together.We then tested our hypothesis by examining whether T-tube choledochostomy was performed and stone recurrence occurred by reviewing each subject's medical records.RESULTS:The overall recurrence rate was 9.3% (24 of 259 patients).The mean value of sums of angles in the recurrence group was 268.3°± 29.6°,while that in the non-recurrence group was 314.8°± 19.9° (P ile that of the non T-tube group was 4.6% (7 of 152) (P ile duct angulation and T-tube choledochostomy may be risk factors of recurrence of bile duct stones.

关键词：胆总管结石复发率胆管平均价值危险因素患者切除术括约肌

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Giant choledocholithiasis treated by mechanical lithotripsy using a gastric bezoar basket

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World Journal of Gastroenterology 2012年第25期18卷 3327-3330页

作者： Hyun jung Chung Seok Jeong Don Haeng lee jung il lee Jin-Woo lee Byoung Wook Bang Kye Sook Kwon Hyung Kil Kim Yong Woon Shin Young Soo Kim Division of Gastroenterology Department of Internal MedicineInha University School of MedicineIncheon 400-711South Korea

Mechanical lithotripsy(ML) is usually considered as a standard treatment option for large bile duct stones.However,it is impossible to retrieve oversized stones because the conventional lithotripsy basket may not be able to grasp the stone.However,there is no established endoscopic extraction method for such giant stone removal.We describe a case of successful extraction of a 4-cm large stone using a gastric bezoar basket.A 78-year-old woman had suffered from upper abdominal pain for 20 d.Contrast-enhanced computed tomogram revealed a 4-cm single stone in the distal common bile duct(CBD).Endoscopic stone retraction was decided upon and endoscopic papillary balloon dilation was performed using a large balloon.An attempt to capture the stone using a standard lithotripsy basket failed due to the large stone size.Subsequently,we used a gastric bezoar basket to successfully capturethe stone.The stone was fragmented into small pieces and extracted.The stone was completely removed after two sessions of endoscopic retrograde cholangiopancreatography;each of which took 30 min.No complications occurred during or after the procedure.The patient was fully recovered and discharged on day 11 of hospitalization.ML using a gastric bezoar basket is a safe and effective retrieval method in select cases,and is considered as an alternative nonoperative option for the management of difficult CBD stones.

关键词：胆总管结石手术治疗碎石机械粪胃提取方法使用标准

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Complete remission of advanced hepatocellular carcinoma by sorafenib: A case report

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World Journal of Gastrointestinal Oncology 2013年第2期5卷 38-42页

作者： Min Su Kim Young-Joo Jin Jin-Woo lee jung-il lee Young soo Kim Sun young lee Myoung Hun Chae Department of Internal Medicine Inha University HospitalInha University School of Medicine

Hepatocellular carcinoma (HCC) is the fifth most common malignant disease worldwide, and curative treatment remains difficult because the majority of cases are diagnosed in the advanced stage. Sorafenib is the only known effective systemic treatment, but patients rarely achieve complete remission (CR). A 66-year-old man with a history of alcoholic liver cirrhosis with a diagnosis of advanced HCC, was initially treated with transarterial chemoembolization on four occasions. However, the disease progressed with portal vein thrombosis. Therefore, sorafenib was started, and 4 mo later, the patient achieved CR. The treatment was continued for 12 mo, and CR was maintained up to 4 mo after sorafenib discontinuation.

关键词： Hepatocellular carcinoma Sorafenib Portal vein thrombosis Complete remission

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从铜合金渣中选择性回收锡及其热处理合成SnO_2(英文)

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Transactions of Nonferrous Metals Society of China 2014年第S1期24卷 157-161页

作者： jung-il lee Jong Bum PARK Tae Wan KIM Man-Sik KONG Jeong Ho RYU Department of Materials Science and Engineering Korea National University of Transportation Functional Materials Research Team Advanced Materials & Processing Center Institute for Advanced Engineering Yongin Gyunggi 449-863 Korea

采用选择性溶解方法对铜合金废渣中的锡进行富集和分离。使用HNO3溶液溶解铜合金废渣,渣中的锡不会溶解从而使其从中得到分离。通过离心分离生成的H2SnO3沉淀相,然后经过干燥加热生成SnO2粉末。对SnO2粉末的相组成、表面形貌和化学成分... 详细信息

采用选择性溶解方法对铜合金废渣中的锡进行富集和分离。使用HNO3溶液溶解铜合金废渣,渣中的锡不会溶解从而使其从中得到分离。通过离心分离生成的H2SnO3沉淀相,然后经过干燥加热生成SnO2粉末。对SnO2粉末的相组成、表面形貌和化学成分进行分析。

关键词：回收锡铜合金渣选择性溶解二氧化锡

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Expression of Ki-67,p53,and K-ras in chronic pancreatitis and pancreatic ductal adenocarcinoma

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World Journal of Gastroenterology 2005年第43期11卷 6765-6769页

作者： Seok Jeong Don Haeng lee jung il lee Jin-Woo lee Kye Sook Kwon Pum-Soo Kim Hyung Gil Kim Yong Woon Shin Young Soo Kim Young Bae Kim Division of Gastroenterology Department of Pathology

AIM: To examine surgical specimens of pancreas with either chronic pancreatitis or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia in pancreas represent precursor lesions for pancreatic cancer.METHODS: We examined expression of Ki-67, CEA,p53, and K-ras, in the surgical specimens of pancreas with adenocarcinomas (n = 11) and chronic pancreatitis (n = 12). Cellular proliferation was assessed by Ki-67proliferation index using the proliferation marker Ki-67.In specimens with pancreas cancer, we divided pancreas epithelium into normal (n=7), ductal hyperplasia (n=3), dysplasia (n=4), and cancerous lesion (n=11) after hematoxylin and eosin staining, Ki-67, and CEA immunohistochemical staining. In cases with chronic pancreatitis, the specimen was pathologically examined as in cases with pancreas cancer, and they were also determined as normal (n=10), ductal hyperplasia (n=4), or dysplasia (n= 5). p53 and K-ras expression were also studied by immunohistochemical staining.RESULTS: In pancreatic cancer, the Ki-67 index was 3.73±3.58 in normal site, 6.62±4.39 in ductalhyperplasia, 13.47±4.02 in dysplasia and 37.03±10.05in cancer tissue, respectively. Overall, p53 was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 14 (0%), 0 of 7 (0%), 7 of 9 (78%),and 10 of 11 (91%), respectively, and K-ras was positive in 0 of 8 (0%), 1 of 3 (33%), 4 of 6 (67%), 4 of 5 (80%),respectively.CONCLUSION: Our results favorably support the hypothesis that ductal hyperplasia and dysplasia of the pancreas might be precursor lesions for pancreas cancer.Further evaluation of oncogenes by the molecular study is needed.

关键词： Ki-67 p53 K-ras 基因表达慢性胰腺炎胰腺导管癌

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Esophageal mucosal metastasis from adenocarcinoma of the distal stomach

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World Journal of Gastroenterology 2013年第23期19卷 3699-3702页

作者： Sung-Ho Ki Seok Jeong In Suh Park Don Haeng lee jung il lee Kye Sook Kwon Hyung Gil Kim Yong Woon Shin Division of Gastroenterology Department of Internal Medicine Pohang St. Mary's HospitalPohang 790-825 South Korea Division of Gastroenterology Department of Internal Medicine Inha University School of MedicineIncheon 400-711 South Korea Department of Pathology Inha University School of MedicineIncheon 400-711 South Korea Center for Advanced Medical Education by BK21 Project Inha University School of Medicine Utah-Inha DDS and Advanced Therapeutics Research CenterIncheon 400-711 South Korea

Dissemination of gastric cancer may usually occur by direct spread through the perigastric tissues to adjacent organ, lymphatic spread, and hematogenous spread. We report a rare case of gastric cancer with mucosal metastastic lesion on the upper esophagus that was diagnosed by endoscopy and endosonography. A biopsy of the esophageal mass was performed and the pathologic findings with immunohistochemical stain for Mucin-5AC are proved to be identical to that of gastric adenocarcinoma, suggesting metastasis from main lesion of the gastric cancer. The lesion could not be explained by lymphatic or hematogenous spread,and its metastasis mechanism is considered to be different from previous studies. We suggest that the gastroesophageal reflux of cancer cells could be one of the possible metastatic pathways for metastasis of esophagus from an adenocarcinoma of the stomach.

关键词： Stomach cancer Neoplasm metastasis Esophagus

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