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Parkin Interacts with the PDZ Domain of Multi-PDZ Domain Protein MUPP1 (Parkin과 Multi-PDZ Domain Protein (MUPP1) 단백질 간의 PDZ 결합)

  • Jang, Won Hee;Jeong, Young Joo;Choi, Sun Hee;Lee, Won Hee;Kim, Mooseong;Kim, Sang-Jin;Urm, Sang-Hwa;Moon, Il Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.24 no.8
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    • pp.820-826
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    • 2014
  • The localization to specific subcellular sites and the regulation of cell surface receptors and channels are crucial for proper functioning. Postsynaptic density-95/Disks large/Zonula occludens-1 (PDZ)-domain is involved in recognition of and interaction between various proteins, by which the localization and the regulation are mediated. Multi-PDZ domain protein 1 (MUPP1) contains 13 PDZ domains. MUPP1 serves a scaffolding function for structure proteins and signaling proteins, but the mechanism how MUPP1 is stabilized and signalized has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and Parkin. Parkin is an E3 ubiquitin ligase. Loss-of-function mutations of Parkin gene are known to cause an autosomal recessive juvenile parkinsonism. Parkin bound to the $12^{th}$ PDZ domain, but not to other PDZ domains of MUPP1. The C-terminal end of Parkin has a type II PDZ-association motif, which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. When co-expressed in HEK-293T cells, Parkin co-localized with MUPP1. When co-expressed with ubiquitin in HEK-293T cells, MUPP1 has been strongly ubiquitinated by Parkin. These findings collectively suggest that MUPP1 is a novel substrate of Parkin and its function or stability could be modulated by Parkin-mediated ubiquitination.

MicroRNA 155 Expression Pattern and its Clinic-pathologic Implication in Human Lung Cancer (폐암에서 microRNA 155의 발현 양상과 임상병리학적 의의)

  • Kim, Mi Kyeong;Moon, Dong Chul;Hyun, Hye Jin;Kim, Jong-Sik;Choi, Tae Jin;Jung, Sang Bong
    • Journal of Life Science
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    • v.26 no.9
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    • pp.1056-1062
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    • 2016
  • Lung cancer is currently the most common malignant disease and the leading cause of mortality in the world and non-small cell lung cancer (NSCLC) accounts for 75-80% of lung cancer cases. miR-155 gene was found to be over expressed in several solid tumors, such as thyroid carcinoma, breast cancer, colon cancer, cervical cancer, pancreatic ductal adenocarcinoma (PDAC) and lung cancer. The aims of this study were to define the expression of miR-155 in lung cancer and its associated clinic-pathologic characteristics. Total RNA was purified from formalin-fixed, paraffin-embedded NSCLC tissues and benign lung tissues. Expression of miR-155 in human lung cancer tissues were evaluated as mean fold changes of miR-155 in cancer tissues compared to benign lung tissues by quantitative real-time reverse transcriptase polymerase chain reaction (real-time qRT-PCR) and associations of miR-155 expression with clinic-pathologic findings of cancer. Compared with the benign control group, miR-155 expression was significantly overexpressed in NSCLCs (p=<0.001). miR-155 was more overexpressed in squamous cell carcinoma than in adenocarcinoma. Poorly differentiated tumors showed significantly overexpression of miR-155 than well-differentiated tumors (p=<0.001). Overexpression of miR-155 was significantly associated with lymph node metastasis (p=<0.05). In survival analysis for all NSCLC patients, high miR-155 expression was significantly correlated with worse overall survival (p=<0.05). These results suggested that miR-155 might play an important role in lung cancer progression and metastasis.

Inhibitory Effects of Tenebrio molitor Larvae Ethanol Extract on RANKL-Induced Osteoclast Differentiation (갈색거저리 유충 에탄올 추출물이 RANKL에 의해 유도되는 파골세포 분화에 미치는 영향)

  • Seo, Minchul;Baek, Minhee;Lee, Hwa Jeong;Shin, Yong Pyo;Lee, Joon Ha;Kim, In-Woo;Kim, Mi-Ae;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.30 no.11
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    • pp.983-989
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    • 2020
  • The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is key to bone health. An imbalance between osteoclasts and osteoblasts leads to various bone-related disorders, such as osteoporosis, osteomalacia, and osteopetrosis. However, the bone-resorption inhibitor drugs that are currently used may cause side effects. Natural substances have recently received much attention as therapeutic drugs for the treatment of bone health. This study was designed to determine the effect of Tenebrio molitor larvae ethanol extract (TME) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. To measure the effect of TME on osteoclast differentiation, RAW264.7 cells were treated with RANKL with or without TME for 5 days. The tartrate-resistant acid phosphatase (TRAP) activity was significantly inhibited by treatment of TME without cytotoxicity up to 2 mg/ml. In addition, TME effectively suppressed expression of osteoclast differentiation-related marker genes and proteins such as TRAP, NFATc1, and c-Src. TME also significantly inhibited the p38 mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and JNK signaling in RANKL-induced RAW264.7 cells. Consequently, we conclude that TME suppresses osteoclast differentiation by inhibiting RANKL-induced osteoclastogenic genes expression through the p38 MAPK signaling pathways. These results suggest that TME and its bioactive components are potential therapeutics for bone-related diseases such as osteoporosis.

Concurrence of Obstetric Brachial Plexus Injury, Congenital Muscular Torticollis and Cleft Palate (분만성 상완 신경총 손상, 선천성근성사경 및 구개열의 병발)

  • Lee, Han-Byul;Park, Myong-Chul;Kim, Chee-Sun;Han, Jae-Deok;Lee, Seung-Jae;Kim, Se-Yon;Yim, Shin-Young
    • Journal of Genetic Medicine
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    • v.8 no.1
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    • pp.71-75
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    • 2011
  • A male infant was diagnosed with obstetric brachial plexus injury, congenital muscular torticollis and cleft palate 17 days after birth. His mother presented with gestational diabetes and premature rupture of membranes. Although it is possible that these three disorders arose independently, it is very likely that all three have the same etiologic cause, and we propose that a possible mechanism for this concurrence is related to maternal gestational diabetes. Maternal hyperglycemia mostly affects fetal structures deriving from the neural crest, including the palatine bone, and may have caused the cleft palate observed in this case. Gestational diabetes is also associated with increased frequency of large for gestational age infants and, by extension, with increased risk of birth injuries such as obstetric brachial plexus injury or congenital muscular torticollis associated with large for gestational age infants. Since the children of mothers with gestational diabetes are at increased risk for congenital defects such as cleft palate as well as being large for gestational age, precautions indicated for each respective disorder must be taken during prenatal testing and during birth. However, further studies of more cases are required to evaluate whether the concurrence of obstetric brachial plexus injury, congenital muscular torticollis and cleft palate in this case are complications specifically associated with gestational diabetes or just a simple coincidence.

Radiotherapy for Locoregional Recurrent Cervix Cancer after Surgery (수술후 국소 재발된 자궁경부암의 방사선 치료)

  • Yang, Mi-Gyoung
    • Radiation Oncology Journal
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    • v.12 no.3
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    • pp.377-386
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    • 1994
  • Purpose: The role of radiotherapy in the management of patients with locoregional recurrent cervix cancer after radical surgery were retrospectively analyzed. Methods and materials: Twenty-eight patients treated with radiotherapy for locoregional recurrence after primary surgery for carcinoma of the cervix between 1989 and 1993 were analyzed. The median follow-up of survivors was 15 months (ranged 7-43 months). Eight patients had their disease confined to the vagina and 19 patients($68\%$) had pelvic mass as part of their locoregional recurrent disease. Within 24 months after the initial surgery, $82\%$ of recurrences manifested themselves. All patients had whole pelvic irradiation with or without intracavitary radiotherapy(ICR). Results: Complete response(CR) was achieved in 18 patients($54\%$). Five of eighteen patients($28\%$) with initial CR developed second locoregional recurrence. Response to radiotherapy correlated strongly with tumor volume, site of recurrence and total radiation dose. The overall 2 year survival rate was $43\%$ and the disease free survival was $31\%$. Survival rate was significantly influenced by the factors of interval from operation to recurrence, size and site of recurrent tumor, radiation dose, response of radiotherapy, lymph node status as initial presentation, The principal cause of death was lung metastasis($36\%$). Conclusion: Radiotherapy is an excellent modality for control of locoregional recurrent cervix cancer. To improve local control and survival rate, whole pelvic external radiotherapy in addition to ICR with more than 75.0Gy at the depth of 1.0cm from vaginal mucosa is needed and frequent follow up and early detection of recurrence is suggested as well.

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Seedling Emergence and Growth Affected by Priming and $GA_3$ Treatments to Three Campanulan Plant Seeds (Priming과 $GA_3$ 처리에 따른 도라지, 더덕 및 만삼의 출아(出芽)와 생장(生長))

  • Kang, Jin-Ho;Kim, Dong-Il;Kang, Shin-Yun;Shim, Young-Do;Han, Kyung-Soo
    • Korean Journal of Medicinal Crop Science
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    • v.5 no.4
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    • pp.307-313
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    • 1997
  • Seed germination test done in laboratory does not coincide with field emergence in general. The experiments were carried out to examine the effect of priming and $GA_3$, treatment to seeds of Platycodon grandiflorum; Codonopsis lanceolata and C. pilosula on lapsed time to first seedling emergence, seedling emergence, morphological characters and growth and the cause of poor emergence of C. pilosula. No-treatment as Control (water), priming or $GA_3$ treatment was done with only distilled water for 2 days, $CA(NO_3)_2$ 150 mM for 2 days or $GA_3$ 0.1 mM for 3 days, respectively. Seedling emergence rate was counted every 2 days but morphological characters and dry weight of shoot and root were measured on 38 days after sowing. Their internal seed structures were examined with Scanning Electron Microscope. C. pilosula had poorer seedling emergence rate than P grandiflorum and C. lanceolata showing nearly same rate: Compared to the other treatment (s) P. grandiflorum displayed higher rate in priming and $GA_3$, treatments but C. lanceolata or C. pilosula did the greatest rate in only $GA_3$ or priming treatment, respectively. $GA_3$ treatment to seeds of P. grandiflorum and C. lanceolata shortened the lapsed time to seedling emergence in comparison with Control, 2-days water imbibition before sowing. In all the species plant height and number of leaves per seedling became shorter and less in priming treatment than the other treatments except plant height of C. Pilosula while their hypocotyl length was nearly same in all treatments. Although priming treatment had nearly similar effect to morphological characters, $GA_3$ treatment forced greater shoot, root and aftermath total dry weight per seedling. Poor seedling emergence of C. pilosula was caused by its seed defect like cleavage or lack of embryo, poor development of embryo and endosperm or their separation.

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Removal of Arsenite by Nanocrystalline Mackinawite(FeS)-Coated Alumina (나노크기 매킨나와이트로 코팅된 알루미나에 의한 아비산염의 제거)

  • Lee, Seungyeol;Kang, Jung Chun;Park, Minji;Yang, Kyounghee;Jeong, Hoon Young
    • Journal of the Mineralogical Society of Korea
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    • v.26 no.2
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    • pp.101-110
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    • 2013
  • Due to the large specific surface area and great reactivity toward environmental contaminants, nanocrystalline mackinawite (FeS) has been widely applied for the remediation of contaminated groundwater and soil. Furthermore, nanocrystalline FeS is rather thermodynamically stable against anoxic corrosion, and its reactivity can be regenerated continuously by the activity of sulfate-reducing bacteria. However, nanocrystalline mackinawite is prone to either spread out along the groundwater flow or cause pore clogging in aquifers by particle aggregation. Accordingly, this mineral should be modified for the application of permeable reactive barriers (PRBs). In this study, coating methods were investigated by which mackinawite nanoparticles were deposited on the surface of alumina or activated alumina. The amount of FeS coating was found to significantly vary with pH, with the highest amount occurring at pH ~6.9 for both minerals. At this pH, the surfaces of mackinawite and alumina (or activated alumina) were oppositely charged, with the resultant electrostatic attraction making the coating highly effective. At this pH, the coating amounts by alumina and activated alumina were 0.038 and 0.114 $mmol{\cdot}FeS/g$, respectively. Under anoxic conditions, arsenite sorption experiments were conducted with uncoated alumina, uncoated activated alumina, and both minerals coated with FeS at the optimal pH for comparison of their reactivity. Uncoated activated alumina showed the higher arsenite removal compared to uncoated alumina. Notably, the arsenite sorption capacity of activated alumina was little changed by the coating with FeS. This might be attributed to the abundance of highly reactive hydroxyl functional groups (${\equiv}$AlOH) on the surface of activated alumina, making the arsenite sorption by the coated FeS unnoticeable. In contrast, the arsenite sorption capacity of alumina was found to increase substantially by the FeS coating. This was due to the consumption of the surface hydroxyl functional groups on the alumina surface and the subsequent occurrence of As(III) sorption by the coated FeS. Alumina, on the surface area basis, has about 8 times higher FeS coating amount and higher As(III) sorption capacity than silica. This study indicates that alumina is a better candidate than silica for the coating of nanocrystalline mackinawite.

Primer Evaluation for the Detection of Toxigenic Microcystis by PCR (독소 생성 Microcystis 검출을 위한 PCR primer의 평가)

  • 이현경;김준호;유순애;안태석;김치경;이동훈
    • Korean Journal of Microbiology
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    • v.39 no.3
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    • pp.166-174
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    • 2003
  • Microcystin produced by cyanobacteria in surface waters, such as eutrophic lake and river, is a kind of serious environmental problems due to its toxicity to human and wild animals. Microcystin is synthesized nonribosomally by the large modular multi-functional enzyme complex known as microcystin synthetase encoded by the mcy gene cluster. Amplification of mcy genes by PCR from cultures and environmental samples is a simple and efficient method to detect the toxigenic Microcystis. In order to evaluate primers designed to detect toxic microcystin-producing strains, 17 cyanobacterial strains and 20 environmental samples were examined by PCR with 7 pairs of primers. Some microcystin-producing cyanobacteria were not detected with FAA-RAA, TOX4F-TOX4R and FP-RP primers. The fragment of unexpected size was amplified with NSZW2-NSZW1 primers in Microcystis strains isolated from the lakes in Korea. TOX1P-TOX1F primers failed in amplification of toxin-producing strains. Only MSF-MSR and TOX2P- TOX2F primers amplified the fragments of mcy genes from 11 strains of microcystin-producing Microcystis. The water samples taken from 20 lakes in Korea were analyzed by PCR using each of the primers. In all the water samples, cyanobacteria capable of producing microcystin were detected by the PCR with TOX2P-TOX2F primers. These results indicate that TOX2P-TOX2F primers are better than the other primers for detection of microcystin-producing Microcystis strains in Korea. The nucleotide sequences of mcy gene in Microcystis aeruginosa NIER10010 suggest genetic diversity of Korean isolates.

Increase of Spoken Number of Syllables Using MIT(Melody Intonation Therapy) : Case Studies on older adult with stroke and aphasia (MIT(Melodic Intonation Therapy) 중심의 음악활동을 이용한 실어증을 가진 뇌졸중 노인의 음절 수 증가에 대한 사례 연구)

  • Hong, Do Kyoung
    • Journal of Music and Human Behavior
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    • v.2 no.2
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    • pp.57-67
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    • 2005
  • Most of stroke patients have not only physical difficulty but speech and neurological disorder because of hemiplegia and such unexpected changes cause psychologic disadaptability and absent-mindedness. Particularly, lowering of physical ability can lead to serious emotional problem from failure or frustration in daily life. Generally, treatment of patient with stroke put emphasis on physical rehabilitation but actually this patient had considerable speech disorder such as aphasia or articulation disorder. Moreover, failing of recognition function, mental disorder as hypochondria, and even visual and auditory disorder are represented. So it is effective to integrate verbal remediation and other treatments in medical care environment. In particular, patients with language disorder very often wither psychologically therefore it is efficient to use of music therapy that gives opulent emotion to aphasia patients. And primarily to investigate the effects of 10 sessions treatments; change in spoken total number of syllables, to confirm their own value by success of given task and reassure about themselves ability. All of 10 sessions stages were scored by MIT manual and its improvement were measured, that is, accomplishment was analyzed within each level in order to prove detail change of spoken total number of syllables. The result of this program organized from 2 syllables to 4 syllables is summarized as follows. Subject A completed in preliminary stage Level I, in 2 syllables case advanced to Level III in fifth session and to Level IV in seventh session, in 3 syllables case advanced to Level III in seventh session and to Level IV in ninth session, and in 4 syllables case showed 8% low success rate in first session but after repeated practice increased considerably in sixth session and in advanced to Level III in eighth session to Level IV in tenth session. Subject B also completed in preliminary stage Level I, in 2 syllables case advanced to Level III in forth session and to Level IV in sixth session, in 3 syllables case advanced to Level III in fifth session and to Level IV in seventh session, and in 4 syllables case showed 10% low success rate in first session and increased considerably in fifth session and in advanced to Level III in seventh session but could not reach to Level IV until tenth session. As a result, it was shown that music therapy using MIT was not statistically meaningful but improved spoken total number of syllables and success rate of task had improved as a whole. Therefore, music intervention using MIT it has positive affect on verbal ability of patients with Broca's Aphasia and their language rehabilitation.

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A Study on etiological factors, symptoms of a disease, and treatments of obesity based on Dong-Yi Bo Gam (동의보감(東醫寶鑑)을 위주(爲主)로한 비만의 원인(原因), 증상(症狀), 치료법(治療法) 연구)

  • Kim, Seok;Jin, Seng-Hee;Kim, Tae-Hee
    • The Journal of Korean Medicine
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    • v.19 no.2
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    • pp.125-136
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    • 1998
  • This study is on the etiological factors of the obesity, symptoms of a disease caused by the etiological factors and the method of medical treatment resulted from symptoms of a disease, it is based on Dong-Yi Bo Gam. The conclusion of this study is as follows. 1. The final metabolic of fat is depend on the defensive energy. The shape of fatty layer is changed by the point where the defensive energy is replenish or not. So 'Goin(暠人)' 'Bein(肥人)' and 'Yuckin(肉人)' is made a discriminated and there is defferent between 'Besudaeso(肥瘦大小)' and 'Herlqidaso(血氣多少)'. 2. Etiological factors of obesity is ; essential substance from cereals overcome the primodial energy, spleen and stomach are strong at once, spleen and stomach are weak at once, spleen is disturbed by evil energy, retention of phlegm and fluid, muscle is weak, blood is excess but energy (qi)is weak, hua-sid(華食) eating the sweat food very often, a rich fatty diet. 3. To investigate each syndrome as etiological factons, essential substance from cereals overcome primodial energy is divided into two case: one is the food increase itself because of the weakness of stomach energy (qi), the other is not to digest the food because liver overact spleen by seven emotion. The obesity because of strengthen of the spleen and stomach at once do not feel hungry very well and spleen and stomach do not damaged easily by overacting. The obesity because of weakness of spleen and stomach at once, and disturbace in spleen cause by evil energy, gain the weight even if they eat food a little. Also it is hard to move four limbs. Weakness of muscle is weakness of spleen and stomach. Weakness of muscle is caused by weakness of spleen and stomach. That is the case of faining the weight because of eating food with an empty stomach. The obsity caused by retention of fluid has intestine rumbling and gain the weight suddenly. 4. The method of medical treatment fallowing to the etiological factors: The food is inclined to increase itself caused by weakness of stomach energy, In case of the obseity caused by this phenomenon. We can use Decoction for Reinforcing Middle wanner and Replenishing Qi(補中益氣湯), five tastes il-going-san(左味異功散) and so on. The method of medical treatment on obsity caused by strengthen of spleen and stomach is not referred yet. But we must investigate about using peptic powder(平胃散), ji-chul-huan(枳朮丸) for strengthen of stomach qi (胃氣). If the obesity appear caused by weakness of spleen and stomach and disturbance in spleen as to evil energy, and in the same time stomach qi is weak, we can use li-gong san(異功散). If not only obesity but also indigestion, we can use Decoction for naurishing the stomach and promotion eating(養胃進食湯). If not only obesity but also weakness of spleen and stomach, we can use Decoction for Reinforcing Middle warmer and replenishing Qi(補中益氣湯). The energy being weak, we can use Decoction for six noble drugs(六君子湯). If the obesity appear because of retention of fluid, we can use sin-chul-huan(神朮丸). On the obesit, caused by excess of blood and weakness of qi(血管氣虛), there is not method of mectical treatment yet, but the method of medical treatment that we count of first important maybe to invigorate the spleen and the lung qi and to disperse and recitify the depressed liver energy(疏肝利氣). The method of medical treament about the obesity caused by a rich fatty diet is not mentioned yet, but it is important to improve the lifestyle of food and we think that invigorate the spleen, and the lung-qi(補疏肝氣) and disperse and recitify the depressed liver-energy (??肝利機) amy count of first important. 5.There is useful medicine for weight down for example Herb tea(茶), red bean, wax gourd, etc. 6.The etiological factors of the obesity that revive frequently is weakness of qi(氣虛), from 形成氣衰, deficiency of yang, hasty of qi, damp and so on. The symptoms and sign of a disease that revive frequently to the obesity is appoplexia(中風), leucorrhea, reddish and whitish turbid, feeling of fullness in the upper abdomen, diabetes and so on.

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