1.Progress of circulating tumor DNA methylation for gastric cancer screening and management
Qinxing CAO ; Li YAN ; Nengyi HOU ; Jinfeng CHEN ; Song YU ; Hejiang LU ; Zhenjia DAN ; Minghui PANG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):535-544
Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.
2.Increased Incidence of Severe Adverse Events in Non-Small Cell Lung Cancer Patients with Previous Tuberculosis Episode Treated with PD-1 Inhibitors
Zhang HUI ; Yuan JINFENG ; Xu YUANYUAN ; Yang MENGJIE ; Lyu JIALIN ; Yang XINJIE ; Sheng SHUYAN ; Qian ZHE ; Wang QUNHUI ; Pang YU ; Hu YING
Biomedical and Environmental Sciences 2024;37(7):785-789
Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs'effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.We compared outcomes and side effects between patients with and without prior TB.Of 116 patients(40 with TB history,76 without),prior TB didn't reduce treatment effectiveness but did increase severe side effects.Notably,older patients(≥65 years)faced a higher risk of severe side effects.Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs,stressing the need for careful monitoring and personalized care.
3.Progress of circulating tumor DNA methylation for gastric cancer screening and management
Qinxing CAO ; Li YAN ; Nengyi HOU ; Jinfeng CHEN ; Song YU ; Hejiang LU ; Zhenjia DAN ; Minghui PANG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):535-544
Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.
4.Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration.
Qiaozi WANG ; Yanan SONG ; Jinfeng GAO ; Qiyu LI ; Jing CHEN ; Yifang XIE ; Zhengmin WANG ; Haipeng TAN ; Hongbo YANG ; Ning ZHANG ; Juying QIAN ; Zhiqing PANG ; Zheyong HUANG ; Junbo GE
Acta Pharmaceutica Sinica B 2023;13(12):4999-5015
The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.
5.Clinical characteristics of 15 cases of renal transplantation with pre-exsiting donor-specific antibody
Hongzhao FAN ; Jia LIU ; Jiajia SUN ; Junxiang WANG ; Xinlu PANG ; Wenjun SHANG ; Guiwen FENG ; Jinfeng LI
Journal of Central South University(Medical Sciences) 2023;48(10):1583-1591
Objective:Currently,patients with pre-exsiting donor-specific antibody(DSA)are prone to antibody-mediated rejection(AMR)after surgery and are at a relatively high risk of postoperative complications and graft failure.The risk of postoperative complications and graft failure is relatively high.This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation,providing single-center treatment experience for DSA-positive kidney transplantation. Methods:We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022.Eight cases were organ donation after citizen's death(DCD)kidney transplant recipients,of which 3 cases in the early stage were not treated with preoperative desensitisation therapy(DCD untreated group,n=3),and 5 recipients were treated with preoperative rituximab desensitisation(DCD preprocessing group,n=5).The remaining 7 cases were living related donors recipients(LRD)who received preoperative desensitisation treatment with rituximab and plasma exchange(LRD preprocessing group,n=7).We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1,3 and 5 years,and to compare the differences in recovery and postoperative complications between 3 groups. Results:All 15 recipients were positive for preoperative panel reactive antibody(PRA)and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation.DCD untreated group all suffered from DSA level rebound,delayed renal graft function(DGF)and rejection reaction after surgery.After the combined treatment,DSA level was reduced and the graft renal function returned to normal.The DCD preprocessing group were all without antibody rebound,1 recipient developed DGF and the renal function returned to normal after plasmapheresis,and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation.In the LRD preprocessing group,2 cases had antibody rebound and 1 case had rejection,but all of them recovered to normal after treatment,and DSA was maintained at a low level or even disappeared.The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group;and there were no significant difference in the incidence of postoperative haematuria,proteinuria,bacterial and fungal infections,and BK virus infection between the 3 groups(all P>0.05).A total of 11 of the 15 recipients were followed up for more than 1 year,6 for more than 3 years,and 1 for more than 5 years,and the survival rates of both the recipients and the transplanted kidneys were 100%. Conclusion:Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.
6.Comparative analysis of single kidney transplantation for children between low weight and high weight pediatric donor
Hongchang XIE ; Ming YI ; Yonghua FENG ; Xianlei YANG ; Zhigang WANG ; Junxiang WANG ; Lei LIU ; Jinfeng LI ; Xinlu PANG ; Wenjun SHANG ; Guiwen FENG
Chinese Journal of Urology 2021;42(5):370-374
Objective:To compare the efficacy of single kidney transplantation for children from pediatric donors between body weight ≤15 kg and >15 kg.Methods:A retrospective review in 156 children with single donor kidney transplantation from August 2010 to December 2019 in the Kidney Transplantation Department of the First Affiliated Hospital of Zhengzhou University was conducted. The patients were classified into the small kidney group (pediatric donor body weight ≤15 kg) and the big kidney group (pediatric donor body weight >15 kg). In this study, 89 cases were concluded in the small kidney group and 67 cases were concluded in the big kidney group. The donor kidneys were obtained from 46 cases of small weight (≤15 kg) pediatric donors and 48 cases of large weight (>15 kg) pediatric donors. There were significant differences in age [1.00 (0.02 - 4.00) years vs. 10.00 (3.00-18.00) years], body weight [10.0 (3.4 - 15.0) kg vs. 35.0 (16.2- 35.0) kg], height [76 (50- 113) cm vs. 144 (67-172) cm], GFR [(31.50±7.46)ml/min vs. (36.79±7.00) ml/min], and renal length to diameter [(5.91±0.48) cm vs. (8.71±1.88) cm] between the small kidney group and the big kidney group ( P < 0.01). There was no significant difference between the two groups of donors in gender, cold/warm ischemia time and cause of death ( P>0.05). There were significant differences in age [(11.28±3.89) years vs. (13.86±3.56) years], body weight [(31.83±10.45)kg vs. (35.13±9.15) kg], and height [(130.02±28.56) cm vs. (143.97±16.59) cm] between recipients of the small kidney group and big kidney group ( P < 0.05). While there were no significant differences in preoperative serum creatinine level [(822.65 ± 135.04) μmol/L vs. (777.31 ± 165.40) μmol/L], HLA mismatch [(3.4 ± 1.4) site vs. (3.2±1.3) site], and primary disease between the two groups ( P > 0.05). The recovery of renal function, postoperative adverse events, postoperative children, and graft survival were compared between the two groups. Results:The renal function of the two groups of recipients returned to normal 3 months after operation. The perioperative complications in the small kidney group and the big kidney group mainly included renal delayed recovery [5.6% (5/89) vs. 7.5% (5/67), P=0.89], renal vascular embolization [3.4% (3/89) vs. 0, P=0.35], and acute rejection [2.2% (2/89) vs. 4.3% (3/67) , P=0.75]. The main cause of recipient death during the follow-up period was pulmonary infection [4.5% (4/89) vs. 6.0% (4/67) , P=0.68]. The postoperative small kidney group was followed up for an average of 30 (3-74) months. The survival rates of children in the small kidney group at the 1, 3 and 5 years after surgery were 96.6% (86/89), 91.0% (81/89) and 91.0%(81/89), while the transplanted renal survival rates were 92.1% (82/89), 86.5% (77/89) and 84.2% (75/89), respectively. The postoperative big kidney group was followed up for an average of 32 (4-89 ) months. The survival rates of children in the big kidney group were 95.5% (64/67), 94.0% (63/67) and 91.0%(61/67) in the first 1, 3 and 5 years postoperatively, while the graft survival rates were 92.5% (62/67), 83.6% (56/67) and 83.6% (56/67), respectively. The postoperative kidneys of two groups were fast-growing, and there was no significant difference between the small kidney group and the big kidney group in graft length to diameter [(9.63±0.31) cm vs. (9.75±0.71) cm] after 1 year ( P>0.05). Conclusions:The effect of single pediatric kidney transplantation for pediatric donor with body weight ≤15 kg is equivalent to that for pediatric donor with body weight >15 kg , which can be carried out clinically.
7.Evaluation with time-zero biopsy in donors with acute kidney function injury and clinical effect after transplantation
Kunlun ZHU ; Lei LIU ; Wenjun SHANG ; Xinlu PANG ; Zhigang WANG ; Yonghua FENG ; Junxiang WANG ; Jinfeng LI ; Xianlei YANG ; Guiwen FENG
Chinese Journal of Organ Transplantation 2021;42(12):717-722
Objective:To evaluate the time-zero biopsy of donor kidney with acute kidney injury(AKI)in organ donation donors and examine the clinical effect after transplantation.Methods:From May 2019 to May 2020, clinical data were retrospectively reviewed for 104 donors assessed by time-zero biopsy at First Affiliated Hospital, Zhengzhou University.According to the definition of AKI and Banff2016 criteria, the kidneys of 104 donors were grouped and evaluated for transplantation.And the post-transplantation effects of donor kidneys with different degrees of pathological changes were analyzed.Results:AKI occurred in 32/104 donors.Compared with non-AKI donors, statistically significant differences existed in degrees of renal interstitial fibrosis and acute renal tubular injury ( P<0.05). However, there were no significant differences in other pathological manifestations ( P>0.05). In AKI group, kidneys of 2 donors with Banff score>3 were abandoned; in non-AKI group, among 12 donors with Banff score>3, 1 donor kidney was abandoned due to a high degree of chronic diseases.No significant inter-group difference existed in creatinine value or estimated glomerular filtration rate(eGFR)( P>0.05). AKI group had a higher incidence of postoperative delayed graft function(DGF)and longer duration.There was no statistical significance in other complications ( P>0.05). Conclusions:AKI donor kidneys with pathological manifestations below moderate renal tubular injury and Banff score<3 are feasible for transplantation.Although renal function recovery is slow after transplantation, safe outcomes may be obtained.
8.Complications and efficacy of kidney transplantation in children and adolescents with infant donors
Hongchang XIE ; Ming YI ; Yonghua FENG ; Zhigang WANG ; Junxiang WANG ; Lei LIU ; Jinfeng LI ; Jianguo WEN ; Xinlu PANG ; Wenjun SHANG ; Guiwen FENG
Chinese Journal of Applied Clinical Pediatrics 2021;36(21):1614-1617
Objective:To retrospectively analyze clinical data of infant donors with body weight ≤15 kg into children recipients, and to investigate the efficacy and complications under the strategy of pediatric donor to pediatric recipient (PTP) of pediatric kidney transplantation allocation.Methods:Clinical data of kidney transplantation for children with infant donors performed in the First Affiliated Hospital of Zhengzhou University from August 2010 to December 2019 were collected.Clinical data of donors and recipients, postoperative adverse events, postoperative renal recovery, and human and renal survival were analyzed.Results:A total of 50 infant donors and 93 pediatric recipients were enrolled in this study.Recipients included 89 patients with single kidney transplantation (SKT) and 4 with en-bloc kidney transplantation (EBKT). The major perioperative complications were delayed graft function (DGF) (5 cases, 5.4%) and vascular thrombosis (VT) (3 cases, 3.2%), followed by recurrence of primary nephropathy (3 cases, 3.2%), respiratory tract infection (3 cases, 3.2%), and acute rejection (AR) (2 cases, 2.2%). During the follow-up period, the main cause of death was respiratory tract infection (4 cases, 4.3%). Except for the cause of death, the main causes of graft loss were rejection (2 cases, 2.2%) and recurrence of primary kidney disease (2 cases, 2.2%). Serum creatinine decreased progressively from (824.77±150.24) μmol/L preoperatively to (90.73±47.24) μmol/L 1 month postoperatively.In SKT group, the median follow-up time was 31 months (3-74 months), and the survival rates of recipients and transplanted kidneys at 1, 3 and 5 years postoperatively were 97.5%/94.2%, 96%/88.8% and 93.1%/86.1%, respectively.In EBKT group, the median follow-up time was 50 months (13-65 months), and the survival rates of recipients and transplanted kidneys at 1, 3 and 5 years postoperatively were all 100.0%.During the fo-llow-up period, there was no significant difference in the human/kidney survival rate between groups (all P>0.05), and well acceptable transplantation outcomes were obtained. Conclusions:Single/double kidney transplantation for children and adolescent recipients from infant donors in the First Affiliated Hospital of Zhengzhou University has achieved acceptable outcomes.Adopted by the PTP strategy, the incidence of complications after kidney transplantation does not increase, indicating its safety and reliability.
9.Therapeutic efficacy of plasmapheresis and intravenous immunoglobulin plus Rituximab for antibody-mediated rejection after kidney transplantation
Lixiang ZHAO ; Zhaoru HUANG ; Jinfeng LI ; Lei LIU ; Keke ZHANG ; Hongchang XIE ; Yonghua FENG ; Xinlu PANG ; Guiwen FENG ; Wenjun SHANG
Chinese Journal of Organ Transplantation 2019;40(8):468-472
Objective To compare the therapeutic efficacy of plasmapheresis (PP ) and intravenous immunoglobulin (IVIG) plus Rituximab for antibody-mediated rejection (AMR) after kidney transplantation .Methods From May 2015 to November 2018 ,a single-center retrospective cohort study was conducted for 540 recipients with high-resolution HLA undergoing kidney transplantation .According to the criteria of diagnosing AMR and patient selection ,20 patients were selected for PP+IVIG (group A ,n=12) ,PP+ IVIG+ Rituximab (group B ,n=8) .The efficacies and outcomes of two groups were compared .Results During a follow-up period of (12 .0 ± 5 .8 ) months ,no significant inter-group differences existed in basic profiles (P> 0 .05) .After AMR treatment ,serum creatinine levels decreased significantly from 283 .4 to 226 .4 μmol/L in group A (P=0 .001) and from 289 .4 to 166 .6 μmol/L in group B (P=0 .049) .And the magnitude of decline was more marked in group B (P=0 .023) .Meanwhile ,antibody MFI (log10) decreased from 3 .73 to 3 .62 in group A (P=0 .012) and from 3 .57 to 3 .02 in group B (P=0 .043) .At months 3 and 6 , serum creatinine level was lower in group B than that in group A (125 .0 vs .166 .1 μmol/L , P=0 .03 ;127 .0 vs .169 .0μmol/L ,P=0 .048) .The serum creatinine levels of AMR patients were 249 .8 and 233 .8 μmol/L respectively ( P= 0 .182 ) .Serum creatinine levels were 176 .1 and 120 .3 μmol/L ( P=0 .045) and 180 .2 and 114 .8 μmol/L at months 3 and 6 (P=0 .044) respectively .Serum creatinine levels were 202 .8 and 122 .5μmol/L (P=0 .049) in group A and 142 .7 and 107 .0μmol/L (P=0 .046) in group B respectively .Four recipients developed allograft failure .At month 6 post-operation ,AMR occurred in group A (n=3 ,25% ) and group B (n=1 ,12 .5% ) .And the incidence of leucopenia was 37 .5% and 0 (P=0 .049) in groups A and B respectively .Conclusions PP and IVIG plus rituximab is more efficacious for AMR .The earlier occurring time ,the better prognosis .
10.Shellfish/crustacean oral allergy syndrome among national service pre-enlistees in Singapore
Bernard Yu Hor THONG ; Shalini ARULANANDAM ; Sze Chin TAN ; Teck Choon TAN ; Grace Yin Lai CHAN ; Justina Wei Lyn TAN ; Mark Chong Wei YEOW ; Chwee Ying TANG ; Jinfeng HOU ; Khai Pang LEONG
Asia Pacific Allergy 2018;8(2):e18-
BACKGROUND: All Singaporean males undergo medical screening prior to compulsory military service. A history of possible food allergy may require referral to a specialist Allergy clinic to ensure that special dietary needs can be taken into account during field training and deployment. OBJECTIVE: To study the pattern of food allergy among pre-enlistees who were referred to a specialist allergy clinic to work up suspected food allergy. METHODS: Retrospective study of all pre-enlistees registered in the Clinical Immunology/Allergy New Case Registry referred to the Allergy Clinic from 1 August 2015 to 31 May 2016 for suspected food allergy. RESULTS: One hundred twenty pre-enlistees reporting food allergy symptoms other than rash alone were referred to the Allergy Clinic during the study period. Of these, 77 (64.2%) had food allergy. Among those with food allergy, mean age was 19.1 ± 1.5 years. They comprised predominantly Chinese (66.2%) and Malays (20.8%). The most commonly reported foods were shellfish/crustaceans (78%), peanut (15.6%), and egg (6.5%). Self-limiting oral allergy syndrome, OAS (itchy lips and throat with/without lip angioedema) was the most common manifestation (n = 33, 42.9%) followed by anaphylaxis (n = 23, 29.9%). Majority of OAS was from shellfish/crustacean (90.6%); of which shrimp (30.3%), crab (15.2%), and lobster (3.0%) were the most common. Mild childhood asthma (69.7%), allergic rhinitis (6.3%), and eczema (6.1%) were the most common atopic conditions among individuals with shellfish/crustacean OAS. This pattern was similar for shellfish/crustacean anaphylaxis. Skin prick tests were most commonly positive for shrimp (OAS 87.1% vs. anaphylaxis 100%), crab (OAS 95.8% vs. 90.9%), and lobster (OAS 91.7% vs. 63.6%). CONCLUSION: OAS to shellfish/crustaceans was more common than anaphylaxis among this study population of young males referred for food allergy symptoms other than rash alone.
Anaphylaxis
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Arachis
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Asian Continental Ancestry Group
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Asthma
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Eczema
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Exanthema
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Food Hypersensitivity
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Humans
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Hypersensitivity
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Lip
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Male
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Mass Screening
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Military Personnel
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Ovum
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Pharynx
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Referral and Consultation
;
Retrospective Studies
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Rhinitis, Allergic
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Shellfish
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Singapore
;
Skin
;
Specialization

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