1.Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis
Wan-Sze HUNG ; Massimiliano GAETANI ; Yiran LI ; Zhouyurong TAN ; Xu ZHENG ; Ruizhe ZHANG ; Yang DING ; Gene Chi Wai Man ; Tao ZHANG ; Yi SONG ; Yao WANG ; Jacqueline Pui Wah Chung ; Hang-Tak CHAN ; Roman A.ZUBAREV ; Chiu-Chi WANG
Journal of Pharmaceutical Analysis 2024;14(1):100-114
Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.
2.Management and outcomes of gastric leak after sleeve gastrectomy: results from the 2010-2020 national registry.
Mengyi LI ; Na ZENG ; Yang LIU ; Xitai SUN ; Wah YANG ; Yanjun LIU ; Zhongqi MAO ; Qiyuan YAO ; Xiangwen ZHAO ; Hui LIANG ; Wenhui LOU ; Chiye MA ; Jinghai SONG ; Jianlin WU ; Wei YANG ; Pin ZHANG ; Liyong ZHU ; Peirong TIAN ; Peng ZHANG ; Zhongtao ZHANG
Chinese Medical Journal 2023;136(16):1967-1976
BACKGROUND:
Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting.
METHODS:
To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks.
RESULTS:
A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor.
CONCLUSIONS
Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans
;
Male
;
Retrospective Studies
;
Diabetes Mellitus, Type 2/complications*
;
Obesity, Morbid
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Anastomotic Leak/epidemiology*
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Gastrectomy/methods*
;
Reoperation/methods*
;
Registries
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Laparoscopy/methods*
;
Treatment Outcome
3.Effects and mechanisms of bariatric surgery on sexual function in males with obesity
Law SAIKAM ; Tse CHIWAI ; Keqi CHEN ; Jingwen CAI ; Wah YANG
Chinese Journal of Gastrointestinal Surgery 2023;26(11):1075-1081
Obesity has been identified as one of the risk factors for male sexual dysfunction, and it also has a certain impact on fertility. For people with obesity, sexual function is an important aspect of quality of life, but it is often overlooked. Society's stigma against obesity exacerbates the psychological stress of patients with obesity and negatively affects sexual function. Current studies have found that bariatric surgery can reduce body weight and improve sexual function in patients with obesity, and obesity-related gonadal dysfunction is also improved or even subsided after surgery. However, attention needs to be paid to postoperative body mass management and mental health status of patients to prevent postoperative body mass recovery and reversal of sex hormones and sexual function. In addition, there is still controversy about the change in sperm quality after bariatric surgery, and there is a lack of research data on sexual function and sperm parameters and mechanisms after bariatric surgery. Therefore, this article reviews the latest research progress of bariatric surgery and sexual dysfunction, as well as related mechanisms and sperm parameters, to provide a reference for bariatric surgery in patients with obesity with sexual dysfunction.
4.Effects and mechanisms of bariatric surgery on sexual function in males with obesity
Law SAIKAM ; Tse CHIWAI ; Keqi CHEN ; Jingwen CAI ; Wah YANG
Chinese Journal of Gastrointestinal Surgery 2023;26(11):1075-1081
Obesity has been identified as one of the risk factors for male sexual dysfunction, and it also has a certain impact on fertility. For people with obesity, sexual function is an important aspect of quality of life, but it is often overlooked. Society's stigma against obesity exacerbates the psychological stress of patients with obesity and negatively affects sexual function. Current studies have found that bariatric surgery can reduce body weight and improve sexual function in patients with obesity, and obesity-related gonadal dysfunction is also improved or even subsided after surgery. However, attention needs to be paid to postoperative body mass management and mental health status of patients to prevent postoperative body mass recovery and reversal of sex hormones and sexual function. In addition, there is still controversy about the change in sperm quality after bariatric surgery, and there is a lack of research data on sexual function and sperm parameters and mechanisms after bariatric surgery. Therefore, this article reviews the latest research progress of bariatric surgery and sexual dysfunction, as well as related mechanisms and sperm parameters, to provide a reference for bariatric surgery in patients with obesity with sexual dysfunction.
5.Coronary Intravascular Lithotripsy Versus Rotational Atherectomy in an Asian Population: Clinical Outcomes in Real-World Patients
Jie Jun WONG ; Sridharan UMAPATHY ; Yann Shan KEH ; Yee How LAU ; Jonathan YAP ; Muhammad IDU ; Chee Yang CHIN ; Jiang Ming FAM ; Boon Wah LIEW ; Chee Tang CHIN ; Philip En Hou WONG ; Tian Hai KOH ; Khung Keong YEO
Korean Circulation Journal 2022;52(4):288-300
Background and Objectives:
We compared real-world clinical outcomes of patients receiving intravascular lithotripsy (IVL) versus rotational atherectomy (RA) for heavily calcified coronary lesions.
Methods:
Fifty-three patients who received IVL from January 2017 to July 2020 were retrospectively compared to 271 patients who received RA from January 2017 to December 2018.Primary endpoints were in-hospital and 30-day major adverse cardiovascular events (MACE).
Results:
IVL patients had a higher prevalence of acute coronary syndrome (56.6% vs 24.4, p<0.001), multivessel disease (96.2% vs 73.3%, p<0.001) and emergency procedures (17.0% vs 2.2%, p<0.001) compared to RA. In-hospital MACE (11.3% vs 5.9%, p=0.152), MI (7.5% vs 3.3%, p=0.152), and mortality (5.7% vs 3.0%, p=0.319) were not statistically significant. 30-day MACE was higher in the IVL cohort vs RA (17.0% vs 7.4%, p=0.035). Propensity score adjusted regression using IVL was also performed on in-hospital MACE (odds ratio [OR], 1.677; 95% confidence interval [CI], 0.588–4.779) and 30-day MACE (OR, 1.910; 95% CI, 0.774–4.718).
Conclusions
These findings represent our initial IVL experience in a high-risk, real-world cohort. Although the event rate in the IVL arm was numerically higher compared to RA, the small numbers and retrospective nature of this study preclude definitive conclusions. Theseclinical outcomes are likely to improve with greater experience and better case selection, allowing IVL to effectively treat complex calcified coronary lesions.
6.The Prevalence and Predictors of Obstructive Sleep Apnea in Chinese Bariatric Surgery Candidates: A Single-Center Study
Wenhui CHEN ; Xiaotao ZHANG ; Chetan PARMAR ; Yucheng WANG ; Wah YANG ; Jiyang PAN ; Zhiyong DONG ; Cunchuan WANG
Journal of Metabolic and Bariatric Surgery 2021;10(1):14-22
Purpose:
The purpose of the study is to determine the prevalence and predictors of OSA in Chinese bariatric surgery candidates.
Materials and Methods:
The clinical data were collected from 326 patients evaluated for bariatric surgery and referred for polysomnography. Multiple logistic regression was used for identifying independent predictors of presence of OSA and ROC curve analysis to determine the best cut-off value for continuous variable.
Results:
Baseline BMI and age were 33.3±3.7 kg/m2 and 24.3±3.1 years. 62.9% of the patients fulfilled the diagnostic criteria for OSA; Of these, 22.7% had mild OSA; 11.3% had moderate OSA, and 28.8% had severe OSA. The prevalence was significantly higher in males (84.2%) than in females (47.3%) (P<0.001). The superobese patients and the obese patients aged older than 50 years that all of those were diagnosed with OSA. A multivariate logistic regression model displayed that increasing age, BMI and neck circumference together with presence of habitual snoring and male sex were identified as risk factors of OSA. The best cut-off values for the presence of OSA for age, BMI, neck circumference were 24.5 years, 39.45 kg/m2 , 40.40 cm.
Conclusion
The prevalence of OSA is very prevalent (62.9%) in Chinese bariatric surgery candidates, especially in male patients (84%). Age, BMI and neck circumference together with presence of habitual snoring and male sex are independent predictors of OSA in these patients. As clinical predictors are not enough to be a properly screening for OSA, routine PSG testing should be recommended to bariatric surgery candidates.
7.The Prevalence and Predictors of Obstructive Sleep Apnea in Chinese Bariatric Surgery Candidates: A Single-Center Study
Wenhui CHEN ; Xiaotao ZHANG ; Chetan PARMAR ; Yucheng WANG ; Wah YANG ; Jiyang PAN ; Zhiyong DONG ; Cunchuan WANG
Journal of Metabolic and Bariatric Surgery 2021;10(1):14-22
Purpose:
The purpose of the study is to determine the prevalence and predictors of OSA in Chinese bariatric surgery candidates.
Materials and Methods:
The clinical data were collected from 326 patients evaluated for bariatric surgery and referred for polysomnography. Multiple logistic regression was used for identifying independent predictors of presence of OSA and ROC curve analysis to determine the best cut-off value for continuous variable.
Results:
Baseline BMI and age were 33.3±3.7 kg/m2 and 24.3±3.1 years. 62.9% of the patients fulfilled the diagnostic criteria for OSA; Of these, 22.7% had mild OSA; 11.3% had moderate OSA, and 28.8% had severe OSA. The prevalence was significantly higher in males (84.2%) than in females (47.3%) (P<0.001). The superobese patients and the obese patients aged older than 50 years that all of those were diagnosed with OSA. A multivariate logistic regression model displayed that increasing age, BMI and neck circumference together with presence of habitual snoring and male sex were identified as risk factors of OSA. The best cut-off values for the presence of OSA for age, BMI, neck circumference were 24.5 years, 39.45 kg/m2 , 40.40 cm.
Conclusion
The prevalence of OSA is very prevalent (62.9%) in Chinese bariatric surgery candidates, especially in male patients (84%). Age, BMI and neck circumference together with presence of habitual snoring and male sex are independent predictors of OSA in these patients. As clinical predictors are not enough to be a properly screening for OSA, routine PSG testing should be recommended to bariatric surgery candidates.
8.Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy
Xu WU ; Chun YIN ; Jiang MA ; Stella CHAI ; Chunyuan ZHANG ; Sheng YAO ; Onat KADIOGLU ; Thomas EFFERTH ; Yang YE ; Kenneth Kin-Wah TO ; Ge LIN
Acta Pharmaceutica Sinica B 2021;11(7):1885-1902
Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of
9.Hyperinsulinemic Hypoglycemia after Bariatric Surgery
Songhao HU ; Hanlin TANG ; Huaxi WANG ; Zhiyong DONG ; Shuwen JIANG ; Cunchuan WANG ; Xiaomei CHEN ; Wah YANG
Journal of Metabolic and Bariatric Surgery 2020;9(1):1-6
Postprandial hyperinsulinemic hypoglycemia (PHH) is one of the serious complications after bariatric surgery, it can lead life-threatening neuroglycopenic symptoms, such as seizures, disorientation, impairment of version and loss of consciousness without any premonitory. The presentation, prevalence, diagnosis, pathology and treatment are reviewed in this summary.
10.Comparison between ABCD and IMS Scores in the Prediction of Long-Term T2DM Remission after Metabolic Surgery in East Asian Obese Patients
Masayuki OHTA ; Yosuke SEKI ; Sungsoo PARK ; Cunchuan WANG ; Wah YANG ; Kazunori KASAMA ;
Journal of Metabolic and Bariatric Surgery 2019;8(2):34-36
Recently, several scoring systems have been proposed to predict remission from type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of the prediction of long-term T2DM remission; however, which of the two scoring systems is better remains controversial. Thus, Three East Asian countries Metabolic Surgery (TEAMS), which has been organized as a study group since 2016, is conducting a retrospective, international, multi-institutional study to compare the two scoring systems in East Asian obese patients after metabolic surgery. The primary study objective is to compare the ABCD score with the IMS score at 3 and 5 years after sleeve gastrectomy (SG), Roux-en-Y gastric bypass, one anastomosis gastric bypass and SG with duodenojejunal bypass. The secondary objectives include evaluating patients who were good candidates for SG, and adjusting the IMS scoring system for East Asian patients.
Asian Continental Ancestry Group
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Bariatric Surgery
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Diabetes Mellitus, Type 2
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Gastrectomy
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Gastric Bypass
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Humans
;
Retrospective Studies

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