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Signal Transduction and Targeted Therapy 2020年第1期5卷 2332-2342页

作者： Daniel A.Luedtke Yongwei Su Jun Ma Xinyu Li Steven ABuck holly Edwards Lisa Polin Juiwanna Kushner Sijana HDzinic Kathryn White Hai Lin Jeffrey WTaub Yubin Ge Cancer Biology Graduate Program Wayne State University School of MedicineDetroitMI 48201USA School of Life Sciences Jilin University130021 ChangchunChina Division of Pediatric Hematology and Oncology Children’s Hospital of MichiganDetroitMIUSA48201 Department of Pediatrics Wayne State University School of MedicineDetroitMI 48201USA Department of Oncology Wayne State University School of MedicineDetroitMI 48201USA Molecular Therapeutics Program Karmanos Cancer InstituteWayne State University School of MedicineDetroitMI 48201USA Department of Hematology and Oncology The First Hospital of Jilin University130021 ChangchunChina

Venetoclax,an FDA-approved Bcl-2 selective inhibitor for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia(AML),is tolerated well in elderly patients with AML and has good overall response rates;however,resistance remains a *** this study,we show that targeting CDK9 with voruciclib in combination with venetoclax results in synergistic antileukemic activity against AML cell lines and primary patient ***9 inhibition enhances venetoclax activity through downregulation of Mcl-1 and ***,downregulation of Mcl-1 is transient,which necessitates an intermittent treatment schedule to allow for repeated downregulation of ***,an every other day schedule of the CDK9 inhibitor is effective in vitro and in vivo in enhancing the efficacy of *** preclinical data provide a rationale for an intermittent drug administration schedule for the clinical evaluation of the combination treatment for AML.

关键词： venetoclax clinical CDK9

Inhalation Bioaccessibility of Potentially Toxic Metals in Tobacco Snuff and Related Exposure Risks

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Journal of Environmental Protection 2021年第4期12卷 237-248页

作者： Boisa Ndokiari Brown holly Odinga Tamuno-Boma Cookey Julie Department of Chemistry Rivers State University Port Harcourt Nigeria Department of Medical Laboratory Science Rivers State University Port Harcourt Nigeria Department of Biochemistry Rivers State University Port Harcourt Nigeria

This study determined the concentrations and inhalation bioaccessibility of cadmium, chromium, nickel and zinc in some foreign and locally available tobacco snuff and leaves. For the determination of the heavy metals concentration, the samples were ashed and washed with hydrochloric acid according to standard method. The bioaccessibility test employed the Stimulated Epithelial Lung Fluid (SELF). The total concentration of heavy metals in the four samples investigated ranged between 9.7 - 14.9 μg/g, 24.1 - 37.0 μg/g, 41 - 69 μg/g and 153 - 183 μg/g for cadmium, chromium, nickel and zinc respectively. The percentage inhalation bioaccessibility fraction of the four samples investigated ranged between 20.8% - 59.8%, 3.3% - 8.1%, 21.7% - 48.8% and 7.6% - 12.5% for cadmium, chromium, nickel, and zinc respectively. Statistical analyses using SPSS 21, revealed significant differences in the total concentration of heavy metals in the samples investigated except for Zinc. Risk assessment based on daily consumption of 10 g of the tobacco snuff employing total concentration of the heavy metals suggests that excluding nickel, all other metals investigated indicated daily intake values above WHO permissible levels. However, with the bioaccessible fractions, only cadmium, a known carcinogen indicated levels above WHO limits. From the results of this study, it can be deduced that consumption of tobacco snuff may induce negative health effects such as cancer and its attendant complications, the risk analysis based on bioaccessible concentration suggests lower health risk than analysis based on total heavy metal concentration;hence the assumption that snuff is a safe alternative to tobacco smoking may be erroneous.

关键词： Tobacco Leaves Snuff Inhalation Bioaccessibility Heavy Metals Stimulated Epithelial Lung Fluid SELF Exposure Risk

LAPAROSCOPIC TREATMENT OF ACUTE CHOLECYSTITIS

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实用临床医药杂志 2003年第5期7卷 397-399页

作者： Davaadorj Nyamkhuu Nyamkhuu Gonchigsenghe Albert holly Rusher Department of Surgery Department of SurgeryDepartment of Surgery Mongolian National Medical UniversityUlaanbaatar MongoliaM DMongolian National Medical UniversityUlaanbaatar MongoliaM D Mongolian National Medical UniversityUlaanbaatar MongoliaM D

Objctive: To assess the current treatment of AC in a single institution in the series, which the best treatment modality for acute cholecystitis (AC) is still under debate, whereas early cholecystectomy is accepted as the optimal timing for ***: From December 1996 to December 2001, 138 (102 women and 36 men) patients underwent laparoscopic cholecystectomy for acute cholecystitis confirmed by histopathological examination. The patients ranged in age from 21 to 85 years of age ( mean age: 45 3 years). Patients were divided into 2 groups (similar in age and ASA classification): group 1 (98 patients) underwent LC within 3 days after the onset of symptoms of acute cholecystitis and group 2 (40 patients) underwent LC after 3 days. Results: Approximately one half of the cases were uncomplicated, 26% were empyema, 13% had gangrenous changes and 7% had hydrops of the gallbladder. Conversion to open cholecystectomy was required in 21 (15 2%) cases. The principal reason for conversion was anatomic uncertainty (14 cases), uncontrolled bleeding (7 cases). The conversion rates in patients who underwent surgery before and after the onset of symptoms were respectively 6∶15. There was no significant difference in operative time (122 0 min in 1 group versus 124 0 min in 2 group) and postoperative stay ( 5 1 days in group 1 vs 6 8 days in group 2). The hepatorenal space was drained in 78 (56 5 %), and the drain is removed in 3rd postoperative days. Twenty six patients (18 8%) had undergone previous abdominal surgery. Thirty seven patients (26 8%) had spillage of bile and/or stones during the procedure. There were no deaths and major complications. Conclusions: LC for acute cholecystitis should be done immediately after the diagnosis is established because delaying surgery allows inflammation to become more intense, thus increasing the technical difficulty of LC. Intraoperative spillage of bile and stones does not lead to an increase in early complications. LC is safe and e

关键词：剖腹术治疗微创手术胆总管

Use of orthotics with orthotic sandals versus the sole use of orthotics for plantar fasciitis:Randomised controlled trial

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World Journal of Orthopedics 2023年第9期14卷 707-719页

作者： Portia Amoako-Tawiah holly Love Jaida Chacko Madathilethu Jessica LaCourse Alice E Fortune Jonathan M G Sims George Ampat School of Medicine University of LiverpoolMerseysideLiverpool L693GEUnited Kingdom Urology Royal Stoke University HospitalStaffordshireStoke ST46QGUnited Kingdom Research Unit Talita Cumi Ltd.MerseysideSouthport PR83NSUnited Kingdom

BACKGROUND Plantar fasciitis(PF)affects around 10%of the *** orthotics with arch support has been shown to provide symptom relief in PF by decreasing the repetitive stress sustained by the plantar ***,prefabricated orthotics are only effective when shoes are worn,meaning the foot may be left unsupported when it is impractical to wear *** orthotic sandals in conjunction with prefabricated orthotics may increase PF symptom relief,as they can be worn inside the home,extending the period in which the foot is *** To compare the combined use of prefabricated orthotics and orthotic sandals vs the sole use of prefabricated orthotics in the treatment of *** 98 participants with PF were randomised into two *** intervention group received the Aetrex L420 Compete orthotics and the Aetrex L3000 Maui Flips(orthotic sandals),whilst the control group received the Aetrex L420 Compete orthotics *** pain was assessed both by the numerical rating scale(NRS)and the pain sub-scale of the foot health status questionnaire(FHSQ).Foot functionality was measured using the function sub-scale of the *** change was measured using the global rating of change scale(GROC).RESULTS Foot pain scores measured both by NRS and FHSQ pain sub-scale showed statistically significant reductions in foot pain in both groups(P<0.05)at six *** groups also reported statistically significant improvements(P<0.05)in function as measured by the FHSQ function subscale and improvement of symptoms as measured by the GROC ***-group analysis showed that the intervention group with the combined use of orthotics and orthotic sandals scored better on all four outcome measures as compared to the control group with the sole use of ***,the between-group analysis only reached statistical significance on the NRS pain score(P<0.05).CONCLUSION Combined use of prefabricated orthotics and orthotic sandals provides a greater d

关键词： Plantar fasciitis Foot diseases Musculoskeletal pain Foot orthoses

IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling

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Cellular & Molecular Immunology 2023年第6期20卷 651-665页

作者： holly Bachus Erin McLaughlin Crystal Lewis Amber M.Papillion Etty N.Benveniste Dave Durell Hill Alexander F.Rosenberg AndréBallesteros-Tato Beatriz León Department of Medicine Division of Clinical Immunology and RheumatologyUniversity of Alabama at BirminghamBirminghamALUSA Department of Microbiology University of Alabama at BirminghamBirminghamALUSA Department of Cell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamALUSA informatics Institute University of Alabama at BirminghamBirminghamALUSA Alexion Pharmaceuticals Inc.New HavenCTUSA

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.

关键词： Th2 cell polarization IL-6 IL-2 SOCS3 JAK1 inhibitor

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101个超酷的简单科学实验

Risk Perception and Knowledge in Fire Risk Reduction in a Dong Minority Rural Village in China: A Health-EDRM Education Intervention Study

2017年

作者： (美)Rachel Miller (美)holly Homer (美)Jamie Harrington

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International Journal of Disaster Risk Science 2018年第3期9卷 306-318页

作者： Emily Ying Yang Chan holly Ching Yu Lam Phoebe Pui Wun Chung Zhe Huang Tony Ka Chun Yung Kelvin Wai Kit Ling Gloria Kwong Wai Chan Cheuk Pong Chiu Collaborating Centre for Oxford University and CUHK for Disaster and Medical Humanitarian Response (CCOUC) The Chinese University of Hong Kong Nuffield Department of Medicine University of Oxford The Jockey Club School of Public Health and Primary Care The Chinese University of Hong Kong Franois-Xavier Bagnoud Center for Health and Human Rights Harvard University Integrated Research on Disaster Risk (IRDR) International Centre of Excellence–CCOUC (ICoE-CCOUC)

Fire is one of the major disasters in rural communities but evidence of the effectiveness of education interventions against fire risks is limited. This was a 2-year study assessed the effectiveness of face-to-face Health Emergency and Disaster Risk Management(HealthEDRM) education interventions for raising fire risk reduction knowledge in a fire-prone rural ethnic minority community. The study was conducted in various pre-set time points of an intervention-based project in a Dongbased community in Nanjiang Village, Guizhou Province in 2015 and 2016 to increase knowledge among the villagers about how to reduce general-and electrical-fire risks. Pre-and post-intervention questionnaires were used to evaluate the effectiveness of increasing fire risk-related knowledge through these interventions, immediately after the 2015 and 2016 interventions, and 17 months after the 2015 intervention. The knowledge of using fire blanket,recalling the correct emergency telephone number,unplugging unused electrical appliances, and not using water to extinguish electrical fires had immediately improved after the interventions. Subjects demonstrated a better understanding that fire blankets can fight a blaze if used appropriately, and that knowledge was sustained for 17 months. The interventions were effective in improving fire prevention and response knowledge. Targeted interventions should be organized according to communities' culture, the evolution of economic prosperity and lifestyle practices.

关键词： Dong village Fire risk education Fire risk perception Fire risk reduction Health education Rural China Health-EDRM

Response to endoscopic therapy for biliary anastomotic strictures in deceased versus living donor liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2013年第5期12卷 488-493页

作者： Calvin HY Chan Fergal Donnellan Michael F Byrne Alan Coss Mazhar Haque holly Wiesenger Charles H Scudamore Urs P Steinbrecher Alan A Weiss Eric M Yoshida Division of Gastroenterology General Hospital University of British Columbia Department of Surgery Vancouver General Hospital University of British Columbia

BACKGROUND:Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation(DDLT) and living donor liver transplantation(LDLT).LDLT is thought to be associated with higher rates of biliary complications,but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two *** study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus ***:This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography(ERCP) after liver *** frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and *** response of anastomotic stricture to endoscopic therapy was also ***:A total of 362 patients underwent liver transplantation between 2003 and 2011,with 125 requiring ERCP to manage biliary ***-three(9.9%) cases of DDLT and 8(27.6%) of LDLT(P=0.01) were found to have anastomotic *** comparing DDLT and LDLT,there was no difference in the mean time to the development of anastomotic strictures(98±17 vs 172±65 days,P=0.11),likelihood of response to ERCP [22(66.7%) vs 6(75.0%),P=0.69],mean time to the resolution of anastomotic strictures(268±77 vs 125±37 days,P=0.34),and the number of ERCPs required to achieve resolution(3.9±0.4 vs 4.7±0.9,P=0.38).CONCLUSIONS:Endoscopic therapy is effective in the majority of biliary complications relating to liver *** strictures occur more frequently in LDLT compared with DDLT,with equivalent endoscopic treatment response and outcomes for both groups.

关键词： endoscopic retrograde cholangiopancreatography liver transplantation biliary tract surgical procedures biliary tree liver failure

Long-Term and Immediate Impacts of Health Emergency and Disaster Risk Management(Health-EDRM) Education Interventions in a Rural Chinese Earthquake-Prone Transitional Village

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International Journal of Disaster Risk Science 2018年第3期9卷 319-330页

作者： Emily Ying Yang Chan Janice Ying-en Ho Zhe Huang Jean Hee Kim holly Ching Yu Lam Phoebe Pui Wun Chung Carol Ka Po Wong Sida Liu Sharon Chow Collaborating Centre for Oxford University and CUHK for Disaster and Medical Humanitarian Response (CCOUC) The Chinese University of Hong Kong Nuffield Department of Medicine University of Oxford The Jockey Club School of Public Health and Primary Care The Chinese University of Hong Kong Franois-Xavier Bagnoud Center for Health & Human Rights Harvard University Integrated Research on Disaster Risk (IRDR) International Centre of Excellence–CCOUC (ICoE-CCOUC) Wu Zhi Qiao (Bridge to China) Charitable Foundation

Ma'an Qiao Village, a Dai and Yi ethnic minority-based community in Sichuan Province, China sustained complete infrastructure devastation during the 2008 Panzhihua earthquake. Health emergency and disaster risk management(Health-EDRM) education intervention programs were implemented in 2010 and 2011. This serial cross-sectional survey study aimed to examine the immediate and long-term impacts of the Health-EDRM interventions in this remote rural community. The findings demonstrate knowledge improvement in areas of water and sanitation, food and nutrition, and disaster preparedness immediately after the Health-EDRM education interventions. Temporal stability of knowledge retention was observed in household hygiene and waste management and smoking beliefs in 2018, 7 years after the *** important findings include knowledge uptake pattern differences of oral rehydration solution(ORS) between earthquake-prone and flood-prone communities. Usage of Internet and mobile technology for accessing disaster-related information was found to be independent of gender and income. Overall, this study demonstrated the knowledge improvement through Health-EDRM education interventions in a remote rural community. Promoting behavioral changes through interventions to raise awareness has the potential to reduce health risks in transitional post-disaster settings. Future programs should aim to identify evidence-based practices and explore how technology can support Health-EDRM education among vulnerable subgroups.

关键词： Earthquake Transitional community Disaster preparedness kit Disaster risk reduction Health emergency and disaster risk management Rural China Sichuan

Rates and risk factors for suicidal ideation,suicide attempts and suicide deaths in persons with HIV:a systematic review and meta-analysis

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General Psychiatry 2021年第2期34卷 60-68页

作者： Matt Pelton Matt Ciarletta holly Wisnousky Nicholas Lazzara Monica Manglani Djibril M Ba Vernon M Chinchillli Ping Du Anna E Ssentongo Paddy Ssentongo Department of Public Health Sciences The Pennsylvania State University College of MedicineHersheyPennsylvaniaUSA Department of Surgery The Pennsylvania State University College of MedicineHersheyPennsylvaniaUSA Center for Neural Engineering Department of Engineering Science and MechanicsThe Pennsylvania State UniversityUniversity ParkPennsylvaniaUSA

Background People living with HIV/AIDS(PLWHA)must contend with a significant burden of ***,current studies of this demographic have yielded wide variations in the incidence of suicidality(defined as suicidal ideation,suicide attempt and suicide deaths).Aims This systematic review and meta-analysis aimed to assess the lifetime incidence and prevalence of suicidality in *** Publications were identified from PubMed(MEDLINE),SCOPUS,OVID(MEDLINE),Joanna Briggs Institute EBP and Cochrane Library databases(from inception to before 1 February 2020).The search strategy included a combination of Medical Subject Headings associated with suicide and *** independently screened records,extracted outcome measures and assessed study *** were pooled using a random-effects *** and meta-regression analyses were conducted to explore the associated risk factors and to identify the sources of *** outcomes were lifetime incidence of suicide completion and lifetime incidence and prevalence of suicidal ideation and suicide *** A total of 185199 PLWHA were identified from 40 studies(12 cohorts,27 cross-sectional and 1 nested case-control).The overall incidence of suicide completion in PLWHA was 10.2/1000 persons(95%CI:4.5 to 23.1),translating to 100-fold higher suicide deaths than the global general population rate of 0.11/1000 *** lifetime prevalence of suicide attempts was 158.3/1000 persons(95%CI:106.9 to 228.2)and of suicidal ideation was 228.3/1000 persons(95%CI:150.8 to 330.1).Meta-regression revealed that for every 10-percentage point increase in the proportion of people living with HIV with advanced disease(AIDS),the risk of suicide completion increased by 34 per 1000 *** quality of evidence by Grading of Recommendations,Assessment,Development and Evaluations for the suicide deaths was graded as‘moderate’*** The risk of suicide death is 100-fold higher in people living wit

关键词： lifetime suicide analysis