These Chinese National Guidelines(GB/T 35892-20181)were issued February 06,2018 and became effective September 01,2018.The authors recognized the urgent need for an authentic English translation to inform the internat...These Chinese National Guidelines(GB/T 35892-20181)were issued February 06,2018 and became effective September 01,2018.The authors recognized the urgent need for an authentic English translation to inform the international community of the compliance requirements in China.It was appreciated that the final translation must reflect the specialist understanding of those working under the Guideline whilst remaining faithful to the meaning of the original Chinese text.A three-step translation process was therefore determined.Step 1:A professional interpretation service(KL Communications,UK)was commissioned to prepare a literal translation of the Chinese text.Supportive documents were provided which explained specialist terminology.This translation was checked by two bilingual experts.Step 2:A workshop was held in Nanjing in May 2019 to which were invited experts in laboratory animal welfare and ethical use.These included international native English-speaking and Chinese-speaking delegates.The delegates worked in multilingual teams to review sections of the literal translation ahead of the workshop,and to agree an authentic interpretation during the workshop.Step 3:Following the workshop,three bilingual experts(two native Chinese speakers and one native English speaker)reviewed the entire document to ensure consistency of terminology and general accuracy.This document is thus not a“literal translation”but an“accurate interpretation”of the original text.Any challenge of work being performed under these Guidelines should rely on the Chinese text in the first place.However,this translation may be used as mitigating evidence,especially where those performing the work are non-Chinese speakers.展开更多
This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the surviva...This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT scans.The findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient prognosis.This noninvasive approach provides valuable insights into the therapeutic management of HCC.展开更多
This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic cancer.Lu et al evaluated the ability of seven biomarkers t...This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic cancer.Lu et al evaluated the ability of seven biomarkers to predict postoperative recovery and long-term outcomes.These biomarkers were albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,nutritional risk index,and geriatric nutritional risk index.The PNI was found to be a strong predictor of both overall and recurrence-free survival,underscoring its clinical relevance in managing patients with pancreatic cancer.展开更多
"The Chinese Dream" and its ideational precursors in official discourse touch upon issues of social policymaking. More specifically, official China has stated the goal of achieving a "moderate" or "appropriate" ..."The Chinese Dream" and its ideational precursors in official discourse touch upon issues of social policymaking. More specifically, official China has stated the goal of achieving a "moderate" or "appropriate" universal welfare state in order to mitigate increasing inequality and the individualization of social risk. Consequently, the new millennium witnessed a wave of social reforms in China's Mainland, the most significant of which were arguably within the policy fields of health insurance, pensions and unemployment protection. This paper reviews reform efforts within these three policy fields and discusses progress and looming challenges with the concept of universalism as the yardstick. From the perspective of universalism, the social right dimensions of coverage (the share of the population included), generosity (benefit levels or adequacy of welfare proved for those included) and financing (such as state, contributions or private) are quintessential. Coverage of social protection has increased significantly with new schemes in all three policy fields. The hukou divide in coverage of social insurance is not as pronounced as before, especially in health insurance. However, major challenges still persist. Declining benefit generosity or adequacy has been a tendency in both pensions and unemployment protection. The pension system also faces problems of financial fragmentation and unsustainability. The health insurance system is still inadequate in terms of protection against health risks, particularly serious or chronic illnesses. These issues are more pronounced in schemes catering to rural residents or urban residents outside the labor market. This reflects that schemes for urban workers are still much more generous. In this regard, recent tentative efforts to integrate the divided welfare system should be noted.展开更多
BACKGROUND We report a case of uterine artery pseudoaneurysm(UAP)occurrence during hysteroscopic endometrial polypectomy and its treatment via uterine artery embolization(UAE).CASE SUMMARY A 48-year-old primigravid,pr...BACKGROUND We report a case of uterine artery pseudoaneurysm(UAP)occurrence during hysteroscopic endometrial polypectomy and its treatment via uterine artery embolization(UAE).CASE SUMMARY A 48-year-old primigravid,primiparous patient was incidentally found to have an endometrial polyp during a health checkup,and underwent a hysteroscopic polypectomy at another hospital.Her cervix was dilated with a Laminken-R®device.After the Laminken-R®was withdrawn,a large amount of genital bleeding was observed.This bleeding persisted after the hysteroscopic polypectomy,and,as hemostasis became impossible,the patient was transferred to our hospital by ambulance.On arrival,transvaginal ultrasonography revealed a 3-cm hypoechoic mass with a swirling internal pulse on the right side of the uterus,and color Doppler ultrasonography showed feeder vessels penetrating the mass.Pelvic contrast-enhanced computed tomography(CT)confirmed the presence of a mass at this site,and vascular proliferation was observed within the uterine cavity.Consequently,UAP was diagnosed,and UAE was performed.The patient’s postoperative course was uneventful,and 6 mo post-UAE,no recurrence of blood flow to the UAP was observed.CONCLUSION When abnormal genital bleeding occurs during hysteroscopic surgery,ultrasonography and contrast-enhanced CT can assist in the detection of early UAPs.展开更多
BACKGROUND Microwave endometrial ablation(MEA)is a minimally invasive treatment method for heavy menstrual bleeding.However,additional treatment is often required after recurrence of uterine myomas treated with MEA.Ad...BACKGROUND Microwave endometrial ablation(MEA)is a minimally invasive treatment method for heavy menstrual bleeding.However,additional treatment is often required after recurrence of uterine myomas treated with MEA.Additionally,because this treatment ablates the endometrium,it is not indicated for patients planning to become pregnant.To overcome these issues,we devised a method for ultrasound-guided microwave ablation of uterine myoma feeder vessels.We report three patients successfully treated for heavy menstrual bleeding,secondary to uterine myoma,using our novel method.CASE SUMMARY All patients had a favorable postoperative course,were discharged within 4 h,and experienced no complications.Further,no postoperative recurrence of heavy menstrual bleeding was noted.Our method also reduced the myoma’s maximum diameter.CONCLUSION This method does not ablate the endometrium,suggesting its potential appli-cation in patients planning to become pregnant.展开更多
Yellow mealworm larvae(YML;Tenebrio molitor) are considered as a valuable insect species for animal feed due to their high nutritional values and ability to grow under different substrates and rearing conditions. Adva...Yellow mealworm larvae(YML;Tenebrio molitor) are considered as a valuable insect species for animal feed due to their high nutritional values and ability to grow under different substrates and rearing conditions. Advances in the understanding of entomophagy and animal nutrition over the past decades have propelled research areas toward testing multiple aspects of YML to exploit them better as animal feed sources. This review aims to summarize various approaches that could be exploited to maximize the nutritional values of YML as an animal feed ingredient. In addition, YML has the potential to be used as an antimicrobial or bioactive agent to improve animal health and immune function in production animals. The dynamics of the nutritional profile of YML can be influenced by multiple factors and should be taken into account when attempting to optimize the nutrient contents of YML as an animal feed ingredient. Specifically, the use of novel land-based and aquatic feeding resources, probiotics, and the exploitation of larval gut microbiomes as novel strategies can assist to maximize the nutritional potential of YML. Selection of relevant feed supplies, optimization of ambient conditions, the introduction of novel genetic selection procedures, and implementation of effective post-harvest processing may be required in the future to commercialize mealworm production. Furthermore, the use of appropriate agricultural practices and technological improvements within the mealworm production sector should be aimed at achieving both economic and environmental sustainability. The issues highlighted in this review could pave the way for future approaches to improve the nutritional value of YML.展开更多
In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ d...In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.展开更多
BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabol...BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains unclear.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections.The mice received oral drugs or saline.Additionally,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,respectively.The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and Bacteroides.Furthermore,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan biosynthesis.Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION The proteins in Poecilobdella manillensis powder were effective for HUA.Mechanistically,they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.展开更多
Objective:To assess the perspectives and barriers towards dengue preventive practices among the residents of Puducherry,India.Methods:A cross-sectional survey was conducted in 300 households in Puducherry,using a popu...Objective:To assess the perspectives and barriers towards dengue preventive practices among the residents of Puducherry,India.Methods:A cross-sectional survey was conducted in 300 households in Puducherry,using a population-proportionate(7:3)distribution from urban and rural areas by grid sampling.One adult interview per household was conducted and the participants were selected using a KISH grid.A semi-structured questionnaire based on the Health Belief Model(HBM)with additional questions on knowledge assessment was used.Knowledge was assessed based on the correctness of answers and the HBM scores were calculated on a 5-point Likert scale.Participants were categorized based on the median score under each domain.Logistic regression was used for adjusted analysis and models were built to predict the performances in each domain.Results:Four percent of the participants lacked basic knowledge regarding dengue transmission.While 208(69.3%)participants did not consider themselves at risk of contracting dengue within the next year,majority perceived dengue as a disease with low severity.Around 49.3%(148)were skeptical about the benefit of time and money spent on dengue prevention.Inadequate government efforts were stated as the major barrier(47.0%)and frequent reminders(142,47.3%)as the major cue to action.Age above 50 years(aOR 1.78,95%CI 1.04-3.06,P=0.037)and rural locality(aOR 2.68,95%CI 1.52-4.71,P=0.001)were found to be significantly associated with poor knowledge scores.Urban participants had a significantly higher chance to perceive low susceptibility as compared to the rural counterparts(aOR 1.74,95%CI 1.05-2.9,P=0.03).Participants with less than a high school education had low perceived benefits(aOR 2.46,95%CI 1.52-3.96,P<0.001)and low self-efficacy scores(aOR 2.66,95%CI 1.61-4.39,P<0.001).Conclusions:This study identifies key gaps in dengue prevention,including low perceived susceptibility,mild disease perception,limited knowledge of breeding sites,and overreliance on government efforts.Tailoring interventions to community needs,stratified to factors influencing the community perspectives can significantly improve dengue prevention efforts.展开更多
BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby cons...BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby considerably reducing the quality of life of females.Given the continuum in weakened ovarian function,progressing from incipient ovarian failure(IOF)to transitional ovarian failure and further to POI,it is necessary to develop biomarkers for predicting POI.The oxidative stress states in IOF and POI were comprehensively evaluated via oxidative stress[diacron-reactive oxygen metabolites(d-ROMs)]test and anti-oxidant capacity[biological antioxidant potential(BAP)].METHODS Females presenting with secondary amenorrhea over 4 mo and a follicle stimulating hormone level of>40 mIU/mL were categorized into the POI group.Females presenting with a normal menstrual cycle and a follicle stimulating hormone level of>10.2 mIU/mL were categorized into the IOF group.Healthy females without ovarian hypofunction were categorized into the control group.Among females aged<40 years who visited our hospital from January 2021 to June 2022,we recruited 11 patients into both POI and IOF groups.For the potential antioxidant capacity,the relative oxidative stress index(BAP/d-ROMs×100)was calculated,and the oxidative stress defense system was comprehensively evaluated.RESULTS d-ROMs were significantly higher in the POI and IOF groups than in the control group,(478.2±58.7 U.CARR,434.5±60.6 U.CARR,and 341.1±35.1 U.CARR,respectively)(U.CARR is equivalent to 0.08 mg/dL of hydrogen peroxide).However,no significant difference was found between the POI and IOF groups.Regarding BAP,no significant difference was found between the control,IOF,and POI groups(2078.5±157.4μmol/L,2116.2±240.2μmol/L,and 2029.0±186.4μmol/L,respectively).The oxidative stress index was significantly higher in the POI and IOF groups than in the control group(23.7±3.3,20.7±3.6,and 16.5±2.1,respectively).However,no significant difference was found between the POI and IOF groups.CONCLUSION High levels of oxidative stress suggest that evaluating the oxidative stress state may be a useful indicator for the early detection of POI.展开更多
BACKGROUND High-dose steroid administration is a common initial therapeutic approach for Vogt–Koyanagi–Harada disease(VKH).Nonetheless,administering substantial doses of steroids to pregnant women necessitates metic...BACKGROUND High-dose steroid administration is a common initial therapeutic approach for Vogt–Koyanagi–Harada disease(VKH).Nonetheless,administering substantial doses of steroids to pregnant women necessitates meticulous consideration due to the potential impacts on the mother and fetus.We present a case wherein steroid pulse therapy was administered to a patient who developed VKH during the late stages of pregnancy.CASE SUMMARY The patient was a 26-year-old nulliparous woman.At 33 weeks and 1 day of her pregnancy,she experienced a decline in visual acuity and noticed metamorphopsia in her left eye.Examination revealed bilateral serous retinal detachment,leading to VKH diagnosis.A collaborative effort involving the departments of ophthalmology,internal medicine,and neonatology was initiated.Steroid pulse therapy was administered at 34 weeks and 1 day of pregnancy under hospital supervision.Complications,such as threatened preterm labor and gestational diabetes,emerged,necessitating the initiation of oral ritodrine hydrochloride and insulin therapy.Then,serous retinal detachment was resolved,and visual acuity was restored.Labor pains initiated 32 days post-initiation of steroid pulse therapy(at 38 weeks and 4 days of gestation),culminating in a normal delivery.Mother and newborn experienced an uneventful puerperal course and were discharged from the hospital on the 5th day following delivery.CONCLUSION VKH management in pregnancy requires multidisciplinary coordination,emphasizing collaboration with ophthalmologists and specialists in internal medicine and neonatology.展开更多
Objective: To examine factors to predict the optimal stent pusher position when inserting ureteral stents under fluoroscopy.Methods: We retrospectively reviewed 327 patients who underwent ureteral stent insertion. We ...Objective: To examine factors to predict the optimal stent pusher position when inserting ureteral stents under fluoroscopy.Methods: We retrospectively reviewed 327 patients who underwent ureteral stent insertion. We considered the pubic bone as a useful anatomical landmark to insert ureteral stents under fluoroscopic guidance. Thus, we categorized patients into three groups (proximal, middle, and distal groups) according to the position of the radiopaque tip of the push catheter when inserting the ureteral stent. Success was defined as a completely curled ureteral stent tail. We compared stent insertion success rates among the three groups. A multivariate analysis was performed to identify the factors affecting stent insertion success.Results: In men, 36 (63.2%) cases were deemed successful in the proximal group compared with 40 (80.0%) cases in the middle group and 12 (20.7%) cases in the distal group (p<0.001). In women, 26 (45.6%) cases were deemed successful in the proximal group compared with 54 (98.2%) cases in the middle group and 38 (76.0%) cases in the distal group (p<0.001). With the multivariate analysis, the stent pusher position was the most significant factor influencing successful stent insertion (men: odds ratio 6.00, 95% confidence interval 2.66-13.51, p<0.001;women: odds ratio 37.80, 95% confidence interval 4.94-289.22, p<0.001).Conclusion: The position of the stent pusher affects stent insertion success. The middle of the pubic symphysis is the optimal position for the radiopaque tip of the pusher when inserting ureteral stents under fluoroscopic guidance.展开更多
Olympus Corporation developed texture and color enhancement imaging(TXI)as a novel image-enhancing endoscopic technique.This topic highlights a series of hot-topic articles that investigated the efficacy of TXI for ga...Olympus Corporation developed texture and color enhancement imaging(TXI)as a novel image-enhancing endoscopic technique.This topic highlights a series of hot-topic articles that investigated the efficacy of TXI for gastrointestinal disease identification in the clinical setting.A randomized controlled trial demonstrated improvements in the colorectal adenoma detection rate(ADR)and the mean number of adenomas per procedure(MAP)of TXI compared with those of white-light imaging(WLI)observation(58.7%vs 42.7%,adjusted relative risk 1.35,95%CI:1.17-1.56;1.36 vs 0.89,adjusted incident risk ratio 1.48,95%CI:1.22-1.80,respectively).A cross-over study also showed that the colorectal MAP and ADR in TXI were higher than those in WLI(1.5 vs 1.0,adjusted odds ratio 1.4,95%CI:1.2-1.6;58.2%vs 46.8%,1.5,1.0-2.3,respectively).A randomized controlled trial demonstrated non-inferiority of TXI to narrow-band imaging in the colorectal mean number of adenomas and sessile serrated lesions per procedure(0.29 vs 0.30,difference for non-inferiority-0.01,95%CI:-0.10 to 0.08).A cohort study found that scoring for ulcerative colitis severity using TXI could predict relapse of ulcerative colitis.A cross-sectional study found that TXI improved the gastric cancer detection rate compared to WLI(0.71%vs 0.29%).A cross-sectional study revealed that the sensitivity and accuracy for active Helicobacter pylori gastritis in TXI were higher than those of WLI(69.2%vs 52.5%and 85.3%vs 78.7%,res-pectively).In conclusion,TXI can improve gastrointestinal lesion detection and qualitative diagnosis.Therefore,further studies on the efficacy of TXI in clinical practice are required.展开更多
Objective:To assess efficacy of albendazole against Ascaris(A.)lumbricoides among school-children at three sites of Rajahmundry,Sundergarh and Wayanad.Methods:Sites were selected based on soil-transmitted helminths pr...Objective:To assess efficacy of albendazole against Ascaris(A.)lumbricoides among school-children at three sites of Rajahmundry,Sundergarh and Wayanad.Methods:Sites were selected based on soil-transmitted helminths prevalence,different sociocultural-geographical characteristics and operational feasibility.9-12 Years old children from 14 schools were included.The study was conducted in two rounds:baseline&follow up survey.All eligible children found positive for A.lumbricoides at baseline were administered supervised single tablet albendazole 400 mg under the National Deworming Day Initiative.During post-treatment follow-up survey,eligible children who provided second stool sample were included in the final analysis.Stool samples were examined using WHO recommended Kato-Katz technique.Efficacy was estimated based on cure rate(CR)and Fecal Egg Count Reduction Rate(FECRR)among children found positive in baseline and follow-up surveys.Results:328 Out of 625(52.5%)were found positive for A.lumbricoides in the baseline survey and 85 out of 178 samples(47.8%)during post-treatment follow-up survey.Overall,the estimated CR was 52.2%.FECRR(95%CI)for albendazole was 72.6%(79.2%-66.0%).The FECRR was highest in East Godaveri[89.7%(96.8%-82.6%)],followed by Sundergarh[86.4%(95.3%-77.5%)]and Wayanad[69%(81.7%-56.4%)].Conclusions:Our study confirmed overall reduction in FEC although with varying albendazole efficacy for A.lumbricoides infection at three different locations in India.However,these finding may be assessed in context of ongoing MDA under Filaria control program and further studies by in vivo as well as in vitro methods are required to reach to a conclusion on possible resistance if any.展开更多
Aging and crises like pandemics and climate change are global concerns that affect community environments. These social and natural changes influence people’s health worldwide. Aging impacts human health, including p...Aging and crises like pandemics and climate change are global concerns that affect community environments. These social and natural changes influence people’s health worldwide. Aging impacts human health, including physical and mental aspects, and increases the need for care. Recent crises have affected not only the elderly but also younger populations, necessitating further efforts to develop a systematic community strategy. The goal of such a strategy is to maintain or enhance people’s well-being. As we face aging and crises like pandemics and climate change, it becomes essential to consider health holistically and globally, taking into account the community environment and social determinants without boundaries. The present study aimed to explore the necessary aspects of incorporating social determinants into clinical practice, enabling healthcare providers to view health from a holistic and planetary perspective. This approach facilitates the development of integrated community strategies. The study reviewed literature from PubMed, MEDLINE, and CINAHL databases, focusing on medicine, health, and welfare. An electronic search for English-language articles in peer-reviewed journals was conducted up to July 2024, using search terms such as “holistic health,” “planetary health,” and “social determinants.” Eight articles were identified through the search. After excluding three based on their titles, abstracts, and full texts, five articles were selected. The research focused on three areas: perceiving health in ecosystems, considering health-related policy in clinical situations, and addressing health in primary care settings. This study emphasizes the need for further research on innovative, integrated community strategies in the context of a globally aging society, focusing on non-medical aspects like pandemics, climate change, and social determinants to achieve a holistic and planetary understanding of people’s health. It suggests that understanding the social aspects of ecosystems in clinical settings, through interdisciplinary collaboration, is crucial for developing systematic community strategies for people’s well-being life in medical, health, and welfare contexts.展开更多
Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phen...Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.展开更多
Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigat...Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.展开更多
基金Astra Zeneca R&DUniversities Federation for Animal Welfare+3 种基金Royal Society for the Prevention of Cruelty to AnimalsNovo Nordisk PharmaceuticalsGovernment of the United KingdomAAALAC International。
文摘These Chinese National Guidelines(GB/T 35892-20181)were issued February 06,2018 and became effective September 01,2018.The authors recognized the urgent need for an authentic English translation to inform the international community of the compliance requirements in China.It was appreciated that the final translation must reflect the specialist understanding of those working under the Guideline whilst remaining faithful to the meaning of the original Chinese text.A three-step translation process was therefore determined.Step 1:A professional interpretation service(KL Communications,UK)was commissioned to prepare a literal translation of the Chinese text.Supportive documents were provided which explained specialist terminology.This translation was checked by two bilingual experts.Step 2:A workshop was held in Nanjing in May 2019 to which were invited experts in laboratory animal welfare and ethical use.These included international native English-speaking and Chinese-speaking delegates.The delegates worked in multilingual teams to review sections of the literal translation ahead of the workshop,and to agree an authentic interpretation during the workshop.Step 3:Following the workshop,three bilingual experts(two native Chinese speakers and one native English speaker)reviewed the entire document to ensure consistency of terminology and general accuracy.This document is thus not a“literal translation”but an“accurate interpretation”of the original text.Any challenge of work being performed under these Guidelines should rely on the Chinese text in the first place.However,this translation may be used as mitigating evidence,especially where those performing the work are non-Chinese speakers.
文摘This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT scans.The findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient prognosis.This noninvasive approach provides valuable insights into the therapeutic management of HCC.
文摘This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic cancer.Lu et al evaluated the ability of seven biomarkers to predict postoperative recovery and long-term outcomes.These biomarkers were albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,nutritional risk index,and geriatric nutritional risk index.The PNI was found to be a strong predictor of both overall and recurrence-free survival,underscoring its clinical relevance in managing patients with pancreatic cancer.
文摘"The Chinese Dream" and its ideational precursors in official discourse touch upon issues of social policymaking. More specifically, official China has stated the goal of achieving a "moderate" or "appropriate" universal welfare state in order to mitigate increasing inequality and the individualization of social risk. Consequently, the new millennium witnessed a wave of social reforms in China's Mainland, the most significant of which were arguably within the policy fields of health insurance, pensions and unemployment protection. This paper reviews reform efforts within these three policy fields and discusses progress and looming challenges with the concept of universalism as the yardstick. From the perspective of universalism, the social right dimensions of coverage (the share of the population included), generosity (benefit levels or adequacy of welfare proved for those included) and financing (such as state, contributions or private) are quintessential. Coverage of social protection has increased significantly with new schemes in all three policy fields. The hukou divide in coverage of social insurance is not as pronounced as before, especially in health insurance. However, major challenges still persist. Declining benefit generosity or adequacy has been a tendency in both pensions and unemployment protection. The pension system also faces problems of financial fragmentation and unsustainability. The health insurance system is still inadequate in terms of protection against health risks, particularly serious or chronic illnesses. These issues are more pronounced in schemes catering to rural residents or urban residents outside the labor market. This reflects that schemes for urban workers are still much more generous. In this regard, recent tentative efforts to integrate the divided welfare system should be noted.
文摘BACKGROUND We report a case of uterine artery pseudoaneurysm(UAP)occurrence during hysteroscopic endometrial polypectomy and its treatment via uterine artery embolization(UAE).CASE SUMMARY A 48-year-old primigravid,primiparous patient was incidentally found to have an endometrial polyp during a health checkup,and underwent a hysteroscopic polypectomy at another hospital.Her cervix was dilated with a Laminken-R®device.After the Laminken-R®was withdrawn,a large amount of genital bleeding was observed.This bleeding persisted after the hysteroscopic polypectomy,and,as hemostasis became impossible,the patient was transferred to our hospital by ambulance.On arrival,transvaginal ultrasonography revealed a 3-cm hypoechoic mass with a swirling internal pulse on the right side of the uterus,and color Doppler ultrasonography showed feeder vessels penetrating the mass.Pelvic contrast-enhanced computed tomography(CT)confirmed the presence of a mass at this site,and vascular proliferation was observed within the uterine cavity.Consequently,UAP was diagnosed,and UAE was performed.The patient’s postoperative course was uneventful,and 6 mo post-UAE,no recurrence of blood flow to the UAP was observed.CONCLUSION When abnormal genital bleeding occurs during hysteroscopic surgery,ultrasonography and contrast-enhanced CT can assist in the detection of early UAPs.
文摘BACKGROUND Microwave endometrial ablation(MEA)is a minimally invasive treatment method for heavy menstrual bleeding.However,additional treatment is often required after recurrence of uterine myomas treated with MEA.Additionally,because this treatment ablates the endometrium,it is not indicated for patients planning to become pregnant.To overcome these issues,we devised a method for ultrasound-guided microwave ablation of uterine myoma feeder vessels.We report three patients successfully treated for heavy menstrual bleeding,secondary to uterine myoma,using our novel method.CASE SUMMARY All patients had a favorable postoperative course,were discharged within 4 h,and experienced no complications.Further,no postoperative recurrence of heavy menstrual bleeding was noted.Our method also reduced the myoma’s maximum diameter.CONCLUSION This method does not ablate the endometrium,suggesting its potential appli-cation in patients planning to become pregnant.
基金supported by research grants from Regionalt Forskningsfond (RFF) Trondelag (In FeedProject number: 309859),where Nord University is the project leading institution,and Gullimunn AS and Mære Landbruksskole are project partnerssupported by the CEER project (Project number: 2021/10345) funded by the Norwegian Agency for International Cooperation and Quality Enhancement in Higher Education (HK-dir) under the Norwegian Partnership Program for Global Academic Cooperation (NORPART ) with support from the Norwegian Ministry of Education and Research (MER)。
文摘Yellow mealworm larvae(YML;Tenebrio molitor) are considered as a valuable insect species for animal feed due to their high nutritional values and ability to grow under different substrates and rearing conditions. Advances in the understanding of entomophagy and animal nutrition over the past decades have propelled research areas toward testing multiple aspects of YML to exploit them better as animal feed sources. This review aims to summarize various approaches that could be exploited to maximize the nutritional values of YML as an animal feed ingredient. In addition, YML has the potential to be used as an antimicrobial or bioactive agent to improve animal health and immune function in production animals. The dynamics of the nutritional profile of YML can be influenced by multiple factors and should be taken into account when attempting to optimize the nutrient contents of YML as an animal feed ingredient. Specifically, the use of novel land-based and aquatic feeding resources, probiotics, and the exploitation of larval gut microbiomes as novel strategies can assist to maximize the nutritional potential of YML. Selection of relevant feed supplies, optimization of ambient conditions, the introduction of novel genetic selection procedures, and implementation of effective post-harvest processing may be required in the future to commercialize mealworm production. Furthermore, the use of appropriate agricultural practices and technological improvements within the mealworm production sector should be aimed at achieving both economic and environmental sustainability. The issues highlighted in this review could pave the way for future approaches to improve the nutritional value of YML.
基金Supported by China Medical University,No.CMU111-MF-10.
文摘In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.
基金Supported by National Natural Science Foundation of China,No.82160843.
文摘BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains unclear.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections.The mice received oral drugs or saline.Additionally,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,respectively.The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and Bacteroides.Furthermore,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan biosynthesis.Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION The proteins in Poecilobdella manillensis powder were effective for HUA.Mechanistically,they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.
基金This work was supported intramurally by Student thesis funding for Masters in public Health Entomology(2022)from the Indian Council of Medical Research-Vector Control Research Centre,Puducherry.
文摘Objective:To assess the perspectives and barriers towards dengue preventive practices among the residents of Puducherry,India.Methods:A cross-sectional survey was conducted in 300 households in Puducherry,using a population-proportionate(7:3)distribution from urban and rural areas by grid sampling.One adult interview per household was conducted and the participants were selected using a KISH grid.A semi-structured questionnaire based on the Health Belief Model(HBM)with additional questions on knowledge assessment was used.Knowledge was assessed based on the correctness of answers and the HBM scores were calculated on a 5-point Likert scale.Participants were categorized based on the median score under each domain.Logistic regression was used for adjusted analysis and models were built to predict the performances in each domain.Results:Four percent of the participants lacked basic knowledge regarding dengue transmission.While 208(69.3%)participants did not consider themselves at risk of contracting dengue within the next year,majority perceived dengue as a disease with low severity.Around 49.3%(148)were skeptical about the benefit of time and money spent on dengue prevention.Inadequate government efforts were stated as the major barrier(47.0%)and frequent reminders(142,47.3%)as the major cue to action.Age above 50 years(aOR 1.78,95%CI 1.04-3.06,P=0.037)and rural locality(aOR 2.68,95%CI 1.52-4.71,P=0.001)were found to be significantly associated with poor knowledge scores.Urban participants had a significantly higher chance to perceive low susceptibility as compared to the rural counterparts(aOR 1.74,95%CI 1.05-2.9,P=0.03).Participants with less than a high school education had low perceived benefits(aOR 2.46,95%CI 1.52-3.96,P<0.001)and low self-efficacy scores(aOR 2.66,95%CI 1.61-4.39,P<0.001).Conclusions:This study identifies key gaps in dengue prevention,including low perceived susceptibility,mild disease perception,limited knowledge of breeding sites,and overreliance on government efforts.Tailoring interventions to community needs,stratified to factors influencing the community perspectives can significantly improve dengue prevention efforts.
文摘BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby considerably reducing the quality of life of females.Given the continuum in weakened ovarian function,progressing from incipient ovarian failure(IOF)to transitional ovarian failure and further to POI,it is necessary to develop biomarkers for predicting POI.The oxidative stress states in IOF and POI were comprehensively evaluated via oxidative stress[diacron-reactive oxygen metabolites(d-ROMs)]test and anti-oxidant capacity[biological antioxidant potential(BAP)].METHODS Females presenting with secondary amenorrhea over 4 mo and a follicle stimulating hormone level of>40 mIU/mL were categorized into the POI group.Females presenting with a normal menstrual cycle and a follicle stimulating hormone level of>10.2 mIU/mL were categorized into the IOF group.Healthy females without ovarian hypofunction were categorized into the control group.Among females aged<40 years who visited our hospital from January 2021 to June 2022,we recruited 11 patients into both POI and IOF groups.For the potential antioxidant capacity,the relative oxidative stress index(BAP/d-ROMs×100)was calculated,and the oxidative stress defense system was comprehensively evaluated.RESULTS d-ROMs were significantly higher in the POI and IOF groups than in the control group,(478.2±58.7 U.CARR,434.5±60.6 U.CARR,and 341.1±35.1 U.CARR,respectively)(U.CARR is equivalent to 0.08 mg/dL of hydrogen peroxide).However,no significant difference was found between the POI and IOF groups.Regarding BAP,no significant difference was found between the control,IOF,and POI groups(2078.5±157.4μmol/L,2116.2±240.2μmol/L,and 2029.0±186.4μmol/L,respectively).The oxidative stress index was significantly higher in the POI and IOF groups than in the control group(23.7±3.3,20.7±3.6,and 16.5±2.1,respectively).However,no significant difference was found between the POI and IOF groups.CONCLUSION High levels of oxidative stress suggest that evaluating the oxidative stress state may be a useful indicator for the early detection of POI.
文摘BACKGROUND High-dose steroid administration is a common initial therapeutic approach for Vogt–Koyanagi–Harada disease(VKH).Nonetheless,administering substantial doses of steroids to pregnant women necessitates meticulous consideration due to the potential impacts on the mother and fetus.We present a case wherein steroid pulse therapy was administered to a patient who developed VKH during the late stages of pregnancy.CASE SUMMARY The patient was a 26-year-old nulliparous woman.At 33 weeks and 1 day of her pregnancy,she experienced a decline in visual acuity and noticed metamorphopsia in her left eye.Examination revealed bilateral serous retinal detachment,leading to VKH diagnosis.A collaborative effort involving the departments of ophthalmology,internal medicine,and neonatology was initiated.Steroid pulse therapy was administered at 34 weeks and 1 day of pregnancy under hospital supervision.Complications,such as threatened preterm labor and gestational diabetes,emerged,necessitating the initiation of oral ritodrine hydrochloride and insulin therapy.Then,serous retinal detachment was resolved,and visual acuity was restored.Labor pains initiated 32 days post-initiation of steroid pulse therapy(at 38 weeks and 4 days of gestation),culminating in a normal delivery.Mother and newborn experienced an uneventful puerperal course and were discharged from the hospital on the 5th day following delivery.CONCLUSION VKH management in pregnancy requires multidisciplinary coordination,emphasizing collaboration with ophthalmologists and specialists in internal medicine and neonatology.
文摘Objective: To examine factors to predict the optimal stent pusher position when inserting ureteral stents under fluoroscopy.Methods: We retrospectively reviewed 327 patients who underwent ureteral stent insertion. We considered the pubic bone as a useful anatomical landmark to insert ureteral stents under fluoroscopic guidance. Thus, we categorized patients into three groups (proximal, middle, and distal groups) according to the position of the radiopaque tip of the push catheter when inserting the ureteral stent. Success was defined as a completely curled ureteral stent tail. We compared stent insertion success rates among the three groups. A multivariate analysis was performed to identify the factors affecting stent insertion success.Results: In men, 36 (63.2%) cases were deemed successful in the proximal group compared with 40 (80.0%) cases in the middle group and 12 (20.7%) cases in the distal group (p<0.001). In women, 26 (45.6%) cases were deemed successful in the proximal group compared with 54 (98.2%) cases in the middle group and 38 (76.0%) cases in the distal group (p<0.001). With the multivariate analysis, the stent pusher position was the most significant factor influencing successful stent insertion (men: odds ratio 6.00, 95% confidence interval 2.66-13.51, p<0.001;women: odds ratio 37.80, 95% confidence interval 4.94-289.22, p<0.001).Conclusion: The position of the stent pusher affects stent insertion success. The middle of the pubic symphysis is the optimal position for the radiopaque tip of the pusher when inserting ureteral stents under fluoroscopic guidance.
文摘Olympus Corporation developed texture and color enhancement imaging(TXI)as a novel image-enhancing endoscopic technique.This topic highlights a series of hot-topic articles that investigated the efficacy of TXI for gastrointestinal disease identification in the clinical setting.A randomized controlled trial demonstrated improvements in the colorectal adenoma detection rate(ADR)and the mean number of adenomas per procedure(MAP)of TXI compared with those of white-light imaging(WLI)observation(58.7%vs 42.7%,adjusted relative risk 1.35,95%CI:1.17-1.56;1.36 vs 0.89,adjusted incident risk ratio 1.48,95%CI:1.22-1.80,respectively).A cross-over study also showed that the colorectal MAP and ADR in TXI were higher than those in WLI(1.5 vs 1.0,adjusted odds ratio 1.4,95%CI:1.2-1.6;58.2%vs 46.8%,1.5,1.0-2.3,respectively).A randomized controlled trial demonstrated non-inferiority of TXI to narrow-band imaging in the colorectal mean number of adenomas and sessile serrated lesions per procedure(0.29 vs 0.30,difference for non-inferiority-0.01,95%CI:-0.10 to 0.08).A cohort study found that scoring for ulcerative colitis severity using TXI could predict relapse of ulcerative colitis.A cross-sectional study found that TXI improved the gastric cancer detection rate compared to WLI(0.71%vs 0.29%).A cross-sectional study revealed that the sensitivity and accuracy for active Helicobacter pylori gastritis in TXI were higher than those of WLI(69.2%vs 52.5%and 85.3%vs 78.7%,res-pectively).In conclusion,TXI can improve gastrointestinal lesion detection and qualitative diagnosis.Therefore,further studies on the efficacy of TXI in clinical practice are required.
文摘Objective:To assess efficacy of albendazole against Ascaris(A.)lumbricoides among school-children at three sites of Rajahmundry,Sundergarh and Wayanad.Methods:Sites were selected based on soil-transmitted helminths prevalence,different sociocultural-geographical characteristics and operational feasibility.9-12 Years old children from 14 schools were included.The study was conducted in two rounds:baseline&follow up survey.All eligible children found positive for A.lumbricoides at baseline were administered supervised single tablet albendazole 400 mg under the National Deworming Day Initiative.During post-treatment follow-up survey,eligible children who provided second stool sample were included in the final analysis.Stool samples were examined using WHO recommended Kato-Katz technique.Efficacy was estimated based on cure rate(CR)and Fecal Egg Count Reduction Rate(FECRR)among children found positive in baseline and follow-up surveys.Results:328 Out of 625(52.5%)were found positive for A.lumbricoides in the baseline survey and 85 out of 178 samples(47.8%)during post-treatment follow-up survey.Overall,the estimated CR was 52.2%.FECRR(95%CI)for albendazole was 72.6%(79.2%-66.0%).The FECRR was highest in East Godaveri[89.7%(96.8%-82.6%)],followed by Sundergarh[86.4%(95.3%-77.5%)]and Wayanad[69%(81.7%-56.4%)].Conclusions:Our study confirmed overall reduction in FEC although with varying albendazole efficacy for A.lumbricoides infection at three different locations in India.However,these finding may be assessed in context of ongoing MDA under Filaria control program and further studies by in vivo as well as in vitro methods are required to reach to a conclusion on possible resistance if any.
文摘Aging and crises like pandemics and climate change are global concerns that affect community environments. These social and natural changes influence people’s health worldwide. Aging impacts human health, including physical and mental aspects, and increases the need for care. Recent crises have affected not only the elderly but also younger populations, necessitating further efforts to develop a systematic community strategy. The goal of such a strategy is to maintain or enhance people’s well-being. As we face aging and crises like pandemics and climate change, it becomes essential to consider health holistically and globally, taking into account the community environment and social determinants without boundaries. The present study aimed to explore the necessary aspects of incorporating social determinants into clinical practice, enabling healthcare providers to view health from a holistic and planetary perspective. This approach facilitates the development of integrated community strategies. The study reviewed literature from PubMed, MEDLINE, and CINAHL databases, focusing on medicine, health, and welfare. An electronic search for English-language articles in peer-reviewed journals was conducted up to July 2024, using search terms such as “holistic health,” “planetary health,” and “social determinants.” Eight articles were identified through the search. After excluding three based on their titles, abstracts, and full texts, five articles were selected. The research focused on three areas: perceiving health in ecosystems, considering health-related policy in clinical situations, and addressing health in primary care settings. This study emphasizes the need for further research on innovative, integrated community strategies in the context of a globally aging society, focusing on non-medical aspects like pandemics, climate change, and social determinants to achieve a holistic and planetary understanding of people’s health. It suggests that understanding the social aspects of ecosystems in clinical settings, through interdisciplinary collaboration, is crucial for developing systematic community strategies for people’s well-being life in medical, health, and welfare contexts.
文摘Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.
基金partially supported by the United States Department of Agriculture National Institute of Food and Agriculture Hatch Grant (Project No.OHO01304)。
文摘Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.