BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metasta...BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.展开更多
BACKGROUND The Rome Foundation’s questionnaires,including the latest version,Rome IV diagnostic criteria since 2016,are widely used globally for diagnosing functional gastrointestinal disorders(FGIDs).However,a tailo...BACKGROUND The Rome Foundation’s questionnaires,including the latest version,Rome IV diagnostic criteria since 2016,are widely used globally for diagnosing functional gastrointestinal disorders(FGIDs).However,a tailored Thai version for diagnosing FGIDs in neonates and toddlers is yet to be developed.AIM To develop and validate the Thai version of the Rome IV diagnostic questionnaire for FGIDs in neonates and toddlers.METHODS This study was conducted at a tertiary hospital in Bangkok.The Rome IV diagnostic questionnaire for neonates and toddlers was translated into Thai following Rome Foundation guidelines.Validity was assessed using item-objective congruence.The final version was administered to 65 caregivers of children under 4 years.Reliability was evaluated using Cronbach’s alpha and intraclass correlation coefficient based on test-retest responses collected over a 4-15 day interval.RESULTS A total of 58 complete questionnaires were returned.The median interval between the first and second time was 7 days(range:4 days to 15 days).The item-objective congruence index for the Thai-adapted Rome IV diagnostic questionnaire was 0.74.Internal consistency,as indicated by Cronbach’s alpha,was 0.753,0.712,and 0.750 for the three respective sections.The intraclass correlation coefficients for test-retest reliability were 0.782,0.782,and 0.807.CONCLUSION The Thai Rome IV diagnostic questionnaire for FGIDs in neonates and toddlers demonstrates acceptable validity and reliability,supporting its use in future clinical and research applications.展开更多
Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa&#...Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa's human capital and accelerating its structural transformation and modernization process.This paper employs“demand–supply–adaptation”as its core analytical framework and aims to systematically explore how the educational cooperation between China and Africa can serve Africa's goal of modernization more precisely and effectively.First,through reviewing and analyzing the domestic and international research literature,this paper clarifies the focus,paradigms,and shortcomings of existing research,identifying the knowledge contribution of this study.Second,utilizing detailed macro-level data,case studies,and comparative research methods,it comprehensively presents the multidimensional status,structural characteristics,and development trends of China–Africa educational cooperation in areas such as student exchanges,cooperative education,vocational and technical training,language and cultural exchange,and emerging digital education.This paper also deeply analyzes the pressing and specific demands placed on the education system by Africa's modernization development across key dimensions like economic diversification,industrialization,agricultural modernization,social governance upgrading,and digital transformation.Third,based on the cooperative principle of“Africa's needs and China's strengths,”this paper innovatively proposes systematic countermeasures and suggestions for constructing new,multi-level,high-quality,sustainable,and future-oriented pathways for China–Africa educational cooperation:(a)promoting the strategic focus of cooperation to extend from“hard infrastructure”support to empowering“soft infrastructure”;(b)deepening the integration of industry and education and school–enterprise collaboration to precisely align with Africa's industrial development needs;vigorously developing digital education and jointly building a smart education ecosystem to help Africa bridge the digital divide;(c)improving an evidence-based,third-party evaluation system for cooperative effectiveness and a full-process quality assurance system;and(d)promoting the collaborative participation of multiple actors including governments,schools,enterprises,think tanks,and social organizations to build a new cooperative pattern of coconstruction,co-governance,and shared benefits.展开更多
Esophageal cancer is one of the most unknown and deadliest cancers worldwide,mainly because of its extremely aggressive nature and poor survival rate.Esophageal cancer is the 6th leading cause of death from cancer and...Esophageal cancer is one of the most unknown and deadliest cancers worldwide,mainly because of its extremely aggressive nature and poor survival rate.Esophageal cancer is the 6th leading cause of death from cancer and the 8th most common cancer in the world.The 5-year survival is around 15%-25%.There are clear differences between the risk factors of both histological types that affect their incidence and distribution worldwide.There are areas of high incidence of squamous cell carcinoma(some areas in China) that meet the requirements for cost-effectiveness of endoscopy for early diagnosis in the general population of those areas.In Europe and United States the predominant histologic subtype is adenocarcinoma.The role of early diagnosis of adenocarcinoma in Barrett's esophagus remains controversial.The differences in the therapeutic management of early esophageal carcinoma(high-grade dysplasia,T1 a,T1 b,N0) between different parts of the world may be explained by the number of cancers diagnosed at an early stage.In areas where the incidence is high(China and Japan among others) early diagnoses is more frequent and has led to the development of endoscopic techniques for definitive treatment that achieve very effective results with a minimum number of complications and preserving the functionality of the esophagus.展开更多
Objective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel...Objective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus(2019-nCoV), an ongoing novel coronavirus that causes pneumonia.Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database.Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion(ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction.In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb.Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response.Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.展开更多
In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding ...In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.展开更多
Abstract： The shortest path problem in a network G is to find shortest paths between some specified source vertices and terminal vertices when the lengths of edges are given. The structure of the optimal solutions se...Abstract： The shortest path problem in a network G is to find shortest paths between some specified source vertices and terminal vertices when the lengths of edges are given. The structure of the optimal solutions set on the shortest paths is studied in this paper. First, the conditions of having unique shortest path between two distinguished vertices 8 and t in a network G are discussed; Second, the structural properties of 2-transformation ^-G graph G on the shortest-paths for G are presented heavily.展开更多
BACKGROUND Genetic testing is widely recommended for all epithelial ovarian cancer(EOC)patients.However,an increased probability of identifying germline mutations has been reported in selected patients with risk facto...BACKGROUND Genetic testing is widely recommended for all epithelial ovarian cancer(EOC)patients.However,an increased probability of identifying germline mutations has been reported in selected patients with risk factors such as a family history or personal history of cancer and high-grade serous carcinoma(HGSC)subtype.HGSC has been reported to be the most common subtype of EOC worldwide(approximately 70%).However,this subtype is less prevalent in Thai patients(reported as only 20%).The difference in the distribution of various subtypes of EOC may reflect the incidence of germline mutations in Thai EOC patients.AIM To evaluate the frequencies of germline mutations in EOC patients and to compare the frequencies in those with and without clinical risk factors for hereditary ovarian cancer.METHODS This cross-sectional study included 112 nonmucinous EOC patients who underwent primary surgery at our tertiary care hospital.Clinical risk factors for hereditary ovarian cancer were defined as follows:Age below 40 years,a significant family history of cancer,synchronous ovarian and endometrial cancer,and HGSC.Comprehensive germline mutations were detected by nextgeneration sequencing.RESULTS Of a total of 112 patients,82(73.2%)patients had≥1 risk factor and 30(26.8%)patients had no risk factors.Germline mutations were detected in 26 patients:20(17.8%)patients had BRCA1/2 mutations,but 6(5.4%)patients had mutations in other genes,including 1 in MLH1,1 in MSH2,1 in RAD51C,2 in ATM and 1 in CDH1.Germline mutations were only detected in patients with risk factors(26 of 82,31.7%),not in patients without risk factors(P<0.001).A significant family history of cancer and HGSC were the only two significant risk factors associated with a higher proportion of germline mutations(56.3%vs 10%for those with and without a history of cancer,respectively,40.8%vs 9.5%for those with and without HGSC).Germline BRCA mutations were detected in 38.8%of patients with HGSC but in only 1.6%of those with non-HGSC.An age below 40 years,personal history of breast cancer,and synchronous ovarian and endometrial cancer were not significant factors(14.3%vs 23.5%,33.3%vs 21%,22.2%vs 22.3%).CONCLUSION Approximately one-third of EOC patients with risk factors had germline mutations.Almost all germline BRCA mutations were found in patients with the HGSC subtype.Selected patients with HGSC and a family history of cancer should be initially considered for genetic analysis in Thailand.展开更多
Objective:To summarize and analyze the application of traditional technology in preparing traditional Chinese medicine(TCM)preparations in medical institutions in Shaanxi Province after implementing the“Implementatio...Objective:To summarize and analyze the application of traditional technology in preparing traditional Chinese medicine(TCM)preparations in medical institutions in Shaanxi Province after implementing the“Implementation Rules for the Record Management of Traditional Chinese Medicine Preparations in Medical Institutions in Shaanxi Province(Trial)”(“Implementation Rules”),and to provide a reference for the filing of TCM preparations.Methods:The TCM preparations recorded by medical institutions in Shaanxi Province since March 2019 were statistically summarized.The filing status was comprehensively and systematically analyzed based on the number of institutions and preparations,the ratio of commissioned to self-production,dosage form distribution,and the level of medical institutions.Results:Since implementing the Implementation Rules,a total of 479 TCM preparations have been filed in the province.Among these,262 were commissioned for production,and 217 were self-produced,covering 17 dosage forms such as granules,pills,capsules,mixtures,and powders.A total of 86 medical institutions have filed preparations,most of which are located in Xi’an,Xianyang,and Weinan,with these three cities accounting for the largest number of filings.Conclusion:The policy on the TCM preparation filing system has been widely recognized and deeply implemented in Shaanxi Province.Third-level medical institutions are the primary contributors to preparation filings.Regional differences exist in the development of preparation filing,indicating significant potential for further growth in the province’s filing efforts.展开更多
Salivary glands(SG)are exocrine organs with secretory units commonly injured by radiotherapy.Bio-engineered organoids and extracellular vesicles(EV)are currently under investigation as potential strategies for SG repa...Salivary glands(SG)are exocrine organs with secretory units commonly injured by radiotherapy.Bio-engineered organoids and extracellular vesicles(EV)are currently under investigation as potential strategies for SG repair.Herein,three-dimensional(3D)cultures of SG functional organoids(SGo)and human dental pulp stem cells(hDPSC)were generated by magnetic 3D bioassembly(M3DB)platforms.Fibroblast growth factor 10(FGF10)was used to enrich the SGo in secretory epithelial units.After 11 culture days via M3DB,SGo displayed SG-specific acinar epithelial units with functional properties upon neurostimulation.To consistently develop 3D hDPSC in vitro,3 culture days were sufficient to maintain hDPSC undifferentiated genotype and phenotype for EV generation.EV isolation was performed via sequential centrifugation of the conditioned media of hDPSC and SGo cultures.EV were characterized by nanoparticle tracking analysis,electron microscopy and immunoblotting.EV were in the exosome range for hDPSC(diameter:88.03±15.60 nm)and for SGo(123.15±63.06 nm).Upon ex vivo administration,exosomes derived from SGo significantly stimulated epithelial growth(up to 60%),mitosis,epithelial progenitors and neuronal growth in injured SG;however,such biological effects were less distinctive with the ones derived from hDPSC.Next,these exosome biological effects were investigated by proteomic arrays.Mass spectrometry profiling of SGo exosomes predicted that cellular growth,development and signaling was due to known and undocumented molecular targets downstream of FGF10.Semaphorins were identified as one of the novel targets requiring further investigations.Thus,M3DB platforms can generate exosomes with potential to ameliorate SG epithelial damage.展开更多
In a recent study in signal transduction and targeted therapy,Zhou et al.provided novel experimental data on the role of DNAdependent protein kinase catalytic subunit(DNA-PKcs)in causing abnormalities in the structure...In a recent study in signal transduction and targeted therapy,Zhou et al.provided novel experimental data on the role of DNAdependent protein kinase catalytic subunit(DNA-PKcs)in causing abnormalities in the structure and function of mitochondria of hepatocytes,leading to liver injury and alcohol-associated liver disease(ALD).展开更多
Dear Editor,Cancer invasion and metastasis are among the most clin-ically relevant cancer hallmarks.Identification of molec-ular pathways that contribute to cancer cell motility a crucial step in cancer invasion/metas...Dear Editor,Cancer invasion and metastasis are among the most clin-ically relevant cancer hallmarks.Identification of molec-ular pathways that contribute to cancer cell motility a crucial step in cancer invasion/metastasis is essential to understanding how cancer motility is regulated and may provide therapeutic targets for treating metastatic can-cer.Brain-specific angiogenesis inhibitor 1-associated pro-tein 2-like protein 1(BAIAP2L1)is a novel oncopro-tein whose high-leveled expressions have been correlated with advanced and metastatic stages of cancer[1-3].展开更多
Superhydrophobic bagasse paper was successfully engineered by facile spray coating with a zeolitic imidazolate framework composite modified by 3,3,3-trifluoropropyltrimethoxysilane(FAS)and used as a filter membrane wi...Superhydrophobic bagasse paper was successfully engineered by facile spray coating with a zeolitic imidazolate framework composite modified by 3,3,3-trifluoropropyltrimethoxysilane(FAS)and used as a filter membrane with special wettability for oil/water separation.Surface characteristics such as surface morphology,surface moieties,roughness,and wettability were observed.The addition of FAS decreased the apparent surface energy between solid surfaces and liquids with a polar contribution of surface free energy as low as 0 mN m−1.The formation of the FAS layer was confirmed by transmission electron microscopy and X-ray photoelectron spectroscopy core-level spectra.Three-dimensional surface topography revealed an increase in the spray coating cycle that enhanced the hydrophobicity of the coated paper.The results confirmed that not only microstructures but also the presence of functional groups with low surface energy(such as FAS)can promote surface hydrophobicity.The spray-coated paper with FAS/ZIF in the presence of a small amount of nanocellulose provided a superhydrophobic surface after the first spray cycle.The separation efficiency was up to 85%and was slightly affected by oil viscosity.Moreover,this can be used as a filter membrane for water-in-oil emulsions.In the present work,simple spray-coated paper is a promising candidate material for gravity-driven oil/water separation and water repellent coating.展开更多
Mechanical forces control a multitude of biological responses in various cells and tissues.The periodontal ligament,located between the tooth’s root and alveolar bone,is a major tissue compartment that is incessantly...Mechanical forces control a multitude of biological responses in various cells and tissues.The periodontal ligament,located between the tooth’s root and alveolar bone,is a major tissue compartment that is incessantly subjected to such mechanical stimulation through either normal or abnormal oral functionality.It is now known that mechanical stimulation activates periodontal ligament stem cells(PDLSCs)to modulate periodontal immunity and regulate inflammation–a basic feature of periodontal disease that affects virtually every human during their lifetime.For instance,shear stress induces the expression of immunomodulatoryrelated gene,indoleamine 2,3-dioxygenase(IDO).IDO cleaves l-tryptophan,resulting in increased l-kynurenine levels that,in turn,further promote regulatory T-cell differentiation and inhibit T cell proliferation.These and other related data reinforce the notion that mechanical stimulation plays a crucial role in controlling inflammation and immunomodulation of periodontal tissues.Further investigations,however,are warranted to evaluate the immunomodulatory features of PDLSCs so as to understand the pathological basis of periodontal disease and translate these into clinical interventions.展开更多
The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients f...The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang,China at 1-year after diagnosis.Among them,chemiluminescence immunoassay-based screening showed 99%(95%CI,98–100%)seroprevalence 10–12 months after infection,comparing to 0.8%(95%CI,0.7–0.9%)in the general population.Total anti-receptor-binding domain(RBD)antibodies remained stable since discharge,while anti-RBD IgG and neutralization levels decreased over time.A predictive model estimates 17%(95%CI,11–24%)and 87%(95%CI,80–92%)participants were still 50%protected against detectable and severe re-infection of WT SARS-CoV-2,respectively,while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced.All non-severe patients showed normal chest CT and 21%reported COVID-19-related symptoms.In contrast,53%severe patients had abnormal chest CT,decreased pulmonary function or cardiac involvement and 79%were still symptomatic.Our findings suggest long-lasting immune protection after SARS-CoV-2 infection,while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.展开更多
Mucoepidermoid carcinoma(MEC)is a rare malignancy of the salivary gland(SG)that poses significant treatment challenges.This highlights the need for in vitro cancer modeling platforms towards anti-cancer drug screening...Mucoepidermoid carcinoma(MEC)is a rare malignancy of the salivary gland(SG)that poses significant treatment challenges.This highlights the need for in vitro cancer modeling platforms towards anti-cancer drug screening applications.Emerging organ-on-a-chip(OoC)microfluidic technologies represent promising new approach methodologies(NAMS)and a real alternative to animal testing.While tissue-specific decellularized extracellular matrix(ECM)can recapitulate in vivo-like microenvironments,its application in SG-on-a-chip(SGoC)is still underexplored.This study developed an injectable porcine decellularized submandibular gland(dSMG)hydrogel for bioengineering an SG MEC tissue chip.dSMG was prepared using a chemical and enzymatic decellularization process with 0.1%or 1%sodium dodecyl sulfate(SDS).Both treatments effectively removed DNA content while preserving key ECM components,including collagens,glycoproteins,and mucins.Proteomic analysis revealed that 1%SDS-treated dSMG contained a greater abundance of ECM components involved in matrix assembly and cell-ECM interactions compared to the 0.1%group.The 1%SDS-treated dSMG was subsequently digested with a pepsin-based buffer to form hydrogels.At 5 mg/mL,dSMG hydrogel exhibited nanofibrous architecture,thermo-responsive gelation,injectability into microfluidic devices,and minimal batch-to-batch biological variations.In static conditions,dSMG hydrogel significantly enhanced SG cell viability and mitochondria-dependent proliferation compared to Matrigel.Under gravity-driven flow,dSMG hydrogel promoted a ductal phenotype on human SG MEC cells,unlike on Matrigel.Additionally,dSMG hydrogel supported cholinergic-specific signaling and functional activity.These findings demonstrate the potential of dSMG hydrogel as a physiologically relevant matrix for SG cancer modeling towards drug screening applications in SGoC microfluidic systems.展开更多
Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vi...Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking,halting the discovery of new drugs.Here,we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling.This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM.After modeling OM with all pro-inflammatory hallmarks,we were able to suppress OM with our in-house plant-produced epidermal growth factor(P-EGF),a well-known re-epithelialization cue.Thus,this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection.This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.展开更多
文摘BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.
基金Supported by Ratchadapiseksompotch Fund,Graduate Affairs,Faculty of Medicines,Chulalongkorn University,No.2566-077,No.2566-078,and No.2566-079and The Royal College of Pediatricians of Thailand,No.2566.2.2.
文摘BACKGROUND The Rome Foundation’s questionnaires,including the latest version,Rome IV diagnostic criteria since 2016,are widely used globally for diagnosing functional gastrointestinal disorders(FGIDs).However,a tailored Thai version for diagnosing FGIDs in neonates and toddlers is yet to be developed.AIM To develop and validate the Thai version of the Rome IV diagnostic questionnaire for FGIDs in neonates and toddlers.METHODS This study was conducted at a tertiary hospital in Bangkok.The Rome IV diagnostic questionnaire for neonates and toddlers was translated into Thai following Rome Foundation guidelines.Validity was assessed using item-objective congruence.The final version was administered to 65 caregivers of children under 4 years.Reliability was evaluated using Cronbach’s alpha and intraclass correlation coefficient based on test-retest responses collected over a 4-15 day interval.RESULTS A total of 58 complete questionnaires were returned.The median interval between the first and second time was 7 days(range:4 days to 15 days).The item-objective congruence index for the Thai-adapted Rome IV diagnostic questionnaire was 0.74.Internal consistency,as indicated by Cronbach’s alpha,was 0.753,0.712,and 0.750 for the three respective sections.The intraclass correlation coefficients for test-retest reliability were 0.782,0.782,and 0.807.CONCLUSION The Thai Rome IV diagnostic questionnaire for FGIDs in neonates and toddlers demonstrates acceptable validity and reliability,supporting its use in future clinical and research applications.
文摘Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa's human capital and accelerating its structural transformation and modernization process.This paper employs“demand–supply–adaptation”as its core analytical framework and aims to systematically explore how the educational cooperation between China and Africa can serve Africa's goal of modernization more precisely and effectively.First,through reviewing and analyzing the domestic and international research literature,this paper clarifies the focus,paradigms,and shortcomings of existing research,identifying the knowledge contribution of this study.Second,utilizing detailed macro-level data,case studies,and comparative research methods,it comprehensively presents the multidimensional status,structural characteristics,and development trends of China–Africa educational cooperation in areas such as student exchanges,cooperative education,vocational and technical training,language and cultural exchange,and emerging digital education.This paper also deeply analyzes the pressing and specific demands placed on the education system by Africa's modernization development across key dimensions like economic diversification,industrialization,agricultural modernization,social governance upgrading,and digital transformation.Third,based on the cooperative principle of“Africa's needs and China's strengths,”this paper innovatively proposes systematic countermeasures and suggestions for constructing new,multi-level,high-quality,sustainable,and future-oriented pathways for China–Africa educational cooperation:(a)promoting the strategic focus of cooperation to extend from“hard infrastructure”support to empowering“soft infrastructure”;(b)deepening the integration of industry and education and school–enterprise collaboration to precisely align with Africa's industrial development needs;vigorously developing digital education and jointly building a smart education ecosystem to help Africa bridge the digital divide;(c)improving an evidence-based,third-party evaluation system for cooperative effectiveness and a full-process quality assurance system;and(d)promoting the collaborative participation of multiple actors including governments,schools,enterprises,think tanks,and social organizations to build a new cooperative pattern of coconstruction,co-governance,and shared benefits.
文摘Esophageal cancer is one of the most unknown and deadliest cancers worldwide,mainly because of its extremely aggressive nature and poor survival rate.Esophageal cancer is the 6th leading cause of death from cancer and the 8th most common cancer in the world.The 5-year survival is around 15%-25%.There are clear differences between the risk factors of both histological types that affect their incidence and distribution worldwide.There are areas of high incidence of squamous cell carcinoma(some areas in China) that meet the requirements for cost-effectiveness of endoscopy for early diagnosis in the general population of those areas.In Europe and United States the predominant histologic subtype is adenocarcinoma.The role of early diagnosis of adenocarcinoma in Barrett's esophagus remains controversial.The differences in the therapeutic management of early esophageal carcinoma(high-grade dysplasia,T1 a,T1 b,N0) between different parts of the world may be explained by the number of cancers diagnosed at an early stage.In areas where the incidence is high(China and Japan among others) early diagnoses is more frequent and has led to the development of endoscopic techniques for definitive treatment that achieve very effective results with a minimum number of complications and preserving the functionality of the esophagus.
基金supported by Shanghai Leading Talent Grants in Medicine(No.2019LG26)Shanghai Traditional Chinese Medicine Content Construction Innovation Project(No.ZY3-CCCX-3-7001)Postdoctoral Funding of Shanghai Gongil Hospital(No.GLBH2017002).
文摘Objective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus(2019-nCoV), an ongoing novel coronavirus that causes pneumonia.Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database.Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion(ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction.In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb.Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response.Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.
基金supported by the Grant for Development of New Faculty Staff,Ratchadaphiseksomphot Endowment Fund,Chula-longkorn University,Thailand(Grant No.:DNS64_047_33_003_1 to Patanachai K.Limpikirati)Grant for Development of New Scholar,Office of the Permanent Secretary,Ministry of Higher Ed-ucation,Science,Research and Innovation,Thailand(Grant No.:RGNS64_012 to Patanachai K.Limpikirati).
文摘In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.
文摘Abstract： The shortest path problem in a network G is to find shortest paths between some specified source vertices and terminal vertices when the lengths of edges are given. The structure of the optimal solutions set on the shortest paths is studied in this paper. First, the conditions of having unique shortest path between two distinguished vertices 8 and t in a network G are discussed; Second, the structural properties of 2-transformation ^-G graph G on the shortest-paths for G are presented heavily.
文摘BACKGROUND Genetic testing is widely recommended for all epithelial ovarian cancer(EOC)patients.However,an increased probability of identifying germline mutations has been reported in selected patients with risk factors such as a family history or personal history of cancer and high-grade serous carcinoma(HGSC)subtype.HGSC has been reported to be the most common subtype of EOC worldwide(approximately 70%).However,this subtype is less prevalent in Thai patients(reported as only 20%).The difference in the distribution of various subtypes of EOC may reflect the incidence of germline mutations in Thai EOC patients.AIM To evaluate the frequencies of germline mutations in EOC patients and to compare the frequencies in those with and without clinical risk factors for hereditary ovarian cancer.METHODS This cross-sectional study included 112 nonmucinous EOC patients who underwent primary surgery at our tertiary care hospital.Clinical risk factors for hereditary ovarian cancer were defined as follows:Age below 40 years,a significant family history of cancer,synchronous ovarian and endometrial cancer,and HGSC.Comprehensive germline mutations were detected by nextgeneration sequencing.RESULTS Of a total of 112 patients,82(73.2%)patients had≥1 risk factor and 30(26.8%)patients had no risk factors.Germline mutations were detected in 26 patients:20(17.8%)patients had BRCA1/2 mutations,but 6(5.4%)patients had mutations in other genes,including 1 in MLH1,1 in MSH2,1 in RAD51C,2 in ATM and 1 in CDH1.Germline mutations were only detected in patients with risk factors(26 of 82,31.7%),not in patients without risk factors(P<0.001).A significant family history of cancer and HGSC were the only two significant risk factors associated with a higher proportion of germline mutations(56.3%vs 10%for those with and without a history of cancer,respectively,40.8%vs 9.5%for those with and without HGSC).Germline BRCA mutations were detected in 38.8%of patients with HGSC but in only 1.6%of those with non-HGSC.An age below 40 years,personal history of breast cancer,and synchronous ovarian and endometrial cancer were not significant factors(14.3%vs 23.5%,33.3%vs 21%,22.2%vs 22.3%).CONCLUSION Approximately one-third of EOC patients with risk factors had germline mutations.Almost all germline BRCA mutations were found in patients with the HGSC subtype.Selected patients with HGSC and a family history of cancer should be initially considered for genetic analysis in Thailand.
文摘Objective:To summarize and analyze the application of traditional technology in preparing traditional Chinese medicine(TCM)preparations in medical institutions in Shaanxi Province after implementing the“Implementation Rules for the Record Management of Traditional Chinese Medicine Preparations in Medical Institutions in Shaanxi Province(Trial)”(“Implementation Rules”),and to provide a reference for the filing of TCM preparations.Methods:The TCM preparations recorded by medical institutions in Shaanxi Province since March 2019 were statistically summarized.The filing status was comprehensively and systematically analyzed based on the number of institutions and preparations,the ratio of commissioned to self-production,dosage form distribution,and the level of medical institutions.Results:Since implementing the Implementation Rules,a total of 479 TCM preparations have been filed in the province.Among these,262 were commissioned for production,and 217 were self-produced,covering 17 dosage forms such as granules,pills,capsules,mixtures,and powders.A total of 86 medical institutions have filed preparations,most of which are located in Xi’an,Xianyang,and Weinan,with these three cities accounting for the largest number of filings.Conclusion:The policy on the TCM preparation filing system has been widely recognized and deeply implemented in Shaanxi Province.Third-level medical institutions are the primary contributors to preparation filings.Regional differences exist in the development of preparation filing,indicating significant potential for further growth in the province’s filing efforts.
基金This research project was supported by:a postdoctoral scholarship grant to A.C.from The Second Century Fund(C2F),Chulalongkorn Universitya Mid-career Research Grant to J.N.F.from the National Research Council of Thailand(NRCT5-RSA63001-12)+3 种基金a training support grant to C.A.from the National Medical Research Council Singapore(NMRC/CNIG/1131/2015)a research grant to J.N.F./R.C./S.Y.for the Avatar Biotechnologies for Oral Health and Healthy Longevity Research Unit,from Ratchadaphiseksomphot Endowment Fund at Chulalongkorn University(33/2565:RU)an internal grant from the Faculty of Dentistry Chulalongkorn University,grant number DRF 65001 to J.N.F.,S.Y.and R.C.and a grant from Mahidol University(Basic Research Fund:fiscal year 2021)to S.R..We would like to give a special thanks to Oral Biology Research Center,Faculty of Dentistry,Chulalongkorn University,Dr.Chatvadee Kornsuthisopon for providing the hDPSC conditioned media for western blotting and to Dr.Muttarin Lothong for all technical assistance.
文摘Salivary glands(SG)are exocrine organs with secretory units commonly injured by radiotherapy.Bio-engineered organoids and extracellular vesicles(EV)are currently under investigation as potential strategies for SG repair.Herein,three-dimensional(3D)cultures of SG functional organoids(SGo)and human dental pulp stem cells(hDPSC)were generated by magnetic 3D bioassembly(M3DB)platforms.Fibroblast growth factor 10(FGF10)was used to enrich the SGo in secretory epithelial units.After 11 culture days via M3DB,SGo displayed SG-specific acinar epithelial units with functional properties upon neurostimulation.To consistently develop 3D hDPSC in vitro,3 culture days were sufficient to maintain hDPSC undifferentiated genotype and phenotype for EV generation.EV isolation was performed via sequential centrifugation of the conditioned media of hDPSC and SGo cultures.EV were characterized by nanoparticle tracking analysis,electron microscopy and immunoblotting.EV were in the exosome range for hDPSC(diameter:88.03±15.60 nm)and for SGo(123.15±63.06 nm).Upon ex vivo administration,exosomes derived from SGo significantly stimulated epithelial growth(up to 60%),mitosis,epithelial progenitors and neuronal growth in injured SG;however,such biological effects were less distinctive with the ones derived from hDPSC.Next,these exosome biological effects were investigated by proteomic arrays.Mass spectrometry profiling of SGo exosomes predicted that cellular growth,development and signaling was due to known and undocumented molecular targets downstream of FGF10.Semaphorins were identified as one of the novel targets requiring further investigations.Thus,M3DB platforms can generate exosomes with potential to ameliorate SG epithelial damage.
文摘In a recent study in signal transduction and targeted therapy,Zhou et al.provided novel experimental data on the role of DNAdependent protein kinase catalytic subunit(DNA-PKcs)in causing abnormalities in the structure and function of mitochondria of hepatocytes,leading to liver injury and alcohol-associated liver disease(ALD).
基金This work is supported by National Science and Technology Development Agency(NSTDA)of Thailand,Japan Science and Technology Agency and National Institute of Allergy and Infectious Diseases of United States as part of the e-ASIA Joint Research ProgramNSTDA(P-15-50208)+3 种基金Thailand Research Fund(RSA5880038)Siriraj Research Fundthe Foundation for Cancer Care,Siriraj Hospitaland the Advanced Research in Pharmacology Fund,Siriraj Foundation(D003421),and Mahidol University’s New Discovery and Frontier Research Grant(NDFR 08/2564),S.J.,and S.S.were sup-ported by the R.E.D program,Faculty of Medicine,Siriraj Hospital,Mahidol University.
文摘Dear Editor,Cancer invasion and metastasis are among the most clin-ically relevant cancer hallmarks.Identification of molec-ular pathways that contribute to cancer cell motility a crucial step in cancer invasion/metastasis is essential to understanding how cancer motility is regulated and may provide therapeutic targets for treating metastatic can-cer.Brain-specific angiogenesis inhibitor 1-associated pro-tein 2-like protein 1(BAIAP2L1)is a novel oncopro-tein whose high-leveled expressions have been correlated with advanced and metastatic stages of cancer[1-3].
基金the Thailand Research Fund under the Distinguished Professor Grant No.DPG6080001 for Professor Suda Kiatkamjornwong,Thammasat University Research Fund(Contract no.TUFT 81/2564)Thammasat University Research Unit in Bioenergy and Catalysis.
文摘Superhydrophobic bagasse paper was successfully engineered by facile spray coating with a zeolitic imidazolate framework composite modified by 3,3,3-trifluoropropyltrimethoxysilane(FAS)and used as a filter membrane with special wettability for oil/water separation.Surface characteristics such as surface morphology,surface moieties,roughness,and wettability were observed.The addition of FAS decreased the apparent surface energy between solid surfaces and liquids with a polar contribution of surface free energy as low as 0 mN m−1.The formation of the FAS layer was confirmed by transmission electron microscopy and X-ray photoelectron spectroscopy core-level spectra.Three-dimensional surface topography revealed an increase in the spray coating cycle that enhanced the hydrophobicity of the coated paper.The results confirmed that not only microstructures but also the presence of functional groups with low surface energy(such as FAS)can promote surface hydrophobicity.The spray-coated paper with FAS/ZIF in the presence of a small amount of nanocellulose provided a superhydrophobic surface after the first spray cycle.The separation efficiency was up to 85%and was slightly affected by oil viscosity.Moreover,this can be used as a filter membrane for water-in-oil emulsions.In the present work,simple spray-coated paper is a promising candidate material for gravity-driven oil/water separation and water repellent coating.
基金supported by the NSRF via the Program Management Unit for Human Resources&Institutional Development,Research and Innovation(B16F640118 to T.O.and H.E.)R.S.is supported by the C2F Scholarship at Chulalongkorn UniversityJ.C.is supported by the Ratchadapiset Somphot Fund for Postdoctoral Fellowship,Chulalongkorn University.
文摘Mechanical forces control a multitude of biological responses in various cells and tissues.The periodontal ligament,located between the tooth’s root and alveolar bone,is a major tissue compartment that is incessantly subjected to such mechanical stimulation through either normal or abnormal oral functionality.It is now known that mechanical stimulation activates periodontal ligament stem cells(PDLSCs)to modulate periodontal immunity and regulate inflammation–a basic feature of periodontal disease that affects virtually every human during their lifetime.For instance,shear stress induces the expression of immunomodulatoryrelated gene,indoleamine 2,3-dioxygenase(IDO).IDO cleaves l-tryptophan,resulting in increased l-kynurenine levels that,in turn,further promote regulatory T-cell differentiation and inhibit T cell proliferation.These and other related data reinforce the notion that mechanical stimulation plays a crucial role in controlling inflammation and immunomodulation of periodontal tissues.Further investigations,however,are warranted to evaluate the immunomodulatory features of PDLSCs so as to understand the pathological basis of periodontal disease and translate these into clinical interventions.
基金This work was supported by Xiangyang Science and Technology Bureau(2020YL10,2020YL14,2020YL17,and 2020YL39)National Natural Science Foundation of China(31501116)+2 种基金Shenzhen Science and Technology Innovation Commission(JCYJ20190809100005672)Shenzhen Sanming Project of Medicine(SZSM201911013)US Department of Veterans Affairs(5I01BX001353).
文摘The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang,China at 1-year after diagnosis.Among them,chemiluminescence immunoassay-based screening showed 99%(95%CI,98–100%)seroprevalence 10–12 months after infection,comparing to 0.8%(95%CI,0.7–0.9%)in the general population.Total anti-receptor-binding domain(RBD)antibodies remained stable since discharge,while anti-RBD IgG and neutralization levels decreased over time.A predictive model estimates 17%(95%CI,11–24%)and 87%(95%CI,80–92%)participants were still 50%protected against detectable and severe re-infection of WT SARS-CoV-2,respectively,while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced.All non-severe patients showed normal chest CT and 21%reported COVID-19-related symptoms.In contrast,53%severe patients had abnormal chest CT,decreased pulmonary function or cardiac involvement and 79%were still symptomatic.Our findings suggest long-lasting immune protection after SARS-CoV-2 infection,while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.
文摘Mucoepidermoid carcinoma(MEC)is a rare malignancy of the salivary gland(SG)that poses significant treatment challenges.This highlights the need for in vitro cancer modeling platforms towards anti-cancer drug screening applications.Emerging organ-on-a-chip(OoC)microfluidic technologies represent promising new approach methodologies(NAMS)and a real alternative to animal testing.While tissue-specific decellularized extracellular matrix(ECM)can recapitulate in vivo-like microenvironments,its application in SG-on-a-chip(SGoC)is still underexplored.This study developed an injectable porcine decellularized submandibular gland(dSMG)hydrogel for bioengineering an SG MEC tissue chip.dSMG was prepared using a chemical and enzymatic decellularization process with 0.1%or 1%sodium dodecyl sulfate(SDS).Both treatments effectively removed DNA content while preserving key ECM components,including collagens,glycoproteins,and mucins.Proteomic analysis revealed that 1%SDS-treated dSMG contained a greater abundance of ECM components involved in matrix assembly and cell-ECM interactions compared to the 0.1%group.The 1%SDS-treated dSMG was subsequently digested with a pepsin-based buffer to form hydrogels.At 5 mg/mL,dSMG hydrogel exhibited nanofibrous architecture,thermo-responsive gelation,injectability into microfluidic devices,and minimal batch-to-batch biological variations.In static conditions,dSMG hydrogel significantly enhanced SG cell viability and mitochondria-dependent proliferation compared to Matrigel.Under gravity-driven flow,dSMG hydrogel promoted a ductal phenotype on human SG MEC cells,unlike on Matrigel.Additionally,dSMG hydrogel supported cholinergic-specific signaling and functional activity.These findings demonstrate the potential of dSMG hydrogel as a physiologically relevant matrix for SG cancer modeling towards drug screening applications in SGoC microfluidic systems.
基金funded by the National Research Council of Thailand(NRCT)and Chulalongkorn University with project number:N42A670176 to JNF(main PI)and to RC(Co-I)supported by the International Association for Dental,Oral and Craniofacial Research(IADR)2022 Innovation in Oral Care Award funded by GlaxoSmithKline to JNF,CHLH,KST,SY and WP+5 种基金supported by Thailand Science Research and Innovation Fund Chulalongkorn University to JNFRC.Center of Excellence and Innovation for Oral Health and Healthy Longevity is funded by the Ratchadaphiseksomphot Endowment Fund,Chulalongkorn University(Grant number:CE68_003_3200_001)supported by a Chulalongkorn University scholarship from Graduate Scholarship Program for ASEAN or Non-ASEAN Countriessupported by the 90th Anniversary of Chulalongkorn University Scholarship under Ratchadapisek Somphot Endowment Fund(Grant number:GCUGR1125662098M)the IADR-Southeast Asia Mentor-Mentee Funding provided to TTTT under the mentorship of JNF and OMsupported by the Second Century Fund(C2F),Chulalongkorn University provided to TVP.
文摘Oral mucositis(OM)remains a painful complication of anticancer chemotherapy(CT),tending to progress in severity in the presence of Fusobacterium nucleatum(Fn).Yet,no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking,halting the discovery of new drugs.Here,we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling.This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM.After modeling OM with all pro-inflammatory hallmarks,we were able to suppress OM with our in-house plant-produced epidermal growth factor(P-EGF),a well-known re-epithelialization cue.Thus,this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection.This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.
