Mycophenolic acid(MPA),the active moiety of both mycophenolate mofetil(MMF)and enteric-coated mycophenolate sodium(EC-MPS),serves as a primary immunosuppressant for maintaining solid organ transplants.Therapeutic drug...Mycophenolic acid(MPA),the active moiety of both mycophenolate mofetil(MMF)and enteric-coated mycophenolate sodium(EC-MPS),serves as a primary immunosuppressant for maintaining solid organ transplants.Therapeutic drug monitoring(TDM)enhances treatment outcomes through tailored approaches.This study aimed to develop an evidence-based guideline for MPA TDM,facilitating its rational application in clinical settings.The guideline plan was drawn from the Institute of Medicine and World Health Organization(WHO)guidelines.Using the Delphi method,clinical questions and outcome indicators were generated.Systematic reviews,Grading of Recommendations Assessment,Development,and Evaluation(GRADE)evidence quality evaluations,expert opinions,and patient values guided evidence-based suggestions for the guideline.External reviews further refined the recommendations.The guideline for the TDM of MPA(IPGRP-2020CN099)consists of four sections and 16 recommendations encompassing target populations,monitoring strategies,dosage regimens,and influencing factors.High-risk populations,timing of TDM,area under the curve(AUC)versus trough concentration(C0),target concentration ranges,monitoring frequency,and analytical methods are addressed.Formulation-specific recommendations,initial dosage regimens,populations with unique considerations,pharmacokinetic-informed dosing,body weight factors,pharmacogenetics,and drug–drug interactions are covered.The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy,promoting standardization of MPA TDM,and enhancing treatment efficacy and safety.展开更多
Rapid and accurate detection of infectious virus particles, not just viral nucleic acid, is essential to avoid unnecessary quarantine and effectively control the spread of viral diseases such as coronavirus disease 20...Rapid and accurate detection of infectious virus particles, not just viral nucleic acid, is essential to avoid unnecessary quarantine and effectively control the spread of viral diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). Real-time quantitative polymerase chain reaction (RT-qPCR) was the most widely used detection technique during the COVID-19 outbreak. However, it cannot discriminate between intact infectious viruses and surface-distorted, non-infectious virus particles or naked viral RNA. In this study, we present a strategy for the specific detection of infectious coronaviruses by combining viral receptor capture and reverse transcription loop-mediated isothermal amplification (RT-LAMP). We successfully applied this strategy to detect infectious virus particles of the SARS-CoV-2 surrogate virus and the human coronavirus NL63 (HCoV-NL63). Virus particles were first captured on ELISA plates coated with the recombinant human angiotensin-converting enzyme 2 (hACE2) receptor. Viral RNA was then extracted from the particles and detected by RT-LAMP using virus-specific primers. In our experimental setting, the proposed method had a minimum detection limit (LOD) of 90 PFU/mL, sensitivity of 96.2%, and specificity of 100%. Our study provides a proof-of-concept that viral receptor capture combined with RT-LAMP can differentiate infectious coronaviruses from non-infectious virions or naked viral RNA. This paves the way for this virus detection strategy to become a mainstream tool for the management, prevention and control of epidemic coronavirus diseases.展开更多
Background: In participating in the medical support work in the Nyingchi area of Tibet, the author found that the medical education resources in this area are scarce, and the clinical nurses in this area have relative...Background: In participating in the medical support work in the Nyingchi area of Tibet, the author found that the medical education resources in this area are scarce, and the clinical nurses in this area have relatively insufficient knowledge about blood glucose monitoring and management. Accurately understanding the knowledge-attitude/belief-practice (KAP) level of nurses in Nyingchi area on blood glucose management is of great significance to the development of blood glucose monitoring management guidance for nurses in this area. Therefore, this study investigated the current status of the management of blood glucose monitoring management standards for clinical nurses in Nyingchi, Tibet. Objective: To investigate and analyze the current situation of clinical nurses in Nyingchi region of Tibet to grasp the regulation of blood glucose monitoring and guide the implementation of the norm of blood glucose monitoring for clinical nurses. Methods: The research survey was carried out from March to April 2020. Random sampling method was used to select 134 clinical in-service nurses in Nyingchii, Tibet. The self-designed knowledge-attitude/belief-practice survey questionnaire for clinical nurses’ blood glucose monitoring and management in Tibet was used. Nurses’ blood glucose monitoring management “KAP” scores and related influencing factors are analyzed. Results: Blood sugar monitoring and management knowledge score is (36.78 ± 6.80), attitude dimension is (42.48 ± 6.42), practice dimension is (61.87 ± 10.24) and total score is (304.73 ± 36.24). The nurse’s department and whether to participate in diabetes training are the main influencing factors of the blood glucose monitoring management norms, knowledge and behavior (both P < 0.05). Conclusion: The standard knowledge of blood glucose monitoring and management of clinical nurses in Nyingchi region of Tibet is at the middle level, positive attitude and unsatisfactory behavior. Nursing managers should conduct standardized training for clinical nurses in blood glucose monitoring, develop the training mode of diabetes specialty nursing talents in Nyingchi area, and construct a complete management system of diabetes specialty nursing.展开更多
Objective: To investigate and analyze the current status of continuing nursing education (CNE) of in-service nurses in Tibet and their demand for continuing education. Methods: 663 active nurses in Tibet were taken as...Objective: To investigate and analyze the current status of continuing nursing education (CNE) of in-service nurses in Tibet and their demand for continuing education. Methods: 663 active nurses in Tibet were taken as the research objects, and the self-developed questionnaire was used to investigate the current status and needs of CNE, and the correlation between the CNE needs of active nurses and their personal conditions was analyzed. Results: This study shows that 65.61% (435/663) of active nurses have not participated in any CNE, and 91.86% (609/663) of active nurses believe that they need to participate in CNE. The problems faced by active nurses in participating in CNE include funding restrictions, time limitation and ability limitation. Logistic stepwise regression analysis reveals that the age of active nurses and working years of nurses are negatively correlated with the funding restrictions for participating in CNE (P < 0.05). It is relatively more difficult for young nurses with less working experience to obtain funding for participating in CNE. Moreover, there is a negative correlation between age, educational level and the ability of nurses to participate in CNE (P < 0.05). Younger nurses with lower educational level are more difficult to participate in CNE due to personal ability. There is a positive correlation between the length of working experience and the time limitation faced to participate in CNE (P < 0.05). Senior nurses are too busy with their work to participate in CNE due to limited time. Conclusion: The problems faced by active nurses in Tibet in participating in CNE come from funding, time and ability. Young nurses with limited working experience cannot participate in CNE resulting from limited ability and funds;while senior nurses are mainly restricted by time. It is recommended that hospitals and nursing management in Tibet should solve these problems faced by nurses in participating in CNE by implementing a flexible scheduling system, and providing funding or implementing an incentive system, to enhance the confidence of active nurses in participating in CNE.展开更多
Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral...Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.展开更多
The essential role of ethylene in fruit ripening has been thoroughly studied.However,the involvement of brassinosteroids(BRs)in the regulation of fruit ripening and their relationship with the ethylene pathway are poo...The essential role of ethylene in fruit ripening has been thoroughly studied.However,the involvement of brassinosteroids(BRs)in the regulation of fruit ripening and their relationship with the ethylene pathway are poorly understood.In the current study,we found that BRs were actively synthesized during tomato fruit ripening.We then generated transgenic lines overexpressing or silencing SlCYP90B3,which encodes a cytochrome P450 monooxygenase that catalyzes the rate-limiting step of BR synthesis.The expression level of SlCYP90B3 was positively related to the contents of bioactive BRs as well as the ripening process in tomato fruit,including enhanced softening and increased soluble sugar and flavor volatile contents.Both carotenoid accumulation and ethylene production were strongly correlated with the expression level of SlCYP90B3,corroborated by the altered expression of carotenoid biosynthetic genes as well as ethylene pathway genes in transgenic tomato fruits.However,the application of the ethylene perception inhibitor 1-methycyclopropene(1-MCP)abolished the promotion effect of SlCYP90B3 overexpression on carotenoid accumulation.Taken together,these results increase our understanding of the involvement of SlCYP90B3 in bioactive BR biosynthesis as well as fruit ripening in tomato,thus making SlCYP90B3 a target gene for improvement of visual,nutritional and flavor qualities of tomato fruits with no yield penalty.展开更多
The catastrophic rockslide,which frequently triggers numerous severe disasters worldwide,has drawn much attention globally;however,understanding the initiation mechanism of catastrophic rockslides in the absence of ty...The catastrophic rockslide,which frequently triggers numerous severe disasters worldwide,has drawn much attention globally;however,understanding the initiation mechanism of catastrophic rockslides in the absence of typical single triggering factors related to strong seismic activity or torrential precipitation continues to be challenging within the global scientific community.This study aims to determine the mechanism of the three largest catastrophic rockslides in the eastern Tibetan Plateau,Yigong,Xinmo,and Baige,over the past 20 years using field investigation,remote sensing,and runoff analysis.Instead of the conventional driving factors of heavy rainfall and strong earthquakes,the multi-wing butterfly effects(MWBE)of climatic factors and weak earthquakes are for the first time identified as drivers of the catastrophic rockslide disasters.First,strong tectonic uplift,fast fluvial incision,high-density faults,and large regional water confluence formed the slopes in the critical regime,creating the source conditions of rockslide.Second,the MWBE of early dry-heat events and antecedent rainfall,combined with imminent weak earthquakes,initiated rockslide.Third,the delayed amplified runoff moving toward the sliding surface and lowering the strength of the locking-rock segment constituted the fundamental mechanism of the MWBE on rockslide.The catastrophic rockslide was ultimately inferred to be a nonlinear chaotic process;however,prediction and forecasting of rockslide based on the MWBE in the early stages are possible and essential.This finding presents a new perspective concerning forecasting progressive landslides.展开更多
The scaled-up synthesis of organic-free monolayer nanomaterials is highly desirable,especially in obtaining green energy by electrocatalysis.In this study,a method for the scaled-up synthesis of the series of monolaye...The scaled-up synthesis of organic-free monolayer nanomaterials is highly desirable,especially in obtaining green energy by electrocatalysis.In this study,a method for the scaled-up synthesis of the series of monolayer layered double hydroxides(LDHs)without the addition of organic solvents is reported via the separate nucleation and aging steps process.The resulting monolayer LDHs with the thicknesses of less than 1 nm showed a narrow thickness distribution.X-ray absorption fine-structure revealed that monolayer NiFe-LDH nanosheets have a number of oxygen and metal vacancies defects.As a practical application,monolayer NiFe-LDH nanosheets containing defects showed an enhanced electrocatalytic water oxidation activity compared with that of bulk NiFe-LDH.Density functional theory calculations uncovered that excellent catalytic activity is attributed to vacancies defects.The proposed method is an economical and universally applicable strategy for the scaled-up production of monolayer LDHs.展开更多
Mercury（Hg）, mainly in cinnabar species, has been used in medicine for thousands of years in China, and worldwide concern has been raised on its toxicity. In this work, the amount of bioaccessible mercury in 16 Chin...Mercury（Hg）, mainly in cinnabar species, has been used in medicine for thousands of years in China, and worldwide concern has been raised on its toxicity. In this work, the amount of bioaccessible mercury in 16 Chinese patent medicines（CPMs） was measured by using an in vitro simulated digestion system, consisting of simulated gastric and intestinal fluid, to investigate the bioavailability of mercury in CPMs and evaluate its potential risk to human health. Total mercury and mercury in the gastrointestinal extracts were measured by inductively coupled plasma mass spectrometry（ICP-MS）. The levels of total Hg in 16 CPMs ranged from not detected to 11.89 mg/g, with a mean value of 1.13 mg/g, while the extractable Hg ranged from not detected to 4.37 μg/g, with a mean value of 0.42 μg/g.Mercury bioaccessibility varied significantly in the investigated CPMs, depending on the ingredient. Compared to the CPMs without cinnabar（2.5%–30.9%）, the percentage of mercury in the gastrointestinal supernatants for CPMs with cinnabar was quite a bit lower（0.037%）. By comparing with the Food and Agricultural Organization/World Health Organization Joint Expert Committee on Food Additives（FAO/WHO） safety guideline, the average daily intake dose（ADD） of Hg in the medicines was then calculated to access the risk of mercury to human health from taking CPMs.展开更多
Cruciferous sprout is a new form of vegetable product rich in bioactive compounds,especially glucosinolates.Previous studies have focused on increasing the accumulation of glucosinolates in cruciferous sprouts by appl...Cruciferous sprout is a new form of vegetable product rich in bioactive compounds,especially glucosinolates.Previous studies have focused on increasing the accumulation of glucosinolates in cruciferous sprouts by applying different chemical regulators,with a particular focus on their contribution to nutritional quality and health benefits.Nevertheless,the effects of melatonin and UV-B irradiation on glucosinolate biosynthesis remain unclear.In this study,it was found that changes in melatonin concentrations significantly affected the contents of individual as well as total aliphatic and indolic glucosinolates.The 5μmol·L^(-1)melatonin was decided as the optimum concentration that could increase the content of beneficial glucosinolates including glucoraphanin and 4-methoxy glucobrassicin in Chinese kale sprouts.Notably,the enhancement of glucosinolate accumulation by melatonin treatment could be further amplified by UV-B irradiation.Furthermore,our results showed that R2R3-MYB transcription factor BoaMYB28 and BoaMYB51,which are central regulators of aliphatic and indolic glucosinolate biosynthesis respectively,were both involved in the regulation of glucosinolate biosynthesis by melatonin and UV-B irradiation.Additionally,the expression of glucosinolate biosynthetic genes,including BoaCYP79F1,BoaCYP83A1,BoaSUR1,BoaUGT74B1,BoaCYP79B2,BoaCYP79B3,and BoaCYP83B1 participated in the formation of core structures and BoaFMOGS-OX5,BoaAOP2,BoaCYP81F2,and BoaIGMT1 involved in the sidechain modification of aliphatic and indolic glucosinolate,was regulated by melatonin or UV-B irradiation.Taken together,these findings provide a potential strategy for improving the nutritional quality and resistance of Chinese kale sprouts.展开更多
The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using p...The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using polyadenine(polyA)-mediated fluorescent spherical nucleic acid(FSNA)for miRNA analysis based on strand displacement reactions on gold nanoparticle(AuNP)surfaces and electrokinetic signal amplification(ESA)on a microfluidic chip.In this FSNA,polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au.The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA,resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer.Reporter DNA was replaced in the presence of target miRNA,leading to the recovery of reporter-DNA fluorescence.Subsequently,reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA.Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM.This method could also be used to detect miRNA-21 in human serum and urine samples,with recoveries of 104.0%-113.3% and 104.9%-108.0%,respectively.Furthermore,we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs(miRNA-21,miRNA-141,and miRNA-375),which increased the detection efficiency.Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.展开更多
Adenine is an essential building block of genetic material and a range of coenzymes.Chemical probes containing an adenine moiety have been used in kinase profiling studies in cell lysates.Here we report that adenine-d...Adenine is an essential building block of genetic material and a range of coenzymes.Chemical probes containing an adenine moiety have been used in kinase profiling studies in cell lysates.Here we report that adenine-derived small-molecule probes with an activated ester reactive group can covalently modify a conserved lysine residue of protein kinases and capture a number of nucleotide-binding proteins within living cells.展开更多
In this paper, we get necessary and sufficient conditions for a Finsler space en- dowed with an （α,β）-metric where its geodesic coefficients G^i （x, y） and the reverse of geodesic coefficients G^i（x,-y） have t...In this paper, we get necessary and sufficient conditions for a Finsler space en- dowed with an （α,β）-metric where its geodesic coefficients G^i （x, y） and the reverse of geodesic coefficients G^i（x,-y） have the same Douglas curvature. They are the conditions such that （α,β）-metrics have reversible geodesics.展开更多
In order to provide evidence for making clinical decision, the role of intravenous and nebulized MgSO4 in treatment of adult＇s acute asthma was systematically estimated in the present study. Pubmed, Embase, Web of Sc...In order to provide evidence for making clinical decision, the role of intravenous and nebulized MgSO4 in treatment of adult＇s acute asthma was systematically estimated in the present study. Pubmed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases （CNKI, WanFang） were systematically searched up to January 2016. Randomized controlled trails （RCTs） that compared the clinical outcomes of MgSO4 groups and placebo groups were included. The primary outcome was hospital admission. Secondary outcomes included pulmonary function, symptom scores, vital signs and adverse events. The methodological quality of the included studies was evaluated, and the forest plots with meta-analysis were drawn by RevMan 5.2. A total of 24 RCTs derived from 2931 patients were included. Both intravenous MgSO4 and nebulized MgSO4 treatments had no effect upon hospital admission （RR 0.91, 95% CI 0.80 to 1.03, P = 0.14; RR 0.78, 95% CI 0.56 to 1.08, P = 0.14）. Both intravenous MgSO4 and nebulized MgSO4 treatments were associated with significant evidence upon respiratory function （SMD 0.23, 95% CI 0.03 to 0.43, P = 0.02; SMD 0.37, 95% CI 0.11 to 0.64, P = 0.006）, but sensitivity analyses showed that outcomes were changed by omitting studies of less than 100 individuals （SMD 0.05, 95% C1-0.05 to 0.15, P = 0.35; SMD 0.05, 95% C1-0.16 to 0.25, P = 0.64）. There were no statistically significant differences in clinical symptom scores and vital signs （heart or pulse rate; systolic blood pressure; respiratory rate） in either form of MgSO4 compared with placebo groups （P〉0.05）. There were no serious adverse events reported in any literature. Overall, there was no role for intravenous and nebulized MgSO4 in the management of acute asthma in adults. Considering the low risk of serious adverse effects and easy availability, it seemed reasonable to use intravenous or nebulized MgSO4 treatment in adults with life threatening asthma in whom any potential benefit would justify the risks of treatment.展开更多
A reflective faceted structure is proposed to reshaping an incoherent light beam into two focalized spots-To obtain the desired irradiance distribution on a detector,custom optimization function is written,and the two...A reflective faceted structure is proposed to reshaping an incoherent light beam into two focalized spots-To obtain the desired irradiance distribution on a detector,custom optimization function is written,and the two dimensional tilt angles of each facet are optimized automatically in a pure non-sequential mode in Zemax OpticStudio 16.The result is also confirmed inside LightTools&2 from Synopsys.For measuring the quality of the optimization result in the case of two spots focalization,four factors including efficiency on the detector,uniformity,the root mean square error and the correlation coefficient are calculated.These four factors are used to evaluate the influence of several parameters on the irradiance distribution.These parameters include the incidence angle,the divergence angle,the facet size,the source type and the resolution of the facet angular positions.Finally,an analysis of those parameters is made and the performance of this type of component is demonstrated.展开更多
Objective:Given the unique cultural background,way of life,and physical environment of the Tibetan Plateau,this study aims to investigate the effects of health education using problem-based learning(PBL)approaches on ...Objective:Given the unique cultural background,way of life,and physical environment of the Tibetan Plateau,this study aims to investigate the effects of health education using problem-based learning(PBL)approaches on the knowledge,attitude,practice,and coping skills of women with high-risk pregnancies in this region.Methods:76 high-risk pregnancy cases were enrolled at Xizang’s Linzhi People’s Hospital between September 2023 and April 2024.30 patients admitted between September 2023 and December 2023 were selected as the control group and were performed with regular patient education.46 patients admitted between January 2024 and April 2024 were selected as the observation group and were performed regular patient education with problem-based learning approaches.Two groups’performance on their health knowledge,attitude,practice and coping skills before and after interventions were evaluated,and patient satisfaction were measured at the end of the study.Results:There was no statistical significance(P P P Conclusions:Health education with problem-based learning approaches is worth promoting as it can help high-risk pregnant women in plateau areas develop better health knowledge,attitude and practice and healthier coping skills.Also,it can improve patient sanctification.展开更多
Objective:to investigate the current situation of insulin injection provided by clinical nurses under KAP(Knowledge-Attitude-Practice)model on Linzhi,Tibet,and to discuss and analyse the influence factors.Methods:usin...Objective:to investigate the current situation of insulin injection provided by clinical nurses under KAP(Knowledge-Attitude-Practice)model on Linzhi,Tibet,and to discuss and analyse the influence factors.Methods:using a selfdesign questionnaire a questionnaire about the current situation of insulin injection provided by clinical nurses under KAP model on Linzhi,Tibet to investigate 268 clinical nurses in Linzhi,Tibet,who were chosen through random sampling method,in order to analyse the‘KAP’scoring and the influencing factors.Results:The scoring of‘Knowledge’is(65.642±10.313),the scoring of‘Attitude’is(55.478±8.099),the scoring of‘Practice’is(42.493±6.647),the total scoring is(163.612±19.292).The related influence factors,including hospital,department,academic credentials,professional qualifications and whether receiving diabetes specialized training,have statistical significance(P value<0.5).Conclusion:The KAP of insulin injection provided by clinical nurses in Linzhi,Tibet is on middle level.For nursing managers,it is strongly advised that a normative.展开更多
基金supported by the National Natural Science Foundation of China(NSFC)(No.72304007)the Huatong Guokang Medical Research Fund(No.2023HT010)。
文摘Mycophenolic acid(MPA),the active moiety of both mycophenolate mofetil(MMF)and enteric-coated mycophenolate sodium(EC-MPS),serves as a primary immunosuppressant for maintaining solid organ transplants.Therapeutic drug monitoring(TDM)enhances treatment outcomes through tailored approaches.This study aimed to develop an evidence-based guideline for MPA TDM,facilitating its rational application in clinical settings.The guideline plan was drawn from the Institute of Medicine and World Health Organization(WHO)guidelines.Using the Delphi method,clinical questions and outcome indicators were generated.Systematic reviews,Grading of Recommendations Assessment,Development,and Evaluation(GRADE)evidence quality evaluations,expert opinions,and patient values guided evidence-based suggestions for the guideline.External reviews further refined the recommendations.The guideline for the TDM of MPA(IPGRP-2020CN099)consists of four sections and 16 recommendations encompassing target populations,monitoring strategies,dosage regimens,and influencing factors.High-risk populations,timing of TDM,area under the curve(AUC)versus trough concentration(C0),target concentration ranges,monitoring frequency,and analytical methods are addressed.Formulation-specific recommendations,initial dosage regimens,populations with unique considerations,pharmacokinetic-informed dosing,body weight factors,pharmacogenetics,and drug–drug interactions are covered.The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy,promoting standardization of MPA TDM,and enhancing treatment efficacy and safety.
基金supported by the National Natural Science Foundation of China(32470160)the National Key Research and Development Program of China(2021YFC2300100,GZNL2023A01008)+2 种基金the Shenzhen Science and Technology Program(#JSGG20200225150431472,JSGG20210901145403012,and JSGG20220301090005007)the“Pearl River Talent Plan”Innovation and Entrepreneurship Team Project of Guangdong Province(2016LJ06Y540 and 2019ZT08Y464)the Science and Technology Program of Guangdong Province,China(2021B1212040017).
文摘Rapid and accurate detection of infectious virus particles, not just viral nucleic acid, is essential to avoid unnecessary quarantine and effectively control the spread of viral diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). Real-time quantitative polymerase chain reaction (RT-qPCR) was the most widely used detection technique during the COVID-19 outbreak. However, it cannot discriminate between intact infectious viruses and surface-distorted, non-infectious virus particles or naked viral RNA. In this study, we present a strategy for the specific detection of infectious coronaviruses by combining viral receptor capture and reverse transcription loop-mediated isothermal amplification (RT-LAMP). We successfully applied this strategy to detect infectious virus particles of the SARS-CoV-2 surrogate virus and the human coronavirus NL63 (HCoV-NL63). Virus particles were first captured on ELISA plates coated with the recombinant human angiotensin-converting enzyme 2 (hACE2) receptor. Viral RNA was then extracted from the particles and detected by RT-LAMP using virus-specific primers. In our experimental setting, the proposed method had a minimum detection limit (LOD) of 90 PFU/mL, sensitivity of 96.2%, and specificity of 100%. Our study provides a proof-of-concept that viral receptor capture combined with RT-LAMP can differentiate infectious coronaviruses from non-infectious virions or naked viral RNA. This paves the way for this virus detection strategy to become a mainstream tool for the management, prevention and control of epidemic coronavirus diseases.
文摘Background: In participating in the medical support work in the Nyingchi area of Tibet, the author found that the medical education resources in this area are scarce, and the clinical nurses in this area have relatively insufficient knowledge about blood glucose monitoring and management. Accurately understanding the knowledge-attitude/belief-practice (KAP) level of nurses in Nyingchi area on blood glucose management is of great significance to the development of blood glucose monitoring management guidance for nurses in this area. Therefore, this study investigated the current status of the management of blood glucose monitoring management standards for clinical nurses in Nyingchi, Tibet. Objective: To investigate and analyze the current situation of clinical nurses in Nyingchi region of Tibet to grasp the regulation of blood glucose monitoring and guide the implementation of the norm of blood glucose monitoring for clinical nurses. Methods: The research survey was carried out from March to April 2020. Random sampling method was used to select 134 clinical in-service nurses in Nyingchii, Tibet. The self-designed knowledge-attitude/belief-practice survey questionnaire for clinical nurses’ blood glucose monitoring and management in Tibet was used. Nurses’ blood glucose monitoring management “KAP” scores and related influencing factors are analyzed. Results: Blood sugar monitoring and management knowledge score is (36.78 ± 6.80), attitude dimension is (42.48 ± 6.42), practice dimension is (61.87 ± 10.24) and total score is (304.73 ± 36.24). The nurse’s department and whether to participate in diabetes training are the main influencing factors of the blood glucose monitoring management norms, knowledge and behavior (both P < 0.05). Conclusion: The standard knowledge of blood glucose monitoring and management of clinical nurses in Nyingchi region of Tibet is at the middle level, positive attitude and unsatisfactory behavior. Nursing managers should conduct standardized training for clinical nurses in blood glucose monitoring, develop the training mode of diabetes specialty nursing talents in Nyingchi area, and construct a complete management system of diabetes specialty nursing.
文摘Objective: To investigate and analyze the current status of continuing nursing education (CNE) of in-service nurses in Tibet and their demand for continuing education. Methods: 663 active nurses in Tibet were taken as the research objects, and the self-developed questionnaire was used to investigate the current status and needs of CNE, and the correlation between the CNE needs of active nurses and their personal conditions was analyzed. Results: This study shows that 65.61% (435/663) of active nurses have not participated in any CNE, and 91.86% (609/663) of active nurses believe that they need to participate in CNE. The problems faced by active nurses in participating in CNE include funding restrictions, time limitation and ability limitation. Logistic stepwise regression analysis reveals that the age of active nurses and working years of nurses are negatively correlated with the funding restrictions for participating in CNE (P < 0.05). It is relatively more difficult for young nurses with less working experience to obtain funding for participating in CNE. Moreover, there is a negative correlation between age, educational level and the ability of nurses to participate in CNE (P < 0.05). Younger nurses with lower educational level are more difficult to participate in CNE due to personal ability. There is a positive correlation between the length of working experience and the time limitation faced to participate in CNE (P < 0.05). Senior nurses are too busy with their work to participate in CNE due to limited time. Conclusion: The problems faced by active nurses in Tibet in participating in CNE come from funding, time and ability. Young nurses with limited working experience cannot participate in CNE resulting from limited ability and funds;while senior nurses are mainly restricted by time. It is recommended that hospitals and nursing management in Tibet should solve these problems faced by nurses in participating in CNE by implementing a flexible scheduling system, and providing funding or implementing an incentive system, to enhance the confidence of active nurses in participating in CNE.
基金funded by the National Natural Science Foundation of China(Grant No.81970188)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Grant No.2016-12M-1-001)。
文摘Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
基金supported by the National Natural Science Foundation of China(Key Program,No.31830078)the Ministry of Agriculture of China(2016ZX08009003-001)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LZ15C150001)the Fundamental Research Funds for the Central University(2020QNA6023).
文摘The essential role of ethylene in fruit ripening has been thoroughly studied.However,the involvement of brassinosteroids(BRs)in the regulation of fruit ripening and their relationship with the ethylene pathway are poorly understood.In the current study,we found that BRs were actively synthesized during tomato fruit ripening.We then generated transgenic lines overexpressing or silencing SlCYP90B3,which encodes a cytochrome P450 monooxygenase that catalyzes the rate-limiting step of BR synthesis.The expression level of SlCYP90B3 was positively related to the contents of bioactive BRs as well as the ripening process in tomato fruit,including enhanced softening and increased soluble sugar and flavor volatile contents.Both carotenoid accumulation and ethylene production were strongly correlated with the expression level of SlCYP90B3,corroborated by the altered expression of carotenoid biosynthetic genes as well as ethylene pathway genes in transgenic tomato fruits.However,the application of the ethylene perception inhibitor 1-methycyclopropene(1-MCP)abolished the promotion effect of SlCYP90B3 overexpression on carotenoid accumulation.Taken together,these results increase our understanding of the involvement of SlCYP90B3 in bioactive BR biosynthesis as well as fruit ripening in tomato,thus making SlCYP90B3 a target gene for improvement of visual,nutritional and flavor qualities of tomato fruits with no yield penalty.
基金supported by the National Natural Science Foundation of China(Grant No.U20A20110)the Second Tibetan Plateau Scientific Expedition and Research Program(Grant No.2019QZKK0906)+2 种基金the Key R&D Projects of Tibet Autonomous Region Science and Technology Pro ject(Grant No.XZ202101ZD0013G)the International Cooperation Overseas Platform Project,CAS(Grant No.131C11KYSB20200033)the Outstanding Talent Project of Thousand Talents Program in China.
文摘The catastrophic rockslide,which frequently triggers numerous severe disasters worldwide,has drawn much attention globally;however,understanding the initiation mechanism of catastrophic rockslides in the absence of typical single triggering factors related to strong seismic activity or torrential precipitation continues to be challenging within the global scientific community.This study aims to determine the mechanism of the three largest catastrophic rockslides in the eastern Tibetan Plateau,Yigong,Xinmo,and Baige,over the past 20 years using field investigation,remote sensing,and runoff analysis.Instead of the conventional driving factors of heavy rainfall and strong earthquakes,the multi-wing butterfly effects(MWBE)of climatic factors and weak earthquakes are for the first time identified as drivers of the catastrophic rockslide disasters.First,strong tectonic uplift,fast fluvial incision,high-density faults,and large regional water confluence formed the slopes in the critical regime,creating the source conditions of rockslide.Second,the MWBE of early dry-heat events and antecedent rainfall,combined with imminent weak earthquakes,initiated rockslide.Third,the delayed amplified runoff moving toward the sliding surface and lowering the strength of the locking-rock segment constituted the fundamental mechanism of the MWBE on rockslide.The catastrophic rockslide was ultimately inferred to be a nonlinear chaotic process;however,prediction and forecasting of rockslide based on the MWBE in the early stages are possible and essential.This finding presents a new perspective concerning forecasting progressive landslides.
基金supported by the National Nature Science Foundation of China(U1707603,21878008,21625101,U1507102,21922801)the Beijing Natural Science Foundation(2182047,2202036)the Fundamental Research Funds for the Central Universities(XK1802-6,XK1902,12060093063,2312018RC07)。
文摘The scaled-up synthesis of organic-free monolayer nanomaterials is highly desirable,especially in obtaining green energy by electrocatalysis.In this study,a method for the scaled-up synthesis of the series of monolayer layered double hydroxides(LDHs)without the addition of organic solvents is reported via the separate nucleation and aging steps process.The resulting monolayer LDHs with the thicknesses of less than 1 nm showed a narrow thickness distribution.X-ray absorption fine-structure revealed that monolayer NiFe-LDH nanosheets have a number of oxygen and metal vacancies defects.As a practical application,monolayer NiFe-LDH nanosheets containing defects showed an enhanced electrocatalytic water oxidation activity compared with that of bulk NiFe-LDH.Density functional theory calculations uncovered that excellent catalytic activity is attributed to vacancies defects.The proposed method is an economical and universally applicable strategy for the scaled-up production of monolayer LDHs.
基金supported by the National Basic Research Program (973) of China (No. 2013CB430004)the National Natural Science Foundation of China (Nos. 21120102040, 21075130)
文摘Mercury（Hg）, mainly in cinnabar species, has been used in medicine for thousands of years in China, and worldwide concern has been raised on its toxicity. In this work, the amount of bioaccessible mercury in 16 Chinese patent medicines（CPMs） was measured by using an in vitro simulated digestion system, consisting of simulated gastric and intestinal fluid, to investigate the bioavailability of mercury in CPMs and evaluate its potential risk to human health. Total mercury and mercury in the gastrointestinal extracts were measured by inductively coupled plasma mass spectrometry（ICP-MS）. The levels of total Hg in 16 CPMs ranged from not detected to 11.89 mg/g, with a mean value of 1.13 mg/g, while the extractable Hg ranged from not detected to 4.37 μg/g, with a mean value of 0.42 μg/g.Mercury bioaccessibility varied significantly in the investigated CPMs, depending on the ingredient. Compared to the CPMs without cinnabar（2.5%–30.9%）, the percentage of mercury in the gastrointestinal supernatants for CPMs with cinnabar was quite a bit lower（0.037%）. By comparing with the Food and Agricultural Organization/World Health Organization Joint Expert Committee on Food Additives（FAO/WHO） safety guideline, the average daily intake dose（ADD） of Hg in the medicines was then calculated to access the risk of mercury to human health from taking CPMs.
基金supported by grants from the National Science Foundation of China (Grant Nos.32202466,32172593,and32272746)。
文摘Cruciferous sprout is a new form of vegetable product rich in bioactive compounds,especially glucosinolates.Previous studies have focused on increasing the accumulation of glucosinolates in cruciferous sprouts by applying different chemical regulators,with a particular focus on their contribution to nutritional quality and health benefits.Nevertheless,the effects of melatonin and UV-B irradiation on glucosinolate biosynthesis remain unclear.In this study,it was found that changes in melatonin concentrations significantly affected the contents of individual as well as total aliphatic and indolic glucosinolates.The 5μmol·L^(-1)melatonin was decided as the optimum concentration that could increase the content of beneficial glucosinolates including glucoraphanin and 4-methoxy glucobrassicin in Chinese kale sprouts.Notably,the enhancement of glucosinolate accumulation by melatonin treatment could be further amplified by UV-B irradiation.Furthermore,our results showed that R2R3-MYB transcription factor BoaMYB28 and BoaMYB51,which are central regulators of aliphatic and indolic glucosinolate biosynthesis respectively,were both involved in the regulation of glucosinolate biosynthesis by melatonin and UV-B irradiation.Additionally,the expression of glucosinolate biosynthetic genes,including BoaCYP79F1,BoaCYP83A1,BoaSUR1,BoaUGT74B1,BoaCYP79B2,BoaCYP79B3,and BoaCYP83B1 participated in the formation of core structures and BoaFMOGS-OX5,BoaAOP2,BoaCYP81F2,and BoaIGMT1 involved in the sidechain modification of aliphatic and indolic glucosinolate,was regulated by melatonin or UV-B irradiation.Taken together,these findings provide a potential strategy for improving the nutritional quality and resistance of Chinese kale sprouts.
基金supported financially by the National Natural Science Foundation of China(Grant No.:81973282)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.:2018A030313843 and 2021A1515011493)+3 种基金National College Students Innovation and Entrepreneurship Training Program(Grant No.:202012121024)Science and Technology Innovation Strategic Special Project of Guangdong Province("Climbing Program"Special ProjectGrantNo.:pdjh2022b0106)Guangdong College Students Innovation and Entrepreneurship Training Program(Grant No.:S202112121154).
文摘The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using polyadenine(polyA)-mediated fluorescent spherical nucleic acid(FSNA)for miRNA analysis based on strand displacement reactions on gold nanoparticle(AuNP)surfaces and electrokinetic signal amplification(ESA)on a microfluidic chip.In this FSNA,polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au.The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA,resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer.Reporter DNA was replaced in the presence of target miRNA,leading to the recovery of reporter-DNA fluorescence.Subsequently,reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA.Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM.This method could also be used to detect miRNA-21 in human serum and urine samples,with recoveries of 104.0%-113.3% and 104.9%-108.0%,respectively.Furthermore,we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs(miRNA-21,miRNA-141,and miRNA-375),which increased the detection efficiency.Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.
基金funding support from the National Natural Science Foundation of China(No.81872749)Shenzhen Science and Technology Innovation Commission(Nos.20200815000631001 and JCYJ20200109120414564)Peking University。
文摘Adenine is an essential building block of genetic material and a range of coenzymes.Chemical probes containing an adenine moiety have been used in kinase profiling studies in cell lysates.Here we report that adenine-derived small-molecule probes with an activated ester reactive group can covalently modify a conserved lysine residue of protein kinases and capture a number of nucleotide-binding proteins within living cells.
基金Supported by the National Natural Science Foundation of China(Grant No.11471246)the Jiangxi Provincial Science and Technology Project(Grant No.20161BAB211021)
文摘In this paper, we get necessary and sufficient conditions for a Finsler space en- dowed with an （α,β）-metric where its geodesic coefficients G^i （x, y） and the reverse of geodesic coefficients G^i（x,-y） have the same Douglas curvature. They are the conditions such that （α,β）-metrics have reversible geodesics.
文摘In order to provide evidence for making clinical decision, the role of intravenous and nebulized MgSO4 in treatment of adult＇s acute asthma was systematically estimated in the present study. Pubmed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases （CNKI, WanFang） were systematically searched up to January 2016. Randomized controlled trails （RCTs） that compared the clinical outcomes of MgSO4 groups and placebo groups were included. The primary outcome was hospital admission. Secondary outcomes included pulmonary function, symptom scores, vital signs and adverse events. The methodological quality of the included studies was evaluated, and the forest plots with meta-analysis were drawn by RevMan 5.2. A total of 24 RCTs derived from 2931 patients were included. Both intravenous MgSO4 and nebulized MgSO4 treatments had no effect upon hospital admission （RR 0.91, 95% CI 0.80 to 1.03, P = 0.14; RR 0.78, 95% CI 0.56 to 1.08, P = 0.14）. Both intravenous MgSO4 and nebulized MgSO4 treatments were associated with significant evidence upon respiratory function （SMD 0.23, 95% CI 0.03 to 0.43, P = 0.02; SMD 0.37, 95% CI 0.11 to 0.64, P = 0.006）, but sensitivity analyses showed that outcomes were changed by omitting studies of less than 100 individuals （SMD 0.05, 95% C1-0.05 to 0.15, P = 0.35; SMD 0.05, 95% C1-0.16 to 0.25, P = 0.64）. There were no statistically significant differences in clinical symptom scores and vital signs （heart or pulse rate; systolic blood pressure; respiratory rate） in either form of MgSO4 compared with placebo groups （P〉0.05）. There were no serious adverse events reported in any literature. Overall, there was no role for intravenous and nebulized MgSO4 in the management of acute asthma in adults. Considering the low risk of serious adverse effects and easy availability, it seemed reasonable to use intravenous or nebulized MgSO4 treatment in adults with life threatening asthma in whom any potential benefit would justify the risks of treatment.
基金supported by Natural Science Foundation of Shandong Province,China(No.ZR2019BF033).
文摘A reflective faceted structure is proposed to reshaping an incoherent light beam into two focalized spots-To obtain the desired irradiance distribution on a detector,custom optimization function is written,and the two dimensional tilt angles of each facet are optimized automatically in a pure non-sequential mode in Zemax OpticStudio 16.The result is also confirmed inside LightTools&2 from Synopsys.For measuring the quality of the optimization result in the case of two spots focalization,four factors including efficiency on the detector,uniformity,the root mean square error and the correlation coefficient are calculated.These four factors are used to evaluate the influence of several parameters on the irradiance distribution.These parameters include the incidence angle,the divergence angle,the facet size,the source type and the resolution of the facet angular positions.Finally,an analysis of those parameters is made and the performance of this type of component is demonstrated.
基金Leading Specialist Construction Project-Department of the First Affiliated Hospital,Jinan University(2022225).
文摘Objective:Given the unique cultural background,way of life,and physical environment of the Tibetan Plateau,this study aims to investigate the effects of health education using problem-based learning(PBL)approaches on the knowledge,attitude,practice,and coping skills of women with high-risk pregnancies in this region.Methods:76 high-risk pregnancy cases were enrolled at Xizang’s Linzhi People’s Hospital between September 2023 and April 2024.30 patients admitted between September 2023 and December 2023 were selected as the control group and were performed with regular patient education.46 patients admitted between January 2024 and April 2024 were selected as the observation group and were performed regular patient education with problem-based learning approaches.Two groups’performance on their health knowledge,attitude,practice and coping skills before and after interventions were evaluated,and patient satisfaction were measured at the end of the study.Results:There was no statistical significance(P P P Conclusions:Health education with problem-based learning approaches is worth promoting as it can help high-risk pregnant women in plateau areas develop better health knowledge,attitude and practice and healthier coping skills.Also,it can improve patient sanctification.
文摘Objective:to investigate the current situation of insulin injection provided by clinical nurses under KAP(Knowledge-Attitude-Practice)model on Linzhi,Tibet,and to discuss and analyse the influence factors.Methods:using a selfdesign questionnaire a questionnaire about the current situation of insulin injection provided by clinical nurses under KAP model on Linzhi,Tibet to investigate 268 clinical nurses in Linzhi,Tibet,who were chosen through random sampling method,in order to analyse the‘KAP’scoring and the influencing factors.Results:The scoring of‘Knowledge’is(65.642±10.313),the scoring of‘Attitude’is(55.478±8.099),the scoring of‘Practice’is(42.493±6.647),the total scoring is(163.612±19.292).The related influence factors,including hospital,department,academic credentials,professional qualifications and whether receiving diabetes specialized training,have statistical significance(P value<0.5).Conclusion:The KAP of insulin injection provided by clinical nurses in Linzhi,Tibet is on middle level.For nursing managers,it is strongly advised that a normative.
