Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

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.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective To investigate the characteristics of adverse drug event(ADE)related to tacrolimus(Tac)in pediatric solid organ transplant recipients.Methods The data were retrieved from the US Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the second quarter of 2023.The ADE data of pediatric organ transplant recipients with Tac as the primary suspected drug were extracted.The relationship between Tac and ADE was quantitatively analyzed by proportional imbalance method.Basic characteristics and signal strength of ADE related to Tac were analyzed.ADE related to Tac in children of different ages and different types of organ transplantation were analyzed.Results A total of 1 443 children's ADE reports involving Tac were screened,including 188 cases(13.0％)of heart transplantation,668 cases(46.3％)of liver transplantation,531 cases(36.8％)of kidney transplantation and 56 cases(3.9％)of lung transplantation.The median age of children was 10 years old.The top three countries with ADE reporting were the United States,France and the United Kingdom.China reported 26 cases,accounting for 1.8％.Infection and infectious diseases accounted for the highest proportion(20.96％)in ADE related to Tac,including EB virus and cytomegalovirus infection,etc.Infection and infectious diseases occupied the largest proportion of ADE related to Tac in children of different ages,whereas the pathogen types were different.Rejection,unstable immunosuppression level and renal function damage were also common ADE related to Tac in children of all ages.Nervous system disease was the main ADE in heart transplant recipients,while infection and infectious diseases were more common in liver and kidney transplant recipients.Rejection was the most common ADE in lung transplant recipients.Conclusions ADE related to Tac possess different distribution characteristics in different types of organ transplantation.Extensive attention should be paid to individualized drug monitoring and risk assessment in pediatric organ transplant recipients,thereby optimizing Tac treatment and reducing the risk of ADE.

Objective:To analyze and evaluate the items of the general module of multidimensional health measurement instruments system for elderly patients with chronic disease (MHIEC-GM)(V1.0) based on classical test theory (CTT) and item response theory (IRT).Methods:A self-administered survey of 2 375 elderly patients with chronic diseases was conducted using the MHIEC-GM(V1.0) scale. The quality of items was analyzed using the variability method, correlation coefficient method, factor analysis method, and Cronbach's α coefficient method based on CTT. The difficulty coefficient, differentiation coefficient, and information content of items were analyzed using the IRT analysis software MULTILOG 7.03.Results:The CTT results showed that the standard deviations of all nine items were greater than 0.9. The results of the correlation coefficient method, the factor analysis method and the Cronbach′s α coefficient method showed that except for the GMI9 item, the correlation coefficients between the other items and the total scale were all greater than 0.5, and the factor loads were all greater than 0.5, and the Cronbach′s α coefficients after the deletion of the items were all less than 0.763. Based on the results of the four analysis methods, except for the GMI9 item, all the other items had good characteristics. The IRT results showed that the information contents of all items were >0.333 (5/15) except for the GMI4, GMI6, and GMI8, and the differentiation coefficient of each item was 1.44. The items that difficulty coefficient met the [-4, 4] inclusion criteria were the GMI2, GMI3, GMI5, GMI7 and GMI9, showing a monotonically increasing trend with increasing difficulty level. The items of GMI1, GMI4, GMI6, and GMI8 needed further improvement.Conclusion:Most of items of the MHIEC-GM(V1.0) scale have good psychometric properties, but some items need to be further revised and validated according to the characteristics of chronic diseases in the elderly.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b.Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases.It is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's disease.Obviously,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases.However,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed.Therefore,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases.Drugs targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

Objective:To explore the clinical efficacy of ceftazidime/avibactam(CZA)plus aztreonam(ATM)for New Delhi metallo-β-lactamase(NDM)carbapenem-resistant Klebsiella pneumoniae(CRKP)infection after kidney transplantation.Methods:Clinical data are retrospectively reviewed for 11 RT recipients infected with NDM metallo-β-lactamase CRKP admitted into First Affiliated Hospital of Xi 'an Jiaotong University and Affiliated Renji Hospital of Shanghai Jiao Tong University from November 2018 to December 2019.Based upon treatment protocol, they are divided into two groups of ceftazidime/avibactam plus aztreonam(CZA-ATM, 5 cases)and other effective antibiotics(OAA, 6 cases).Age, gender, infection type, drug resistance gene, changes in body temperature and leucocyte count, treatment course and prognosis are summarized.Results:A total of 11 patients with NDM-producing CRKP infection after RT are recruited.There are seven males and four females with an age range of(19~66)(38.9±14.4)years.There are mixed pulmonary and urinary tract infections(3 cases), urinary tract infection(2 cases), pulmonary infection(1 case)and perirenal infection(5 cases).All isolates harbore NDM carbapenemase gene, 5 isolates carry Klebsiella pneumoniae carbapenemase(KPC)gene and 1 isolate contained both imipenemase metallo-β-lactamase(IMP)and verona integron-encoded metallo-β-lactamase(VIM)gene concurrently.Ceftazidime-avibactam plus aztreonam(CZA-ATM)is prescribed in five patients while the remainders receive OAA.No adverse reactions occurred in individuals on CZA-ATM and 2 cases on OAA have adverse reactions with a poor appetite and diarrhea.After 30-day infection, the curative cases of CZA-ATM and OAAs groups reach 4 and 5 respectively.No death occurred in neither groups at Day 30.And 90-day mortality is 0 and 1 respectively.Conclusions:For RT patients infected with NDM-producing CRKP, CZA-ATM combination therapy may be another effective treatment.

On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARS-CoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after re-covery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12-18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.

Objective:To compare the clinical characteristics and etiology changes of patients with bronchiolitis before the pandemic of coronavirus disease 2019(COVID-19)with those after the pandemic, and to provide a basis for the clinical diagnosis, treatment and prevention of bronchiolitis.Methods:Retrospective analysis were made on the clinical characteristics and etiological changes of patients who were hospitalized with bronchiolitis in the Department of Pulmonology, Children′s Hospital of Soochow University before COVID-19 pandemic(from February 1, 2019 to January 31, 2020, called as Group 2019-2020)and after COVID-19 pandemic(from February 1, 2020 to January 31, 2021, called as Group 2020-2021). Medical records were reviewed to compare general conditions, clinical manifestations, and laboratory tests.Nasopharyngeal secretion examination results were collected to compare the differences in pathogenic composition.Results:A total of 285 patients were enrolled in the Group 2019-2020, while 190 patients in the Group 2020-2021.There were no significant differences in gender, age, symptom duration prior to admission and length of stay between the two groups( P>0.05). The proportion of moderate/severe cases in the Group 2020-2021 was lower than that in the Group 2019-2020[10.53%(20/190)vs 21.75%(62/285)]and the difference was statistically significant( χ2=10.062, P<0.05). The proportion of stuffy nose rhinorrhea in the Group 2020-2021 was higher than that in the Group 2019-2020, while the proportion of gastrointestinal symptoms(vomiting and diarrhea)in the Group 2020-2021 was lower than that in the Group 2019-2020 [57.37%(109/190)vs 47.37%(135/285)and 15.79%(30/190)vs 24.56 %(70/285)]and the differences were statistically significant( χ2 were 4.563 and 5.278 respectively, all P<0.05). There were no significant differences in the proportions of fever, dyspnea, shortness of breath and cyanosis between the two groups(all P>0.05). The creatine kinase isoenzyme(CK-MB)in the Group 2020-2021 was lower than that in the Group 2019-2020[4.15(2.90~5.60)vs 6.70(4.20~22.10)]and the difference was statistically significant( Z=-8.757, P<0.05). There were no statistically significant differences in white blood cell count(WBC), percentage of neutrophil(N%), blood platelet count(PLT), percentage of eosinophil(EOS%), C-reactive protein(CRP), alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)between the two groups(all P>0.05). The total pathogen detection rate, positive rate of respiratory syncytial virus(RSV), positive rate of mycoplasma pneumoniae(MP)and mixed infection rate in the Group 2020-2021 were lower than those in the Group 2019-2020[65.26%(124/190)vs 75.09%(214/285), 14.21%(27/190)vs 30.18%(86/285), 6.32%(12/190)vs 15.09%(43/285), 16.84%(32/190)vs 25.61%(73/285)], with statistically significant differences( χ2 were 5.361, 16.026, 8.568 and 5.094 respectively, all P<0.05). The positive rate of rhinovirus in the Group 2020-2021 was higher than that in the Group 2019-2020[13.16%(25/190)vs 4.91%(14/285)]and the difference was statistically significant( χ2=10.285, P<0.05). There were no significant differences in the positive rates of human metapneumovirus, Boca virus and parainfluenza virus 3 between the two groups(all P>0.05). Conclusion:The clinical characteristics and etiology of patients with bronchiolitis have changed after the COVID-19 pandemic.The quarantine and protection measures reduce the transmission of associated pathogens and the severity of the disease.