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

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Objective To explore a standardized approach for indicating dosages in Chinese patent medicines(CPM)instructions.Methods A review of 1 378 classic formulas of traditional Chinese medicine in the 2020 edition of the Pharmaco-poeia of the People's Republic of China(Chinese Pharmacopoeia)was conducted,focusing on three aspects:overdose,different dosage forms,and inclusion of toxic herbs.Approximately 50 representative formulas were selected,and their daily dosage of herbal pieces and the corresponding dosage of individual herbs were calculated.These results were then compared and analyzed against the dosages stipulated in the Chinese Pharmacopoeia.Results ①Overdose:Among the 1 378 reviewed formulas,146(10.60％)were found to involve overdose.Specifically,eight formulas were identified as having an overdose of approximately 3 to 5 times the recommended dose,including Duanxueliu tablets and Zhixue Fumai mixture.②Dosage variations across dosage forms:Based on the conversion of the Ming-Qing dynasty dosage of one liang(Chinese traditional weight unit)to 36 g,the estimated dai-ly dose per component of crude herbs in Yinqiao powder was close to the upper limit specified in the Chinese Pharmacopoeia.The total daily dose of crude herbs(75.60 g)was approximately five times that of the Yinqiao powder(15 g)listed in the Chinese Pharmacopoeia and three times that of the Japanese Kampo Yinqiao powder(23.868 g).Significant differences in dosage were ob-served among Yinqiao Jiedu preparations of different dosage forms.In terms of total daily dose of crude herbs,granules(52.50 g)had the highest dose,approximately 3-5 times that of tablets/capsules(11.20 g),soft capsules(13.44 g),and powders(15.00 g),but still 30％ lower than the original prescription from ancient texts(75.6 g).Comparing the daily dose per compo-nent,granules fell within the Chinese Pharmacopoeia dose range,while tablets,capsules,soft capsules,and powders were all below the Chinese Pharmacopoeia dose.③Inclusion of toxic herbs:Among the 20 oral formulations containing Strychnos nux-vomica(Maqianzi)listed in the Chinese Pharmacopoeia,seven species exceeded the pharmacopoeial dose of 0.3-0.6 g per day.Notably,Shenjin Huoluo pill and Shufeng Dingtong pill exceeded the Chinese Pharmacopoeia dose by 1.5-2 times.The daily dose of strych-nosine in Shenjin Huoluo pill was 21.3 mg,exceeding the toxic dose range of 5-10 mg.Conclusions The dosage indications in CPM instructions must adhere to a unified format,clearly stating the daily dose per component of crude herbs,the total daily dose of crude herbs,and the total number of administrations under the"Dosage and Administration"section.For instance,"Yinqiao Jiedu granules,with a total daily dose equivalent to 60 g of crude herbs taken in four doses(including:Flos Lonicerae 10.71 g,Fructus Forsythiae 10.71 g,Radix Platycodi 6.43 g,Herba Menthae Haplocalycis 6.43 g,Fructus Arctii 6.43 g,Semen Sojae Preparatum 5.36 g,Radix Glycyrrhizae 5.36 g,Herba Lophatheri 4.29 g,Herba Schizonepetae 4.29 g)."For CPM containing tox-ic herbs,dosage indications are even more crucial,such as specifying the daily dose of Maqianzi powder/processed Maqianzi and strychnosine in formulations containing this herb.

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

Objective To explore a standardized approach for indicating dosages in Chinese patent medicines(CPM)instructions.Methods A review of 1 378 classic formulas of traditional Chinese medicine in the 2020 edition of the Pharmaco-poeia of the People's Republic of China(Chinese Pharmacopoeia)was conducted,focusing on three aspects:overdose,different dosage forms,and inclusion of toxic herbs.Approximately 50 representative formulas were selected,and their daily dosage of herbal pieces and the corresponding dosage of individual herbs were calculated.These results were then compared and analyzed against the dosages stipulated in the Chinese Pharmacopoeia.Results ①Overdose:Among the 1 378 reviewed formulas,146(10.60％)were found to involve overdose.Specifically,eight formulas were identified as having an overdose of approximately 3 to 5 times the recommended dose,including Duanxueliu tablets and Zhixue Fumai mixture.②Dosage variations across dosage forms:Based on the conversion of the Ming-Qing dynasty dosage of one liang(Chinese traditional weight unit)to 36 g,the estimated dai-ly dose per component of crude herbs in Yinqiao powder was close to the upper limit specified in the Chinese Pharmacopoeia.The total daily dose of crude herbs(75.60 g)was approximately five times that of the Yinqiao powder(15 g)listed in the Chinese Pharmacopoeia and three times that of the Japanese Kampo Yinqiao powder(23.868 g).Significant differences in dosage were ob-served among Yinqiao Jiedu preparations of different dosage forms.In terms of total daily dose of crude herbs,granules(52.50 g)had the highest dose,approximately 3-5 times that of tablets/capsules(11.20 g),soft capsules(13.44 g),and powders(15.00 g),but still 30％ lower than the original prescription from ancient texts(75.6 g).Comparing the daily dose per compo-nent,granules fell within the Chinese Pharmacopoeia dose range,while tablets,capsules,soft capsules,and powders were all below the Chinese Pharmacopoeia dose.③Inclusion of toxic herbs:Among the 20 oral formulations containing Strychnos nux-vomica(Maqianzi)listed in the Chinese Pharmacopoeia,seven species exceeded the pharmacopoeial dose of 0.3-0.6 g per day.Notably,Shenjin Huoluo pill and Shufeng Dingtong pill exceeded the Chinese Pharmacopoeia dose by 1.5-2 times.The daily dose of strych-nosine in Shenjin Huoluo pill was 21.3 mg,exceeding the toxic dose range of 5-10 mg.Conclusions The dosage indications in CPM instructions must adhere to a unified format,clearly stating the daily dose per component of crude herbs,the total daily dose of crude herbs,and the total number of administrations under the"Dosage and Administration"section.For instance,"Yinqiao Jiedu granules,with a total daily dose equivalent to 60 g of crude herbs taken in four doses(including:Flos Lonicerae 10.71 g,Fructus Forsythiae 10.71 g,Radix Platycodi 6.43 g,Herba Menthae Haplocalycis 6.43 g,Fructus Arctii 6.43 g,Semen Sojae Preparatum 5.36 g,Radix Glycyrrhizae 5.36 g,Herba Lophatheri 4.29 g,Herba Schizonepetae 4.29 g)."For CPM containing tox-ic herbs,dosage indications are even more crucial,such as specifying the daily dose of Maqianzi powder/processed Maqianzi and strychnosine in formulations containing this herb.

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Chronic thromboembolic pulmonary hypertension is a serious pulmonary vascular disease with diagnostic and therapeutic challenges.As a non-invasive screening technique,lung ventilation/perfusion imaging plays a key role in the diagnosis,disease assessment and treatment decision-makings in patients with chronic thromboembolic pulmonary hypertension.This article comprehensively analyzes the application of lung ventilation/perfusion imaging in the diagnosis and evaluation of chronic thromboembolic pulmonary hypertension,and discusses its technical principles,advantages,and potential directions for future technical development.

Chronic thromboembolic pulmonary hypertension is a serious pulmonary vascular disease with diagnostic and therapeutic challenges.As a non-invasive screening technique,lung ventilation/perfusion imaging plays a key role in the diagnosis,disease assessment and treatment decision-makings in patients with chronic thromboembolic pulmonary hypertension.This article comprehensively analyzes the application of lung ventilation/perfusion imaging in the diagnosis and evaluation of chronic thromboembolic pulmonary hypertension,and discusses its technical principles,advantages,and potential directions for future technical development.