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

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 analyze the risk factors for aspiration pneumonia m patients with post-stroke dysphagia based on quantitative analysis of videofluoroscopic swallowing study(VFSS),and to construct a prediction model and validate it in order to standardize the management of high-risk patients with post-stroke dysphagia complicating aspiration pneumonia.Method:A total of 556 patients with post-stroke dysphagia admitted to Xiamen Hospital of Beijing University of Traditional Chinese Medicine from July 2021 to June 2023 were selected for the study and divided into a modeling group(n=436)and an external validation group(n=120).The model group was divided into pneumo-nia group(n=113,25.9％)and non-pneumonia group(n=323,74.1％)according to the occurrence of aspiration pneumonia.Clinical data and VFSS results were collected for all participants.Logistic regression identified the risk factors for aspiration pneumonia,and a nomogram predictive model was constructed.Model perfonnance was evaluated using receiver operating characteristic(ROC)curves,the area under the ROC curve(AUC),and the Hosmer-Lemeshow goodness-of-fit test.External validation was conducted to assess the sensitivity,spec-ificity and consistency of the model.Result:Logistic regression analysis showed that advanced age,poor oral hygiene,tracheotomy,Penetration-As-piration Scale(PAS)grade≥5,pharyngeal residue and prolonged pharyngeal transport time were risk factors for aspiration pneumonia,and active cough and eating instruction were protective factors(P＜0.05 for both).The predictive risk index(C-index)of the nomogram prediction model was 0.957,AUC=0.957,sensitivity was 93.8％,specificity was 86.4％,and the Hosmer-Lemeshow goodness of fit test showed P=0.6.Conclusion:The predictive model can be used to predict the occurrence of aspiration pneumonia in stroke pa-tients with dysphagia.Its use in clinical practice allows for the development of targeted and individualized inter-ventions according to patient risk levels,thereby improving the quality of nursing.

Objective:To analyze the risk factors for aspiration pneumonia m patients with post-stroke dysphagia based on quantitative analysis of videofluoroscopic swallowing study(VFSS),and to construct a prediction model and validate it in order to standardize the management of high-risk patients with post-stroke dysphagia complicating aspiration pneumonia.Method:A total of 556 patients with post-stroke dysphagia admitted to Xiamen Hospital of Beijing University of Traditional Chinese Medicine from July 2021 to June 2023 were selected for the study and divided into a modeling group(n=436)and an external validation group(n=120).The model group was divided into pneumo-nia group(n=113,25.9％)and non-pneumonia group(n=323,74.1％)according to the occurrence of aspiration pneumonia.Clinical data and VFSS results were collected for all participants.Logistic regression identified the risk factors for aspiration pneumonia,and a nomogram predictive model was constructed.Model perfonnance was evaluated using receiver operating characteristic(ROC)curves,the area under the ROC curve(AUC),and the Hosmer-Lemeshow goodness-of-fit test.External validation was conducted to assess the sensitivity,spec-ificity and consistency of the model.Result:Logistic regression analysis showed that advanced age,poor oral hygiene,tracheotomy,Penetration-As-piration Scale(PAS)grade≥5,pharyngeal residue and prolonged pharyngeal transport time were risk factors for aspiration pneumonia,and active cough and eating instruction were protective factors(P＜0.05 for both).The predictive risk index(C-index)of the nomogram prediction model was 0.957,AUC=0.957,sensitivity was 93.8％,specificity was 86.4％,and the Hosmer-Lemeshow goodness of fit test showed P=0.6.Conclusion:The predictive model can be used to predict the occurrence of aspiration pneumonia in stroke pa-tients with dysphagia.Its use in clinical practice allows for the development of targeted and individualized inter-ventions according to patient risk levels,thereby improving the quality of nursing.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective:To systematically evaluate the relationship between thiazide diuretics and the risk of hip fracture in the elderly patients.Methods:The relevant databases at home and abroad were searched up to December 31, 2023 and case-control studies and cohort studies on the relationship between thiazide diuretics and the risk of hip fractures in the elderly patients were collected. Quality of the enrolled studies was evaluated by bias risk assessment tool of Newcastle-Ottawa Scale (NOS). RevMan 5.4 software was used for meta-analysis on related outcome indicators, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Funnel plots, Egger′s method and Begg′s method were performed using Stata 15.1 software to analyze the inclusion literature for publication bias. Results:A total of 18 studies were enrolled in the study, including 7 case-control studies and 11 cohort studies and involving 175 200 patients in the trial group (thiazide diuretics) and 1 574 989 in the control group (placebo or other medications). All 18 studies scored ≥5 on the NOS (15 articles of high quality and 3 articles of medium quality). The meta-analysis results indicated that the risk of hip fractures in the trial group was lower than that in the control group ( OR=0.82, 95% CI: 0.75-0.89, P<0.001). Subgroup analyses by study type and gender both revealed that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR in case-control studies was 0.78, 95% CI: 0.72-0.84, P<0.001; adjusted OR in cohort studies was 0.83, 95% CI: 0.74-0.93, P=0.002; adjusted OR in female was 0.78, 95% CI: 0.72-0.85, P<0.001; adjusted OR in male was 0.73, 95% CI: 0.68-0.80, P<0.001). The subgroup analysis of 11 large-sample studies (≥2 000 cases) indicated that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR=0.79, 95% CI: 0.72-0.87, P<0.001). However, 6 small-sample studies did not find the similar correlation. A combined analysis of studies that rigorously controlled for confounding factors revealed that thiazide diuretics were associated with a lower risk of hip fractures in the elderly ( OR=0.79, 95% CI: 0.74-0.84, P<0.001), and the combined results showed no heterogeneity ( P=0.72, I2=0%). Conclusions:Thiazide diuretics were associated with a reduced risk of hip fractures in the elderly patients. Based on a comprehensive assessment of the risks and benefits of medication for elderly patients, clinicians may prioritize thiazide diuretics as a component of combination therapy for eligible patients, which may be beneficial in reducing their risk of hip fractures.

Objective:To systematically evaluate the relationship between thiazide diuretics and the risk of hip fracture in the elderly patients.Methods:The relevant databases at home and abroad were searched up to December 31, 2023 and case-control studies and cohort studies on the relationship between thiazide diuretics and the risk of hip fractures in the elderly patients were collected. Quality of the enrolled studies was evaluated by bias risk assessment tool of Newcastle-Ottawa Scale (NOS). RevMan 5.4 software was used for meta-analysis on related outcome indicators, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Funnel plots, Egger′s method and Begg′s method were performed using Stata 15.1 software to analyze the inclusion literature for publication bias. Results:A total of 18 studies were enrolled in the study, including 7 case-control studies and 11 cohort studies and involving 175 200 patients in the trial group (thiazide diuretics) and 1 574 989 in the control group (placebo or other medications). All 18 studies scored ≥5 on the NOS (15 articles of high quality and 3 articles of medium quality). The meta-analysis results indicated that the risk of hip fractures in the trial group was lower than that in the control group ( OR=0.82, 95% CI: 0.75-0.89, P<0.001). Subgroup analyses by study type and gender both revealed that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR in case-control studies was 0.78, 95% CI: 0.72-0.84, P<0.001; adjusted OR in cohort studies was 0.83, 95% CI: 0.74-0.93, P=0.002; adjusted OR in female was 0.78, 95% CI: 0.72-0.85, P<0.001; adjusted OR in male was 0.73, 95% CI: 0.68-0.80, P<0.001). The subgroup analysis of 11 large-sample studies (≥2 000 cases) indicated that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR=0.79, 95% CI: 0.72-0.87, P<0.001). However, 6 small-sample studies did not find the similar correlation. A combined analysis of studies that rigorously controlled for confounding factors revealed that thiazide diuretics were associated with a lower risk of hip fractures in the elderly ( OR=0.79, 95% CI: 0.74-0.84, P<0.001), and the combined results showed no heterogeneity ( P=0.72, I2=0%). Conclusions:Thiazide diuretics were associated with a reduced risk of hip fractures in the elderly patients. Based on a comprehensive assessment of the risks and benefits of medication for elderly patients, clinicians may prioritize thiazide diuretics as a component of combination therapy for eligible patients, which may be beneficial in reducing their risk of hip fractures.

OBJECTIVES: This study aimed to use modified articular disc anchorage in treating old irreducible temporomandibular joint (TMJ) disc displacement with perforation and rupture, as well as to explore its efficacy. METHODS: A total of 31 patients (34 sides) with 47 TMJ disc perforations who underwent surgical treatment in the Affiliated Stomatolo-gical Hospital of Nanchang University from January 2018 to December 2021 were selected. According to the location of disc perforation, it has five types: posterior disc perforation (typeⅠ), anterior disc perforation (typeⅡ), lateral disc perforation (type Ⅲ), composite disc perforation, and destruction disc perforation. The modified methods of disc anchoring were divided into two types according to the location of the perforation. TypesⅠandⅢ disc perforation were trea-ted by posterior anchoring method. For posterior ancho-ring, a screw was implanted into the posterolateral side of the condylar neck, and the disc was fixed on the screw by horizontal mattress suture. TypeⅡdisc perforation and compo-site disc perforation combined typeⅡperforation were treated by anterior and posterior double-anchoring method. For anterior anchoring, anchor screws or holes were placed at the anterior edge of the condylar neck, and horizontal mattress suture was performed at the posterior edge of the anterior perforation with an anchor wire. The articular disc was then fixed on the anchor screws or holes. For the posterior anchoring method, it was the same as the previous one. Paired t test was used to analyze the visual analog scale (VAS), maximum interincisal opening (MIO), and TMJ disorder index (CMI) of the patient before surgery and 1, 3, and 6 months after surgery. Disk-condyle position relationship by magnetic resonance imaging and postoperative quality of life in postoperative were analyzed. RESULTS: The incidence of perforation was 41.2% (14/34) in typeⅠ, 11.8% (4/34) in typeⅡ, 8.8% (3/34) in typeⅢ, 29.4% (10/34) in composite type, and 8.8% (3/34) in destruction type. The VAS, MIO, and CMI at 3, 6 months after operation significantly improved compared with those before operation (P<0.05). The effective reduction rate of disc was 96.77% (30/31). The quality of life at 6 months after surgery was 47.22±2.13, and the rate of excellent evaluation was 96.4% (27/28). CONCLUSIONS Modified articular disc anchorage achieves a good curative effect for treating temporomandibular joint disc perforation and rupture. Nevertheless, its long-term effect requires further observation.
Humans ; Temporomandibular Joint Disc/surgery* ; Quality of Life ; Joint Dislocations/surgery* ; Temporomandibular Joint Disorders/surgery* ; Magnetic Resonance Imaging/methods* ; Temporomandibular Joint/pathology* ; Mandibular Condyle

Systemic lupus erythematosus （SLE） is an autoimmune disease in which the immune system mistakenly attacks multiple tissues and organs of the body. The comorbid anxiety and depression are highly prevalent conditions among SLE， thereby worsening the prognosis of patients and posing a serious diagnostic challenge to the clinicians. The purpose of this article is to review the literature available for the influencing factors of comorbid anxiety and depression in SLE， and to provide references for optimizing treatment strategies for SLE patients with comorbid anxiety and depression. A total of 25 original research articles are included to provide a systematic and quantitative review， in which the genetic， immune， central nervous system and socio-psychological factors affecting the comorbid anxiety and depression in SLE are explored.