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

Objective:To compare the clinical characteristics of nasal NK/T-cell lymphoma（NKTL） and diffuse large B-cell lymphoma（DLBCL） to improve the diagnosis and differential diagnosis of nasal lymphomas. Methods:A retrospective analysis of cases of nasal NKTL and DLBCL was conducted. The clinical symptoms, signs, and imaging features of both groups were compared and statistically analyzed. Results: The DLBCL group showed more symptoms like exophthalmos/diplopia and epiphora compared to the NKTL group （both P=0.040）. NKTL cases were more likely to be misdiagnosed as sinusitis（P=0.007）. In NKTL cases, nasal mucosal swelling（P<0.01）, destruction of nasal structures（P=0.002）, and external nasal structural abnormalities（P=0.003） were more prevalent. In imaging, the DLBCL group more commonly demonstrated worm-eaten destruction of sinus bones （P=0.004）, sinus masses （P=0.018）, and invasion of adjacent structures including the pterygopalatine fossa, infratemporal fossa （P<0.01）, orbit （P=0.039）, and skull base （P=0.011）. NKTL involved the turbinates（P=0.001）, nasal cavity and septum（P=0.016）, nasopharynx（P<0.01）, and "skip" infiltration of external nasal tissues（P=0.042） more frequently. No statistically significant differences were found in other clinical features between the two groups. Conclusion:For patients with nasal obstruction and discharge, it is essential to inquire about systemic B symptoms, such as fever, and eye symptoms, such as periorbital swelling, diplopia, and lacrimation. Lymphoma should be suspected if local examination reveals diffuse nasal swelling, destruction of turbinates or septum, and external nasal structural abnormalities. Worm-eaten bone destruction and "cast-like" changes of the turbinates, septum, and nasal cavity, as well as "skip" infiltration of the external nose, are more common in NKTL. Sinus masses with invasion of the pterygopalatine fossa, infratemporal fossa, skull base, and orbit are more typical of DLBCL.
Humans ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/diagnosis* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Nasal Cavity/pathology* ; Male ; Diagnosis, Differential ; Female ; Middle Aged ; Nose Neoplasms/diagnosis* ; Adult ; Aged

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.

BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Nicotinamide adenine dinucleotide (NAD⁺) is a central and pleiotropic metabolite involved in multiple cellular energy metabolism, such as cell signaling, DNA repair, protein modifications, and so on. Evidence suggests that NAD⁺ levels decline with age, obesity, and hypertension, which are all significant CVD risk factors. In addition, the therapeutic elevation of NAD⁺ levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances antioxidation and metabolism in vascular cells of humans with vascular disorders. In preclinical animal models, NAD⁺ boosting also extends the health span, prevents metabolic syndrome, and decreases blood pressure. Moreover, NAD⁺ storage by genetic, pharmacological, or natural dietary NAD⁺-increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models and humans. Here, we discuss NAD⁺-related mechanisms pivotal for vascular health and summarize recent research on NAD⁺ and its association with vascular health and disease, including hypertension, atherosclerosis, and coronary artery disease. This review also assesses various NAD⁺ precursors for their clinical efficacy and the efficiency of NAD⁺ elevation in the prevention or treatment of major CVDs, potentially guiding new therapeutic strategies.
Humans ; Cardiovascular Diseases/physiopathology* ; NAD/metabolism* ; Animals ; Hypertension/metabolism*

Objective: Machine learning (ML) has been reported to have better predictive capability than traditional statistical techniques. The aim of this study was to assess the efficacy of ML algorithms and logistic regression (LR) for predicting depressive symptoms during the COVID-19 pandemic. Methods: Analyses were carried out in a national cross-sectional study involving 21,916 participants. The ML algorithms in this study included random forest (RF), support vector machine (SVM), neural network (NN), and gradient boosting machine (GBM) methods. The performance indices were sensitivity, specificity, accuracy, precision, F1-score, and area under the receiver operating characteristic curve (AUC). Results: LR and NN had the best performance in terms of AUCs. The risk of overfitting was found to be negligible for most ML models except for RF, and GBM obtained the highest sensitivity, specificity, accuracy, precision, and F1-score. Therefore, LR, NN, and GBM models ranked among the best models. Conclusion Compared with ML models, LR model performed comparably to ML models in predicting depressive symptoms and identifying potential risk factors while also exhibiting a lower risk of overfitting.

ObjectiveTo analyze the protective effect of different types of influenza vaccines (InfV) against influenza A among the individuals aged between 3‒17 years old, and to provide a scientific basis for the prevention and control of influenza in the future. MethodsA retrospective cohort study was conducted to collect data on the incidence and InfV vaccination of the individuals aged between 3‒17 years during the influenza epidemic season from 2022 to 2023. Vaccine effectiveness (VE) was calculated, and a log-binomial regression model was used to calculate the corrected VE. ResultsThe incidence rate of influenza in InfV vaccinated and un-vaccinated groups was 7.32% (1 937/ 26 446) and 9.65% (4 421/45 837), respectively. After adjusting for age and gender factors, the unadjusted VE (95%CI) was 54.57% (52.24%‒56.78%). The unadjusted VE (95%CI) was 53.66% (50.36%‒56.74%) for males and 55.60% (52.24%‒58.72%) for females, respectively. The unadjusted VE (95%CI) for the age group of 3‒ years, 6‒ years, 9‒ years, 12‒ years, and 15‒17 years were 64.08% (60.89%‒67.01%), 57.40% (53.71%‒60.80%), 57.77% (52.49%‒62.47%), 24.36% (9.49%‒36.79%), and 24.09% (-17.59%‒51.00%), respectively. The unadjusted VE (95%CI) for quadrivalent split-virion inactivated influenza vaccine, trivalent split-virion inactivated influenza vaccine, trivalent subunit influenza vaccine, and trivalent live attenuated influenza vaccine were 53.84% (51.32%‒56.24%), 62.17% (56.28%‒67.26%), 79.83% (69.94%‒86.46%), and 31.59% (19.07%‒42.18%), respectively. ConclusionThe InfV used during the 2022‒2023 influenza season had a good protective effect against influenza A among the individuals aged between 3‒17 years old, especially in those aged between 3‒11 years old.

Based on the theory of "three regions and sanjiao" in traditional Chinese medicine (TCM), the acupuncture-moxibustion differentiation and treatment system is explored and constructed for spasm syndrome, so as to provide a clearer guiding framework for TCM treatment of spasm syndrome. This disorder is caused essentially by the invasion of pathogenic wind, and located in brain marrow. The key regions of illness cover five zang organs and five tissues, and the core pathogenesis is associated with wind disturbance in brain marrow. In differentiation, spasm syndrome refers to overall transmission (from the upper to the lower) and local transmission (from exterior to interior). This disorder can be classified into sanjiao spasm (heart-lung spasm of the upper jiao, liver-spleen spasm of the middle jiao, and liver-kidney spasm of the lower jiao) and three-region spasm (skin-vessel spasm of the upper region, tendon-muscle spasm of the middle region, and tendon-bone spasm of the lower region). Based on "three regions and sanjiao" theory of acupuncture and moxibustion, 7 "expelling-wind" points can be selected in terms of the etiology of this disease. Baihui (GV20)-toward-Taiyang (EX-HN5) needling is applied to regulate the brain marrow, focusing on the core location of illness; and regarding the key location of illness, the combination of back-shu and front-mu points and that of jing-well and xing-spring points are adopted to regulate five zang organs. The five needling techniques (half needling, leopard-spot needling, joint needling, Hegu needling and shu needling) are used to regulate five tissues.
Humans ; Acupuncture Therapy ; Spasm/diagnosis* ; Moxibustion ; Acupuncture Points ; Medicine, Chinese Traditional ; Diagnosis, Differential