OBJECTIVE: To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province, and to analyze the genotypes and hematological phenotypes. METHODS: Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province, whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations. The mutations of β-globin gene clusters were confirmed by polymerase chain reaction (PCR) and Sanger DNA sequencing technology. RESULTS: The 3.5 kb deletion in β-globin gene cluster (NC_000011.10: g. 5224302-5227791del3490bp) was detected in 4 patients' samples, of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation. These 2 patients displayed moderate anemia phenotype, while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype. CONCLUSION Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia, compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia. In areas with a high incidence of thalassemia, suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.
Humans ; beta-Globins/genetics* ; Multigene Family ; beta-Thalassemia/genetics* ; Mutation ; Genotype ; Sequence Deletion ; Phenotype ; Male ; Female

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

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

OBJECTIVE: As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS). METHODS: This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA). RESULTS: The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS. CONCLUSION The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans ; Cognitive Dysfunction/diagnosis* ; Aged ; Male ; Female ; Machine Learning ; Spleen ; Aged, 80 and over ; Kidney ; Medicine, Chinese Traditional

Objective:To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above.Methods:Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis.Results:The M( Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions:The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.

Objective:To learn about physicians’ concepts and commonly employed method in hyaluronic acid injection and provide reference data for the standardization of pain management.Methods:This study was a cross-sectional study. Convenient sampling method was used to distribute questionnaires to cosmetic injectors and patients experienced with hyaluronic acid injections to collect data on their views of pain associated with hyaluronic acid injections. The physician portion was collected offline from June 15 to July 20, 2022, and the patient portion was collected from November 14, 2022, to December 6, 2022, via the Questionnaire Star platform. The physician questionnaire consisted of 17 questions, question types included single choice, multiple choice and essay questions. The patient questionnaire consisted of 6 questions, question types included single choice and multiple choice. Relevant data were analyzed using SPSS 22.0 software for descriptive statistics, and data were presented in the form of cases and percentages (%).Results:Sixty-two physician questionnaires and 123 patient questionnaires were collected. 42 (67.74%) physicians observed from their daily practice that more than 50% of their patients were very concerned about pain during injection; 101 (82.11%) patients scored ≥5 out of 10 for concern about impending pain prior to hyaluronic acid filler injection. At the time of treatment, 48 (77.42%) physicians advised patients to choose a lidocaine-containing hyaluronic acid filler for reasons including a significant reduction in injection pain (53 cases, 85.48%) and patient comfort with the treatment experience (59 cases, 95.16%). 60 (48.78%) patients were willing to choose an anesthesia-containing product at the time of injection, but the price of the anesthesia-containing product influenced the patient’ s choice (55 cases 44.72%) .Conclusions:Pain from cosmetic injectable treatments is an important issue to both physicians and patients. Lidocaine-containing hyaluronic acid is recognized by physicians and patients for its analgesic effect and high safety profile. There is no perfect solution for pain in cosmetic injection treatment, and multidisciplinary collaboration may be needed to solve the problem.

Objective:To learn about physicians’ concepts and commonly employed method in hyaluronic acid injection and provide reference data for the standardization of pain management.Methods:This study was a cross-sectional study. Convenient sampling method was used to distribute questionnaires to cosmetic injectors from plastic surgery department of public hospitals or medical beauty institutions and patients experienced with hyaluronic acid injections to collect data on their views of pain associated with hyaluronic acid injections. The physician portion was collected offline from June 15 to July 20, 2022, and the patient portion was collected from November 14 to December 6, 2022, via the Questionnaire Star platform. The physician questionnaire consisted of 17 questions, question types included single choice, multiple choice and essay questions. The patient questionnaire consisted of 6 questions, question types included single choice and multiple choice. Relevant data were analyzed using SPSS 22.0 software for descriptive statistics, and data were presented in the form of cases(%).Results:Sixty-two physician questionnaires and 123 patient questionnaires were collected. 42 (67.74%) physicians observed from their daily practice that more than 50% of their patients were very concerned about pain during injection; 101 (82.11%) patients scored ≥5 out of 10 for concern about impending pain prior to hyaluronic acid filler injection. At the time of treatment, 48 (77.42%) physicians advised patients to choose a lidocaine-containing hyaluronic acid filler for reasons including a significant reduction in injection pain (53 cases, 85.48%) and patient comfort with the treatment experience (59 cases, 95.16%). 60 (48.78%) patients were willing to choose an anesthesia-containing product at the time of injection, but the price of the anesthesia-containing product influenced the patient’s choice (55 cases, 44.72%).Conclusion:Pain from cosmetic injectable treatments is an important issue to both physicians and patients. Lidocaine-containing hyaluronic acid is recognized by physicians and patients for its analgesic effect and high safety profile. There is no perfect solution for pain in cosmetic injection treatment, and multidisciplinary collaboration may be needed to solve the problem.

Objective:To learn about physicians’ concepts and commonly employed method in hyaluronic acid injection and provide reference data for the standardization of pain management.Methods:This study was a cross-sectional study. Convenient sampling method was used to distribute questionnaires to cosmetic injectors from plastic surgery department of public hospitals or medical beauty institutions and patients experienced with hyaluronic acid injections to collect data on their views of pain associated with hyaluronic acid injections. The physician portion was collected offline from June 15 to July 20, 2022, and the patient portion was collected from November 14 to December 6, 2022, via the Questionnaire Star platform. The physician questionnaire consisted of 17 questions, question types included single choice, multiple choice and essay questions. The patient questionnaire consisted of 6 questions, question types included single choice and multiple choice. Relevant data were analyzed using SPSS 22.0 software for descriptive statistics, and data were presented in the form of cases(%).Results:Sixty-two physician questionnaires and 123 patient questionnaires were collected. 42 (67.74%) physicians observed from their daily practice that more than 50% of their patients were very concerned about pain during injection; 101 (82.11%) patients scored ≥5 out of 10 for concern about impending pain prior to hyaluronic acid filler injection. At the time of treatment, 48 (77.42%) physicians advised patients to choose a lidocaine-containing hyaluronic acid filler for reasons including a significant reduction in injection pain (53 cases, 85.48%) and patient comfort with the treatment experience (59 cases, 95.16%). 60 (48.78%) patients were willing to choose an anesthesia-containing product at the time of injection, but the price of the anesthesia-containing product influenced the patient’s choice (55 cases, 44.72%).Conclusion:Pain from cosmetic injectable treatments is an important issue to both physicians and patients. Lidocaine-containing hyaluronic acid is recognized by physicians and patients for its analgesic effect and high safety profile. There is no perfect solution for pain in cosmetic injection treatment, and multidisciplinary collaboration may be needed to solve the problem.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective To explore the postmortem diffusion rule of Aconitum alkaloids and their metabo-lites in poisoned rabbits,and to provide a reference for identifying the antemortem poisoning or post-mortem poisoning of Aconitum alkaloids.Methods Twenty-four rabbits were sacrificed by tracheal clamps.After 1 hour,the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration.Then,they were placed supine and stored at 25℃.The biological samples from 3 randomly selected rabbits were collected including heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney tissues at 0 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h after intragastric administration,respectively.Aconitum alkaloids and their metabolites in the biological samples were ana-lyzed by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Results At 4 h after intragastric administration,Aconitum alkaloids and their metabolites could be detected in heart blood,peripheral blood and major organs,and the contents of them changed dynamically with the preservation time.The contents of Aconitum alkaloids and their metabolites were higher in the spleen,liver and lung,especially in the spleen which was closer to the stomach.The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration.In contrast,the contents of Aconitum alkaloids and their metabolites in kidney were all lower.Aconi-tum alkaloids and their metabolites were not detected in urine.Conclusion Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits,diffusing from high-content organs(stomach)to other major organs and tissues as well as the heart blood.The main mechanism is the dispersion along the concentration gradient,while urine is not affected by postmortem diffusion,which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.