OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

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: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Objective To observe the clinical efficacy of acupuncture combined with rehabilitation training under the guidance of Chinese medicine-enhanced recovery after surgery(CMERAS)in postoperative rehabilitation of tibial plateau fracture.Methods Sixty patients with tibial plateau fracture in postoperative rehabilitation period were randomly divided into observation group and control group,30 cases in each group.The control group was given routine postoperative rehabilitation training,and the observation group was treated with combined acupuncture treatment on the basis of the rehabilitation training of the control group.Both groups were treated for 3 consecutive months.After 3 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Visual Analogue Scale(VAS)scores of pain were observed before and after treatment,and the changes in the knee scores of the Hospital for Special Surgery knee score(HSS)of the United States were compared before and after treatment between the two groups.As well as the time of fracture healing on the operative side of the two groups of patients,and the fracture healing rate within 3 months of the two groups of patients were compared.Results(1)After 1 week,1 month and 3 months of postoperative treatment,the VAS scores of patients in the two groups were significantly improved compared with the pre-treatment period(P＜0.05),and the observation group was significantly superior to the control group in improving the VAS scores,with a statistically significant difference(P＜0.05).(2)After treatment,the HSS scores of patients in the two groups were significantly improved compared with those before treatment(P＜0.05),and the observation group was significantly superior to the control group in improving the HSS scores,and the difference was statistically significant(P＜0.05).(3)After 3 months of treatment,the fracture healing rate was 56.67%(17/30)in the observation group and 30.00%(9/30)in the control group.The fracture healing rate of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(4)After 3 months of acupuncture treatment,the total effective rate was 96.67%(29/30)in the observation group and 73.33%(22/30)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The clinical efficacy of acupuncture in postoperative rehabilitation of tibial plateau fractures under the guidance of CMERAS is significant,which reduces the clinical symptom of postoperative pain of the patients,shortens the healing time of fracture breaks,and significantly improves the patients'knee joint function.

ObjectiveTo reveal the molecular pathogenesis of Hunter syndrome in three families in southern China and to clarify the correlation between phenotype and genotype， so as to lay a foundation for future prenatal or preimplantation genetic diagnosis. MethodsOn the basis of initial clinical diagnosis and pedigree analysis， qualitative detection of glycosaminoglycans in urine was performed first， and then anticoagulant blood samples were collected from the children and their relatives. DNA was extracted and the IDS gene sequence was analyzed by PCR and Sanger sequencing. Various methods such as RT-PCR and bioinformatics analysis were used to identify the pathogenicity of the new variants. ResultsThe urine test results of the patients in the three families were all strongly positive（++）. Probands were all male， with hemizygous mutations in IDS gene from their mothers， and the mutation sites were c.615_622delCATACAGT， c.847_848delGT and IVS7 ds+1 G>A， respectively. The cross-species conservation analysis showed that the amino acid of IDS gene mutation site was highly conserved during species evolution. Compared with the normal protein， mutant proteins exhibited significant differences in the predicted results of advanced structure. The variants identified in the three families were classified as pathogenic by ACMG criteria. ConclusionsThe three probands were diagnosed with Hunter syndrome. The c.615_622del（p.Il206Valfs*18）， c.847_848del（p.Val283Alafs*57） and IVS7 ds+1 G>A （p.G336Dfs*12） of IDS gene are all novel pathogenic mutations， which are the underlying causes of morbidity in children. This study has further enriched the mutation spectrum of IDS gene.

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ² or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ²=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ²=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.
Male ; Female ; Humans ; Child ; Nephrotic Syndrome/drug therapy* ; Retrospective Studies ; Hospitalization ; Hospitals ; Immunosuppressive Agents/therapeutic use*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

ObjectivePeriprosthetic joint infections （PJI） are currently the most calamitous complication after arthroplasty. Although achievements have been made in many markers for the diagnosis of PJI， the lack of a gold standard remains a great obstacle for early diagnosis. This study aimed to investigate the association between coagulation markers and the development of PJI in patients undergoing revision total joint arthroplasty （TJA）. MethodsWe conducted a retrospective cohort study with a total of 2 517 patients who underwent hip or knee arthroplasties from January 2011 to January 2022 （2 394 with primary TJA， 87 with aseptic revision and 36 with PJI）. We applied univariate analysis and multivariate logistic regression to analyze differences of coagulation factors between primary TJA and aseptic revision or PJI group. Receiver operating characteristic （ROC） curve and area under the curve （AUC） were used to measure the diagnostic value of coagulation factors in predicting PJI. ResultsCoagulation factors and their ratios including plasma fibrinogen （FBG）， prothrombin time （PT）， thrombin time （TT）， activated partial thromboplastin time （APTT）， platelet （PLT）， mean platelet volume （MPV）， platelet distribution width （PDW）， plateletcrit （PCT）， PLT / MPV， PLT / PDW and PLT / PCT were included in this study. High FGB level was strongly correlated with the risk of PJI compared to other coagulation factors. The optimal threshold value of FBG was 4.53 g/L with a sensitivity of 47.22%， a specificity of 93.07% （Primary TJA group vs. PJI group）. Similarly， the optimal threshold value of FBG was 4.44 g/L with a sensitivity of 47.22%， a specificity of 95.40% between the other two groups （Aseptic revision group vs. PJI group）. ROC curve analysis demonstrated moderate diagnostic performance of FBG （AUC value）， indicating a potential to be a diagnostic marker for PJI. ConclusionsFBG is significantly correlated with PJI and it can be used as a potential non-invasive marker for early detection. It may serve as a safe and cost-effective tool for assessing PJI in clinical work.

Background Front-line power grid workers are required to face a variety of occupational hazards (such as aerial work), which make them susceptible to psychological problems and further reduce their performance efficiency and safety level. Objective To investigate the mental health status of front-line power grid workers and explore the influence of personality traits on mental health and the potential mediating role of work-family support between them. Methods This study was designed as a cross-sectional study. From January to June 2019, a cluster random sampling method was used to select two of the 20 power supply stations owned by a Guangdong power company. A total of 485 front-line power grid workers were included in the study. Sociodemographic characteristics were investigated, and NEO Five-Factor Inventory, Work-Family Support Scale, and Symptom Checklist 90 (SCL-90) were used in the survey. Spearman correlation analysis was conducted to analyze the correlations between measured variables. Structural equation modeling was used to analyze the relationships of personality traits, work-family support, and mental health, and Bootstrap analysis was used to test the mediating effect of work-family support on the relationship of personality traits and mental health. Results The M (P₂₅, P₇₅) of total SCL-90 score was 134.00 (110.00, 167.00）, and 139 (28.66%) front-line power grid workers showed positive mental health symptoms. The correlation analysis indicated that among the front-line power grid workers, neuroticism score was negatively correlated with work-family support total score (r_s=−0.356, P<0.001), and positively correlated with the total score of SCL-90 (r_s=0.557, P<0.001) as well as all the scores of its sub-dimensions (r_s=0.436-0.550, P<0.001). Openness score was positively correlated with work-family support total score (r_s=0.269, P<0.001), and except for paranoid ideation (P>0.05), openness score was negatively correlated with the scores of all the other sub-dimensions of SCL-90 (r_s=−0.091-−0.147, P<0.05). The scores of the other three personality traits (extroversion, agreeableness, and conscientiousness) were positively correlated with work-family support total score (r_s=0.331-0.466, P<0.001), and negatively correlated with the total score of SCL-90 as well as the scores of all its sub-dimensions (P<0.001). The modified structural equation modeling indicated that the direct effect of work-family support on mental health symptoms was −0.225 (P<0.001). The direct effects of extraversion and openness on work-family support were 0.241 (P<0.001) and 0.123 (P<0.05), respectively, while the effect on mental health symptoms was not statistically significant. The direct effects of neuroticism on work-family support and mental health symptoms were -0.152 (P<0.01) and 0.467 (P<0.001), respectively. The direct effects of conscientiousness on work-family support and mental health symptoms were not statistically significant (P>0.05). The direct effect of agreeableness on work-family support was not statistically significant (P>0.05), while the direct effect on mental health symptoms was −0.180 (P<0.001). Conclusion The front-line power grid workers show a high score of SCL-90. Workers with higher neuroticism are more vulnerable to mental health symptoms. Work-family support fully mediates the effects of extraversion and openness on mental health symptoms, and partially mediates the effects of neuroticism on mental health symptoms, while does not mediate the effects of agreeableness on mental health symptoms. Sufficient work-family support may improve mental health status.