OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

ObjectiveTo investigate the disease burden of non-alcoholic fatty liver disease （NAFLD） among young people in East Asian countries （including China， North Korea， Japan， Mongolia， and South Korea） in 1990—2023， and to provide a basis for formulating and adjusting the prevention and treatment strategies for NAFLD. MethodsRelated disease burden data of NAFLD among the young people in these five East Asian countries were collected from the Global Burden of Disease 2023 （GBD 2023） database， including incidence rate， prevalence rate， and disability-adjusted life years （DALY）， and the young people were divided into groups based on country， sex， and age. Estimated annual percentage change （EAPC） was used to comprehensively evaluate the changing trend of the disease burden of NAFLD among young people from 1990 to 2023， and the Autoregressive Integrated Moving Average model was used to predict the disease burden of NAFLD among the young people in China. ResultsIn 2023， the standardized incidence rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 926.57/100 000， 805.83/100 000， 412.66/100 000， 747.66/100 000， and 534.08/100 000， respectively； the standardized prevalence rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 16 817.94/100 000， 14 500.98/100 000， 8 534.40/100 000， 13 705.28/100 000， and 11 587.93/100 000， respectively； the standardized DALY rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 6.34/100 000， 10.18/100 000， 5.23/100 000， 47.93/100 000， and 6.76/100 000， respectively. From 1990 to 2023， there was a tendency of increase in the standardized incidence rate of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea， with an EAPC of 0.87%， 0.52%， 0.26%， 0.48%， and 0.87%， respectively； there was also a tendency of increase in the standardized prevalence rate of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea， with an EAPC of 0.99%， 0.49%， 0.24%， 0.59%， and 0.93%， respectively； conversely， there was a tendency of reduction in the standardized DALY rate of NAFLD among the young people in China， Japan， Mongolia， and South Korea， with an EAPC of -2.21%， -2.01%， -0.37%， and -4.62%， respectively， while the standardized DALY rate of NAFLD among the young people in North Korea remained relatively stable， with an EAPC of -0.01%. The subgroup analysis based on sex showed that there was a significant difference in the disease burden of NAFLD between the young people with different sexes in the five East Asian countries， and the subgroup analysis based on age showed that the incidence rate of NAFLD in young people decreased with the increase in age， while the prevalence rate and DALY rate of NAFLD increased with age. In addition， the standardized incidence rate and standardized prevalence rate of NAFLD among Chinese young people would further increase in the future， while there would be a reduction in standardized DALY rate in the future. ConclusionThere is a significant difference in the disease burden of NAFLD in young people across different countries， sexes， and age groups. In the future， targeted prevention and treatment measures should be developed based on the distribution characteristics of the disease burden of NAFLD， in order to effectively reduce the disease burden of NAFLD among young people.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

ObjectiveTo evaluate the clinical efficacy of Zuogui Pill （左归丸，ZGP） decoction on neurological function， motor function， and activities of daily living in patients with ischemic stroke （IS） of liver-kidney yin deficiency syndrome， and to assess its potential mechanisms from the perspectives of cerebral perfusion and corticospinal tract （CST） remodeling. MethodsA total of 108 patients with IS of liver-kidney yin deficiency syndrome and onset time ≤14 days were enrolled and randomly divided into a control group and a treatment group， with 54 cases in each group. The control group received conventional western medicine， while the treatment group received ZGP decoction （one dose per day） in addition to the conventional treatment. Both groups were treated for 90 days. The National Institutes of Health Stroke Scale （NIHSS）， modified Rankin Scale （mRS）， modified Barthel Index （MBI）， Fugl-Meyer Assessment （FMA）， and Chinese medicine syndrome score （CMS） were evaluated before treatment and after （90±3） days of treatment. Three-dimensional arterial spin labeling （3D-ASL） and diffusion tensor imaging （DTI） were performed to obtain ipsilesional cerebral blood flow （CBF） in the unaffected and affected hemispheres， relative CBF （rCBF）， and fractional anisotropy （FA） of the CST. Nodal analysis of FA values along the CST was also conducted. Correlation analysis was used to assess the relationships between post-treatment cerebral perfusion parameters （CBF and rCBF）， and FA values with clinical neurological function scores. ResultsAfter treatment， both groups showed significantly decreased NIHSS， mRS and CMS scores， together with significantly increased FMA and MBI scores （P＜0.01）. Intergroup comparison showed that NIHSS， mRS， and CMS scores in the treatment group were significantly lower than those in the control group ， while MBI and FMA scores were significantly higher （P＜0.01）. The 3D-ASL results revealed that CBF and rCBF values in the affected hemisphere significantly increased in both groups after treatment， and the treatment group had significantly higher values （P＜0.01）. DTI showed that the FA value of the CST on the affected side in the treatment group was significantly higher than that in the control group after treatment （P＜0.05）. Nodal analysis along the CST further demonstrated that the continuity of FA values at lesion-related nodes 45~99 in the treatment group was significantly better than that in the control group （P＜0.01）， with significant increases at nodes 65~71 and 76~81 compared with baseline （P＜0.05 or P＜0.01）， whereas the control group showed a decreasing trend at nodes 80~93 （P＜0.05）. Correlation analysis indicated that CBF and rCBF values in the affected hemisphere were negatively correlated with NIHSS and mRS scores and positively correlated with MBI score （P＜0.05）. FA value of the CST on the affected side， both before and after treatment， were negatively correlated with NIHSS score and positively correlated with FMA score （P＜0.05 or P＜0.01）. ConclusionZGP decoction can effectively improve neurological function， motor function， and activities of daily living in IS patients with liver-kidney yin deficiency syndrome， and its mechanism may be related to enhanced cerebral perfusion in the affected hemisphere and corticospinal tract structural remodeling.

Objective:To systematically evaluate the fairness of traditional Chinese medicine (TCM) healthcare resource allocation at the prefecture-level in China using the healthcare resource agglomeration degree (HRAD) method, so as to provide empirical evidence for optimizing resource distribution.Methods:Data on TCM healthcare resources (including the number of TCM institutions, public TCM hospitals, TCM hospital beds, and TCM healthcare technicians) were collected from 333 prefecture-level regions in 2023. The HRAD method was employed to assess fairness in geographic allocation (HRAD i) and population-based allocation (HRAD i/PAD i). A multi-indicator comprehensive evaluation was conducted using the entropy weight method to determine weighting coefficients. Results:Significant disparities were observed in the geographic agglomeration of TCM resources (HRAD i) in China. Resource-rich regions (HRAD i>5) were primarily concentrated in eastern and some central-western provinces, while resource-scarce regions (HRAD i<1) were mainly distributed in western, northeastern, and parts of central and eastern provinces. Analysis of population-based fairness (HRAD i/PAD i) revealed that most prefecture-level cities nationwide had ratios<1, with only 8 provinces having more cities with ratios>1 than<1. The comprehensive evaluation showed that top-ranked cities in the east (e.g., Hangzhou, Dongying, Shenzhen), central region (e.g., Taiyuan, Zhengzhou), and west (e.g., Hainan Prefecture, Alxa League) were predominantly core cities or sparsely populated areas. Conclusions:China′s prefecture-level TCM healthcare resource allocation exhibits significant geographic and population-based inequities, with excessive concentration in provincial capitals and developed cities. Urgent strategies are needed to optimize resource allocation, enhance fairness and accessibility, including promoting the decentralization of high-quality resources, strengthening regional collaborative support, enhancing talent attraction in underdeveloped areas, and leveraging information technology to improve efficiency.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

Objective:To evaluate the value of peripheral blood systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), D-dimer, and albumin (ALB) alone or their combination in the diagnosis of early-onset colorectal cancer (EOCRC).Methods:From January 1, 2023 to November 30, 2024, 104 patients with EOCRC (EOCRC group) hospitalized at Renmin Hospital of Wuhan University were enrolled. During the same period, by simple random sampling method, 104 patients with benign colorectal polyps (benign polyp group) and 104 healthy individuals for health examinations (healthy control group) from outpatient department were enrolled. The peripheral blood parameters (including neutrophil count, lymphocyte count, CEA, and others) and pathological characteristics of EOCRC (including TNM stage, tumor differentiation grade, and depth of invasion) were collected. The relationship between peripheral blood parameters and EOCRC pathological features were analyzed. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the diagnostic value. Multivariate logistic regression analysis was performed to analyze the peripheral blood parameters which independently correlated with EOCRC and a combined diagnostic model was established. Simple random sampling method was used to divide the subjects in the negative control group (healthy control group + benign polyp group) and positive group (EOCRC group) into a training set (218 cases) and a validation set (94 cases) at a ratio of 7∶3, and the diagnostic performance of the combined diagnostic model in the training and validation sets was assessed. Hosmer-Lemeshow test and calibration curve were used to evaluate the fit and consistency of the model. Independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis. Results:EOCRC group had the highest levels of SII(744.03 (473.01, 1 246.28), 437.77 (342.28, 607.47), 497.31 (385.76, 721.63)×10 9/L), NLR(2.42 (1.76, 3.94), 1.96 (1.54, 2.52), 1.91 (1.55, 2.75)), CEA (3.58 (1.96, 20.85), 1.31 (0.95, 1.93), 1.21 (0.76, 2.11) μg/L) and D-dimer (0.36 (0.20, 0.90), 0.19 (0.12, 0.28), 0.18 (0.12, 0.30) mg/L), and the lowest levels of LMR(3.51±1.56, 4.38±1.37, 4.72±1.84) and ALB(42.40 (39.90, 44.70), 44.57 (42.83, 46.25), 44.95 (43.10, 46.58) g/L) than benign polyp group and healthy control group, and the differences were statistically significant ( H=31.18, 16.21, 76.72 and 47.72, F=15.40, H=34.19; all P<0.001). In EOCRC patients, there were statistically significant differences in SII and LMR between patients with different tumor invasion depth ( Z=-2.48, t=2.31; both P<0.05), in CEA between patients with different TNM stage, with or without lymph node metastasis and distant metastasis( Z=-2.68, -2.50 and -2.65; all P<0.05), in D-dimer between patients with different TNM stage, differentiation grade, invasion depth, and with or without lymph node metastasis and distant metastasis ( Z=-2.50, -2.60, -2.06, -2.14 and -3.33; all P<0.05), and in ALB between patients with or without distant metastasis ( Z=-2.52, P=0.012).The AUC of combination of SII, NLR, LMR, CEA, D-dimer, and ALB in differential diagnosis of the healthy control group and the EOCRC group was 0.914 (95% confidence interval (95% CI): 0.870 to 0.958, P<0.001), and the AUC of the combination in differential diagnosis of the benign polyp group and the EOCRC group was 0.904 (95% CI: 0.857 to 0.950, P<0.001). The results of multivariate logistic regression analysis revealed that SII, NLR, LMR, CEA, and ALB were all independently correlated with EOCRC (all P<0.05). The diagnostic model for EOCRC was established by the combination of SII, NLR, LMR, CEA, and ALB, and the AUC of the model in the training set and validation set was 0.911 and 0.883, respectively. The Hosmer-Lemeshow goodness-of-fit test indicated good model fit ( P=0.437). Calibration curve analysis showed strong consistency between predicted probabilities and actual probabilities, and the mean absolute error was 0.015. Conclusions:SII, NLR, LMR, CEA, D-dimer, and ALB all demonstrate diagnostic value in the diagnosis of EOCRC. The combined diagnostic model based on SII, NLR, LMR, CEA, and ALB demonstrates excellent diagnostic performance, which may serve as an adjunctive diagnostic approach for EOCRC.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Removal of endogenic renal sinus tumors which are located at the renal hilum,is recognized as one of the most challenging surgeries in urology due to the complex anatomical structure.With the help of the high-definition field of vision and flexible robotic arms of the Da Vinci robot system,our team have carried out precision intra-sinus tumor enucleation based on preoperative interactive qualitative and Interactive Quantitative Quality Assurance for 3D Imaging(IQQA-3D)accurate reconstruction technology,as well as the clinical anatomical characteristics of patients with renal sinus tumors.During operation,the renal pedicle is fully dissected,the perihilar fat is cleared,and the tumor capsule is exposed.Subsequently,the blood supply to the kidney is blocked,and the tumor is precisely excised along the tumor capsule.The vascular stumps are sutured point-to-point,and the wound is closed and locked.After the blood supply restores,regional arterial occlusion is performed if necessary to ensure the safety of the surgery and maximize the preservation of renal function.This article discusses the definition of tumor boundaries during robot-assisted endogenic sinus tumor enucleation,the use of intraoperative cooling techniques,and the improvement of surgical safety.