1.Annual review of clinical research on lung transplantation worldwide in 2025
Linxi LIU ; Jingchen XU ; Rui YANG ; Xinchen JIANG ; Ting DENG ; Ling ZHOU ; Kaiyue YANG ; Xiaohan JIN ; Zhiqiang DENG ; Xiangyun ZHENG ; Dong TIAN
Organ Transplantation 2026;17(4):574-581
Lung transplantation is currently the only effective treatment for end-stage lung disease. However, the field of lung transplantation still faces numerous challenges, including donor shortage, primary graft dysfunction, rejection, infection and others. In 2025, scholars worldwide have made remarkable progress in clinical research on lung transplantation. This article systematically reviews the cutting-edge developments in clinical research on lung transplantation in 2025, focusing on the application of novel evaluation tools in donor lung screening, optimization of lung perfusion techniques, exploration of extracorporeal membrane oxygenation and robot-assisted minimally invasive surgery, as well as mechanistic research and intervention strategies for primary graft dysfunction, acute kidney injury and chronic lung allograft dysfunction. Meanwhile, hot topics such as the management of special populations, prevention and control of postoperative infections, and improvement of quality of life are summarized. This review aims to conclude the important annual research findings and provide references for the clinical practice and research development of lung transplantation in China.
2.Changes in Astronaut Brain Function and Behavior Associated With Habitation on Low-Earth-orbit Space Stations
Hong-Ting JIANG ; You-Fu LUO ; Zheng-Jiang YANG ; Yuan YAO ; De-Zhong YAO ; Ke CHEN
Progress in Biochemistry and Biophysics 2026;53(10):2786-2796
During habitation on low-Earth-orbit (LEO) space stations, astronauts are exposed to a combination of orbital microgravity, space radiation, an enclosed and artificially controlled cabin environment, altered sleep-wake rhythms, and sustained operational and psychosocial demands. These factors can modify sensorimotor inputs, body-fluid distribution, arousal state, and task-related neural processing, thereby affecting brain function and behavior. Because evidence from real spaceflight remains limited by small samples, heterogeneous mission durations, and different measurement time points, this review integrates findings from real human spaceflight with relevant ground-based analog studies while treating real orbital studies as the primary source of evidence. We focus on electroencephalography (EEG) and event-related potentials (ERPs), structural and functional neuroimaging, and sensorimotor and cognitive outcomes, with particular attention to the direction, anatomical distribution, temporal course, and possible physiological significance of the reported changes. EEG studies indicate that long-duration spaceflight is associated with increased resting-state beta activity, particularly in sensorimotor and frontotemporal regions, together with state-dependent alterations in beta-band functional connectivity. In contrast, alpha source power and functional connectivity associated with the default mode network are reduced during long-duration missions, and some of these effects may persist into the early postflight period. Task-related electrophysiological findings further suggest that sustained mental workload can weaken frontocentral theta-temporoparietal gamma phase-amplitude coupling, whereas in-flight decision-making is accompanied by reduced P300 amplitude and reorganization of feedback-related potentials. Short-duration missions, however, have shown relative preservation of posterior dominant rhythms and some ERP measures, indicating that mission duration, recording state, and task demands substantially influence the observed electrophysiological phenotype. Neuroimaging provides complementary evidence at structural and network levels. Long-duration spaceflight has been associated with upward brain displacement, ventricular and cerebrospinal fluid expansion, regional gray- and white-matter remodeling, and alterations in white-matter structural connectivity. Functional magnetic resonance imaging (fMRI) studies further indicate reorganization of vestibular-sensorimotor, visual, and default mode networks. Some network changes recover after return to Earth, whereas others may remain detectable for months. Importantly, most MRI measurements are obtained after landing rather than in orbit; therefore, postflight findings may reflect a mixture of in-flight adaptation, the rapid transition back to 1 g, and subsequent readaptation rather than a single spaceflight effect. Behavioral evidence is most consistent for sensorimotor function. Early after return, astronauts frequently show impaired postural control, gait, spatial orientation, and coordination, consistent with reweighting among vestibular, visual, and proprioceptive information. By comparison, simple cognition and some critical operational tasks are often preserved. More subtle or high-load processes-including sustained attention, feedback evaluation, temporal processing, error monitoring, and metacognitive calibration may be more sensitive than global cognitive performance. This dissociation between neural change and preserved behavior suggests that altered brain activity should not automatically be interpreted as functional deterioration. Integrating the available modalities, we propose that LEO space-station habitation is better characterized by system-specific and stage-dependent neural adaptation than by a generalized increase or decline in brain function. The most coherent cross-modal pattern involves sensorimotor reorganization: reduced gravitational reference and weight-bearing feedback under microgravity may drive reweighting of vestibular, visual, and proprioceptive inputs, accompanied by changes in beta activity and vestibular-sensorimotor networks and followed by transient postflight sensorimotor deficits. A second major process involves fluid-related structural remodeling, in which cephalad fluid shifts and altered hydrostatic gradients may contribute to changes in cerebrospinal fluid spaces, ventricular volume, and brain tissue configuration. Resting-state and cognitive electrophysiological changes likely represent additional adjustments in network regulation and resource allocation, but their functional interpretation remains more dependent on sleep, workload, recording conditions, and individual differences. Future studies should move beyond isolated pre-post comparisons and group averages toward standardized longitudinal designs spanning preflight, multiple in-flight time points, and postflight recovery. Synchronized assessment of brain function, behavior, sleep, and key environmental parameters should be used to characterize individual adaptation trajectories and determine which neural changes reflect successful compensation, which predict delayed recovery, and which have genuine value for brain-health risk prediction and individualized countermeasures.
3.Clinical application of single-balloon and double-balloon enteroscopy in pediatric small bowel diseases: a retrospective study of 576 cases.
Can-Lin LI ; Jie-Yu YOU ; Yan-Hong LUO ; Hong-Juan OU-YANG ; Li LIU ; Wen-Ting ZHANG ; Jia-Qi DUAN ; Na JIANG ; Mei-Zheng ZHAN ; Chen-Xi LIU ; Juan ZHOU ; Ling-Zhi YUAN ; Hong-Mei ZHAO
Chinese Journal of Contemporary Pediatrics 2025;27(7):822-828
OBJECTIVES:
To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard.
METHODS:
Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard.
RESULTS:
Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively.
CONCLUSIONS
SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies
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Treatment Outcome
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Double-Balloon Enteroscopy/statistics & numerical data*
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Single-Balloon Enteroscopy/statistics & numerical data*
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Humans
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Male
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Female
;
Child
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Operative Time
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Tomography, X-Ray Computed/statistics & numerical data*
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Sensitivity and Specificity
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Intestine, Small/surgery*
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Intestinal Diseases/surgery*
4.Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia.
Yan ZHANG ; Xin-Yue ZHAO ; Meng-Ting LIU ; Zhu-Chen ZHOU ; Hui-Bin CHENG ; Xu-Hong JIANG ; Yan-Rong ZHENG ; Zhong CHEN
Journal of Integrative Medicine 2025;23(2):169-181
OBJECTIVE:
Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied.
METHODS:
A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels.
RESULTS:
Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein-protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds.
CONCLUSION
Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med. 2025; 23(2): 169-181.
Animals
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Nerve Regeneration/drug effects*
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Mice
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Peripheral Nerve Injuries/physiopathology*
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Male
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Ganglia, Spinal/enzymology*
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Axons/physiology*
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Peroxidase/antagonists & inhibitors*
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Mice, Inbred C57BL
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Drugs, Chinese Herbal/pharmacology*
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Disease Models, Animal
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Strychnine/pharmacology*
5.Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods.
Xiao-Yan ZHENG ; Zi-Yi JIANG ; Yi-Ting LI ; Chao-Liang LI ; Hao ZHU ; Zheng YU ; Si-Yi YU ; Li-Li YANG ; Song-Yuan TANG ; Xing-Yu LÜ ; Fan-Rong LIANG ; Jie YANG
Journal of Integrative Medicine 2025;23(5):528-536
OBJECTIVE:
To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods.
METHODS:
In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator.
RESULTS:
The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups.
CONCLUSION
This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans
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Female
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Propensity Score
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Embryo Transfer
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Adult
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Acupuncture Therapy
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Retrospective Studies
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Pregnancy
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Live Birth
;
Birth Rate
;
Cohort Studies
6.Needs for rehabilitation in China: Estimates based on the Global Burden of Disease Study 1990-2019.
Tian TIAN ; Lin ZHU ; Qingzhen FU ; Shiheng TAN ; Yukun CAO ; Ding ZHANG ; Mingxue WANG ; Ting ZHENG ; Lijing GAO ; Daria VOLONTOVICH ; Yongchen WANG ; Jinming ZHANG ; Zhimei JIANG ; Hongbin QIU ; Fan WANG ; Yashuang ZHAO
Chinese Medical Journal 2025;138(1):49-59
BACKGROUND:
As an essential part of health services, rehabilitation is of great significance to improve the health and quality of life of the whole population. Accelerating aging calls for a significant expansion of rehabilitation services in China, but rehabilitation needs remain unclear. We conducted the study to explore the rehabilitation needs in China and project the trend of rehabilitation needs from 2020 to 2034.
METHODS:
The data of health conditions that might potentially benefit from rehabilitation were obtained from Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of rehabilitation needs were made until 2034 using Bayesian age-period-cohort analysis (BAPC).
RESULTS:
Approximately 460 million persons (33.3% of the total population) need rehabilitation in China, contributing to 63 million years lived with disabilities (YLDs) in 2019. The number of prevalent cases that need rehabilitation increased from around 268 (95% uncertainty interval [UI]: 257-282) million in 1990 to almost 460 (95% UI: 443-479) million in 2019, representing an increase of 71.3%. The highest contribution to the need for rehabilitation was musculoskeletal disorders with about 322 (95% UI: 302-343) million persons in seven aggregate disease and injury categories, and hearing loss with over 95 (95% UI: 84-107) million people among 25 health conditions. Based on the projection results, there will be almost 636 million people (45% of the total population) needing rehabilitation services in China by 2034, representing an increase of 38.3%. The rehabilitation needs of neoplasms, cardiovascular diseases, and neurological disorders are expected to increase significantly from 2019 to 2034, with increases of 102.3%, 88.8% and 73.2%, respectively.
CONCLUSIONS
The need for rehabilitation in China substantially increased over the last 30 years. It is predicted that over two in five people will require rehabilitation by 2034, thus suggesting the need to develop rehabilitation services that meet individuals' rehabilitation needs.
Humans
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China/epidemiology*
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Global Burden of Disease
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Female
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Male
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Musculoskeletal Diseases/epidemiology*
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Rehabilitation/trends*
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Quality of Life
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Middle Aged
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Aged
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Bayes Theorem
7.Development of oral preparations of poorly soluble drugs based on polymer supersaturated self-nanoemulsifying drug delivery technology.
Xu-Long CHEN ; Jiang-Wen SHEN ; Wei-Wei ZHA ; Jian-Yun YI ; Lin LI ; Zhang-Ting LAI ; Zheng-Gen LIAO ; Ye ZHU ; Yue-Er CHENG ; Cheng LI
China Journal of Chinese Materia Medica 2025;50(16):4471-4482
Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility
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Administration, Oral
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Polymers/chemistry*
;
Drug Delivery Systems/methods*
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Humans
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Emulsions/chemistry*
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Biological Availability
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Animals
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Pharmaceutical Preparations/administration & dosage*
8.Effectiveness of autologous platelet-rich plasma for blood conservation and its prognostic impact in patients with type A aortic dissection
Qian ZHENG ; Shoumei CHEN ; Ming XIE ; Shenshen ZHI ; Kun LIU ; Ting JIANG
Chinese Journal of Blood Transfusion 2025;38(8):1035-1042
Objective: To investigate the effects of autologous platelet-rich plasma (aPRP) collected using a continuous blood cell separator on blood conservation and prognosis in patients with type A aortic dissection. Methods: The clinical data of patients who underwent emergency aortic replacement for acute type A aortic dissection at our hospital from January 2020 to December 2023 were respectively analyzed. Patients were divided into two groups based on whether they received aPRP collection before surgery for subsequent reinfusion: the aPRP group (n=32) and the control group (n=35). The volume of aPRP collected and the platelet concentration in the aPRP were recorded. The volumes of allogeneic blood and blood products transfused, and the associated costs during hospitalization were compared between two groups. Intraoperative blood loss, perioperative laboratory parameter changes, 24-hour postoperative drainage volume, duration of ICU stay and mechanical ventilation, length of hospital stay, and mortality rate of the two groups were also compared. Results: The platelet concentration in aPRP was (491.5±85.4)×10
/L, accounting for (24.1±9.6)% of the patient's total platelet count. The volume of aPRP collected accounted for (23.0±6.3)% of the patient's total plasma volume. Compared with the control group, the aPRP group demonstrated significantly reduced transfusion volumes of allogeneic red blood cells, plasma, and platelets (P<0.05), along with significantly lower blood-related costs during hospitalization (P<0.05). Postoperative coagulation parameters (APTT, PT, INR, and TEG) were significantly improved (P<0.05), and platelet counts were markedly increased (P<0.05) in aPRP group as compared with the control group. No statistically significant differences were observed in postoperative use of prothrombin complex concentrate and fibrinogen between the two groups. Similarly, there were no significant differences in postoperative 24-hour drainage volume, 24-hour extubation rate, ICU length of stay, duration of mechanical ventilation, or total hospital length of stay. The incidence of complications and mortality did not differ significantly between the two groups. Conclusion: The administration of aPRP significantly reduces the requirement for perioperative allogeneic blood transfusion in patients undergoing surgery for type A aortic dissection. Furthermore, it enhances coagulation function and reduces associated transfusion costs, thereby establishing itself as an effective and safe strategy for blood conservation.
9.To investigate the association between gout-related gene polymorphisms and clinical phenotypic heteroge-neity in gout patients from the Foshan region
Qihong GUO ; Baolin ZHENG ; Ting LI ; Yutong JIANG ; Junli CHEN ; Yuanyi LI ; Haimei YANG ; Junguang LU
The Journal of Practical Medicine 2025;41(19):3060-3064
Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region,thereby providing a scientific basis for stratified clinical management.Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study.The collected data included demo-graphic characteristics,frequency of gout attacks,presence of tophi,levels of uric acid,creatinine,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),gout-related genes(ABCG2,SLC2A9,SLC22A12,MTHFR),and joint ultrasound findings.Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity.Results The male-to-female ratio was 11∶1;the mean age was(35.28±2.67)years;the mean disease duration was(6.03±0.68)years;and the mean frequency of acute attacks in the past 12 months was 4(2.0,7.25).Genotype distributions were as follows:ABCG2:wild-type(C/C),23.8%;heterozygous(C/A),53.2%;homozygous(A/A),23%.SLC2A9:wild-type(A/A),24.6%;heterozygous(A/G),50%;homozygous(G/G),25.4%.SLC22A12:wild-type(A/A),4.8%;heterozygous(A/C),31.7%;homozygous(C/C),63.5%.MTHFR:wild-type(C/C),68.3%;heterozygous(C/T),28.6%;homozygous(T/T),3.2%.Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation(ρ=0.193,P=0.031)and crystal deposition on ultrasound(ρ=0.202,P=0.025).SLC22A12 polymorphisms were associated with hypertension(ρ=0.269,P=0.003)and diabetes(ρ=0.200,P=0.026).MTHFR polymorphisms showed a correlation with diabetes(ρ=0.224,P=0.012).Conclusions Polymorphisms in SLC2A9,SLC22A12,and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients.Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.
10.Three-dimensional ultrasonography assessment of fetal auricle for predicting congenital aural atresia
Youlu LIU ; Ting LEI ; Yuting JIANG ; Ju ZHENG ; Qiao ZHENG ; Miao HE ; Lihe ZHANG ; Hongning XIE
Chinese Journal of Ultrasonography 2025;34(2):155-160
Objective:To explore the value of prenatal three-dimensional ultrasonography(3DUS)in displaying auricular morphotyping and dimensions for predicting congenital aural atresia(CAA).Methods:A retrospective collection of 227 fetuses who underwent ultrasound scans and retained auricular 3DUS volumes from January 2018 to December 2023 at the First Affiliated Hospital of Sun Yat-sen University was conducted. Fetuses were divided into two groups:a CAA group(52 fetuses,62 auricles)and a non-CAA group(175 fetuses,202 auricles),based on the presence or absence of external auditory canal identified through postnatal examination. According to 3DUS auricular contour and presence or absence of the concha,the auricles were divided into 4 types:type Ⅰ,C-shaped auricle with a concha;type Ⅱ,Irregular auricle with a concha;type Ⅲ,C-shaped auricle without a concha;type Ⅳ,Irregular auricle without a concha. And auricular length(AL)and width(AW)were measured to calculate the product of the auricular length and width(ALW). Normal reference ranges for ALW from the non-CAA group were developed. Differences of the auricular morphotyping and Z-score of ALW(ALWZ)were compared between the two groups. Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic efficiency of auricular morphotyping,ALWZ and the regression model. A Logistic regression model for CAA based on auricular morphotyping and ALWZ were established.Results:The auricular morphotyping and ALWZ between the two groups were different statistically(both P<0.05). The AUC of the auricular morphotyping and ALWZ predicting CAA were 0.960(95% CI = 0.923 - 0.997)and 0.975(95% CI = 0.959 - 0.991)individually. Formula for CAA prediction model combining the two indicators(5.379 × morphotyping - 2.386 × ALWZ - Conclusions:The auricular morphotyping and dimensions can effectively predict CAA.

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