As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

ObjectiveTo investigate differential metabolites associated with browning in the post-harvest processing of Pinelliae Rhizoma， providing data support for elucidating the key metabolites and metabolic pathways involved in browning， and developing safe and efficient sulfur-free processing techniques. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS） was used to detect the metabolites of Pinelliae Rhizoma at different browning stages（0， 8， 16 h） for widely targeted metabolomics. Subsequently， Multivariate statistical analysis of metabolites was conducted using principal component analysis（PCA）， hierarchical cluster analysis（HCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， and K-means cluster analysis. Differential metabolites at different browning stages were screened based on variable importance in the projection（VIP） value>1 and |log₂fold change（FC）|≥1， and metabolic pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsA total of 1 416 metabolites were identified across the three browning stages of Pinelliae Rhizoma， predominantly comprising amino acids and their derivatives（239）， lipids（219）， alkaloids（156）， phenolic acids（121）， terpenoids（113）， and flavonoids（111）. A two-by-two comparison of the three browning phases， yielded 622 differential metabolites that were significantly enriched in the phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolic pathway. Further analysis revealed that carbohydrates such as D-mannose and turanose， phenolic acids such as 1-O-caffeoyl-6-O-glucosyl-β-D-glucose， dicaffeoylshikimic acid， and flavonoids such as epigallocatechin gallate， vitexin-7-O-rutinoside， luteolin-7-O-（6″-malonyl）glucoside-5-O-arabinoside， catechin gallate， epicatechin gallate， isovitexin-7-O-glucoside-2″-O-rhamnoside， apigenin-7-O-rutinoside-4ʹ-O-sophoroside， 3，5，3ʹ，4ʹ，5ʹ-penta-hydroxyflavan-7-gallate may act as browning substrates and play important roles in the browning process. ConclusionCarbohydrates， phenolic acids， and flavonoids may serve as key substrates in the browning process of Pinelliae Rhizoma， involving pathways such as phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolism， which can provide a theoretical basis for further exploration of the browning mechanism.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Objective: To evaluate the feasibility of re-entry for blood donors deferred for single-reagent reactive anti-TP ELISA results, to assess the ability of ELISA S/CO values of different kits to discriminate true-from false-positive samples and to determine the optimal cutoff value for each kit, thereby providing a scientific basis for improving blood donor reentry strategies. Methods: Data of two donor cohorts were retrospectively collected: (1) a re-entry cohort of 106 donors who applied for re-entry at Jiangsu Province Blood Center from January 1, 2018 to December 31, 2025, all previously deferred for single-reagent reactive anti-TP ELISA results (58 reactive with the Xinchuang kit and 48 with the Kehua kit); (2) a routine screening confirmation cohort of 39 donors found to be single-reagent reactive in routine donation screening and additionally tested by TPPA between April 2024 and June 2026 (17 Xinchuang and 22 Kehua). Using TPPA results as the gold standard, the two cohorts were pooled (75 Xinchuang, 70 Kehua), and receiver operating characteristic (ROC) curves were constructed separately for each kit. The 95% confidence interval (CI) of the area under the curve (AUC) was estimated with 2 000 bootstrap replicates, and the optimal S/CO cutoff of each kit was determined by the maximum Youden index; sensitivity analysis was performed by cohort source. In addition, TPPA-confirmed positivity rates were compared between single-and dual-reagent reactive samples at re-entry testing. Results: Of the 106 donors in the re-entry cohort, 73 were successfully requalified and 33 failed. The mean S/CO value at deferral testing in successfully requalified donors was 1.930 (median 1.570), significantly lower than 3.487 (median 2.592) in failed donors (P<0.001). Among the 33 donors who failed requalification, 16 samples were TPPA positive; at re-entry testing, 7 were dual-reagent reactive (6 TPPA positive), 25 remained single-reagent reactive (9 TPPA positive), and 1 was ELISA non-reactive (TPPA positive). The TPPA positivity rate of dual-reagent reactive samples at re-entry testing was 85.7% (6/7), significantly higher than 36.0% (9/25) of single-reagent reactive samples (P=0.033); the agreement between the two kits at re-entry testing was poor (Kappa=0.231). ROC analysis of pooled samples showed that for the Xinchuang kit (n=75, 14 TPPA positive), the AUC was 0.837 (95%CI:0.731-0.929) with an optimal cutoff of 2.025, corresponding to a sensitivity of 92.9% (13/14), a specificity of 65.6% (40/61) and a negative predictive value of 97.6% (40/41); for the Kehua kit (n=70, 13 TPPA positive), the AUC was 0.787 (95%CI:0.649-0.900) with an optimal cutoff of 1.733, corresponding to a sensitivity of 92.3% (12/13), a specificity of 56.1% (32/57) and a negative predictive value of 97.0% (32/33). Sensitivity analysis by cohort showed that the AUCs calculated separately for the re-entry and screening cohorts were consistent in direction with the pooled analysis. Conclusion: S/CO values of both the Xinchuang and Kehua ELISA kits can discriminate TPPA-confirmed true from false positives, but their optimal cutoffs differ. Dual-reagent reactivity at re-entry testing strongly indicates TPPA-confirmed positivity; the TPPA positivity rate of single-reagent reactive samples increases in a gradient with rising S/CO values, and single-reagent reactive samples with low S/CO values are mostly false positives. Incorporating kit-specific stratified management based on quantitative S/CO thresholds into the re-entry mechanism may help establish a fast-track re-entry pathway for low-risk false-positive donors.

Objective To analyze the disease burden and its changing trends of tracheal, bronchus, and lung cancer (TBL) attributable to high fasting plasma glucose (HFPG) in China from 1990 to 2021, and to provide key strategic evidence for the prevention and treatment of TBL. Methods Data related to TBL attributable to HFPG in China from 1990 to 2021 were collected from the Global Burden of Disease Study 2021 database, including mortality rate, disability-adjusted life years (DALYs), age-standardized rates, and other indicators. The Joinpoint regression model was applied to analyze the temporal trends of these indicators. Furthermore, the grey prediction model GM (1, 1) was used to forecast the disease burden of TBL attributable to HFPG in China from 2022 to 2031. Results From 1990 to 2021, the overall disease burden of TBL attributable to HFPG in China showed an upward trend. The total number of deaths, DALYs, crude mortality rate, age-standardized mortality rate, crude DALYs rate, and age-standardized DALYs rate increased from 4700, 121300 person-years, 0.40/100000, 0.61/100000, 10.31/100000, and 14.10/100000 in 1990 to 17400, 386500 person-years, 1.22/100000, 0.82/100000, 27.16/100000, and 17.72/100000 in 2021, with growth rates of 270.21%, 218.63%, 205.00%, 34.43%, 163.43%, and 25.67%, respectively. The increase rates among females were higher than those among males. Analysis using the Joinpoint regression model indicated that both the age-standardized mortality rate and age-standardized DALYs rate exhibited a significant upward trend, with average annual percentage changes (AAPC) of 1.01% and 0.82%, respectively, during 1990-2021 (P<0.05). The disease burden across different age and gender groups generally increased from 1990 to 2021. Mortality and DALYs rates for both males and females rose with advancing age, with elderly individuals and males constituting the primary affected populations. The GM (1, 1) grey prediction model projected continued increases in mortality rate, age-standardized mortality rate, DALYs rate, and age-standardized DALYs rate of TBL attributable to HFPG in China from 2022 to 2031, reaching 1.64/100000, 1.06/100000, 36.45/100000, and 21.81/100000, respectively, by 2031. Conclusion The disease burden of TBL attributable to HFPG remains substantial in China from 1990 to 2021, with males and elderly populations bearing the highest burden. However, the growth rate of disease burden is faster among females compared to males. It is predicted that the disease burden will continue to rise over the next decade, necessitating enhanced focus on early diagnosis and treatment for women and older adults.

To explore the predictive value of carotid corrected flow time (FTc) and velocity time integral (VTI) for post-induction hypotension (PIH) in elderly patients undergoing gastrointestinal tumor surgery.

Xenogeneic kidney transplantation is an important approach to alleviate the shortage of donor kidneys, but acute rejection remains the main obstacle in its clinical application. Xenogeneic acute rejection shows a clear temporal sequence: in the early stage, it is mainly mediated by antibodies and occurs through humoral rejection, with pre-existing antibodies targeting α-Gal and non-Gal antigens, activating complement and inducing thrombotic microangiopathy; in the later stage, it gradually transforms into a cellular rejection driven by infiltration of T cells and macrophages. In terms of diagnosis, donor-derived cell-free DNA can serve as an early non-invasive warning indicator, and histopathological biopsy remains the gold standard. In 2024, the Banff Working Group on Transplant Pathology of xenogeneic kidney transplantation released the first consensus on the pathological assessment of pig-human kidney/heart xenogeneic transplantation. However, this is currently only a reporting framework, and an independent grading system still awaits more clinical data. The treatment mainly focuses on multi-gene-modified donors combined with intensified immunosuppression, but it still faces challenges such as immature immunization regimens, the absence of monitoring systems and prominent infection risks. This article reviews the mechanisms, diagnostic monitoring, treatment strategies and clinical dilemmas of acute rejection, providing a reference for subsequent research.

Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

OBJECTIVE: To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance. METHODS: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated. RESULTS: Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818]. CONCLUSION Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans ; Female ; Tongue/diagnostic imaging* ; Adult ; Anemia/diagnosis* ; Middle Aged ; Face/diagnostic imaging* ; Young Adult ; Machine Learning