Objective: To investigate the impact of RhE antigen-matched transfusion during liver transplantation on early postoperative recovery and complications. Methods: In this retrospective cohort study, ninety-five patients undergoing liver transplantation at Kunming First People's Hospital between January 2022 and July 2025 were enrolled. Patients were divided into two groups: Group 1 (RhE-mismatched transfusion, n=57) and Group 2 (RhE-matched transfusion, n=38). The baseline data, complete blood counts, hepatic and renal function, coagulation parameters, and complication rates between the two groups were compared at postoperative days 1, 3, 5, 7, and 10. Survival analysis was performed using the Kaplan-Meier method. Results: The baseline characteristics were well-balanced and comparable between the two groups (all P>0.05). The early postoperative mortality rate in the mismatched group (31.58%, 18/57) was significantly higher than that in the matched group (10.53%, 4/38) (P=0.017). The incidence of postoperative hepatic encephalopathy was significantly higher in the mismatched group (50.88%, 29/57) than in the matched group (10.53%, 4/38) (P<0.001). The incidence of postoperative haemorrhage in the mismatched group (24.56%, 14/57) was higher than that in the matched group (5.26%, 2/38), with a statistically significant difference (P=0.014). The incidence of perioperative infection in the mismatched group (28.07%, 16/57) was higher than that in the matched group (10.53%, 4/38), with a statistically significant difference (P=0.04). Corresponding odds ratios (OR) and 95% confidence intervals indicated a lower risk of these adverse events in the matched group. On postoperative day 1, the change in activated partial thromboplastin time (-1.6, 20.5) in the mismatched group was greater than in the matched group (-0.2, 5.5). The change in international normalised ratio (-0.56, 1.22) in the mismatched group was greater than in the matched group (-0.18, 0.32), while the change in albumin (-4.0, 4.8) was smaller in the mismatched group than in the matched group (-2.5, 8.8). On postoperative day 5, the change in albumin (-0.41±7.83) in the mismatched group was smaller than in the matched group (2.68±4.53). At postoperative day 7, the change in albumin in the mismatched group (-0.61±7.38) was smaller than that in the matched group (2.51±5.85), while the change in D-dimer in the mismatched group (0.73, 7.4) was greater than that in the matched group (-1.6, 4.3). On postoperative day 10, the mismatched group exhibited significantly higher fibrinogen levels (-1.21, 1.78) than the matched group (-0.49, 0.97), and significantly longer prothrombin times (-11.3, -2.7) than the matched group (-6.2, -0.8) (all P<0.05). The matched group exhibited a mean overall survival (OS) of 32.803 months (95% CI:29.171-36.436 months), significantly exceeding the mismatched group's 28.996 months (95% CI:24.202-33.790 months). The log-rank test yielded statistically significant results (χ =4.307, P=0.038). Conclusion: Implementing RhE blood group-matched transfusion during liver transplantation may help reduce early postoperative mortality and the incidence of major complication rates, promote faster recovery of coagulation and liver function, and thereby improve short-term patient outcomes.

ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

BACKGROUND:The previous study of the research group confirmed that Bushen Zhuangjin Decoction can regulate bone metabolism and play an anti-osteoporosis role,and nanocrystalline collagen-based bone can assist in the repair of limb bone defects.OBJECTIVE:To explore the repair effect of nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction on osteoporotic bone defects.METHODS:Totally 84 female SD rats were randomly divided into a sham operation group(n=6,no modeling)and a bilateral ovariectomy group(n=78).After 12 weeks of bilateral ovariectomy,the sham operation group(n=6)and the bilateral ovariectomy group(n=6)were selected for osteoporosis modeling verification.The remaining 72 rats in the bilateral ovariectomy group were randomly divided into 6 intervention groups,with 12 rats in each group:groups A-E had femoral defect models(diameter 3.5 mm,depth 4 mm)established 12 weeks after bilateral ovariectomy.Group A was given double distilled water by gavage(once a day)after surgery;group B was given Bushen Zhuangjin Decoction by gavage(once a day)after surgery;group C had nanocrystalline collagen-based bone filled in the bone defect and then given double distilled water by gavage(once a day);group D had nanocrystalline collagen-based bone filled in the bone defect and then given alendronate sodium by gavage(once a week);group E had nanocrystalline collagen-based bone filled in the bone defect and then given Bushen Zhuangjin Decoction by gavage(once a day);group F had femoral defect models established at the same time after bilateral ovariectomy,and bone defect sites were filled with nanocrystalline collagen-based bone and then given Bushen Zhuangjin Decoction by gavage(once a day).All drugs were given continuously for 12 weeks.12 hours after the last administration,serum levels of type Ⅰ procollagen amino-terminal propeptide,type Ⅰ collagen cross-linked C-terminal peptide,and estradiol were detected;bone volume in the bone defect area was detected by Micro-CT.The expression of type Ⅰ collagen and vascular endothelial growth factor in the bone defect area was detected by immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with group A,the serum level of type Ⅰ procollagen amino-terminal propeptide in groups D and E was decreased(P＜0.05).Compared with groups A and C,the serum estradiol level in groups D,E,and F was increased(P＜0.05).There was no significant difference in the bone volume in the defect area between groups A-F(P＞0.05).(2)Immunohistochemical staining showed that compared with group A,the expression of typeⅠ collagen and vascular endothelial growth factor in groups B,D,and E increased(P＜0.05).Compared with group C,the expression of type Ⅰ collagen in groups B,D,E,and F increased(P＜0.05),and the expression of vascular endothelial growth factor in groups D,E,and F increased(P＜0.05).(3)The results show that nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction may have the potential to repair bone defects in ovariectomized osteoporotic rats.

BACKGROUND:The previous study of the research group confirmed that Bushen Zhuangjin Decoction can regulate bone metabolism and play an anti-osteoporosis role,and nanocrystalline collagen-based bone can assist in the repair of limb bone defects.OBJECTIVE:To explore the repair effect of nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction on osteoporotic bone defects.METHODS:Totally 84 female SD rats were randomly divided into a sham operation group(n=6,no modeling)and a bilateral ovariectomy group(n=78).After 12 weeks of bilateral ovariectomy,the sham operation group(n=6)and the bilateral ovariectomy group(n=6)were selected for osteoporosis modeling verification.The remaining 72 rats in the bilateral ovariectomy group were randomly divided into 6 intervention groups,with 12 rats in each group:groups A-E had femoral defect models(diameter 3.5 mm,depth 4 mm)established 12 weeks after bilateral ovariectomy.Group A was given double distilled water by gavage(once a day)after surgery;group B was given Bushen Zhuangjin Decoction by gavage(once a day)after surgery;group C had nanocrystalline collagen-based bone filled in the bone defect and then given double distilled water by gavage(once a day);group D had nanocrystalline collagen-based bone filled in the bone defect and then given alendronate sodium by gavage(once a week);group E had nanocrystalline collagen-based bone filled in the bone defect and then given Bushen Zhuangjin Decoction by gavage(once a day);group F had femoral defect models established at the same time after bilateral ovariectomy,and bone defect sites were filled with nanocrystalline collagen-based bone and then given Bushen Zhuangjin Decoction by gavage(once a day).All drugs were given continuously for 12 weeks.12 hours after the last administration,serum levels of type Ⅰ procollagen amino-terminal propeptide,type Ⅰ collagen cross-linked C-terminal peptide,and estradiol were detected;bone volume in the bone defect area was detected by Micro-CT.The expression of type Ⅰ collagen and vascular endothelial growth factor in the bone defect area was detected by immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with group A,the serum level of type Ⅰ procollagen amino-terminal propeptide in groups D and E was decreased(P＜0.05).Compared with groups A and C,the serum estradiol level in groups D,E,and F was increased(P＜0.05).There was no significant difference in the bone volume in the defect area between groups A-F(P＞0.05).(2)Immunohistochemical staining showed that compared with group A,the expression of typeⅠ collagen and vascular endothelial growth factor in groups B,D,and E increased(P＜0.05).Compared with group C,the expression of type Ⅰ collagen in groups B,D,E,and F increased(P＜0.05),and the expression of vascular endothelial growth factor in groups D,E,and F increased(P＜0.05).(3)The results show that nanocrystalline collagen-based bone combined with Bushen Zhuangjin Decoction may have the potential to repair bone defects in ovariectomized osteoporotic rats.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective: To explore the clinical characteristics of transfusion-associated graft-versus-host disease (TA-GVHD) in Chinese population, and to provide reference for effective prevention. Methods: Chinese and English medical databases were searched, and literature was screened based on inclusion and exclusion criteria. Data on patient information, clinical manifestations, outcomes and related risk factors from the selected studies were summarized and systematically analyzed. Results: A total of 17 studies were included in this study, involving 55 non-duplicated patients [14 males (14/55, 25.45%) and 41 females (41/55, 74.55%)], with a mean age of 51.72±18.34 years, (range: 2 months to 82 years). Among these cases, 2 had congenital immune deficiency (2/55, 3.64%), 16 had malignant hematological diseases (16/55, 29.09%), 4 had a history of surgery or trauma (4/55, 7.27%), 2 received non-surgical treatment (2/55, 3.64%), 31 were critically ill patients (31/55, 56.36%). Whole blood was transfused in 3 cases (3/55, 5.45%), erythrocyte in 9 (9/55, 16.36%), plasma in 2 (2/55, 3.64%), platelets in 7(7/55, 12.73%), human fibrinogen in 1 (1/55, 1.82%), and granulocytes in 2 (2/55, 3.64%). Two or more types of blood components were transfused in 16 cases (16/55, 29.09%). The main clinical signs and symptoms included fever (23/55, 41.82%), rash (22/55, 40.00%), diarrhea (14/55, 25.45%), abnormal liver function (18/55, 32.73%), bone marrow suppression and pancytopenia (22/55, 40.00%). The survival rate of 55 patients was 43.64% (24/55), and the mortality was 56.36% (31/55). Logistic regression analysis suggested that gender, misdiagnosis or missed diagnosis were major risk factors for mortality in TA-GVHD patients. Conclusion: The lack of specific indications for TA-GVHD often causes clinical misdiagnosis and missed diagnosis, and current treatments have limited efficacy. Therefore, it is of great significance to standardize clinical diagnosis criteria and improve prevention techniques to reduce the risk and mortality rate of TA-GVHD.

ObjectiveTo evaluate the clinical efficacy of different acupuncture-related therapies in treating postoperative pain in patients with osteoporotic vertebral compression fractures (OVCFs) after percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP) using a network meta-analysis.MethodsA systematic search was conducted in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database (SinoMed) from their inception to January 15, 2025. Outcome measures included the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, and overall efficacy rate. Literature screening, data extraction, and risk-of-bias assessment were independently performed by two researchers. Data analysis was conducted using Stata 17.0 software.ResultsA total of 35 randomized controlled trials involving 2860 patients were included. The data analysis revealed that, in terms of improving VAS and ODI scores, the top three effective therapies were Fu's subcutaneous needling, wrist-ankle acupuncture, and acupotomy. For the overall efficacy rates in pain treatment, the top three therapies were wrist-ankle acupuncture, warm acupuncture and moxibustion, and Fu's subcutaneous needling. Based on the combined results across the three outcome measures, Fu's subcutaneous needling was found to be the most effective in relieving pain and improving lumbar function.ConclusionFu's subcutaneous needling, wrist-ankle acupuncture, warm acupuncture and moxibustion, and acupotomy were all effective in treating postoperative pain post-PKP/PVP and improving lumbar function. However, further high-quality, large-sample studies are required to confirm these findings.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.