Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4⁺T cells and CD8⁺T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4⁺T cells and CD8⁺T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4⁺T cells and CD8⁺T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.

After the occurrence of acute rejection following solid organ transplantation, high-dose glucocorticoid (steroid) pulse therapy is commonly used. However, high-dose steroid pulse therapy is ineffective for some patients, leading to steroid resistant acute rejection, which may easily result in graft loss and severely affect patient prognosis. It is currently believed that both cell-mediated rejection and antibody-mediated rejection are involved in the occurrence and development of steroid resistant acute rejection. The diagnosis and treatment of steroid resistant acute rejection after kidney transplantation have become relatively mature, while the focus on steroid resistant acute rejection after liver transplantation has been relatively low in the past in China, and a unified standardized treatment plan has not yet been formed. Therefore, this article reviews the pathogenesis, diagnosis, and treatment of steroid resistant acute rejection after liver transplantation, in order to provide a reference for the diagnosis and treatment of steroid resistant acute rejection after liver transplantation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

The mortality rates are significantly elevated with the rapid progression of acute liver failure in the absence of timely diagnosis and treatment. Liver transplantation is an effective therapeutic approach that can halt disease progression, but transplantation timing is a crucial factor affecting prognosis. Patients with acute liver failure should be promptly transferred to hospitals equipped for liver transplantation while simultaneously preparing for the procedure during the course of treatment to avoid missing the opportunity to save lives when the condition suddenly worsens. Auxiliary liver transplantation preserves the patient's native liver while transplanting a new liver. Therefore, patients are expected to gradually reduce immunosuppressants following the regeneration of the autologous liver, so avoiding the problem of lifelong use of immunosuppressants. This is also a unique advantage, offering benefits to patients undergoing auxiliary liver transplantation therapy for acute liver failure, while simultaneously presenting challenges for clinicians in terms of technical skill and comprehensive management.

Objective:To evaluate the safety and efficacy of using small and ultra-small sized grafts for in situ auxiliary liver transplantation in the treatment of portal hypertension.Methods:A prospective single-arm cohort study was conducted. Patients who underwent liver transplantation at Beijing Friendship Hospital from December 2014 to July 2025 were included. Intraoperative portal vein pressure was routinely monitored, with the target regulation for portal vein blood flow set at<15 mmHg (1 mmHg=0.133 kPa) and follow-up continued until September 2025. The primary endpoints were the patient's status and graft survival. The secondary endpoints were small-for-size syndrome and perioperative complications. The small-for-size syndrome was graded according to the 2023 International Liver Transplantation Society consensus statement.Results:A total of 33 cases were enrolled. Among them, 22 had ultra-small size grafts, 11 had small-size grafts, 28 had living donor grafts, and five had split grafts. The graft-to-recipient weight ratio in living donor liver transplantation was 0.31%～0.79%, while in split liver transplantation it was 0.45%～1.02%. Intraoperative portal vein pressure of ≥15 mmHg was observed in 11 cases, who underwent portal vein blood flow adjustment via splenic artery ligation (2 cases), partial splenectomy (8 cases), and/or restrictive portocaval shunting (1 case), after which all patients achieved the target portal vein pressure. All cases completed at least one month of follow-up, with 28 cases following for more than one year, and the median follow-up period was 36.5 months. Early-stage postoperative small-for-size syndrome occurred in eight cases (24.2%, 8/33), all classified as grade A, with improvements following supportive treatment. Severe complications (Clavien-Dindo≥Ⅲ) occurred in three cases (9.1%, 3/33). The one-year survival rate was 92.9% (26/28). The overall survival rate at the end of follow-up was 90.9% (30/33). No patients experienced graft loss or death due to small-for-size syndrome. Graft tissue tested negative for hepatitis B core antibody and covalently closed circular DNA, and hepatitis B surface antigen seroconversion was achieved following second-stage residual liver resection and under a combined strategy of potent nucleos(t)ide analogs and hepatitis B immunoglobulin in ten cases of hepatitis B-related disease.Conclusions:With standardized portal vein blood flow monitoring and individualized portal vein blood flow adjustment, in situ auxiliary liver transplantation can safely and effectively use small and even ultra-small sized grafts, thereby significantly expanding graft sources and ensuring donor and recipient safety. These findings warrant further validation and promotion in multicenter controlled studies.

Objective:To observe the effect of mirror threshold load training on respiration of persons with respiratory muscle fatigue after a cerebral hemorrhage.Methods:Fifty cerebral hemorrhage patients with respiratory muscle fatigue were randomly divided into an observation group and a control group, each of 25. In addition to routine rehabilitation training, the control group was given threshold load training of the respiratory muscles, while the observation group was provided with mirror threshold load training, twice a day in the morning and afternoon, 5 days a week for 4 weeks. Before the experiment and after 1, 2, 3 and 4 weeks of the treatment, everyone′s maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was recorded. Before and after the 4 weeks forced expiration volume in the first second (FEV1) was measured along with 25% of the forced expiration volume (FEF25), maximum sound time (MPT) and respiration rate (RR).Results:At each time point the MIP and MEP values of both groups were significantly better than those before the treatment. After 4 weeks the average MIP and MEP values of the observation group were significantly better than those of the control group. And after 4 weeks the FEV1, FEF25, MPT and RR values of both groups had also improved significantly, on average. All of the observation group′s averages except MPT were then significantly better than the control group′s averages.Conclusions:Mirror threshold load training of the respiratory muscles can significantly improve the respiration of persons with respiratory muscle fatigue after a cerebral hemorrhage. It is more effective than respiratory muscle threshold load training.

Objective:To explore the clinical characteristics and healthcare burden in patients with McCune-Albright syndrome (MAS).Methods:A cross-sectional study was conducted at the Children′s Hospital, Zhejiang University School of Medicine. Clinical and healthcare burden data were systematically collected through structured questionnaires in 164 children with MAS from February 2022 to May 2023. According to the clinical characteristics, patients were categorized into 3 groups: monosymptomatic, bisymptomatic and trisymptomatic groups. Patients were also divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Comparative analyses of clinical characteristics and healthcare burden were conducted across age, sex, and symptom categories.Results:The cohort comprised 59 males (36.0%) and 105 females (64.0%) with an age of 4.6 (2.0, 7.4) years. Age stratification revealed 117 cases (71.3%) aged 0-<7 years, 29 cases (17.7%) aged 7-<10 years, and 18 cases (11.0%) aged 10-<18 years. Among monosymptomatic (67 cases, 40.9%), the cohort comprised 32 females (47.8%) and 35 males (52.2%), predominantly presenting with fibrous dysplasia (57 cases, 85.1%). This subgroup showed peak prevalence in the 0-<7 years age range (29 cases (50.9%)). The bisymptomatic cohort (56 cases, 34.1%) consisted of 39 females (69.6%) and 17 males (30.4%), predominantly manifesting fibrous dysplasia with skin hyperpigmentation (25 cases, 44.6%). Peak prevalence occurred in the 0-<7 years subgroup(16 cases (64.0%)). The trisymptomatic cohort (41 cases, 25.0%) consisted of 34 females (82.9%) and 7 males (17.1%), with peak prevalence occurring in the 0-<7 years subgroup (36 cases (87.8%)). The diagnostic journey analysis revealed 94 cases (57.3%) required 1-3 referrals, and 34 cases (20.7%) necessitated >3 referrals from symptom onset to definitive diagnosis. Healthcare expenditure analysis revealed 69 families (42.1%) incurred direct medical costs of 10 000-100 000 CNY, with 11 families (6.7%) exceeding >100 000 CNY. Direct non-medical costs reached of 10 000-100 000 CNY for 62 families (37.8%) and >100 000 CNY for 4 families (2.4%). Productivity loss affected 58 families (35.4%) at 10 000-100 000 CNY and 8 families (4.9%) above 100 000 CNY during the study period.Conclusion:MAS requires increased attention to skeletal manifestations, especially in children aged 0-<7 years. Moreover, the significant financial burden on families necessitates a society-wide support system.