BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

Objective:To analyze the X-ray imaging characteristics of calcaneus in adult patients with osteoarticular diseases and its impact on disease diagnosis.Methods:Totally 78 patients (156 ankle joints) with osteoarticular diseases admitted to the Affiliated Hospital of Jining Medical University from June 2019 to June 2022 were selected as research subjects, including 72 cases of osteoarthritis and 6 cases of Kashin-Beck disease. Another 50 volunteers who underwent health examination in this hospital during the same period were selected as control group, all of them underwent calcaneal X-ray examination. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of calcaneal X-ray parameters in predicting adult osteoarticular diseases.Results:Among 72 patients with osteoarthritis, 63 cases (87.50%) showed joint surface sclerosis in the calcaneal X-ray changes. Forty-seven cases (65.28%) had narrowing of the subtalar joint space; 14 cases showed disappearance of the subtalar joint space, accounting for 19.44%. Among the 6 patients with Kashin-Beck disease, the X-ray changes of the calcaneus showed joint surface sclerosis in 6 cases, narrowing of the subtalar joint space in 4 cases, and disappearance of the subtalar joint space in 2 cases. The length, height, Bohler angle, Gissane angle, and inclination angle of the calcaneus in patients with Kashin-Beck disease were all smaller than those in the osteoarthritis group and the control group, the height to length ratio of the calcaneus was higher than that in the osteoarthritis group and the control group, and the difference was statistically significant ( P < 0.05). The length, height, Bohler angle, Gissane angle, and inclination angle of the calcaneus in patients of the osteoarthritis group were all smaller than those in the control group, and the height to length ratio of the calcaneus was higher than that in control group, and the difference was statistically significant ( P < 0.05). ROC curve analysis showed that the sensitivity of Bohler angle, Gissane angle, and the height to length ratio of the calcaneus in predicting osteoarticular diseases (72 patients with osteoarthritis) were 92.5%, 87.6% and 80.4%, respectively, with specificity of 73.0%, 68.8% and 63.1%, respectively. Conclusion:The calcaneal X-ray manifestations of adult patients with osteoarticular diseases vary greatly, among which Bohler angle, Gissane angle, and height to length ratio of the calcaneus have certain accuracy in diagnosis of osteoarthritis.

Stenotrophomonas species are non-fermentative Gram-negative bacteria that are widely distributed in environment and are highly resistant to numerous antibiotics. Thus, Stenotrophomonas serves as a reservoir of genes encoding antimicrobial resistance (AMR). The detection rate of Stenotrophomonas is rapidly increasing alongside their strengthening intrinsic ability to tolerate a variety of clinical antibiotics. This review illustrated the current genomics advances of antibiotic resistant Stenotrophomonas, highlighting the importance of precise identification and sequence editing. In addition, AMR diversity and transferability have been assessed by the developed bioinformatics tools. However, the working models of AMR in Stenotrophomonas are cryptic and urgently required to be determined. Comparative genomics is envisioned to facilitate the prevention and control of AMR, as well as to gain insights into bacterial adaptability and drug development.
Stenotrophomonas/genetics* ; Drug Resistance, Bacterial/genetics* ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Genomics ; Microbial Sensitivity Tests

Objective To investigate the role of intestinal flora in the development of irritable bowel syndrome with diarrhea(IBS-D).Methods The mice treated with antibiotics were randomly assigned to experimental group or control group.IBS-D mouse feces and normal mouse feces were given to the experimental group and control group for fecal microbiota transplantation,respectively.The fecal water content,intestinal transit time,and intestinal sensitivity were observed.qRT-PCR was used to determine the mRNA expression of nuclear factor kappa-B(NF-κB),Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),interleukin-1β(IL-Iβ),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α)in colon tissue.Western blotting was used to determine the protein levels of the above-mentioned parameters.Results IBS-D related symptoms presented in the mice of the experimental group,such as increased fecal water content and intestinal sensitivity,and shortened intestinal transit time.The expression levels of inflammatory factors(IL-Iβ,IL-6,and TNF-α),NF-κB,TLR4,and MyD88 in the colon tissue of experimental group were significantly higher than those in the control group(P<0.05).Conclusion Intestinal flora inbalance is involved in the development and progression of IBS-D as an initiating important driver.Dysbiosis-induced hypo-inflammation of the intestinal mucosa and abnormal activation of NF-κB-related pathways may play key roles in this process.

OBJECTIVE: To analyze the research status and developmental trend of open-access patents at home and abroad of radioactive decontamination technology for human body surface. METHODS: The basic information of open-access patents related to human body radioactive decontamination was searched and collected from the IncoPat Global Patent Database. Based on patent analysis method, the number of patent application, legal status, patent types, application trends, applicants, functional application fields, and citations were analyzed and compared, with focus on their research and development capabilities in domestic and foreign patent application status.RESULTS: A total of 981 patents of radioactive decontamination technology for human body surface were retrieved. Among them, 144 were domestic(14.7%) and 837 were from abroad(85.3%). After merge, 207 patents were confirmed, 88 were from domestic(42.5%) and 119 from abroad(57.5%). The top 5 countries with the most patents were China, Japan, the United States, France and Germany with patent amount of 88, 47, 20, 14 and 13 respectively,accounting for 87.9%(182/207) of all patents. Japan had a large number of patents with a stable growth; France and Germany started patent research very early; the United States focused on technology inheritance; Chinese patent applications are developing rapidly, followed by South Korea, and Russia had few open-access patents. Chinese patent applicants were mainly from Beijing with major enterprises and government organizations. Patents in China had few patent family, foreign patents had a wide distribution, 35.3% of which had more than five of the same family. The proportions of valid patents, utility model patents and patents of integrated device & technology in China were higher than that from abroad(35.2% vs 17.6%, 53.4% vs 3.4%, 62.5% vs 26.9%, P<0.01). The proportion of domestic patents citing other patents in China was lower than that from abroad(13.6% vs 52.1%, P<0.01), but the proportion of Chinese patents cited by other patents showed no statistical significance compared with that of abroad(27.3% vs 39.5%, P>0.05). CONCLUSION: Patents of radioactive decontamination technology for human body surface in China have developed rapidly in recent years. Patent emphasis is placed on integration and multifunctionality. However, the awareness of patent protection and regional layout is not strong enough, and the technical level needs to be improved. It is suggested to propose strategic deployment as soon as possible and strengthen technological research, development and innovation.

OBJECTIVE: To explore the effect of long-term low-dose ionizing radiation exposure on arterial vascular elasticity in female residents. METHODS: A cluster random sampling method was used,95 female residents in 2 regions with high external γ radiation dose rate in the high radiation background area( HBRA) in Yangjiang City were selected as the HBRA group,and 96 female residents from the control area( CA) in Enping City were chosen as the CA group. The height,body mass,waist circumference,hip circumference and blood pressure were measured in individuals of these two groups. The fasting blood samples of elbow vein were collected to measure high-density lipoprotein cholesterol( HDL-C),low-density lipoprotein cholesterol( LDL-C),triglycerides( TG) and blood glucose. The cardio-ankle vascular index( CAVI) was measured using the blood pressure and pulse check device. RESULTS: The CAVI of the CA and HBRA groups were( 8. 09 ±1. 03) and( 8. 35 ± 1. 60) m/s,respectively. The abnormal rates of CAVI were 25. 00% and 29. 47%,respectively. The results of multiple linear regression analysis showed that after adjustment for age,HDL-C,LDL-C,TG,hypertension,abnormal glucose metabolism and abdominal obesity,the CAVI adjustment mean values of the CA and HBRA groups were8. 19 and 8. 25 m/s,respectively. The HBRA group was about 0. 73% higher than the CA group,but the difference was not statistically significant( standardized partial regression coefficient = 0. 021,P > 0. 05). After matching age of both groups,the difference of the adjusted mean of CAVI between the two groups was not statistically significant( P > 0. 05).CONCLUSION: Long-term low-dose radiation exposure is not associated with atherosclerosis in female population.

Purpose To perform MRI examination after the death of SD rat model due to cerebral infarction and to investigate the changing characteristics of cerebral infarction during postmortem examination. Materials and Methods Middle cerebral artery occlusion (MCAO) model was established on 21 SD rats by applying modified suture method. 13 to 56 h after modeling, 12 dead SD rats were collected for the experiment. The bodies were stored at an environment with a temperature of 10-15°C and relative humidity of 45%-55%. Head MRI was performed 12 h after modeling and at 8, 24, 48, 72 and 96 h after death respectively, and apparent diffusion coefficient (ADC) values of infarction and contralateral brain tissue were calculated. At each post-mortem time point, ADC values of bilateral cerebral hemispheres, ADC values of infarction and living infarction, and ADC values of non-infarcted brain and living non-infarcted zone were compared. Brain tissue was taken after scan for pathological diagnosis and compared with diagnostic results of postmortem MRI (pmMRI). Results The right cerebral signal of rats was abnormal 12 h after cerebral infarction and after death. Eight rats were found to have shifted cerebral middle-line structure to the left. ADC values of infarction at each time point after death were lower than that of non-infarction, the difference of which was statistically significant (P<0.05); ADC values of infarction were lower than that of living infarction, the difference of which was statistically significant (P<0.05); ADC value of non-infarcted area at each time point was lower than that of living non-infarcted area, the difference of which was statistically significant (P<0.05). Necrosis and disintegration of neurons, disintegration and liquefaction of glial fibers, infiltration of inflammatory cells and leakage of red blood cells were spotted in necrotic areas after receiving cerebral HE staining in rat. HE staining was consistent with the infarction zone indicated by pmMRI. Conclusion pmMRI can be used for the diagnosis of cerebral infarction via virtual necropsy.

Objective To explore the effect of long-term low dose ionizing radiation on telomere length in adults. Methods Forty female residents aged more than 55 years old from high level natural background radiation area in Yangjiang city and forty age-matched female residents from control area in Enping city were selected by quota sampling as high background group and control group, respectively. Genomic DNA was isolated from their peripheral blood. Telomere length was determined using real time q-PCR. The t-test was used to compare the square roots of the means of two groups. The individuals were divided into four groups based on ages ( 55 -, 60 -, 65 - and ≥70 ) and four groups based on BMI ( <18. 5, 18. 5-23. 99, 24. 0 -27. 99 and ≥28. 0). After adjusting age and BMI, multivariate linear regression analysis was performed to study the relationship between telomere length and cumulative exposure dose. The individuals were divided into longer telomere length group (≥2 ) and shorter telomere length group ( <2). Logistic regression analysis was performed to study the relationship between telomere length and cumulative exposure dose. Results The average cumulative dose was(169. 52 ± 27. 43)mSv for high background group and(47. 52 ± 6. 50)mSv for control group. The telomere length of high background group was( 1. 98 ± 1. 25 ) , shorter than that of control group ( 2. 69 ± 1. 44 ) with statis-tically significant difference(t=2. 24, P <0. 05). The multivariate linear regression analysis revealed that the effect of cumulative dose on telomere length was not significant ( P>0. 05 ) . Association between telomere length and cumulative dose was explored through Logistic regression, and odds ratio was taken as 0. 992(95% CI, 0. 985-0. 999 ) . There was a weak inverse association between telomere length and cumulative dose, because the odds ratio ( OR) was very close to 1. Conclusions No obvious dose-effect relationship between telomere length of residents and cumulative radiation doses was found. But the long-term low dose ionizing radiation may lead to the shortening of the telomere length in adults.

OBJECTIVETo initially explore the clinical effect of cool-tip radiofrequency ablation combined with enucleation for the giant hamartoma of kidney with narrow base and export-oriented way of growth.

METHODSThe clinical date of 15 patients including 6 male and 9 female with special hamartoma of kidney underwent cool-tip radiofrequency ablation assisted enucleation from July 2011 to October 2014 were reviewed.The median age was 49 years (ranging from 35 to 71 years). There were 6 cases with left renal tumor, 8 cases with right renal tumor and 1 case with solitary kidney tumor.All patients were confirmed by B ultrasound or CT scan, the mean diameter of hamartoma of kidney was 9.7 cm(8.5-12.7)cm, all tumors were located distant from the collecting system and presents with a special way of growth.The preoperative hemoglobin was (129±18)g/L, SCr was (92±41)μmol/L, glomerular filtration rate (GFR) was (32±12)ml·min(-1)·1.73 m(-2).

RESULTSCool-tip radiofrequency ablation assisted enucleation was technically successful in all patients.The mean operative duration was (115±31)minutes, and the average intraoperative bleeding was (72±21)ml with no blooding transfusion.The postoperative hospital stay was(7±2)days, and the postoperative hemoglobin was(129±18)g/L, SCr (92±41)μmol/L, GFR(30±15)ml·min(-1)·1.73 m(-2). No statistic change of hemoglobin and SCr or glomerular filtration rate after operations(all P>0.05). Postoperative pathology showed that all cases were hamartoma of kidney.During a mean follow-up period of 19.5 months, none of them had local tumor recurrence or chronic renal insufficiency.

CONCLUSIONSCool-tip radiofrequency ablation assisted enucleation is both safe and effective in the treatment of huge hamartoma of kidney with a narrow base and export-oriented way of growth. The short-term follow-up shows a satisfactory therapeutic effect.

Adult ; Aged ; Angiomyolipoma ; surgery ; Blood Transfusion ; Catheter Ablation ; methods ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Neoplasms ; surgery ; Length of Stay ; Lipoma ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Postoperative Period ; Treatment Outcome