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

Objective:To explore the feasibility of active surveillance for multifocal papillary thyroid microcarcinoma(PTMC).Methods:It was a cross-sectional study. The thyroid ultrasonography data from 124 580 health check-up participants in the Health Management Center at the Affiliated Zhongshan Hospital of Dalian University between March 2017 and December 2023 were retrospectively analyzed. The patients were divided into unifocal or multifocal group according to the number of PTMC. The rates of growth, lymph node metastasis and progression in the unifocal and multifocal PTMC group during active surveillance were compared by using the Kaplan-Meier method and the log-rank test. The patients were divided into the group of progression or no-progression according to the outcome of active surveillance, and the basic clinical characteristics between the groups were compared. The Cox proportional hazards regression analysis was used to identify the risk factors for the progression of PTMC.Results:A total of 304 patients were enrolled in this study, among them, there were 239 cases of unifocal PTMC and 65 cases of multifocal PTMC. There was no significant differences in the rates of growth, lymph node metastasis and progression in the PTMC between the two groups during active surveillance (all P>0.05). During the active surveillance period, a total of 47 cases of PTMC progressed, while 257 cases did not. The progression rate was 15.5%. There was statistically significant difference in the initial age of PTMC diagnosis between the progression and non-progression group ( P<0.05). Multivariate regression analysis showed that age of initial diagnosis was the only risk factor for the progression of PTMC, the risk of progression decreased by 0.079 for every one-year increase in the initial diagnosis age [ HR=0.921, (95% CI: 0.888-0.955), P<0.001], multifocality was not a risk factor[ HR=1.973, 95% CI(0.972-4.462), P=0.103]. Conclusion:Active surveillance can be performed for multifocal PTMC in patients of appropriate age.

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.

Alzheimer's disease(AD)is an age-related neurodegenerative disease with an increasing incidence worldwide.A large number of studies have shown that the incidence rates of hearing loss is high in patients with mild cognitive impairment and Alzheimer's disease,and may be a risk factor for the occurrence and development of cognitive impairment.There is an interaction between the two,but the causal mechanism is still unclear.Early screening and management of hearing impairment may play an important role in the early diagnosis,symptom im-provement and disease progression of Alzheimer's disease.This paper reviews relevant clinical and basic research to discuss the correlation between hearing loss and Alzheimer's disease,and the possible causal mechanism between them.

Alzheimer's disease(AD)is an age-related neurodegenerative disease with an increasing incidence worldwide.A large number of studies have shown that the incidence rates of hearing loss is high in patients with mild cognitive impairment and Alzheimer's disease,and may be a risk factor for the occurrence and development of cognitive impairment.There is an interaction between the two,but the causal mechanism is still unclear.Early screening and management of hearing impairment may play an important role in the early diagnosis,symptom im-provement and disease progression of Alzheimer's disease.This paper reviews relevant clinical and basic research to discuss the correlation between hearing loss and Alzheimer's disease,and the possible causal mechanism between them.

Objective:To explore the feasibility of active surveillance for multifocal papillary thyroid microcarcinoma(PTMC).Methods:It was a cross-sectional study. The thyroid ultrasonography data from 124 580 health check-up participants in the Health Management Center at the Affiliated Zhongshan Hospital of Dalian University between March 2017 and December 2023 were retrospectively analyzed. The patients were divided into unifocal or multifocal group according to the number of PTMC. The rates of growth, lymph node metastasis and progression in the unifocal and multifocal PTMC group during active surveillance were compared by using the Kaplan-Meier method and the log-rank test. The patients were divided into the group of progression or no-progression according to the outcome of active surveillance, and the basic clinical characteristics between the groups were compared. The Cox proportional hazards regression analysis was used to identify the risk factors for the progression of PTMC.Results:A total of 304 patients were enrolled in this study, among them, there were 239 cases of unifocal PTMC and 65 cases of multifocal PTMC. There was no significant differences in the rates of growth, lymph node metastasis and progression in the PTMC between the two groups during active surveillance (all P>0.05). During the active surveillance period, a total of 47 cases of PTMC progressed, while 257 cases did not. The progression rate was 15.5%. There was statistically significant difference in the initial age of PTMC diagnosis between the progression and non-progression group ( P<0.05). Multivariate regression analysis showed that age of initial diagnosis was the only risk factor for the progression of PTMC, the risk of progression decreased by 0.079 for every one-year increase in the initial diagnosis age [ HR=0.921, (95% CI: 0.888-0.955), P<0.001], multifocality was not a risk factor[ HR=1.973, 95% CI(0.972-4.462), P=0.103]. Conclusion:Active surveillance can be performed for multifocal PTMC in patients of appropriate age.

Objective:To explore the effectiveness and safety of percutaneous radiofrequency ablation for renal tumors, guided by both ultrasound and CT, under local anesthesia.Methods:A retrospective analysis was conducted on the clinical data of 40 patients with renal tumors admitted to Nanjing Drum Tower Hospital between January 2018 and December 2022. This treatment involved ultrasound/CT dual-guided radiofrequency ablation under local anesthesia. The cohort included 33 males and 7 females, with an average age of (61.5±11.9) years old and a body mass index (BMI) of (24.79±3.37) kg/m 2. The tumors were located in the left kidney in 20 cases and the right kidney in 16 cases, with 4 cases involving bilateral renal tumors. There were 44 tumors in 40 patients, with the maximum tumor diameter ranging from 1.0 to 4.0 cm [mean (2.3 ± 0.7) cm]. Distribution by kidney pole was as follows: 15 cases at the upper pole, 21 at the middle pole, and 8 at the lower pole. Of the tumors, 23 were exophytic, 5 were endophytic, and 16 exhibited mixed features. There were 2 patients with multiple metastases before surgery(including 1 patient with bilateral renal tumor). Preoperative serum creatinine level was 68.0(56.5, 87.5)μmol/L, and the estimated glomerular filtration rate (eGFR) was 114.2 (79.6, 132.4) ml/(min·1.73 m 2). All patients underwent renal biopsy before or during radiofrequency ablation. Percutaneous radiofrequency ablation surgery was performed using ultrasound and CT dual guidance on all patients, ensuring complete tumor destruction during the procedure as confirmed by dual positioning. Patients with bilateral tumors underwent two separate surgeries, spaced one month apart. Postoperatively, closely monitor the patient's vital signs and conduct long-term follow-ups to record any recurrence and metastasis. Results:In this series, all 40 procedures (involving 44 renal units) were successfully completed under local anesthesia without any need for blood transfusion, conversion to open surgery, or perioperative deaths. The average radiofrequency ablation time was (9.5 ± 3.6) min. Tumor characteristics included predominantly exophytic growths (23 cases, 52.3%), with 31 cases (70.5%) located more than 7 mm from the collecting system and 28 cases (63.6%) positioned posteriorly. Thirteen cases (29.5%) were entirely outside the polar line. The average R. E.N.A.L. nephrometry score was 6.1±0.2. Pathological examination revealed 34 cases of clear cell carcinoma, 2 of papillary renal cell carcinoma, 4 of unclassified renal cell carcinoma, and 4 benign renal tumors. In this cohort, two patients with bilateral renal tumors exhibited benign tumors on one side, while two other patients had malignant tumors in both kidneys. All 40 malignant tumors identified in 38 cases were classified at stage cT 1a.Postoperative serum creatinine level was 71.5 (59.0, 94.3) μmol/L, showing no statistically significant change from preoperative levels ( P > 0.05). Similarly, the eGFR post-operation was 107.4 (79.7, 132.2) ml/(min·1.73 m 2), which also did not differ significantly from preoperative values ( P > 0.05). There were no postoperative complications of Clavien-Dindo grade ≥Ⅱ, except for one case of severe pain (score 7-10). The follow-up period ranged from 15 to 70 months. Among the 38 cases, 36 patients did not have distant metastasis before surgery. There were 2 patients (5.5%) with local recurrence within 60 months after surgery. Among them, one case relapsed 6 months after radiofrequency ablation and was treated with partial nephrectomy. The patient was followed up for 60 months after the second treatment, and no local recurrence occurred. Another patient relapsed 41 months after surgery and was treated with radiofrequency ablation again. The patient was followed up for 12 months after the second treatment, and no local recurrence occurred. Two patients with distant metastasis before surgery were treated with targeted therapy plus immunotherapy for 12 months after surgery. One case had local recurrence 8 months after surgery and was treated with partial nephrectomy. The patient was followed up for 60 months after partial nephrectomy and no local recurrence occurred. Another patient with bilateral renal tumors developed left kidney recurrence 34 months after radiofrequency ablation, and underwent left partial nephrectomy. The right kidney recurred 42 months after radiofrequency ablation and underwent radiofrequency ablation again. After the second right renal radiofrequency ablation, no local recurrence occurred during 12 months of follow-up. Conclusions:Ultrasound/CT dual-guided percutaneous radiofrequency ablation, performed under local anesthesia for treating renal tumors, has minimal impact on the patient's renal function. The procedure boasts a low complication rate, with no postoperative severe complications. Additionally, the postoperative tumor control is effective, making it a safe and minimally invasive surgical option.

Objective:To investigate the factors related to the tumor growth in subjects with low-risk papillary thyroid microcarcinoma (PTMC) based on ultrasonography.Methods:This was a cross-sectional study. A total of 136 subjects who received health check-up in Health Management Center, the Affiliated Zhongshan Hospital of Dalian University from October 2017 to December 2023 were enrolled in the study. Low-risk PTMC were detected by ultrasonogrphy in those subjects and ultrashonography was followed up to observe the changes of maximum diameter and volume of the tumor, and metastasis of cervical lymph nodes. The clinical characteristics and ultrasonic image features were compared between the subjects with the tumor growth and without tumor growth, and the influencing factors of tumor growth were analyzed.Results:Among 136 subjects with low-risk PTMC, there were 23 cases (16.9%) with tumor growth (growth group) and 113 cases (83.1%) without tumor growth (non-growth group). Cervical lymph node metastasis occurred in 8 cases (5.9%: 7 (30.4%) in the growth group and 1 (0.9%) in non-growth group), no distant metastasis were detected. There were significantly differences in patients age of initial diagnoisi, maximum diameter and volume of tumors between the growth group and non-growth group (all P<0.05). Logistic regression analysis showed that age of initial diagnoisi ≤40 years ( OR=4.299, 95% CI:1.662-12.175, P=0.003) was an independent risk factor for tumor growth and the maximum diameter of the initial examination was independent protective factor for tumor growth (increasing 1 mm of initial diameter: OR=0.554, 95% CI:0.317-0.969, P=0.038). Conclusion:The size of most low-risk PTMC detected by ultrasonography during the health check-up does not grow and the risk of cervical lymph node metastasis is low; however, for those with age of initial diagnoisi ≤40 years and smaller size tumor, the risk of PTMC growth would be increased.

Objective:To study a quality control method of digital single photon emission computed tomography for heart,so as to provide references for formulating a standards of quality control(QC)of digital SPECT equipment.Methods:Based on the American Electrical Manufacturers Association(AEMA)"Gamma Camera Performance Test"(NU 1-2018)and the test method of routine quality assurance of equipment that was performed by related manufacturers of digital SPECT equipment for heart,a general QC method was constructed,which suited to the digital SPECT equipment for heart that used semiconductor cadmium zinc telluride(CZT)material,and turned prober on multi-angle in scanning.The test content included 5 test items,such as system energy resolution,system uniformity,sensitivity of system scanning,tomographic spatial resolution with scattering and maximum count rate of system.Results:Compared with the manufacturer's requirements,the test results indicated that the test results of the first time of 5 items included system energy resolution,system uniformity,sensitivity of system scanning,tomographic spatial resolution with scattering and maximum count rate of system were respectively 5.8%,8%,67 811 counts/(min·MBq),4.91mm,1.8×106s-1.The test results of the second time of them were respectively 5.6%,6%,68 297 counts/(min·MBq),4.96mm and 1.8×106s-1.The results of all test items met the requirements of the manufacturer's indicators.Conclusion:The established QC method can scientifically and objectively evaluate the operating state of this kind of equipment,which can provide data support for formulating QC standard of digital SPECT equipment.

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.