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 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 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 observe the size changes under ultrasound of 4C type thyroid micronodules classified by 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS)during follow-up.Methods:In this cross-sectional study, the data of thyroid ultrasonography in physical examination center in the Affiliated Zhongshan Hospital of Dalian University between December 2017 and December 2021 were retrospectively included, thyroid nodules were classified according to C-TIRADS, to observe the changes by ultrasound of maximum diameter and volume of 4C type thyroid micronodules during follow-up.Results:A total of 102 subjects receiving physical examinations with 103 thyroid micronodules were enrolled in this study. The maximum diameter and volume of thyroid micronodules at initial examination was 5.0 (4.0, 7.0) mm and 52.5 (25.2, 113.4) mm 3 respectively, and it was 6.0 (4.0,7.0) mm、65.6 (25.2,147.0) mm 3 at the last examination, respectively. Of the thyroid micronodules, 79 (76.7%) remained stable, 14 (13.6%) magnified and 10 (9.7%) shrunk during the follow-up. The cervical lymph nodes in all physical examiners were normal. There were significant changes in the maximum diameter and volume in the thyroid micronodules between the initial and last examination in subjects whose micronodules shrunk or magnified during the follow-up (all P<0.05). Conclusion:Size of most C-TIRADS 4C thyroid micronodules remains stable or even decreases during ultrasound follow-up observation, for such thyroid nodules, follow-up observation appears to be a safe and feasible way to postpone surgery.

Objective:A single-center analysis was performed to assess the significant clinical features and prognostic factors of TFE3-rearranged renal cell carcinoma (TFE3 rRCC).Methods:The clinical data of 85 confirmed cases of TFE3 rRCC patients at the Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2007 to February 2023 were analyzed retrospectively. Among these patients, there were 39 males and 46 females, with a median age of 32 (26, 45) years. All patients underwent preoperative CT scans, 21/85 cases (24.7%) of TFE3 rRCC exhibited the characteristic feature of "circular calcification" with plain CT imaging, and enhanced CT scan showed that the tumor enhancement during the arterial phase was lower than the adjacent renal cortex. Among the 85 patients in this cohort, the median tumor diameter was 4.8(3.2, 6.5). Thirty-two patients underwent partial nephrectomy (NSS), while 51 patients underwent radical nephrectomy (RN). Two patients with distant metastasis at the time of diagnosis received only sunitinib therapy. Forty-three patients received adjuvant treatment, including 14 patients who received targeted therapy. There were 29 patients in AJCC stage Ⅲ/Ⅳ, with 10 patients presenting with venous tumor thrombus and 14 patients with lymph node metastasis. Histopathology, TFE3 immunohistochemistry, and break-apart TFE3 FISH probe detection were performed on all 85 cases, while 52 patients underwent RT-PCR and/or DNA sequencing. By combining the clinical and pathological data, we summarized the diagnostic Methods for TFE3 rRCC, evaluated the impact of surgical approaches (RN and NSS) on the survival outcomes of cT 1a/b patients, and assessed the influence of genetic subtypes (ASPL, NONO, PRCC, SFPQ, and others) on the survival outcomes of all patients. Furthermore, we analyzed the risk factors for disease progression. Results:TFE3 rRCC exhibited variable histopathological features, and the presence of acinar-like structures with psammoma bodies may be a relatively typical characteristic. All 85 patients showed positive TFE3 immunohistochemical staining. In 6 cases of TFE3 rRCC, break-apart TFE3 FISH probe yielded negative results. However, final confirmation was achieved through genetic sequence, with 5 cases diagnosed as NONO-TFE3 subtype and 1 case as RBM10-TFE3 subtype. Among the 85 patients, 52 underwent RT-PCR and/or DNA sequencing, revealing a total of 8 TFE3 fusion subtypes, including 11 cases of ASPL-TFE3, 8 cases of PRCC-TFE3, 10 cases of NONO-TFE3, 15 cases of SFPQ-TFE3, 1 case of CLTC-TFE3, 2 cases of LUC7L3-TFE3, 4 cases of MED15-TFE3, and 1 case of RBM10-TFE3. The survival analysis results revealed that among the 12 patients with cT 1b stage tumors who underwent radical nephrectomy (RN), the progression-free survival (PFS) was 35 (14, 109) months, which was significantly better than the NSS group ( P=0.041). However, for the 14 patients with cT 1a stage tumors who underwent RN, there was no statistically significant difference in overall survival (OS) and PFS compared to the NSS group, with OS being 55(27, 134) months and PFS being 71(41, 134) months. Stratifying according to TFE3 fusion subtypes, it was found that patients with ASPL-TFE3 fusion had a significantly lower PFS compared to those with non-ASPL-TFE3 fusion subtypes ( P=0.029). Survival analysis revealed that tumor diameter, surgical approach, adjuvant therapy, AJCC staging, venous tumor thrombus, and lymph node metastasis were associated with OS and PFS( P<0.05). The results of the multivariate Cox regression analysis showed that AJCC stage Ⅲ/Ⅳ( HR=2.393, 95% CI 1.418-4.039, P=0.001) and venous tumor thrombus ( HR=3.543, 95% CI 1.159-10.827, P=0.026) were independent risk factors for progression-free survival (PFS). Conclusions:During the non-enhanced phase of CT scan, TFE3 rRCC tumors can exhibit a circular calcification. TFE3 immunohistochemistry is an important screening method for TFE3 rRCC.Break-apart TFE3 FISH probe detection is considered the diagnostic gold standard, and gene sequencing, if feasible, can provide the subtype diagnosis of TFE3 rRCC. For cT 1a stage TFE3 rRCC, partial nephrectomy (NSS) is a viable option, while caution should be taken in selecting NSS for cT1b stage patients. Patients with ASPL-TFE3 fusion subtype have a worse prognosis. AJCC stage Ⅲ/Ⅳ and venous tumor thrombus indicate poor prognosis in TFE3 rRCC.

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 investigate the differences in output results between difference analysis software, and to provide a reference for the improvement of quality control and the standard revision of SPECT equipment. Methods The image analysis software for quality control held by 14 radiological health technical service institutions was selected as the research subjects using the cluster sampling method. The results of the comparison were analyzed and evaluated according to the Z-score method with certified reference values. Results In the comparison items of “intrinsic uniformity” and “intrinsic spatial linearity”, the number of software with suspicious, deviated and incorrect results accounted for a relatively high proportion, while the results of other comparison items were satisfactory. Conclusion The applicability of SPECT image analysis software lacks effective supervision measures. Relevant departments should introduce feasible measures to standardize the software production and update process, accelerate the construction of radiological health information reporting platform, and promote the healthy development of the radiation health testing industry.

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.