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:The temporal and spatial expression of fibroblast growth factor receptors 1 and 2 remains a controversial issue during kidney development,so the relationship between them and kidney development remains unclear. OBJECTIVE:To observe the dynamic expression of fibroblast growth factor receptors 1 and 2 during kidney development of mice,and to investigate the relationship between them and kidney development. METHODS:The kidneys of fetal mice[embryotic days(E)12,14,16,and 18]and neonatal mice[neonatal days(N)1,3,7,14,24,and 40]were selected to examine the temporal and spatial expression of fibroblast growth factor receptors 1 and 2 by immunohistochemistry method in kidney tissues,and quantitative analysis was performed using western blot assay. RESULTS AND CONCLUSION:(1)Immunohistochemistry showed that fibroblast growth factor receptor 1 was mainly localized in metanephric tissue surrounding the tip of the ureteral bud at E12.Subsequently,fibroblast growth factor receptor 1 was expressed in immature renal corpuscles at various stages,some distal convoluted tubules and capillary loops.The positive site was mainly concentrated in the generative region.Fibroblast growth factor receptor 2 was initially expressed in both ureteral buds and metanephric tissue.Fibroblast growth factor receptor 2 was localized in immature renal corpuscles,distal tubules,collecting ducts and thin segments of medullary loops with kidney development.However,the expression of renal corpuscles was weak.(2)Stereology and western blot assay showed that the expression of fibroblast growth factor receptor 1 was high before birth and gradually decreased after birth,while the expression was very low after N7 day.The expression level of fibroblast growth factor receptor 2 increased gradually with the kidney development and tended to be stable after N7 day.(3)The results exhibit that fibroblast growth factor receptors 1 and 2 are expressed spatially and temporally during kidney development.It is speculated that fibroblast growth factor receptors 1 and 2 may influence nephron development and maturation,and fibroblast growth factor receptor 2 is critical during the formation of ureteral buds and morphology.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

In recent years，with the change in lifestyle and social environment and the increase in pressure in both life and work，male fertility has decreased significantly in China，and the incidence of male infertility has increased year by year，which has brought great challenges to andrologists. Traditional Chinese medicine （TCM） has a definite curative effect in the treatment of male infertility and is widely applied in clinical practice. In order to clarify the role of TCM in different types and each stage of male infertility，the China Association of Chinese Medicine （CACM） invited outstanding young andrologists in the clinic of TCM and western medicine to discuss topics such as idiopathic oligospermia and teratospermia，abnormal semen liquefaction，varicocele，immune infertility，improving success ratio of assisted reproductive technology，and ameliorating depression or anxiety. They conducted in-depth discussions on the advantages，characteristics，disadvantages，diseases responding specifically，and advantageous aspects of TCM treatment. The causes of male infertility and related links of treatment were summarized. Due to the unclear etiology and complex pathogenesis of male infertility，western medicine cannot achieve a good curative effect，while TCM，taking the holistic view as the core，specializes in improving functional diseases and can correspond to multiple targets and factors，with comprehensive treatments such as internal treatment and external treatment. This study summarized the advantageous diseases and advantageous stages of TCM treatment alone and integrated TCM and western medicine treatment and put forward suggestions for the treatment of the diseases by TCM and western medicine in order to promote the therapeutic effects and advantages of TCM among andrologists，increase mutual learning and communication between TCM and western physicians，provide patients with excellent and personalized treatment plans in clinical practice，and improve the curative effect of male infertility and fertility of males in China.

【Objective】 To investigate the efficacy of low intensity pulsed ultrasound (LIPUS) in the treatment of erectile dysfunction (ED). 【Methods】 A total of 121 ED patients treated during June 2020 and June 2022 were selected as the research objects. According to the International Erectile Index Score (IIEF-EF), the patients were divided into three subgroups:mild (17-25 points), moderate (11-16 points), and severe (0-10 points). The total effective rate, erectile hardness scale (EHS), sex life log questions (SEP), general assessment questionnaire (GAQ), peak systolic velocity (PSV), end diastolic velocity (EDV), and adverse reactions of the three groups before treatment, 4 weeks and 12 weeks after treatment were analyzed. 【Results】 A total of 119 patients completed the follow-up. There were significant increases in IIEF-EF and EHS at week 4 and 12 (P<0.05), and the total effective rate was 69.75% and 76.47%, respectively. The total effective rate was significantly higher in the mild and moderate groups than in the severe group at week 4 and 12 (P<0.05). The patients who answered "yes" to SEP2 and SEP3 accounted for 91.60% and 71.43%, respectively at week 4, and 92.44% and 78.15% at week 12, both significantly higher than the rates before treatment (52.10% and 27.73%, P<0.05). The proportion of patients who answered "yes" to GAQl and GAQ2 at week 4 were 84.87% and 71.43%, respectively, and were 82.35% and 70.59% respectively at week 12, with no significant difference. The PSV level significantly increased at week 12 compared to that before treatment [(48.85±14.11) cm/s vs. (41.42±14.90) cm/s] (P<0.05), while the EDV level significantly decreased [(-0.57±7.01) cm/s vs. (2.25± 5.68)cm/s] (P<0.05). 【Conclusion】 LIPUS can improve erectile function in ED patients without obvious adverse reactions.

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.
Humans ; Rats ; Animals ; Benzhydryl Compounds/toxicity* ; Phenols/toxicity* ; Auditory Perception/physiology* ; Neurons/physiology*

Copper is an important trace element in the human body, and copper deficiency or overload can lead to a series of body dysfunctions. This review focuses on hepatolenticular degeneration and related diseases of abnormal copper metabolism. Hepatolenticular degeneration has various clinical phenotypes, and related diseases, such as cholestatic liver disease, hereditary ceruloplasmin deficiency, and congenital abnormal glycosylation, may bring confusion to the clinical diagnosis of hepatolenticular degeneration. With reference to the latest research advances and experience in the diagnosis and treatment of hepatolenticular degeneration, this article discusses the pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism from the perspective of liver diseases.

Objective: To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients. Methods: A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data. Results: 80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment. Conclusion In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.

Objective To study the application of the cold cutting technique in transumbilical sin gle-incision laparoscopic liver resection (TUSI-LLR),and to evaluate its feasibility and treatment results.Methods The clinical data of 35 patients with liver lesions treated by transumbilical single-incision laparoscopic liver resection from 2013 to 2017 were retrospectively analyzed in Shengjing Hospital of China Medical University.In all these patients,the liver parenchyma was transected with the cold cutting technique.The operation time,intraoperative blood loss,postoperative complications,time to remove abdominal drain,and total hospital stay in the patients were analyzed.Results 11 of the 35 patients were male.The average age was (49.9 ± 10.8) years.The average body weight was (63.2 ± 11.1) kg.The diagnoses were hemangiomas in 18 patients,hepatolithiasis in 5 patients,malignant hepatocellular tumors in 5 patients,focal nodular hyperplasia in 3 patients,and others in 4 patients.There were 22 left lateral sectionectomies,2 left hemihepatectomies,11 wedge resections (8 in the left and 3 in the right).The operations were all successfully performed,with no conversion to conventional laparoscopic hepatectomy or open surgery.The average operation time was (112.2 ±51.0) minutes,and the intraoperative blood loss was (105.4 ±70.1) ml.No patients required intraoperative blood transfusion.The average surgery cost was (36 336.7 ± 5 938.2) yuan.All patients recovered well,with no postoperative hemorrhage,bile leakage,or incisional wound infection.The average time periods for removal of the abdominal drain,and hospital stay were (4.5 ± 1.2) days and (5.2 ± 1.4) days,respectively.All the 35 patients were followed up (1 ～ 3 months),with no patients complaining of abdominal distension or abdominal pain.Conclusions The cold cutting technique in transumbilical single-incision laparoscopic liver resection was safe and feasible.Its benefits included the operative speed,the small amount of intraoperative blood loss and the rapid postoperative recovery of the patients.

Objective To investigate the application value of the adhesive suspension of left lateral lobe of liver in transumbilical single-port laparoscopic left upper abdominal surgery.Methods The retrospective crosssectional study was conducted.The clinical data of 112 patients who underwent single-port laparoscopic left upper abdominal surgery in the Shengjing Hospital of China Medical University between January 2010 and October 2016 were collected.Patients underwent single-port laparoscopic left upper abdominal surgery,and intraoperative surgical fields were exposed through adhesive suspension of left lateral lobe of liver.Observation indicators:(1)intraoperative situations:surgical completion,surgical procedures,time of liver adhesive suspension,total operation time and intraoperative liver adhesive suspension-related complications;(2) postoperative situations:pre-and post-operative alanine transaminase (ALT) and aspartate transaminase (AST) levels,hospital expenses and duration of hospital stay;(3) follow-up:number of patients with follow-up,follow-up time,complications during follow-up.Follow-up using outpatient examination and telephone interview was performed to detect postoperative complications up to June 2017.Measurement data with normal distribution were represented as (x)+s.Repeated measurement data were analyzed using the repeated measures ANOVA.Results (1) Intraoperative situations:112 patients underwent successfully single-port laparoscopic left upper abdominal surgery,without conversion to multi-port surgery or open surgery.Of 112 patients,30,23,13,11,11,10,3,3,3,3,1 and 1 underwent radical resection of gastric cancer,partial gastrectomy,esophageal Heller myotomy + Dor fundoplication,subtotal gastrectomy,resection of body and tail of pancreas,paraoesophageal hiatal hernia repair + fundoplication,total gastrectomy,splenectomy,splenectomy + devascularization,pancreatic tail resection,simple fundoplication and splenic artery aneurysm resection,respectively.Time of liver adhesive suspension and total operation time in 112 patients were respectively (1.4±0.4)minutes and (192.0±91.3) minutes.There was no hepatic laceration,hepatic subcapsular hematoma and other complications.(2) Postoperative situations:of 112 patients,preoperative ALT and AST levels of 6 patients were mildly elevated,postoperative ALT and AST levels in 2 of 6 patients returned to normal,that in 1 of 6 patients were elevated at day 1 postoperatively and returned to normal at day 3 postoperatively,and that in 2 of 6 patients remained mildly elevated at week 1 postoperatively;preoperative ALT and AST levels of 106 patients were normal,ALT and AST levels in 31 of 106 patients were elevated at day 1 postoperatively (that in 28 patients returned to normal within week 1 postoperatively,and that in 3 patients remained mildly elevated),and that in 75 of 106 patients returned to normal.ALT and AST levels of 112 patients were (16± 11) U/L,(18±7) U/L before operation and (31 ±21) U/L,(34±26) U/L at day 1 postoperatively and (19 ± 17) U/L,(19 ± 12) U/L at week 1 postoperatively,respectively,with statistically significant differences in ALT and AST levels before operation and at day 1 postoperatively (F=36.353,29.792,P＜ 0.05),and no statistically significant difference in ALT and AST levels before operation and at week 1 postoperatively (F=2.905,1.284,P＞0.05).Hospital expenses,surgery-related expenses and duration of hospital stay were (45 231±20 440)yuan,(23 511±9 609)yuan and (6.0±l.9)days,respectively.(3) Follow-up:112 patients were followed up for 1.0-3.0 months,with a median time of 1.6 months.During the follow-up,there were no obvious complications.Conclusion Adhesive suspension of left lateral lobe of liver is simple and safe,with satisfactory exposure effects,and it is suitable for the better operative field exposure in single-port laparoscopic left upper abdominal surgery.