[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with giant cell carcinoma of the lung (GCCL).Methods:A retrospective case series study was conducted. The clinical data and the survival related information of patients with GCCL in Surveillance, Epidemiology and End Results (SEER) database from the establishment of the databank to April 2019 were collected, and the clinicopathological characteristics of patients were summarized. Cox proportional hazards model was used for univariate and multivariate analysis of the overall survival (OS) and the independent influencing factors for poor OS were screened. Kaplan-Meier method was used to analyze the OS and cancer-specific survival (CSS) of the entire group and the patients stratified by the independent influencing factors. The log-rank test was used for inter-group comparisons.Results:A total of 248 GCCL cases were included. Among them, 64.9% (161 cases) were aged ≤70 years, 60.1% (149 cases) were male, and 57.7% (143 cases) were married. GCCL was more commonly found in the right lung [58.5% (145 cases)], and 64.1% (159 cases) were classified as TNM stage Ⅲ-Ⅳ. No high differentiation cases were observed, and there was only 1 case (0.4%) of moderate differentiation, while the remaining cases were poorly differentiated [56.0% (139 cases)] or undifferentiated [43.5% (108 cases)]. Lymph node metastasis was observed in 55.6% (138 cases), and distant metastasis occurred in 35.5% (88 cases). Regarding treatment, 50.4% (125 cases) underwent surgery, 18.5% (46 cases) received radiotherapy, and 39.1% (97 cases) underwent chemotherapy. Kaplan-Meier analysis showed that the 1-year and 5-year OS rates for all 248 cases were 38.8% and 21.3%, respectively, while the 1-year and 5-year CSS rates were 47.7% and 32.3%, respectively. Univariate and multivariate Cox regression analyses revealed that age (≥71 years vs. <70 years, HR = 1.526, 95% CI: 1.145-2.033, P = 0.004), marital status (married vs. others, HR = 0.755, 95% CI: 0.569-1.000, P = 0.049), N stage (all compared to N 0 stage; N 1 stage: HR = 1.876, 95% CI: 1.212-2.903, P = 0.005; N 2 stage: HR = 1.560, 95% CI: 1.074-2.265, P = 0.020; N 3 stage: HR = 1.902, 95% CI: 1.089-3.323, P = 0.024), M stage (M 1vs. M 0, HR = 2.122, 95% CI: 1.488-3.026, P < 0.001), and surgical treatment (surgery vs. no surgery, HR = 0.542, 95% CI: 0.361-0.813, P = 0.003) were independent risk factors for poor OS. Kaplan-Meier analysis demonstrated that patients aged >70 years, married, without lymph node metastasis, without distant metastasis, and those who underwent surgery had better OS, and the differences were statistically significant (all P < 0.05). Conclusions:GCCL is more common in elderly men and is more frequently found in the right lung. Most patients have lymph node metastasis and the patients with the distant metastasis are relatively common. The majority of cancer patients have an undifferentiated or poorly differentiated degree. Age, marital status, N stage, M stage, and whether surgery was performed are independent prognostic factors for GCCL.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Castleman’s disease(CD) is a rare lymphoproliferative disorder that is classified based on the affected sites and pathological features. The pathogenesis of CD remains not fully understood and may be associated with viral infections, genetic abnormalities, and immunological factors. Clinically, CD is categorized into two types based on lymph node involvement: Unicentric Castleman Disease(UCD) and Multicentric Castleman Disease(MCD). Treatment options include surgery, chemotherapy, immunotherapy, and targeted therapy. This article summarizes recent advancements in the understanding of the pathogenesis, clinical characteristics, diagnosis, and treatment of CD, aiming to provide assistance for future clinical work.

Castleman’s disease(CD) is a rare lymphoproliferative disorder that is classified based on the affected sites and pathological features. The pathogenesis of CD remains not fully understood and may be associated with viral infections, genetic abnormalities, and immunological factors. Clinically, CD is categorized into two types based on lymph node involvement: Unicentric Castleman Disease(UCD) and Multicentric Castleman Disease(MCD). Treatment options include surgery, chemotherapy, immunotherapy, and targeted therapy. This article summarizes recent advancements in the understanding of the pathogenesis, clinical characteristics, diagnosis, and treatment of CD, aiming to provide assistance for future clinical work.

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with giant cell carcinoma of the lung (GCCL).Methods:A retrospective case series study was conducted. The clinical data and the survival related information of patients with GCCL in Surveillance, Epidemiology and End Results (SEER) database from the establishment of the databank to April 2019 were collected, and the clinicopathological characteristics of patients were summarized. Cox proportional hazards model was used for univariate and multivariate analysis of the overall survival (OS) and the independent influencing factors for poor OS were screened. Kaplan-Meier method was used to analyze the OS and cancer-specific survival (CSS) of the entire group and the patients stratified by the independent influencing factors. The log-rank test was used for inter-group comparisons.Results:A total of 248 GCCL cases were included. Among them, 64.9% (161 cases) were aged ≤70 years, 60.1% (149 cases) were male, and 57.7% (143 cases) were married. GCCL was more commonly found in the right lung [58.5% (145 cases)], and 64.1% (159 cases) were classified as TNM stage Ⅲ-Ⅳ. No high differentiation cases were observed, and there was only 1 case (0.4%) of moderate differentiation, while the remaining cases were poorly differentiated [56.0% (139 cases)] or undifferentiated [43.5% (108 cases)]. Lymph node metastasis was observed in 55.6% (138 cases), and distant metastasis occurred in 35.5% (88 cases). Regarding treatment, 50.4% (125 cases) underwent surgery, 18.5% (46 cases) received radiotherapy, and 39.1% (97 cases) underwent chemotherapy. Kaplan-Meier analysis showed that the 1-year and 5-year OS rates for all 248 cases were 38.8% and 21.3%, respectively, while the 1-year and 5-year CSS rates were 47.7% and 32.3%, respectively. Univariate and multivariate Cox regression analyses revealed that age (≥71 years vs. <70 years, HR = 1.526, 95% CI: 1.145-2.033, P = 0.004), marital status (married vs. others, HR = 0.755, 95% CI: 0.569-1.000, P = 0.049), N stage (all compared to N 0 stage; N 1 stage: HR = 1.876, 95% CI: 1.212-2.903, P = 0.005; N 2 stage: HR = 1.560, 95% CI: 1.074-2.265, P = 0.020; N 3 stage: HR = 1.902, 95% CI: 1.089-3.323, P = 0.024), M stage (M 1vs. M 0, HR = 2.122, 95% CI: 1.488-3.026, P < 0.001), and surgical treatment (surgery vs. no surgery, HR = 0.542, 95% CI: 0.361-0.813, P = 0.003) were independent risk factors for poor OS. Kaplan-Meier analysis demonstrated that patients aged >70 years, married, without lymph node metastasis, without distant metastasis, and those who underwent surgery had better OS, and the differences were statistically significant (all P < 0.05). Conclusions:GCCL is more common in elderly men and is more frequently found in the right lung. Most patients have lymph node metastasis and the patients with the distant metastasis are relatively common. The majority of cancer patients have an undifferentiated or poorly differentiated degree. Age, marital status, N stage, M stage, and whether surgery was performed are independent prognostic factors for GCCL.

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

Objective:To establish a method for determining the concentration of gatifloxacin in rabbit ocular tissue and compare the ocular pharmacokinetics of 0.3% gatifloxacin eye gel after a single and multiple topical instillations in rabbits.Methods:Ninety-four healthy New Zealand rabbits were selected.Ten rabbits were randomly selected without any treatment for blank tissue collection, and the remaining 84 rabbits were randomly divided into a single-dose group (36 rabbits) and a multiple-dose group (48 rabbits) equally between males and females using a random number table.The left eye was taken as the experimental eye.The single-dose group was given one drop of 0.3% gatifloxacin eye gel into the left eyes, and the rabbits were divided evenly into six subgroups.In each subgroup, tear specimens and blood specimens were collected at 0.5, 1, 3, 5, 7, 10 hours after gel application, then cardiac blood samples were taken, after which animals were sacrificed immediately to collect ocular tissue including aqueous humor, conjunctiva, cornea, sclera, iris-ciliary body, lens, vitreous body, retina, and choroid.The multiple-dose group was given 1 drop of gatifloxacin ophthalmic gel in the left eye three times a day.At 0.5 hour after the first administration days 4 and 6, and 0.5, 1, 3, 5, 7, and 10 hours after the first administration on day 7, the cardiac blood sampling and ocular tissue collection were performed.The methanol precipitation protein method was used to pretreat samples, and the concentration of gatifloxacin in rabbit plasma and eye tissue was measured and calculated by high-performance liquid chromatography-tandem mass spectrometry method to obtain pharmacokinetic-related parameters such as peak concentration (C max), peak time (T max), and area under curve (AUC).The mobile phase was a methanol-0.1% acetic acid aqueous solution (volume ratio=70∶30), and a positive ion multiple reaction detection mode was used.Ciprofloxacin was used as the internal standard, the selectivity, standard curve and lower limit of quantification, accuracy and precision, extraction recovery rate, matrix effect, and stability of the method were validated in accordance with the 9012 Guidelines for Validation of Quantitative Analysis Methods for Biological Samples in Chinese Pharmacopoeia ( 2020 edition).Combined with the minimum inhibitory concentration (MIC 90) of gatifloxacin on common ocular infectious bacteria, C max/MIC 90 and AUC/MIC 90 were calculated.The study protocol was reviewed and approved by the Animal Ethics Committee of Shenyang Xingqi Pharmaceutical Co., Ltd.(No.XQ-2016-011). Results:Gatifloxacin has a good linear relationship in various eye tissues and plasma.The between-run precision in corneal tissue is within the range of -1.5%-6.0%, and the daytime precision was not greater than 15%.The extraction recovery rate in corneal tissue ranged from 92.0% to 94.8%, and the precision of the matrix effect at low, medium, and high concentrations calculated by internal standard normalization was not greater than 3.3%.After a single topical instillation, gatifloxacin reached a high concentration in anterior and posterior segment ocular tissues and its distribution ranked in order from the highest to the lowest by AUC 0-t as follows, tears, cornea, conjunctiva, iris-ciliary body, sclera, aqueous humor, choroid, retina, lens and vitreous body, with the C max of 94.90 μg/g, 7.34 μg/g, 3.65 μg/g, 1.81 μg/g, 1.75 μg/g, 1.31 μg/ml, 0.86 μg/g, 0.53 μg/g, 0.13 μg/g and 0.07 μg/ml, respectively.T max was 1 hour in all ocular tissues except in the lens, choroid, and vitreous body fluid, where T max was 0.5 hour.There was no significant difference among the concentrations of gatifloxacin in ocular tissues at 0.5 hour on days 4, 6 and 7 after multiple dosing ( P>0.05), and the AUC 0-t in the cornea, conjunctiva, and sclera was approximately 2.04, 2.12, and 2.32 times that of the single dosing.The concentration of gatifloxacin released into the systemic circulation after single and multiple dosing was less than 25.00 ng/ml.For both Staphylococcus aureus and Staphylococcus epidermidis, pharmacokinetic/pharmacodynamics in the conjunctiva, cornea, sclera, iris-ciliary body, aqueous humor, and choroid were satisfied with C max/MIC 90≥10 and AUC/MIC 90≥30 after continuous administration of gatifloxacin ophthalmic gel. Conclusions:A rapid and sensitive method for measuring gatifloxacin concentration in ocular tissues is successfully constructed.Gatifloxacin ophthalmic gel administered three times a day for three days can achieve stable concentrations in ocular tissues, and the concentration of gatifloxacin in ocular tissues is increased compared with a single dose.Effective treatment of common bacterial infections of the conjunctiva, cornea, sclera, and iris-ciliary body can be achieved with topical application of gatifloxacin ophthalmic gel.

Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal failure.However,it has poor elasticity and compliance,leading to stenosis and thrombosis.The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial cells.Studies have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM fibers.Furthermore,mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure.Based on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV infection.Subsequently,these HBX-HSCs were implanted into a polycaprolactone-polyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold.We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization.Then,the vessel scaffold was implanted into a rabbit's neck arteriovenous fistula model.It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit's body.Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.