Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

Objective:To investigate the therapeutic effects of Akkermansia muciniphila (AKK) on liver injury induced by cholestasis and its mechanisms in regulating bile acid metabolism. Methods:The cholestatic mouse model was established by bile duct ligation (BDL). A total of 35 male C57BL/6J mice (8 weeks old) were divided into 5 groups using a random numder table method (7 mice per group): group A (control group), group B (BDL group), group C (BDL+AKK group), group Z (BDL+AKK+Z/E-guggulsterone group), and group G (BDL+AKK+Gly-β-muricholic acid group). Preoperative and postoperative changes in liver function and bile acid metabolism indicators was observed of mice in groups A, B, and C. The liver function and fibrosis markers were compared between groups, as well as serum, liver, and fecal total bile acid levels, fecal bile acid composition, liver histopathology, and the mRNA expression of key proteins involved in the bile acid enterohepatic circulation and the farnesoid X receptor (FXR) signaling pathway were compared. Multiple groups of data were compared using analysis of variance or nonparametric Kruskal Wallis H test. Results:Twelve days after BDL, in groups A, B, and C, mice in group C exhibited milder postoperative jaundice and their body weights on postoperative days 4-5 and 7-11 were heavier than those in group B mice (all P<0.05). The liver tissues of mice in group C were milder than those in group B in terms of appearance, histopathology, inflammation and liver fibrosis (all P<0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, as well as the expression levels of liver α-smooth muscle actin and type Ⅰ collagen, and the levels of total liver bile acid and fecal β-murine bile acid in the C group mice were all lower than those of group B mice ((46±20) vs. (90±34) U/L, (96±17) vs.(122±31) U/L, (2.01±0.11)% vs. (7.55±0.21)%, (1.92±0.10)% vs. (7.28±0.51)%, (62±14) vs. (124±39) μmol/mg, 3 052 (1 522, 6 406) vs. 14 756 (6 582, 33 474) ng/g,all P<0.05). And the mRNA expression levels of cholesterol 7α-hydroxylase and bile salt export pump of the ileum, etc. in group C mice were lower than those in group B mice (all P<0.05), while the mRNA expression levels of FXR and fibroblast growth factor 15 in the intestine were higher than those in group B mice (all P<0.05). In groups B, C, Z, and G, compared with group C, mice in groups Z and G had aggravated liver injury and fibrosis, increased total bile acid levels in the liver, and increased serum alanine aminotransferase, total bilirubin, and expression levels of liver α-smooth muscle activator protein and type I collagen (all P<0.05). There was no statistically difference in the above indicators between group Z and group G (all P<0.05). Conclusion:AKK reduces liver bile acid synthesis, regulates bile acid metabolism, alleviate liver function damage and fibrosis, and improves clinical phenotypes by activating the intestinal FXR-fibroblast growth factor 15 signaling pathway.

Objective:To investigate the therapeutic effects of Akkermansia muciniphila (AKK) on liver injury induced by cholestasis and its mechanisms in regulating bile acid metabolism. Methods:The cholestatic mouse model was established by bile duct ligation (BDL). A total of 35 male C57BL/6J mice (8 weeks old) were divided into 5 groups using a random numder table method (7 mice per group): group A (control group), group B (BDL group), group C (BDL+AKK group), group Z (BDL+AKK+Z/E-guggulsterone group), and group G (BDL+AKK+Gly-β-muricholic acid group). Preoperative and postoperative changes in liver function and bile acid metabolism indicators was observed of mice in groups A, B, and C. The liver function and fibrosis markers were compared between groups, as well as serum, liver, and fecal total bile acid levels, fecal bile acid composition, liver histopathology, and the mRNA expression of key proteins involved in the bile acid enterohepatic circulation and the farnesoid X receptor (FXR) signaling pathway were compared. Multiple groups of data were compared using analysis of variance or nonparametric Kruskal Wallis H test. Results:Twelve days after BDL, in groups A, B, and C, mice in group C exhibited milder postoperative jaundice and their body weights on postoperative days 4-5 and 7-11 were heavier than those in group B mice (all P<0.05). The liver tissues of mice in group C were milder than those in group B in terms of appearance, histopathology, inflammation and liver fibrosis (all P<0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, as well as the expression levels of liver α-smooth muscle actin and type Ⅰ collagen, and the levels of total liver bile acid and fecal β-murine bile acid in the C group mice were all lower than those of group B mice ((46±20) vs. (90±34) U/L, (96±17) vs.(122±31) U/L, (2.01±0.11)% vs. (7.55±0.21)%, (1.92±0.10)% vs. (7.28±0.51)%, (62±14) vs. (124±39) μmol/mg, 3 052 (1 522, 6 406) vs. 14 756 (6 582, 33 474) ng/g,all P<0.05). And the mRNA expression levels of cholesterol 7α-hydroxylase and bile salt export pump of the ileum, etc. in group C mice were lower than those in group B mice (all P<0.05), while the mRNA expression levels of FXR and fibroblast growth factor 15 in the intestine were higher than those in group B mice (all P<0.05). In groups B, C, Z, and G, compared with group C, mice in groups Z and G had aggravated liver injury and fibrosis, increased total bile acid levels in the liver, and increased serum alanine aminotransferase, total bilirubin, and expression levels of liver α-smooth muscle activator protein and type I collagen (all P<0.05). There was no statistically difference in the above indicators between group Z and group G (all P<0.05). Conclusion:AKK reduces liver bile acid synthesis, regulates bile acid metabolism, alleviate liver function damage and fibrosis, and improves clinical phenotypes by activating the intestinal FXR-fibroblast growth factor 15 signaling pathway.

BACKGROUND:Quantitative measurement of knee laxity after partial anterior cruciate ligament injury is crucial for timely diagnosis,post-treatment,and rehabilitation.There is a lack of research on the use of articular ligament digital arthrometer in the diagnosis of partial anterior cruciate ligament injury.OBJECTIVE:To investigate the diagnostic value of a new articular ligament digital arthrometer in partial anterior cruciate ligament injury.METHODS:Totally 30 patients with partial anterior cruciate ligament injury and 20 healthy volunteers were included.The anterior tibial translation values under 80,120,and 150 N loads were measured by a homebred digital arthrometer.The anterior tibial translation and side-to-side difference were compared between the partial anterior cruciate ligament group and control group.The receiver operating characteristic curve was analyzed and area under curve was calculated,and the diagnostic sensitivity and specificity of the digital arthrometer were determined.RESULTS AND CONCLUSION:(1)There was no significant difference in age,sex,body mass index,and course of disease between the partial anterior cruciate ligament injury group and control group(P＞0.05).(2)The side-to-side difference values of the partial anterior cruciate ligament injury group were significantly higher than those of the control group(P＜0.05),and the anterior tibial translation values of the injured side were significantly higher than those of the healthy side in the partial anterior cruciate ligament injury group(P＜0.05).(3)When the load was applied at 80 N,the diagnostic accuracy was highest(cutoff value=10.45 mm);the area under curve was 0.813(95％CI:0.708-0.919),and the sensitivity and specificity were 76.7％and 70.0％,respectively.(4)It is indicated that the digital arthrometer can objectively and quantitatively evaluate knee laxity after partial anterior cruciate ligament injury,and provide objective diagnostic basis for patients with partial anterior cruciate ligament iniurv.

BACKGROUND:Mammary stem cells are vital for the development and homeostasis of mammary gland tissue.The occurrence of breast cancer has a close relationship with the mammary stem cells.Recent studies have shown that Hopx,as an important transcriptional regulator of morphogenesis and cell differentiation,has been confirmed to be expressed in a variety of adult stem cells such as nerves,intestines,hair follicles and lungs.However,its role in mammary stem cells has not been reported so far.OBJECTIVE:To investigate whether Hopx expression marks mammary stem cells.METHODS:(1) Female Hopx-LacZ transgenic mice aged 8 weeks were selected to detect the background expression of Hopx in breast tissue by β-galactosidase staining.(2) Female wild-type mice at 4,6,and 8 weeks of age and 14.5 days of gestation were selected for whole-tissue magenta staining and K14 and K8 immunofluorescence staining,respectively.(3) Female Hopx-CreERT2;Rosa26LacZ transgenic mice aged 8 weeks and 17.5 days of gestation were selected and stained with breast β-galactosidase.(4) The 4-week-old female Hopx-CreERT2;Rosa26LacZ transgenic mice were selected.The Cre/loxp system was activated by intraperitoneal injection of tamoxifen (once every other day,three times),and breast β-galactosidase staining was performed 4 weeks after injection.The 8-week-old female Hopx-CreERT2;Rosa26LacZ transgenic mice were selected.The Cre/loxp system was activated by intraperitoneal injection of tamoxifen (once every other day,three times),and breast β-galactosidase staining was performed 4 and 10 weeks after the last injection.(5) Female Hopx-CreERT2;Rosa26LacZ transgenic mice aged 8 weeks were selected.The Cre/loxp system was activated by intraperitoneal injection of tamoxifen (once every other day,three times).Hopx-CreERT2;Rosa26LacZ transgenic mice were pregnant 2 weeks after injection.The mammary tissue of mice at 17.5 days of the first pregnancy and 17.5 days of the third pregnancy was stained with β-galactosidase.RESULTS AND CONCLUSION:(1) The results of β-galactosidase staining showed that the mammary ducts of Hopx-LacZ transgenic mice at 8 weeks of age did contain Hopx-positive cells and were located in the basal epithelia,with a small number.(2) Whole-mount staining of mammary glands and immunofluorescence staining results exhibited that the mammary glands of mice had different characteristics with corresponding developmental stages such as puberty,maturity,and pregnancy,and underwent a series of complex epithelial remodeling processes.(3) The results of β-galactosylase staining showed that Hopx-labeled positive cells in the mammary duct of Hopx-CreERT2;Rosa26LacZ transgenic mice at 17.5 days of gestation increased compared with female Hopx-CreERT2;Rosa26LacZ transgenic mice at 8 weeks of age.(4) The results of β-galactosylase staining showed that the Hopx-labeled positive cells in the mammary glands of 4-and 8-week-old female Hopx-CreERT2;Rosa26LacZ transgenic mice after tamoxifen injection were located in the basal epithelium with a small number.(5) The results of β-galactosidase staining showed that Hopx-labeled positive cells in the mammary glands of mice at 17.5 days of the first and third gestation were located in the basal epithelia around the alveoli,and the number of Hopx-labeled positive cells at 17.5 days of the third gestation was more.(6) In conclusion,Hopx reporter-marked basal epithelial cells belong to dormant mammary stem cells,which are responsible for the growth of the mammary glands during pregnancy and contribute to acinar formation.

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 evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

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.

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

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.