To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

OBJECTIVE: To investigate the effectiveness of arthroscopic multi-point fixation with anchor and suture in the treatment of tibial insertion avulsion fracture of anterior cruciate ligament (ACL) involving the anterior root of lateral meniscus (LM). METHODS: A retrospective analysis was conducted on the clinical data of 28 patients with tibial insertion avulsion fracture of ACL involving the anterior root of LM who were treated with arthroscopic multi-point fixation with anchor and suture between October 2017 and January 2023. There were 12 males and 16 females with the mean age of 26 years (range, 13-57 years). There were 20 cases of sports injury and 8 cases of traffic accident injury. In 2 cases of old fracture, the time from injury to operation was 45 days and 90 days, respectively; in 26 cases of fresh fracture, the time from injury to operation was 3-20 days (mean, 6.7 days). According to the Meyers-McKeever classification, there were 4 cases of type Ⅱ, 11 cases of type Ⅲ, and 13 cases of type Ⅳ. The preoperative Lysholm knee function score was 42.1±9.0, the International Knee Documentation Committee (IKDC) score was 40.0±7.3, and the Tegner score was 0.7±0.7. RESULTS: All operations were successfully completed, and the incisions healed by first intention. All the 28 patients were followed up 5-60 months (mean, 20.4 months). During the follow-up, there was nocomplication such as infection, vascular or nerve injury, loosening or breakage of internal fixator, or stiffness of knee joint. Postoperative X-ray films showed satisfactory fracture reduction and firm fixation. All fractures healed clinically, and the healing time was 8-16 weeks (mean, 10.3 weeks). At last follow-up, Lachman test and anterior drawer test were negative. At last follow-up, Lysholm knee function score was 92.4±5.5, IKDC score was 91.6±4.4, and Tegner score was 5.2±1.1, which significantly improved when compared with preoperative scores ( t=-22.899, P<0.001; t=-29.870, P<0.001; t=-19.979, P<0.001). CONCLUSION Multi-point fixation with anchor and suture in the treatment of tibial insertion avulsion fracture of ACL involving the anterior root of LM can not only fix the LM, but also effectively reduce and fix the avulsion fracture, which can obtain good effectiveness.
Male ; Female ; Humans ; Adult ; Anterior Cruciate Ligament/surgery* ; Menisci, Tibial/surgery* ; Fractures, Avulsion/surgery* ; Retrospective Studies ; Anterior Cruciate Ligament Injuries/surgery* ; Treatment Outcome ; Arthroscopy ; Tibial Fractures/surgery* ; Knee Joint/surgery* ; Sutures ; Suture Techniques

There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.
Humans ; Thrombotic Microangiopathies ; Transplantation, Homologous ; Tissue Donors ; Kidney ; Allografts

Objective:To explore the influencing factors of acute rejection (AR) within one year after pediatric kidney transplantation (KT) and the effect of AR onset time on prognosis.Methods:From January 2011 to October 2021, a total of 112 patients aged under 18 years at the time of transplantation were selected.After excluding 6 of them with early renal non-function caused by non-rejection, 106 cases were examined.There were 63 males and 43 females with the age of 15(12, 16) years.The donors were living related (n=26) and deceased (n=80).According to the presence/absence and onset time of AR, they were assigned into three groups of AR within one year, AR after one year and non-AR.The relevant clinical data of donor/recipient, influencing factors of AR and therapeutic outcomes of AR were retrospectively compared.One-way ANOVA or Kruskal-Wallis test was utilized for comparing 1-year renal function after the occurrence of AR among three groups.With graft-function loss as an end-point event of follow-up, the effects of AR within one year and AR after one year on survival rate and function of graft-kidney were analyzed by Kaplan-Meier survival curve.Results:The median follow-up period of 106 pediatric KT recipients was 35 months.During follow-ups, 19 episodes of AR occurred in 17(16.0%) patients and 89 recipients exhibited no AR episode by the end of follow-up (non-AR group).As for initial AR, 9 episodes of AR occurred within one year (AR within one year group) and 8 episodes of AR after one year (AR after one year group).After anti-rejection treatment, 8 patients (47.1%) achieved full recovery and 6 patients (35.3%) failed to completely normalize and 3 patients (17.6%) developed graft failure.Univariate analysis indicated that, as compared with non-AR group, female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 were risk factors of AR within one year ( P=0.032, P=0.039, P=0.047).Kaplan-Meier survival analysis revealed that the incidence rates of AR within one year in patients with donors aged under 8 years and early postoperative parvoviral infection were 14.5%(8/55) and 30.0%(3/10) respectively.They were significantly higher than 2.0%(1/51) and 6.3%(6/96) of patients with donors aged above 8 years and those without parvoviral infection ( P=0.012, P=0.004).With graft-function loss as an end-point event of follow-up, Kaplan-Meier survival analysis showed that 10-year kidney graft survival rate in AR within one year and AR after one year groups were 88.9% and 65.6%.Both were significantly lower than that in non-AR group (98.9%).And the inter-group differences were statistically significant ( χ2=4.286, P=0.038; χ2=7.787, P=0.005).However, no significant difference existed in survival rate between AR within one year and AR after one year groups ( P=0.689).One-way ANOVA and Kruskal-Wallis test indicated that estimated glomerular filtration rates at 3/6/12 months after an onset of AR in AR within one year group were (76.8±51.6), (80.6±56.6) and (85.6±40.2) ml·min -1·1.73 m -2.The values of 3/6 months were lower than (125.3±39.2) and (124.7±38.2) ml·min -1·1.73 m -2 in AR after one year group.And the inter-group differences were statistically significant ( P=0.021, P=0.039).The values of 3/6/12 months were lower than (112.2±34.2), (115.3±33.2) and (117.4±30.2) ml·min -1·1.73 m -2 in non-AR group.And the inter-group differences were also statistically significant ( P=0.019, P=0.020, P=0.020). Conclusions:Female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 may elevate the risks of AR in children within one year of KT.AR within one year affects the survival rate of graft-kidney and renal function.

Fibroblast growth factor receptor (FGFR) 2 gene fusion plays an important role in the pathogenesis of cholangiocarcinoma (CCA) . The method of targeting FGFR2 has been listed as the major therapy for advanced CCA. Adenosine triphosphate (ATP) -competitive FGFR inhibitors, represented by infigratinib and pemigatinib, effectively delay tumor progression and prolong patients survival, and are the first-line drugs for advanced CCA patients with FGFR2 fusion. However, almost all the patients treated with infigratinib eventually develop resistance, which require the combination with other drugs. Futibatinib may serve as a later-line drug for advanced CCA patients with V564F mutation after infigratinib resistance. For the infigratinib-resistant CCA patients harboring aberrant activation of the mitogen-activated protein kinase (MAPK) pathway, combination of the MAPK inhibitor or the heat shock protein 90 inhibitor may be considered as a novel therapeutic option.

BACKGROUND: The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer. METHODS: One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared. RESULTS: The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type. CONCLUSIONS The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.
B7-H1 Antigen/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immunohistochemistry ; Lung Neoplasms/drug therapy* ; Male

Objective: To analyze the distribution of glomerular immunofluorescence IgG4 subtypes in primary membranous nephropathy, and to explore the relationship between IgG4 deposit intensity and renal pathology, clinical manifestations and prognosis. Methods: All the patients of biopsy-proven primary membranous nephropathy with IgG staining and at least one IgG subtype staining 1+ or higher on capillary loops from September 2015 to April 2017 were retrospectively enrolled. The distribution of IgG4 deposits were analyzed, and the relationship between IgG4 positive intensity and clinical manifestations, pathological indexes and clinical remission was investigated. Results: A total of 250 cases were enrolled, including 157 males (62.8%) and 93 females (37.2%), and age was (54.4 ± 14.6) years. There were 40 patients in IgG4-negative group, and 210 patients in IgG4-positive group. The IgG4-positive group was divided into subgroups as 114 cases of the mild positive subgroup (1+) and 62 cases of the moderate positive subgroup (2+), and 34 cases of the strong positive subgroup (3+, 4+). The IgG4-positive group had higher 24-hour urine protein and higher positive rate of phospholipase A2 receptor staining than those in the negative group (both P<0.05), while the strong positive subgroup had lower serum albumin and higher IgG1 staining than those in the mild positive subgroup (both P<0.05). There was no difference in the ratio of glomerular sclerosis, tubular atrophy, IgG2, IgG3 or other immunofluorescence between the groups. After a median follow-up of 180(122, 209) days, 32 individuals were lost to follow-up. Among the rest 218 patients, 45 patients (20.6%) got complete remission, 104 patients (47.7%) got partial remission, and 69 patients (31.7%) showed no response. For no response as the outcome event, multivariate Cox regression analysis showed that higher IgG4 staining intensity (HR=1.371, 95%CI 1.068-1.759, P=0.013), male (HR=1.818, 95%CI 1.028-3.214, P=0.040), higher 24-hour urine protein level (HR=1.108, 95%CI 1.003-1.225, P=0.043) were independent risk factors for disease remission. Conclusions The glomerular IgG4 positivity and intensity are related to the severity of primary membranous nephropathy. The glomerular IgG4 deposit degree may be an effective prognostic marker for the treatment response of primary membranous nephropathy.