[Clinical characteristics and management status of Turner syndrome in 1 089 children].

Objective: To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China. Methods: As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed. Results: Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 µg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years. Conclusions: The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

[Conbercept reverses TGF-ß2-induced epithelial-mesenchymal transition in human lens epithelial cells by regulating the TGF-ß/Smad signaling pathway].

OBJECTIVE: To investigate the mechanism by which conbercept reverses transforming growth factor-ß2 (TGF-ß2)-induced epithelial-mesenchymal transition (EMT) in human lens epithelial cells (HLECs). METHODS: Cultured HLEC SRA01/04 cells were treated with TGF-ß2, conbercept, or both, and the changes in cell proliferation, apoptosis, and migration were observed using MTT assay, flow cytometry, scratch assay, and Transwell assay. Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers (E-Cadherin, α-SMA, and Snail), extracellular matrix components, and genes related to the TGF-ß/Smad signaling pathway. RESULTS: Conbercept significantly reduced TGF-ß2-induced EMT of SRA01/04 cells, decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA, Snail, collagen I, collagen IV, and FN1, and upregulated the protein and mRNA expressions of E-cadherin (P <0.05). Transwell assay showed significantly lower cell migration ability in TGF-ß2+conbercept group than in TGF-ß2 group (P <0.05). Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-ß2-induced EMT (P <0.01). CONCLUSION: Conbercept inhibits TGF-ß2 induced EMT by downregulating the expression of pSmad2/3 in TGF-ß/Smad signaling pathway, indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

[Assessment of baseline CCL19+ dendritic cell infiltration for predicting responses to immunotherapy in lung adenocarcinoma patients].

OBJECTIVE: To explore the correlation of baseline CCL19+ dendritic cell (CCL19+ DC) infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+ T cell infiltration. METHODS: We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January, 2020 to December, 2023, and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+ DC and CD8+ T cell infiltration using immunofluorescence assay. We evaluated the predictive value of baseline CCL19+ DCs for patient responses to immunotherapy using receiver-operating characteristics (ROC) curves and analyzed the correlations of baseline CCL19+ DC expression with immunotherapy efficacy and CD8+ T cell and cytotoxic T lymphocyte (CTL) infiltrations. In co-culture systems of lung adenocarcinoma PC9 cells, CD8+ T cells and DCs (overexpressing CCL19 with or without anti PD-1 antibody treatment), the expressions of granzyme B, perforin, IFN-γ, and Ki-67 in T cells were analyzed using flow cytometry. RESULTS: The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+ DC infiltration level in lung adenocarcinoma tissues than those with poor responses. CCL19+ DC infiltration had an area under ROC curve of 0.785, a sensitivity of 75.6%, and a specificity of 62.8% for predicting immunotherapy efficacy. The expression of CD8+ T cell surface molecules Granzyme B (P<0.01), Perforin (P<0.01), IFN-γ (P<0.01) and Ki-67 (P<0.001) in patients with high expression of CCL19+ DC were higher than those in patients with low expression of CCL19+ DC. The baseline CCL19+ DC infiltration level was positively correlated with immunotherapy efficacy (P=0.003), CTL infiltration of (r=0.6657, P<0.001) and CD8+ T cell infiltration (P=0.007). In the co-cultured cells, CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+ T lymphocytes than either of the single treatments (P<0.01 or 0.001). CONCLUSION: The baseline CCL19+ DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.

Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma.

BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review. RESULTS: Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1 months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

[Comparison of prognosis of elderly patients with gastric and colorectal tumors receiving different nutritional support treatments].

Objective: To compare the prognosis of elderly patients with gastric and colorectal cancer treated with different nutritional support methods. Methods: Elderly patients with gastrointestinal tumors who received surgical treatment in Beijing Hospital from January 2019 to June 2020 were retrospectively included and divided into malnourished group and non-malnourished group according to the Global Leadership Initiative on Malnutrition (GLIM). The patients were divided into parenteral nutrition (PN) group, enteral nutrition (EN) group and enteral+parenteral nutrition (EN+PN) group according to the nutritional support. The prognosis of patients with different nutritional support treatment was compared. Results: A total of 426 elderly patients with gastric and colorectal tumors underwent surgical treatment were included, including 287 males and 139 females, aged 65-91 (72±6) years. There were 186 cases in malnourished group and 240 cases in non-malnourished group. A total of 257 patients received nutritional support therapy, including 108 cases in PN group, 48 cases in EN group and 101 cases in EN+PN group. The body mass index (BMI) of malnutrition group was lower than that of non-malnutrition group [(20.5±3.4) vs (23.7±2.8) kg/m2, P<0.001], and the score of nutritional risk screening 2002 (NRS 2002) [M (Q1, Q3)] was higher than that of non-malnutrition group [4 (4, 5) vs 2 (2, 3) points, P<0.001]. The total hospitalization time of patients in EN group was shorter than that in PN group and EN+PN group [(11.9±4.0) vs (16.5±6.5) and (19.2±7.1) d, all P<0.001]. The total hospitalization time in PN group was shorter than that in EN+PN group [(16.5±6.5) vs (19.2±7.1) d, P=0.005]. The total incidence of complications in EN group was lower than that in PN group [0 vs 9.3% (10/108), P=0.030] and EN+PN group [0 vs 19.8% (20/101), P<0.001]. The incidence of total complications in PN group was lower than that in EN+PN group [9.3% (10/108) vs 19.8% (20/101), P=0.030]. Conclusion: Among the three nutritional supportive treatment modalities: EN, PN, and EN+PN, patients receiving EN support treatment have a shorter total hospitalization time and a lower complication rate.

Long-term outcomes of fistula-tract laser closure for complex perianal fistulizing Crohn's disease.

BACKGROUND: Fistula-tract laser closure (FiLaC™) has shown promising outcomes in perianal fistulizing Crohn's disease (pfCD). However, most studies assessed a mixed cohort encompassing pfCD and cryptoglandular fistulas during a short follow-up period. This study aimed to evaluate the long-term treatment outcomes of FiLaC™ in patients with complex pfCD. METHODS: Data from patients with complex pfCD who underwent FiLaC™ during deep remission of Crohn's disease between January 2019 and December 2020 were retrospectively analyzed. Patient demographics, surgery history, and medication strategy were registered before surgery. Follow-ups were scheduled at 1, 2, and 3 months after FiLaC™, and at 2-month intervals thereafter. The primary endpoint was clinic healing, while clinic remission/unhealed/recurrence were classified as unhealed. Additionally, adverse events and Wexner fecal incontinence score were documented. RESULTS: Forty-nine patients (40 men and 9 women) with a median age of 26.0 (19.0-35.5) years were included with a median follow-up of 50.0 (39.5-54.0) months. Of these, 31 (63.3%) patients achieved fistula healing, 3 (6.1%) experienced improvement, 3 (6.1%) remained unhealed, and 12 (24.5%) experienced recurrence. Montreal A category was lower in the healed group (P < 0.001). No major complications, such as bleeding or fecal or urinary incontinence, were observed, and pain was transient. The Wexner incontinence score decreased significantly at the last available follow-up, indicating an intact postoperative continence function (P = 0.014). PCDAI scores were significantly higher in the unhealed group (P = 0.041). CONCLUSION: FiLaC™ is an efficient and safe sphincter-saving procedure for patients with complex pfCD.

[Comparison of quantitative detection of BCR::ABL1 p210 transcript levels: a multicenter study].

Objective: To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories. Methods: The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory. Results: In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%). Conclusions: A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

[Risk factors for progression to chronic kidney disease in patients with cardiac valve replacement surgery-associated acute kidney injury].

Objective: To explore the risk factors for progression to chronic kidney disease (CKD) in patients with cardiac valve replacement surgery-associated acute kidney injury (AKI). Methods: A retrospective, nested case-control study was conducted at Fuwai Central China Cardiovascular Hospital. The study subjects were patients who underwent cardiac valve replacement surgery from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min-1·(1.73 m2)-1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint event. The baseline clinical data were compared between the two groups. The measurement data with non-normal distribution was represented as M (Q1,Q3). Logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic (ROC) curve was drawn to evaluate the performance for predicting CKD in cardiac valve replacement surgery-associated AKI patients. Results: A total of 149 cardiac valve replacement surgery-associated AKI patients (86 males and 63 females) were included in the study, aged (59.0±10.2) years. There were 27 patients (18.1%) who progressed to new-onset CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. Compared with non-CKD group, patients in CKD group had older age [66 (58, 70) vs 59 (53, 64) years], lower baseline eGFR [76.3 (65.8, 98.5) vs 92.7 (78.5, 101.6) ml·min-1·(1.73 m2)-1], higher proportion of preoperative hypertension [51.9% (14/27) vs 27.9% (34/122)] and serum creatinine at discharge [136 (101, 165) vs 86 (65, 104) µmol/L], and the differences were statistically significant (all P<0.05). The multivariate logistic regression analysis results revealed that older age (OR=1.063, 95%CI: 1.001-1.129, P=0.047), preoperative hypertension (OR=3.070, 95%CI: 1.105-8.532, P=0.031) and higher serum creatinine at discharge (OR=1.026, 95%CI:1.013-1.038, P<0.001) were risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI. The clinical risk model including age, preoperative hypertension, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting progression to CKD in patients with cardiac valve replacement surgery-associated AKI [the area under the curve (AUC)=0.865, 95%CI: 0.790-0.940, P<0.001]. Conclusion: Older age, preoperative hypertension and higher serum creatinine at discharge are risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI.

Identification of potential candidate genes for the Huoyan trait in developing Wulong goose embryos by transcriptomic analysis.

1. The Wulong goose is a Chinese breed and a source of high-quality meat and eggs. A characteristic of the Wulong goose is that a proportion of the birds do not have eyelids, known as the Huoyon trait.2. Wulong geese exhibiting the Huoyan trait at embryonic stages of 9 days (E9), 12 days (E12) and 14 days (E14) were selected alongside those with normal eyelids for comprehensive transcriptome sequencing. Differentially expressed gene (DEG) and functional enrichment analyses were performed and finally, eight DEG were chosen to verify the accuracy of qPCR sequencing.3. Overall, 466, 962 and 550 DEG were obtained from the three control groups, D9 vs. N9, D12 vs. N12 and D14 vs. N14, respectively, by differential analysis (p < 0.05). CDKN1C, CRH, CROCC and TYSND1 were significantly expressed in the three groups. Enrichment analysis revealed the enrichment of CROCC and TYSND1 in pathways of cell cycle process, endocytosis, microtubule-based process, microtubule organising centre organisation, protein processing and protein maturation. CDKN1C and CRH were enriched in the cell cycle and cAMP signalling pathway.4. Some collagen family genes were detected among the DEGs, including COL3A1, COL4A5, COL4A2 and COL4A1. FREM1 and FREM2 genes were detected in both Huoyan and normal eyelids. There was a significant difference (p < 0.01) in FREM1 expression between ED9 and ED14 in female embryos, but this difference was not observed in male embryos.

Myokines and Biomarkers of Frailty in Older Inpatients with Undernutrition: A Prospective Study.

BACKGROUND: Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. METHODS: The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. RESULTS: The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. CONCLUSIONS: Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.

[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

[Arterial spin labeling in assessment of interstitial fibrosis in renal allografts].

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)-1·min-1; ci1 group: (181.7±29.3) ml·(100 g)-1·min-1; ci2 group: (158.8±39.2) ml·(100 g)-1·min-1; ci3 group: (123.1±27.2) ml·(100 g)-1·min-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

[Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome].

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

[Experimental study on the therapeutic effect and mechanism of erlotinib on non-proliferative diabetic retinopathy].

Objective: To investigate the therapeutic effect and mechanism of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, on non-proliferative diabetic retinopathy (NPDR). Methods: An experimental research was conducted. Human retinal Müller cells (RMC) were MIO-M1 cells from Moorfields Ophthalmology Hospital and the Institute of Ophthalmology at London University College. MIO-M1 cells were divided into normal, hypertonic, high glucose, high glucose+dimethyl sulfoxide (DMSO), high glucose+erlotinib 0.5 mmol/L, high glucose+erlotinib 1 mmol/L, and high glucose+erlotinib 2 mmol/L groups using a random number table method. Detection of the effect of erlotinib on the proliferation of MIO-M1 cells under high glucose conditions was performed by 5-ethynyl-2'-deoxyuridine (EdU) method. Western blotting (WB) was used to detect the effect of erlotinib on the activation markers of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) protein levels in MIO-M1 cells under high glucose conditions. WB was used to detect the effect of erlotinib on the protein levels of nerve growth factor receptor (p75NTR), vimentin, and cell retinol binding protein (CRALBP) in RMC under high glucose conditions. MIO-M1 cells were divided into normal group, high glucose group, high glucose+DMSO group, and high glucose+erlotinib (1 mmol/L) group using random number table method. The effect of erlotinib on EGFR nuclear translocation under high glucose conditions was detected by cell immunofluorescence staining. Immunoprecipitation was used to detect the effect of erlotinib on the interaction between EGFR and transcription intermediate factor 2 (TIF2) in MIO-M1 cells under high glucose conditions. MIO-M1 cells were randomly divided into normal group, high glucose group, high glucose+DMSO group, high glucose+Myc-DDK empty body group, high glucose+erlotinib group, high glucose+erlotinib+human doublet protein group, high glucose+erlotinib+TIF2 plasmid group, and high glucose+erlotinib+human doublet protein+TIF2 plasmid group. Cell immunofluorescence staining was used to detect the effect of erlotinib on the binding of EGFR and TIF2 in MIO-M1 cells under high glucose conditions through the EGFR/TIF2 axis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the regulatory effect of EGFR and TIF2 binding on cyclin D1 transcription in MIO-M1 cells under high glucose conditions. The mouse model of diabetes retinopathy (DR) was constructed and divided into normal group, DR group, DR+DMSO group, DR+erlotinib 0.25 mg·kg-1·d-1 group, DR+erlotinib 0.5 mg·kg-1·d-1 group and DR+erlotinib 1 mg·kg-1·d-1 group. 25 mice in total, 5 in each group. Tissue immunofluorescence staining was used to detect the expression of RMC activation marker GFAP. The FITC-dextran injection experiment was used to detect the effect of erlotinib on retinal vascular leakage in a murine DR model. Results: Compared with the normal group (32.4%±3.0%), the proportion of EdU positive cells in RMC in the high glucose group (59.2%±3.8%) increased (P<0.001). Compared with the high glucose group (59.2%±3.8%), the proportion of EdU positive cells in the high glucose+1 mmol/L erlotinib group (37.6%±4.4%) decreased (P<0.001). Compared with the normal group, the expression of GFAP in RMC in the high glucose group increased (1 in the normal group, 2.27±0.11 in the high glucose group, P<0.001), while the expression of GS decreased (1 in the normal group, 0.32±0.03 in the high glucose group, P<0.001). 1 mmol/L erlotinib treatment reduced the expression of GFAP in RMC under high glucose conditions (1.32±0.13 and 2.27±0.11, respectively; P<0.001), and increased the expression of GS (0.71±0.06 and 0.32±0.03, respectively; P<0.001). The colocalization of EGFR and DAPI in RMC of the high glucose+1 mmol/L erlotinib group was lower than that of the high glucose group (52.2%±4.1% and 76.4%±5.7%, respectively; P<0.001). The expression of TIF2 or EGFR both increased while using EGF or TIF2 antibodies to precipitate TIF2 or EGFR under high glucose conditions compared to the normal group (1 in the normal group, 2.27±0.20 in the high glucose group, 2.17±0.21 in the EGFR, all P<0.05). And the expression of TIF2 (1.38±0.10) or EGFR (1.32±0.13) in the high glucose+erlotinib group was lower than that in the high glucose group (2.27±0.20) and the high glucose group (2.17±0.21) (all P<0.05). The colocalization of EGFR and TIF2 (17.2%±3.9%) and the mRNA level of Cyclin D1 (1.32±0.16) in the RMC of the high glucose+erlotinib group were lower than those in the high glucose group (54.6%±3.7% of EGFR and TIF2 colocalization ratio, 2.58±0.19 of Cyclin D1 mRNA level,all P<0.05). The high glucose+erlotinib+AREG (EGFR agonist) group, high glucose+erlotinib+Myc DDK-TIF2 plasmid group and high sugar+erlotinib+AREG+Myc-DDK-TIF2 plasmid group EGFR colocalization with TIF2 (colocalization ratios 24.1%±1.9%, 26.0%±2.3%, 35.3%±2.5%) and TIF2 mRNA levels (1.71±0.16, 1.72±0.18, 2.20±0.18). Compared with the high glucose+erlotinib group, The increases were statistically significant (all P<0.05). Compared to the normal group, the expression of GFAP in mouse retina tissue was increased in the DR group (1 in the normal group, 3.07±0.19 in the DR group, P<0.001), and 0.5 mg·kg-1·d-1 erlotinib (1.73±0.30) significantly reduced the expression of GFAP in the retina of DR group mice (P<0.05). Compared to the normal group (3.97±0.47), the DR group (23.13±2.15) showed an increase in fluorescein leakage, while the DR+erlotinib group (11.66±1.45) showed a significant decrease in leakage compared to the DR group (all P<0.05). Conclusions: Erlotinib inhibits the proliferation and activation of RMC induced by high glucose, inhibits the entry of EGFR into the nucleus, inhibits the binding of EGFR to TIF2 in RMC, and reduces the transcription of Cyclin D1 in RMC by inhibiting the interaction between EGFR and TIF2. At the same time, erlotinib inhibits the proliferation and activation of RMC in the mouse DR model, ameliorating retinal vascular leakage in mice. These results suggest that erlotinib inhibits the activation and proliferation of RMC by downregulating the EGFR/TIF2/Cyclin D1 pathway under high glucose conditions, thereby alleviating the progression of NPDR.

[Clinical outcomes of endovascular therapy in acute stroke patients with anterior circulation tandem occlusions due to atherosclerosis and dissection].

Objective: To compare the clinical outcomes of endovascular therapy in acute stroke patients with anterior circulation tandem occlusions caused by atherosclerosis or dissection. Methods: A retrospective cohort study. A total of 98 patients with anterior circulation tandem lesions undergoing endovascular therapy in the Wuhan NO.1 Hospital (March 2016 to March 2022) were analyzed. Median age was 64(55,71) years old, and 82.7% (81/98 cases) were males. According to the lesion etiology, the patients were divided into atherosclerosis and dissection groups. The differences in clinical outcomes between the two groups were investigated, including favorable 90-day functional outcome (modified Rankin Scale score of 0-2), successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction score of 2b-3), symptomatic intracranial hemorrhage, stroke-associated pneumonia, 90-day all-cause mortality, and average hospitalization days. Logistic regression analysis was used to adjust for potential confounders affecting functional outcomes in both groups, and to determine odds ratios and 95% confidence intervals. Results: Seventy-one patients were grouped into the atherosclerotic cause and 27 into the dissection cause cohorts. The rate of favorable 90-day functional outcome was 43.7% (31/71 cases) in the atherosclerosis group versus 55.6% (15/27 cases) in the dissection group (adjusted odds ratio=1.339; 95% confidence interval, 0.374-4.798; P=0.654). No significant differences were found in other clinical outcomes between the two groups (all P>0.05). Conclusion: The clinical prognosis of patients with tandem lesions caused by atherosclerotic stenosis or artery dissection was similar after endovascular therapy. Future studies are still needed to verify our results.

[Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study].

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.