Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective To evaluate the predictive value of different anthropometric indices in as-sessing body fat content in patients with chronic kidney disease(CKD).Methods Bioelectrical im-pedance analysis was used to measure body fat percentage and visceral fat area in 279 non-dialysis CKD patients.Height and body mass were measured to calculate body mass index(BMI).Waist and hip circumferences were measured to calculate waist-to-hip ratio.Skinfold thickness(triceps skinfold thickness and subscapular skinfold thickness)was also measured.Pearson correlation analysis was employed to explore the correlations between anthropometric indices and body fat percentage as well as visceral fat area.Receiver operating characteristic(ROC)curves were plotted,and the DeLong test was conducted to compare the differences in the area under the curve(AUC)of the ROC curves.Results Pearson correlation analysis revealed significant correlations between body fat percentage and BMI(r=0.419,P＜0.001),hip circumference(r=0.450,P＜0.001),triceps skinfold thickness(r=0.229,P＜0.001),and subscapular skinfold thickness(r=0.324,P＜0.001).Significant correlations were also observed between visceral fat area and BMI(r=0.658,P＜0.001),hip circumference(r=0.648,P＜0.001),triceps skinfold thickness(r=0.194,P=0.001),and subscapular skinfold thickness(r=0.333,P＜0.001).ROC curve analysis demonstrated that the triceps skinfold thickness had the largest AUC value(0.732)for diagnosing obesity in CKD patients,with a sensitivity of 62.1％and specificity of 78.8％,indicating a moderate diagnostic performance.BMI and hip circumference had AUC values of 0.806 and 0.804,respectively,for as-sessing visceral obesity in CKD patients,showing good diagnostic performance.In contrast,the waist-to-hip ratio exhibited poor diagnostic value for both overall obesity and visceral obesity.Conclusion Measuring BMI and hip circumference is valuable for diagnosing visceral fat accumula-tion in CKD patients.However,when assessing overall obesity in CKD patients,multiple anthropo-metric indices should be combined for comprehensive evaluation.Additionally,our results indicate that different anthropometric indices have varying diagnostic values for different types of obesity,ne-cessitating appropriate selection based on actual circumstances.

Objective: To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

Objective:To investigate the efficacy of tibiofibular-based reconstruction technique with single femoral tunnel for Fanelli type C posterolateral complex (PLC) injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 16 patients with Fanelli type C PLC injury admitted to Tianjin Hospital from July 2016 to July 2019, including 10 males and 6 females, aged 20-61 years [(36.5±13.9)years]. PLC reconstruction was performed by tibiofibular-based technique with single femoral tunnel using gracilis tendon and semi-tendinosus autografts. If the posterior and anterior cruciate ligaments (PCL/ACL) rupture were combined, arthroscopic single bundle reconstruction was performed simultaneously. If the posteromedial corner (PMC) injury was combined, PMC repair or reconstruction surgery was performed simultaneously. Operation time and intraoperative blood loss were recorded. When the bone needle and tunnel for PLC were drilled during the operation, the interference of the femoral tunnel through the cruciate ligament was observed under the arthroscope. Before and at 6 and 12 months after operation, the varus stability of the knee joint was evaluated with the difference of lateral joint space width of both knees and the International Knee Documentation Committee (IKDC) objective classification of varus stability of the knee joint; the external rotation stability was evaluated with the difference of external rotation angle of both knees and the IKDC objective classification of external rotation stability of the knee joint. Before, at 6 and 12 months after operation and at the last follow-up, IKDC 2000 subjective score and Lysholm score were compared. The occurrence of complications was observed.Results:All the patients were followed up for 12-36 months [24(15, 33)months]. The operation time was 100-220 minutes [175.0(111.3, 200.0)minutes], with intraoperative blood loss of 30-150 ml [(84.3±36.5)ml]. Intraoperative arthroscopy showed no interference of perforation between PLC and cruciate ligament femoral tunnel. The differences of lateral joint space width of both knees at 6 and 12 months after operation were 0.5(0.2, 1.4)mm and 0.6(0.2, 1.5)mm respectively, which were both significantly improved compared with 12.1(10.8, 12.6)mm before operation ( P<0.05), while there was no significant difference at 6 and 12 months after operation ( P>0.05). The IKDC objective classification of varus stability of the knee joint was grade A in 13 patients, grade B in two and grade C in one at 6 or 12 months after operation, and showed statistical difference from grade D in all the patients before operation ( P<0.01). At 6 and 12 months after operation, the difference of external rotation angle of both knees was -2.0(-3.2, 1.3)° and -1.4(-3.0, 1.7)° respectively, which were significantly improved compared with 16.8(13.9, 18.4)° before operation ( P<0.05), while there was no significant difference at 6 and 12 months after operation ( P>0.05). IKDC objective classification of external rotation stability of the knee joint was grade A in 14 patients, grade B in one and grade C in one at 6 or 12 months after operation, and showed statistical difference from grade C in 14 patients and grade D in 2 before operation ( P<0.01). At 6 and 12 months after operation and at the last follow-up, the IKDC 2000 subjective scores [(76.3±4.7)points, (80.3±4.4)points, (79.9±3.8)points respectively] and the Lysholm scores [(76.1±3.9)points, (81.1±4.3)points, (82.8±3.2)points respectively] were significantly improved compared with those before operation [(48.6±3.7)points and (52.6±2.4)points] ( P<0.05). The IKDC 2000 subjective scores and Lysholm scores were significantly improved at 12 months after operation and at the last follow-up than those at 6 months after operation ( P<0.05). There were no significant differences in the IKDC 2000 subjective scores and Lysholm scores at 12 months after operation and at the last follow-up ( P>0.05). There were no complications such as wound infection, vascular and nerve injury, joint stiffness or ectopic ossification. Conclusion:For Fanelli type C PLC injury, tibiofibular-based reconstruction technique with single femoral tunnel reduces the interference between the lateral femoral tunnels, significantly improves the varus and external rotation stability and the function of the knee joint, and has few complications and satisfactory short-term clinical efficacy.

Objective To investigate the feasibility and safety of using catheter fenestration technology in transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)supplied by the right inferior phrenic artery(RIPA).Methods From March 2023 to May 2023,five HCC patients,whose HCC lesions were supplied by RIP A,received TACE by using catheter fenestration technology to accomplish the superselective catheterization of RIPA after the conventional microcatheter catheterization of RIPA failed.Results Superselective catheterization of RIPA and TACE were successfully accomplished in all the 5 patients,with a surgical success rate of 100％.The time spent for superselective catheterization of RIPA was(3.2±2.39)minutes.After TACE,the levels of the tumor indicators were decreased when compared with the pre-TACE values,while the liver function indexes showed no obvious damage.Based on the mRECIST criteria,PR was obtained in 3 patients and CR was obtained in 2 patients.None of the five patients developed serious adverse reactions.Conclusion In treating patients with HCC supplied by RIPA,the use of catheter fenestration technology can safely and effectively improve the success rate of superselective catheterization of RIPA during TACE.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors.Methods:In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children′s Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors.Results:Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis ( HR=2.55, 95% CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant ( HR=2.96, 95% CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions:Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

Proliferative verrucous leukoplakia (PVL) is one of the oral potentially malignant disorders (OPMD) with the highest malignant potential. PVL tends to be easily misdiagnosed owing to the resemblance in clinical manifestations between PVL and other diseases such as oral leukoplakia or oral lichen planus. PVL is considered as a special type of oral leukoplakia by some scholars, which is characterized by its tendency of recurrence and metastasis, along with its high risk of malignant transformation. So far, the accurate clinic diagnosis and management of PVL are still intractable due to the lack of definite histopathological definition, unified diagnostic criteria and effective treatment modalities. This review aims to provide the clinical practitioners with a series of advices on the clinical diagnosis and management of PVL by systematically reviewing the diagnostic logistics, therapeutic strategies, malignant transformation detection based on tremendous relevant data and evidence-based medicine.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To evaluate the efficacy and safety of unrelated umbilical cord blood stem cell transplantation (UCBT) with reduced-intensity conditioning regimens in the treatment of hyper-IgM syndrome (HIGM) caused by CD40 ligand gene (CD40LG) mutation.Methods:Clinical features, laboratory data and treatment prognosis of 3 patients with HIGM caused by CD40LG mutation treated with UCBT in Children′s Hospital of Fudan University from May 2018 to August 2019 were analyzed retrospectively. The literature search was conducted with "CD40 ligand deficiency" and "hematopoietic stem cell transplantation" as keywords at China National Knowledge Infrastructure, Wanfang, Weipu and Pubmed databases (up to February 2021) to summarize donor selection, stem cell source, conditioning regimen and prognostic factors of this disease.Results:Three boys with recurrent respiratory tract infection were diagnosed as HIGM with CD40LG mutation. The age of UCBT was 1.0, 1.4 and 0.5 years respectively. Reduced-intensity conditioning regimen including busulifan, fludarabine and cyclophosphamide were used in all patients. Human leucocyte antigen matching of patients and umbilical cord blood was 8/10, 10/10 and 9/10 respectively. All patients achieved complete donor chimerism 14 days after UCBT. All patient suffered grade Ⅰ acute skin graft-versus-host disease without other severe complications. Up to the last follow-up, their disease-free survival time were 33, 18, 18 months after transplantation respectively. No reports were found in Chinese journals, while 24 publications were found in English journals. According to the literature, 258 HIGM patients with CD40LG mutation were treated with hematopoietic stem cell transplantation (HSCT). Matched sibling donors (30.6%(79/258)) and unrelated donors (40.3% (104/258)) were main donor types. Bone marrow (50.8%(131/258)) was the main source of grafts, myeloablative conditioning (66.7% (172/258)) was the main conditioning regimen, and the overall survival rate after transplantation was 70.9% (183/258). Lung injury and liver complications before transplantation were adverse factors affecting prognosis. Among the 14 patients who received UCBT, 2 patients suffered from engraftment failure, 2 patients had mixed chimerism and 3 patients died after transplantation.Conclusions:UCBT is safe and effective in the treatment of HIGM caused by CD40LG mutation. Reduced-intensity conditioning regimen is worthy of further study.

Objective:To search for circulating complement-related proteins that predict hypertensive disorders of pregnancy (HDP) based on reports of the development of gestational hypertension and proteinuria and to investigate the role of the complement system in the development of HDP.Methods:A nested case-control study was used, the serum samples of pregnant women who had been given birth or cesarean section in Guangzhou Women and Children′s Medical Center from November 2014 to March 2017 were collected. A total of 60 HDP and 60 normal pregnant women were included and matched 1∶1 by age and gestational week. Unlabeled mass spectrometry was used to screen the differential expression of complement factors in serum samples of 12 pairs of HDP patients and normal pregnancy collected before 20 weeks of pregnancy, and another 48 pairs of serum samples of HDP patients and normal pregnant women were used for preliminary verification. It was selected when the fold change (FC) of complement factor expression was>1.2 or <0.8 and P<0.05. ROC curve was used to evaluate the diagnostic value of corresponding factors. Results:FC of serum C1s, C8 beta chain (C8β) and C1 inhibitor (C1-INH) of HDP patients were 1.19, 1.23, 0.73 ( t=2.07, 2.06, -3.40; P<0.05), respectively. FC of serum C1s, C8 β, C1-INH, factor H-related protein 5 (CFHR5), clusterin (CLU), and C-reactive protein (CRP) of PE patients were 1.39, 1.50, 0.72, 2.49,4.38, and 1.82 respectively ( t=4.36, 5.61, -3.70, 6.82, 8.70, 7.27; P<0.05).The AUC of combining C1s, C8 β and C1-INH was 0.89 in HDP. The AUC of CFHR5, CLU, and CRP in preeclampsia was 0.88, 0.92, and 0.91. Conclusions:Before HDP, the activation and regulation of classic complement pathway and alternative pathway were disordered in pregnant women. The combined detection of complement C1s, C8 β and C1-INH is expected to be used in the prediction of HDP, and CFHR5, CLU, and CRP are expected to be used in the prediction of preeclampsia.