Sampling is the first stage of the DNA Typing in forensic science,and some studies found that the sampling technology affected the outcomes of"Contact DNA"testing.Since swabs are the most commonly used collection instrument for"Contact DNA",the researchers in forensic science field should pay more attention to study the collection efficiency of swabs.However,currently the majority of relevant research is focused on downstream testing processes,such as typing and amplification;the corresponding work on sampling performance by swabs is quite limited.Furthermore,the absence of an internationally recognized standard procedure makes it impossible to directly compare the collection results among laboratories.In this paper,a review on the use of swabs in the forensic science field is presented.It analyzes the collection efficiency,advantages and disadvantages of different swabs,and investigates the need and feasibility of developing a standardized method to evaluate the swab collection efficiency,for improving the sampling performance of swabs and ultimately increasing the detection rate of"Contact DNA"in forensic science.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Sampling is the first stage of the DNA Typing in forensic science,and some studies found that the sampling technology affected the outcomes of"Contact DNA"testing.Since swabs are the most commonly used collection instrument for"Contact DNA",the researchers in forensic science field should pay more attention to study the collection efficiency of swabs.However,currently the majority of relevant research is focused on downstream testing processes,such as typing and amplification;the corresponding work on sampling performance by swabs is quite limited.Furthermore,the absence of an internationally recognized standard procedure makes it impossible to directly compare the collection results among laboratories.In this paper,a review on the use of swabs in the forensic science field is presented.It analyzes the collection efficiency,advantages and disadvantages of different swabs,and investigates the need and feasibility of developing a standardized method to evaluate the swab collection efficiency,for improving the sampling performance of swabs and ultimately increasing the detection rate of"Contact DNA"in forensic science.

OBJECTIVETo explore the clinical phenotype and genotype in a Chinese family affected with early-onset familial Alzheimer's disease (EOFAD).

METHODSPotential mutation of beta-amyloid precursor protein (APP) gene, presenilin 1 (PSEN1) gene and apolipoprotein E (APOE) gene was detected with polymerase chain reaction (PCR) and direct sequencing.

RESULTSHomozygous APOE ε 2 allele and no gene mutation of APP gene were detected in the proband (III1). A 488A>G mutation (His163Arg) of the PSEN1 gene was found in the proband and other 4 family members (IV1, IV12, IV21, V2).

CONCLUSIONA mutation (c.488A>G, p.His163Arg) of PSEN1 gene was found in a Chinese family affected with EOFAD.

Adult ; Age of Onset ; Aged ; Alzheimer Disease ; genetics ; Child ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Presenilin-1 ; genetics

OBJECTIVETo explore the clinical efficacy and safety of the early use of urokinase in the prevention and treatment on tunneled hemodialysis catheter related fibrin sheaths.

METHODSThirty-eight hemodialysis patients with tunneled central venous catheter and good catheter function were randomly divided into experimental group and control group. Urokinase was given after 3 days of indwelling catheter in the experimental group and after the onset of catheter dysfunction in the control group. The catheter function, mean blood flow and venous pressure of dialysis, coagulation, and side effects in the two groups were observed for 6 months.

RESULTSThe rates of catheter dysfunction on the arterial side were 0.65% and 2.71% in the experimental group and control group, respectively (P<0.05), with catheter dysfunction rates on the vein side of 0.92% and 2.41%, respectively (P<0.05). Catheter dysfunction occurred for the first time at 87.9 ± 24.1 days in the experimental group, and at 31.3 ± 11.5 days in the control group (P<0.05). The mean blood flow showed no significant difference between the two groups at 1 month after tube insertion (P>0.05), but was higher in the experimental group at 3 and 6 months after the tube insertion (P<0.05). The mean venous pressure in two groups was similar 1 and 3 months after tube insertion (P>0.05), but was significantly lower in the experimental group at 6 months (P<0.05). Compared with control group, the experimental group showed significantly prolonged prothrombin time (P<0.05) but similar rest coagulation parameters. No serious drug-related side effects occurred in these two groups.

CONCLUSIONEarly use of urokinase is safe and effective for prevention and treatment of tunneled hemodialysis catheter-related fibrin sheaths with minimal side effects.

Catheterization ; adverse effects ; Catheters, Indwelling ; Fibrin ; Humans ; Renal Dialysis ; adverse effects ; Urokinase-Type Plasminogen Activator ; therapeutic use

Objective To explore the clinical efficacy and safety of the early use of urokinase in the prevention and treatment on tunneled hemodialysis catheter related fibrin sheaths. Methods Thirty-eight hemodialysis patients with tunneled central venous catheter and good catheter function were randomly divided into experimental group and control group. Urokinase was given after 3 days of indwelling catheter in the experimental group and after the onset of catheter dysfunction in the control group. The catheter function, mean blood flow and venous pressure of dialysis, coagulation, and side effects in the two groups were observed for 6 months. Results The rates of catheter dysfunction on the arterial side were 0.65%and 2.71%in the experimental group and control group, respectively (P<0.05), with catheter dysfunction rates on the vein side of 0.92% and 2.41%, respectively (P<0.05). Catheter dysfunction occurred for the first time at 87.9±24.1 days in the experimental group, and at 31.3±11.5 days in the control group (P<0.05). The mean blood flow showed no significant difference between the two groups at 1 month after tube insertion (P>0.05), but was higher in the experimental group at 3 and 6 months after the tube insertion (P<0.05). The mean venous pressure in two groups was similar 1 and 3 months after tube insertion (P>0.05), but was significantly lower in the experimental group at 6 months (P<0.05). Compared with control group, the experimental group showed significantly prolonged prothrombin time (P<0.05) but similar rest coagulation parameters. No serious drug-related side effects occurred in these two groups. Conclusions Early use of urokinase is safe and effective for prevention and treatment of tunneled hemodialysis catheter-related fibrin sheaths with minimal side effects.

Objective To explore the clinical efficacy and safety of the early use of urokinase in the prevention and treatment on tunneled hemodialysis catheter related fibrin sheaths. Methods Thirty-eight hemodialysis patients with tunneled central venous catheter and good catheter function were randomly divided into experimental group and control group. Urokinase was given after 3 days of indwelling catheter in the experimental group and after the onset of catheter dysfunction in the control group. The catheter function, mean blood flow and venous pressure of dialysis, coagulation, and side effects in the two groups were observed for 6 months. Results The rates of catheter dysfunction on the arterial side were 0.65%and 2.71%in the experimental group and control group, respectively (P<0.05), with catheter dysfunction rates on the vein side of 0.92% and 2.41%, respectively (P<0.05). Catheter dysfunction occurred for the first time at 87.9±24.1 days in the experimental group, and at 31.3±11.5 days in the control group (P<0.05). The mean blood flow showed no significant difference between the two groups at 1 month after tube insertion (P>0.05), but was higher in the experimental group at 3 and 6 months after the tube insertion (P<0.05). The mean venous pressure in two groups was similar 1 and 3 months after tube insertion (P>0.05), but was significantly lower in the experimental group at 6 months (P<0.05). Compared with control group, the experimental group showed significantly prolonged prothrombin time (P<0.05) but similar rest coagulation parameters. No serious drug-related side effects occurred in these two groups. Conclusions Early use of urokinase is safe and effective for prevention and treatment of tunneled hemodialysis catheter-related fibrin sheaths with minimal side effects.

Inosiplex is a compound formulation composed of inosine and p-acetaminobenzoic acid (PABA) salt of N,N-dimethylamino-2-propanol (DIP). This study was to investigate the clinical plasma pharmacokinetic properties of DIP and PABA after single and multiple oral doses of inosiplex tablets in healthy Chinese volunteers. The established LC/MS/MS method for plasma DIP determination had a linear range of 0.02-10 mg/mL, and the HPLC method for plasma PABA determination had a linear range of 0.05-40 mg/mL. Linear pharmacokinetic characteristics were found with single oral doses of 0.5, 1.0 and 2.0 g. No obvious accumulation effects were observed for DIP and PABA.