OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Objective To explore the causes of related medical damage risks and preventive measures by analyzing the identification results of medical damage in 20 urological death cases.Methods A retro-spective analysis was conducted on 20 death cases of medical damage identification involving urology diagnosis and treatment accepted by the Judicial Appraisal Center,School of Forensic Medicine,Gui-zhou Medical University,and Academy of Forensic Science from 2010 to 2023.Results Among the 20 cases,the male-to-female ratio was 1.5∶1.The age of the identified persons ranged from 37 to 84 years old,with an average age of 59.2 years.There were 21 medical institutions involved,with 81.0%being tertiary medical institutions.The statistical results of the causes of death showed that 60.0%deaths were due to infectious shock or hemorrhagic shock.Conclusion The causative potency analysis of medical damage in urological death cases is closely related to the patients'diseases,the death con-sequences of medical damage,and medical errors.Analyzing characteristics of typical cases can im-prove the comprehensive analysis ability of forensic examiners in similar cases,help them understand the rationality and compliance of medical behaviors in different situations,in order to make more accu-rate and comprehensive judgments.

Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100％,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P＞0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.

Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group (P<0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope (P<0.01), but had no significant effect on the ECAP latency (P>0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Cochlea ; Cochlear Implantation/methods* ; Cochlear Implants ; Cochlear Nerve ; Electric Stimulation ; Evoked Potentials, Auditory/physiology*

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.
Humans ; Middle Aged ; Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Biopsy ; Disease Progression

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA CONCLUSION AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA
DNA-Binding Proteins/genetics* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins/genetics* ; Remission Induction

Objective: To analyze the temporal bone CT and inner ear magnetic resonance imaging characteristics of cochlear implant patients with no cochlear nerve display in the inner auditory canal under MRI. To retrospectively analyze the long-term hearing and speech rehabilitation effects of such patients after cochlear implant. And to analyze the correlation between the results of imaging examinations and the postoperative effects of cochlear implant patients with this type of cochlear nerve deficiency. Methods: A total of 88 children with cochlear nerve deficiency, who underwent cochlear implantation in Shandong Provincial ENT Hospital from May 2014 to October 2018, were enrolled. Patients with cochlear malformations were excluded,only the patients with cochlear nerve deficiency whose cochlear structure was normal and no cochlear nerve displayed in inner auditory canal under MRI were enrolled. There were 64 patients, including 4 bilaterally implanted, 68 ears in total, with an average age of (2.8±1.7) years (range 1-6 years) at the time of implantation. The implanted product was Cochlear, including 24RECA and 512 models. All patients underwent inner ear magnetic resonance imaging and temporal bone CT scan before operation. Auditory speech function assessments were performed at 12 months, 24 months, and 36 months after surgery, including categories of auditory performance (CAP), speech intelligibility rating (SIR) and hearing aid threshold test. The imaging evaluation content included the width of the cochlear nerve canal of temporal bone CT, the width of the internal auditory canal, the width of the auditory nerve at the cerebellopontine angle of the inner ear MRI, and the ratio of the facial nerve to the width of the auditory nerve at the cerebellopontine angle. The correlations between the results of postoperative hearing aid hearing threshold, CAP, SIR and imaging results were analyzed. Results: Among the 64 cases of cochlear nerve not shown under MRI, 56 ears with CT data showed that the width of the cochlear nerve canal in temporal bone CT was (0.72±0.30) mm (mean±standard deviation, the same below), and the width of the internal auditory canal was (4.07±1.10) mm; 66 ears with MRI data showed that the diameter of the auditory nerve at the cerebellopontine angle of the inner ear MRI was (1.58±0.27) mm, the diameter of the facial nerve was (1.57±0.27) mm, and the ratio of the diameter of the facial nerve to the auditory nerve was (1.02±0.23). The average hearing thresholds at 12, 24, and 36 months after surgery were (46.8±2.5) dB HL, (40.7±0.8) dB HL, and (36.8±1.5) dB HL, respectively. The preoperative and postoperative CAP scores at 12, 24 and 36 months were (1.0±1.0), (3.8±1.4), (4.5±1.4) and (5.1±0.7) points, respectively. The preoperative and postoperative SIR scores at 12, 24, and 36 months were (1.1±0.3), (1.9±0.9), (2.5±0.9), and (2.9±0.6) points, respectively. The hearing threshold at 24 months after surgery was negatively correlated with the width of the internal auditory canal of temporal bone CT (r=-0.349, P=0.037), and the hearing threshold at 36 months after surgery was positively correlated with the ratio of the diameter of the facial nerve to the auditory nerve at the cerebellopontine angle of the inner ear MRI (r=0.740, P=0.001). Conclusions: Children with cochlear implants whose cochlear nerves are not shown on MRI can benefit from cochlear implantation, and their speech and auditory functions can improve significantly after surgery. The width of the internal auditory canal in the temporal bone CT and the ratio of the diameter of the facial nerve to the auditory nerve at the cerebellopontine angle of the inner ear MRI may be related to the long-term hearing threshold after surgery.
Child ; Child, Preschool ; Cochlear Implantation ; Cochlear Implants ; Cochlear Nerve/diagnostic imaging* ; Hearing Loss, Sensorineural/surgery* ; Humans ; Infant ; Magnetic Resonance Imaging ; Prognosis ; Retrospective Studies ; Speech Intelligibility

As one of the most lethal diseases, pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities. Furthermore, pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found. Although combinations of new drugs, multimodal therapies, and adjuvants prolong survival, most patients still relapse after surgery and eventually die. Consequently, the search for more effective treatments for pancreatic cancer is highly relevant and justified. As a newly re-discovered mediator of gasotransmission, hydrogen sulfide (H

Aim To study the effect of three kinds of active ingredients of traditional Chinese medicine (sinomenine, rhynchophylline and isorhynchophylline) on dre-miR-723-5p expression in morphine-induced zebrafish brain. Methods Morphine was injected intraperitoneally to zebrafish, conditional position preference (CPP) was trained and then the behavioral of animals were observed; the miRNA expression profiles of morphine-additive zebrafish were determined by small RNA sequencing; qRT-PCR was used to verify the expression of dre-miR-723-5p, three target gene databases (miRanda, miRDB, andRNAhybrid) were used to predict the target genes of dre-miR-723-5p; Kobas 3.0 was used to perform Gene Ontology (GO) and KEGG pathway analysis of these target genes. Results Morphine-induced CPP model was established successfully. Compared with control group, the resident time and movement map in drug-pair box of zebrafish in model group significantly increased. After drug administration, the resident time and movement map in drug-pair box of zebrafish decreased. The verification results of qRT-PCR were consistent with the results of small RNA sequencing. Ninety-nine putative target genes of dremiR-723-5p that were common to all three target gene databases, which were mainly enriched in biological process, cell composition and molecular function, involved in the positive regulation of MAPK signaling pathway, lysosome, cytokine-cytokine receptor interaction, and apoptosis. Conclusion Morphine can increase the expression of dre-miR-723-5p in the zebrafish brain, which can be reversed by sinomenine, isorhynchophylline, and rhynchophylline treatment, and dre-miR-723-5p may participate in the mechanism underlying morphine-induced damage of brain.