Traditional manual testing of ventilator performance is labor-intensive, time-consuming, and prone to errors in data recording, making it difficult to meet the current demands for testing efficiency in the development and manufacturing of ventilators. Therefore, in this study we designed an automated testing system for essential performance parameters of ventilators. The system mainly comprises a ventilator airflow analyzer, an automated switch module for simulated lungs, and a test control platform. Under the control of testing software, this system can perform automated tests of critical performance parameters of ventilators and generate a final test report. To validate the effectiveness of the designed system, tests were conducted on two different brands of ventilators under four different operating conditions, comparing tidal volume, oxygen concentration, and positive end expiratory pressure accuracy using both the automated testing system and traditional manual methods. Bland-Altman statistical analysis indicated good consistency between the accuracy of automated tests and manual tests for all respiratory parameters. In terms of testing efficiency, the automated testing system required approximately one-third of the time needed for manual testing. These results demonstrate that the designed automated testing system provides a novel approach and means for quality inspection and measurement calibration of ventilators, showing broad application prospects.
Ventilators, Mechanical/standards* ; Equipment Design ; Humans ; Automation

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

OBJECTIVE: To investigate the clinical and genetic characteristics of a Chinese pedigree affected with Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) due to variant of WASF1 gene, and to review the literature on NEDALVS associated with WASF1 gene variants. METHODS: A 4-year-and-8-month-old boy with NEDALVS diagnosed at Linyi People's Hospital in July 2024 due to "discovering language development delay for more than 2 years" and his family members were selected as the study subjects. Clinical data of the family members were collected. Peripheral venous blood samples were collected from family members. Whole-exome sequencing (WES) was performed, and candidate variants were verified, by Sanger sequencing. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Using the MUpro website, SWISS-MODEL, PyMOL, Clustal X, PolyPhen-2, and Mutation Taster software, bioinformatics analysis of protein three-dimensional structure modeling for gene mutations, cross-species conservation of mutant amino acids, and pathogenicity prediction of mutation sites. Relevant literature was retrieved from databases such as CNKI, Wanfang Data Knowledge Service Platform, and PubMed, and the clinical phenotypes and genotypes of patients with WASF1 gene mutations reported in the literature were summarized and analyzed. This study was approved by the Medical Ethics Committee of Linyi People's Hospital (Ethics No.: YX200303). RESULTS: The proband, a 4-year and 8-month-old male, mainly presented with delayed language and motor development, accompanied by autistic behaviors; the proband's younger brother was 2 years and 7 months old at the time of consultation, mainly presented with delayed language and motor development, accompanied by short stature; the proband's mother mainly presents with limited language expression and poor interpersonal interaction; the proband's maternal grandmother mainly presents with soliloquizing?behavior. The results of WES showed that the proband carried a heterozygous mutation c.214C>T (p.Arg72Cys) in the WASF1 gene, and this site has not been recorded in the database. Sanger sequencing confirmed that the proband's younger brother, mother, and maternal grandmother had harbored the same variant. Based on the guidelines from the ACMG, this variant was rated as likely pathogenic (PM2_Supporting+PP1+PP3+PP4). Through SWISS-MODEL homology modeling and PyMOL structure visualization analysis, it was further confirmed that this variant can lead to a decrease in protein stability. Amino acid sequence conservation analysis of the WASF1 protein using Clustal X software suggested that the c.214C>T (p.Arg72Cys) variant has caused replacement of a highly conserved amino acid. According to the results of PolyPhen-2 and Mutation Taster, the p.Arg72Cys variant was predicted to be a hazardous. By following the retrieval strategy set in this study, a total of 5 research articles regarding to patients with NEDALVS caused by WASF1 gene mutations were retrieved, which involved 15 patients. Combining the proband and their family members discovered in this study, there were a total of 19 NEDALVS patients. The main clinical features included: motor developmental delay (100%, 17/17), language/intellectual developmental delay (100%, 17/17), epilepsy (64.7%, 11/17), autistic behavior (76.5%, 13/17), hypotonia (70.6%, 12/17), abnormal electroencephalogram (64.7%, 11/17), and short stature (17.6%, 3/17). All 19 patients had heterozygous mutations, with 8 mutation sites. Missense mutations were the most common, accounting for 84.2% (16/19). CONCLUSION A pathogenic variant of the WASF1 gene was identified in a pedigree affected with NEDALVS. Discovery of the novel variant has, expanded the mutational spectrum of the WASF1 gene.
Child, Preschool ; Female ; Humans ; Infant ; Male ; China ; Exome Sequencing ; Mutation ; Neurodevelopmental Disorders/genetics* ; Pedigree ; Seizures/genetics* ; East Asian People/genetics*

OBJECTIVE: To investigate the clinical and genetic characteristics of a family with Vissers-Bodmer Syndrome (VIBOS) and to review the relevant literature on VIBOS caused by CNOT1 gene variants. METHODS: A child diagnosed with VIBOS due to "growth retardation for over 6 years" at the Linyi People's Hospital on March 1, 2024 and her family members were selected as the study subjects. Clinical data of the family were collected. Peripheral venous blood samples were collected from the family members. Whole-exome sequencing (WES) was performed on the proband's peripheral blood, and Sanger sequencing was used for verification of the candidate variant in the family. Pathogenicity of the candidate variant was classified according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). Bioinformatics analysis, including pathogenicity prediction using Mutation Taster, three-dimensional protein structure modeling using SWISS-MODEL, and functional impact assessment using PyMOL, was performed. Relevant literature on VIBOS patients due to variants of the CNOT1 gene was retrieved from databases such as CNKI, Wanfang Data, and PubMed. The clinical phenotypes and genotypes of the patients were summarized. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: YX200303). RESULTS: The proband, a 6-year-and-7-month-old female, presented with short stature, distinctive facial features (esotropia, hypertelorism, prominent nasolabial folds), webbed neck, clinodactyly, and intellectual disability. WES revealed that she has carried a heterozygous c.736delG (p.V246*) variant of the CNOT1 gene, which was unreported previously. The proband's father exhibited borderline intellectual function but no short stature or distinctive facial features. Sanger sequencing confirmed that he has carried the same heterozygous variant. According to the ACMG guidelines, this genetic variant was predicted as "likely pathogenic" (PVS1+PM2_Supporting). The c.736delG (p.V246*) variant was predicted to have a deleterious effect by Mutation Taster. Subsequent homology modeling using SWISS-MODEL, coupled with structural visualization and comparison using PyMOL, confirmed that it may cause premature termination of translation and produce a truncated protein. Literature search has retrieved five articles on VIBOS due to CNOT1 gene variants, which included 45 cases. Together with the proband and her father, the common clinical features among these 47 patients included distinctive facial features (83.0%, 39/47), speech delay (70.2%, 33/47), motor delay (70.2%, 33/47), intellectual disability (59.6%, 28/47), and short stature (48.9%, 23/47). In terms of the types of the variants, missense variants were the most common (47.4%, 18/38), followed by frameshift variants (21.0%, 8/38). The variant sites have mainly located in exons 7, 25, and 31. No significant genotype-phenotype correlation was noted. CONCLUSION The c.736delG (p.V246*) frameshift variant of the CNOT1 gene is likely the genetic etiology of VIBOS in this proband. The clinical manifestations of the proband were more severe than in her fathers, which suggested phenotypic variability associated with this variant. This study has provided new evidence for the understanding of the genetic basis of VIBOS.
Child ; Female ; Humans ; Male ; Exome Sequencing ; Intellectual Disability/genetics* ; Mutation ; Pedigree ; Transcription Factors/genetics* ; East Asian People/genetics*

Abstract Child abuse is a global public health problem, which has emerged as a neglected yet pressing issue in global development. Early and accurate identification of abuse at a lower-age group is of great significance for treatment, which might reduce the risk of re-maltreatment and promote children s physical and mental health development. Therefore, by reviewing the clinical characteristics, risk factors and existing abuse identification and screening tools of child abuse, the study aims at providing basic evidence for the development of child abuse risk identification tools and the establishment of child maltreatment system in China, so as to take timely intervention measures to prevent adverse outcomes or reduce their severity.

Objective:To evaluate the association of HbA 1C level and variability with annual decline in glomerular filtration rate in elderly patients with type 2 diabetes. Methods:A total of 527 elderly type 2 diabetic patients with baseline estimated glomerular filtration rate(eGFR)≥60 mL·min -1·(1.73 m 2) -1 at the diabetes center of a tertiary hospital in Jiangsu province were included and followed up. The mean value and the variability of HbA 1C, including standard deviation(HbA 1C-SD), variation coefficient(HbA 1C-CV), and adjusted standard deviation(Adj-HbA 1C-SD) were calculated. According to the annual decreased rate of eGFR, the patients were divided into △eGFR>5% group and △eGFR≤5% group. Cox proportional risk regression model was used to evaluate the relationship between HbA 1C variability and the risk of decreased glomerular filtration rate. Results:With a mean follow-up time of 19 months, there were 176 patients whose △eGFR>5%. Compared with △eGFR≤5% group, the HbA 1C-mean and HbA 1C variability were significantly higher in △eGFR>5% group( P<0.05). Cox regression analysis showed that HbA 1C-mean, HbA 1C-SD, HbA 1C-CV, and Adj-HbA 1C-SD were significantly correlated with decreased glomerular filtration rate. After adjustment for age, gender, HbA 1C-mean, and other factors, only Adj-HbA 1C-SD was correlated with renal insufficiency [ HR=3.32(1.68-6.57)]. Conclusions:HbA 1C variability is independently associated with annual decline in glomerular filtration rate in elderly patients with type 2 diabetes. The Adj-HbA 1C-SD is the most sensitive indicator in predicting decreased glomerular filtration rate.

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development.Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations.To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia,we examined patterns of dysmorphology caused by Hh signalling inhibition.Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 or 150 mg·kg-1 body weight at preselected time points between embryonic days (E)8.5 and 12.5.The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg·kg-1.Exposure between E9.5 and E10.5 induced frontal bone dysplasia,micrognathia and limb defects,with administration at E10.5 producing the most pronounced effects.This model showed decreased ossification of the frontal bone with downregulation of Hh signalling.The osteoid thickness of the frontal bone was significantly reduced.The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.

Objective To study the influence of Annao tablet on the expression of transforming growth factor beta 1 (TGF-β1) in acute graft-versus-host disease (aGVHD) murine and to explore the interventional mechanism of TGF-β1 on aGVHD. Methods Hematopoietic stem cells of male Balb/c mice were transplanted to female C57BL/6 mice for the development of aGVHD murine model. Recipient mice were divided into Annao group and blank group randomly and respectively administrated with Annao soup (a kind of Chinese herb) and 0.9% sodium chloride intragastrically. Clinical symptom, survival time and body weight were recorded at 14th and 30th day and some sections of liver, small bowel and skin were taken for histological changes. Serum level of TGF-β1 were measured by enzyme-labeled immunosorbent assay (ELISA), splenocyte protein of TGF-β1 by Western Blot and TGF-β1 mRNA by fluorescent quantitation polymerase chain reaction (PCR). Results Serum level of TGF-β1 in both groups had no statistical difference (P = 0.305), but it rose to (148.31 ± 7.95) ng/mL at 14th day and (183.48 ± 5.91) ng/mL at 30th day in Annao group, which had significant difference when compared with that in blank group (P = 0.000). IOD/IODβ-actin value of TGF-β1 protein in Annao group was 0.33 ± 0.05 at 14th day and 0.56 ± 0.04 at 30th day, which was higher than that in blank group (P = 0.000) and the expression of TGF-β1 mRNA of splenocyte in Annao group was 1.24 ± 0.04 at 14th day and 2.14 ± 0.33 at 30th day which was much higher than that in blank group (P = 0.000). Conclusion Annao tablet helps to relieve symptoms of acute GVHD by raising serum level of TGF-β1 and intensifying expression of protein of TGF-β1 and its mRNA.

Objective To investigate the therapeutic effects of haploidentical hematopoietic stem-cell transplantation (Haplo-PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty-nine cases of AML in first relapse after complete remission by standard DA/Hi-Ara-C regimens induction chemotherapy were evaluated retrospectively. Fiftythree cases were grafted by haplo-PBSCT and 26 cases were treated with iDA/Mid-Ara-C or MA/ Mid- Ara-C agents. Results The second remission rate in haplo-PBSCT group and continuous chemotherapy group was 86. 7 % (46/53 cases) and 38. 1% (9/23 cases) respectively (P＜0. 01). Survival postprogression (SPP) at 36th month was 43. 4 % (23/53 cases) in haplo-PBSCT group and 11.5 % (3/26 cases) in continuous chemotherapy group (P ＜ 0. 05). Conclusion Haplo-PBSCT could significantly increase the second remission rate and prolong the survival time of patients with acute myeloid leukernia in first relapse after complete remission by standard induction chemotherapy.