Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans ; Biomarkers/cerebrospinal fluid* ; Nervous System Diseases/diagnosis* ; Brain Injuries/metabolism* ; Phosphopyruvate Hydratase/cerebrospinal fluid* ; Glial Fibrillary Acidic Protein/blood* ; S100 Calcium Binding Protein beta Subunit/blood* ; tau Proteins/cerebrospinal fluid* ; Ubiquitin Thiolesterase/blood* ; Myelin Basic Protein/cerebrospinal fluid* ; Neurofilament Proteins/blood* ; MicroRNAs/blood* ; Brain Injuries, Traumatic/metabolism*

This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

Objective To investigate the efficacy of flupentixol combined with ondansetron in preventing postoperative nausea and vomiting(PONV)in patients receiving sufentanil and dezocine patient-controlled intravenous analgesia(PCIA).Methods Surgical patients receiving sufentanil and dezocine PCIA were randomly divided into treatment and control groups using a random number table.The control group received sufentanil 150 μg,dezocine 20 mg,and ondansetron 8 mg for PCIA,while the treatment group received sufentanil 150 μg,dezocine 20 mg,flupentixol 5 mg,and ondansetron 8 mg for PCIA.The incidence of PONV,severity of PONV,heart rate(HR),mean arterial pressure(MAP),blood oxygen saturation(SPO2)levels at different time points after surgery,surgery-related indicators,visual analogue scale(VAS)scores,Ramsay scores,PCIA pressing times,and incidence of adverse drug reactions were compared between the two groups.Results The incidence of PONV in the treatment group and the control group at 2,12,24,36 and 48 hours after surgery were 1.64％,4.84％,6.56％,3.28％,0 and 14.75％,18.03％,19.67％,16.39％,9.84％,respectively.The HR at 24 hours after surgery in the treatment group and the control group were(91.42±8.75)and(98.13±9.62)beat·min-1,respectively;the MAP were(91.98±4.56)and(99.05±4.17)mmHg;SPO2 were(98.13±1.65)％and(98.95±1.82)％;VAS scores were 2.68±0.49 and 2.97±0.63;Ramsay scores were 2.27±0.65 and 2.05±0.32;PCIA pressing times were(2.14±0.37)and(4.36±0.78)times,respectively.The differences in the above indicators between the treatment group and the control group were statistically significant(all P＜0.05).The incidence of total adverse drug reactions after surgery in the treatment group and the control group were 13.12％and 8.20％,respectively,with no statistically significant difference(P＞0.05).Conclusion Flupentixol combined with ondansetron can reduce the risk of PONV caused by sufentanil combined with dezocine PCIA after surgery,ensuring good analgesic effects and safety.

Adequate inflammation can effectively eliminate harmful substances and prevent disease as a self-protective measure to prevent further damage to the body,while abnormally activated inflammation is detrimental to the body.Nucleotide binding and oligomerization domain-like receptor protein 3(NLRP3)inflammasome that participates in inflammatory responses are closely related to many physiological and pathological processes and play an important role in the occurrence and development of pulmonary diseases.This article mainly reviewed the activation mechanism and hypothesis of NLRP3 inflammasome,as well as the research on treating respiratory diseases by interfering with NLRP3 inflammasome.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Objective:To evaluate the efficacy and safety of triamcinolone acetonide-saline submucosal injection for prevention of esophageal stricture after endoscopic submucosal dissection (ESD) for extensive superficial esophageal neoplasms.Methods:A total of 75 patients who underwent ESD for superficial esophageal neoplasms involving larger than 2/3 of the esophageal circumference at the Department of Gastroenterology, Northern Jiangsu People's Hospital from January 2018 to December 2020 were enrolled. Patients were randomly assigned to triamcinolone acetonide-saline submucosal injection group (group A, n=25), triamcinolone acetonide injections immediately after ESD group (group B, n=25) and the control group undergoing only ESD (group C, n=25). Serial gastroscopy was performed to assess wound healing and esophageal stricture. Endoscopic balloon dilatation (EBD) was performed when patients experienced esophageal stricture. The completion of ESD, time of operation, the amount of triamcinolone acetonide, the incidences of esophageal stricture and the time of EBD treatment of the three groups were compared. Results:All ESD procedures were successfully performed without complications such as intraoperative perforation, massive bleeding or postoperative delayed perforation. The operation time of group A, B and C were 72.87±12.99 min, 94.15±14.22 min and 74.08±11.86 min, respectively, with significant difference ( F=20.925, P<0.001). In pairwise comparison the above indicator in group A and group C was significantly shorter than that of group B (LSD- t=5.759, P<0.001; LSD- t=5.432, P<0.001), but there was no difference between group A and group C (LSD- t=0.327, P=0.745). There was no significant difference in the amount of triamcinolone acetonide between group A and group B (125±15 mg VS 133±19 mg, t=1.673, P=0.101). The rates of wound healing under endoscopy after 1 month of group A, B and C were 76% (19/25), 84% (21/25), and 76% (19/25), respectively, with no significant difference ( χ2=0.636, P=0.728). The esophageal stricture rates were 52% (13/25) in both group A and B, and 84% (21/25) in group C, with significant difference among the three groups ( χ2=7.295, P=0.026), and group A and B showed a significantly lower stricture rate than that of group C ( P=0.015; P=0.015). The median time of EBD treatment of group A, B and C were 4 (range 0 to 9), 5 (range 0 to 13) and 9 (range 0 to 16), respectively, with significant difference ( H=17.58, P<0.001). In pairwise comparison the above indicator in group A and B was significantly less than that of group C ( H=23.96, P<0.001; H=19.00, P=0.002), but there was no significant difference between group A and group B ( H=4.96, P=0.407). Esophageal stricture was observed in all patients with circumferential mucosa resected in the three groups. But the times of EBD treatment were 6.90±1.10 in group A, 10.13±2.42 in group B and 15.29±0.76 in group C with significant difference ( F=57.754, P<0.001). In pairwise comparison the above indicator in group A was less than that in group B (LSD- t=4.294, P<0.001) and this indicator in group B was less than that in group C (LSD- t=6.294, P<0.001). Median EBD times in patients with non-circumferential mucosal defects in the three groups were 0 (range 0 to 9), 0 (range 0 to 6) and 8 (range 0 to10), respectively, with significant difference ( H=19.72, P<0.001). In pairwise comparison, the EBD time in group A and B was less than that in group C ( H=17.93, P<0.001; H=16.62, P<0.001), but there was no statistical difference between group A and B ( H=1.31, P=0.779). Conclusion:Triamcinolone acetonide-saline submucosal injection ESD can safely and effectively prevent esophageal stricture after ESD for large-area superficial esophageal neoplasms, reduce the operation time and time of EBD treatment in patients with circumferential mucosa defect compared with local injections of triamcinolone acetonide after ESD.

Objective To propose a YOLOv5 lightweight network-based face mask recognition method to solve the problems due to limited storage and computation resources of edge and mobile devices.Methods A YOLOv5 model composed of a backbone network(Backbone),a neck module(Neck)and a head module(Head)was selected as the base framework.Firstly,the Backbone part was modified and replaced using the ShuffleNetv2 lightweight network;secondly,a Ghost module and a C3_S module were introduced in the Neck part;finally,a Shuffle_Yolo_GS_CBAM model was formed by incorporating a convolutional block attention module(CBAM)to improve the detection accuracy.The model was trained and verified with the AIZOO dataset,which was evaluated for face mask recognition by mean average precision(mAP),frames per second(FPS),giga floating-point operations per second(GFLOPS)and parameters.Results The model proposed recognized face masks with the mAP being 89.5％,FPS being 158.7 frames/s,parameters being 2.38 M and and GFLOPS being 4.5 GFLOPS,which had the detection speed enhanced by 39.7％,parameters decreased by 67.3％and operations reduced by73.8％when compared with the YOLOv5s model.Conclusion The method proposed behaves well in increasing detection speed,decreasing parameters and operations and ensuring detection precision,and thus is worthy promoting for face mask recognition on edge and mobile devices.[Chinese Medical Equipment Journal,2024,45(9):7-13]

As a unique gene in the genome,FLASH(FADD-like interleukin-1β-converting enzyme asso-ciated huge protein)/CASP8AP2 is involved in multiple cellular processes,including apoptosis,histone gene pre-mRNA processing,transcriptional regulation,and cell cycle progression.Clinical studies have shown that FLASH is a valuable prognostic marker for acute lymphoblastic leukemia,and a crucial factor for the survival of various cancer cells.Therefore,in-depth research into the function of FLASH may offer new perspectives for the treatment of related diseases.Our previous research identified FLASH as a bind-ing partner of p53,demonstrating that FLASH enhances the transcriptional activity of p53.Here we fur-ther investigate the molecular mechanisms of the interaction between FLASH and p53,revealing that the p53-K386R mutation(SUMOylation residue)attenuated its interaction with FLASH(aa 51-200)and FLASH-SIM(SUMO-interacting motif)(aa 1 534-1 806)significantly.However,SUMO can bind to FLASH-SIM directly,instead of FLASH(aa 51-200).Subsequent research shows that overexpression of FLASH in cells enhances global SUMO1 conjugation and p53-SUMO1 conjugation,therefore providing a plausible explanation for the underlying mechanism of FLASH enhancing the transcriptional activity of p53.Since promyelocytic leukemia protein nuclear body(PML NB)serves as subcellular reactors for SUMO conjugation within the cell,and the PML Ⅳ isoform can specifically enhance the SUMO modifica-tion of p53,we have investigated the interaction between FLASH and PML Ⅳ,and elucidated the struc-tural basis of their interaction:both FLASH-N3A(501-802)and FLASH-C2(1 807-1 981)bind to PML Ⅳ(aa 228-633).Further investigations reveal that they can synergistically enhance global SUMO1 modification as well as SUMO1 modification of p53.The interaction between FLASH and tumor suppres-sors p53 or PML Ⅳ enriches our understanding of its function and reveals the potential mechanism of FLASH in tumor development,therefore offering novel insights into cancer diagnosis and treatment.

ObjectiveTo explore the co-expression of PTBP1 and p-AXL in osteosarcoma and its clinicopathological significance for prognosis evaluation. MethodsThe expression of PTBP1 and AXL and their prognostic value in osteosarcoma were analyzed by GEO and Target data. Paraffin biopsy specimens and clinical information from 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue （callus， osteofibrous dysplasia and osteoid ostema） were obtained from the First Affiliated Hospital of Sun Yat-sen University from March 2016 to October 2020. The expressions of PTBP1 and p-AXL proteins in osteosarcoma were detected by immunohistochemistry. ResultsGEO database showed that the expression levels of PTBP and AXL in osteosarcoma tumor group were higher than those in normal tissues， but did not reach statistical significance. Target database showed that the high expression of PTBP1 had shorter Overall survival（OS） and Progression-free survival（PFS） than low PTBP1 expression， but did not reach statistical significance （P=0.064； P=0.134）. Immunohistochemical staining included 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue. The expression rate of PTBP1 and p-AXL protein in osteosarcoma tissues was higher than that in non-malignant bone tissue. The expression of p-AXL is correlated with lung metastasis （P=0.025）. Kaplan-Meier analysis showed that lung metastasis， recurrence， PTBP1 expression， co-expression of PTBP1/p-AXL influence the prognosis of patients in OS. Multivariate Cox regression analysis showed that lung metastasis （P<0.000 1） and positive expression of PTBP1 （P=0.041） were independent risk factors for osteosarcoma patients in OS. Co-expression of PTBP1 and p-AXL had shorter OS （P=0.017） and PFS （P=0.043） than non-coexpression osteosarcoma patients. ConclusionsPTBP1 and p-AXL were highly expressed in osteosarcoma tissues. The co-expression of PTBP1 and p-AXL was associated with poor prognosis of patients， and PTBP1 could be used as an independent prognostic indicator of patients with osteosarcoma.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.