SGMS1-AS1/MicroRNA-106a-5p/CPT2 Axis as a Novel Target for Regulating Lactate Metabolism in Colon Cancer.

PURPOSE: The malignant transformation of cells can lead to aerobic glycolysis, an important form of metabolic reprogramming in colon cancer cells, which can cause the accumulation of lactate and accelerate the proliferation of tumor cells also enhance their chemotherapy drug resistance. The aim of this study was to investigate the possible molecular mechanisms responsible for the increased lactate expression in colon cancer. METHODS: Several bioinformatics methods, including differential analysis, gene ontology enrichment, univariate and multivariate Cox regression analysis were used to find the lactic acid-related gene carnitine palmitoyltransferase 2. We analyzed the relationship between carnitine palmitoyltransferase 2 and clinical features as well as immune microenvironment. To further explore the mechanism of carnitine palmitoyltransferase 2 in colon cancer, we performed methylation analysis and constructed a competitive endogenous RNA network, which was validated in cell lines and clinical specimens. RESULTS: We used bioinformatics to select the lactic acid-related gene carnitine palmitoyltransferase 2 and found low expression of carnitine palmitoyltransferase 2 was associated with poor prognosis in colon cancer. An inhibitory tumor microenvironment was created when carnitine palmitoyltransferase 2 expression was reduced, with decreased CD4 T cells, CD8 T cells, dendritic cells, and B cells but increased cancer-associated fibroblasts. Methylation analysis showed that the abnormal decrease in carnitine palmitoyltransferase 2 might be caused by hypermethylation. We constructed a network of SGMS1-AS1/microRNA-106a-5p/carnitine palmitoyltransferase 2 and verified their expression in cell lines and clinical specimens. CONCLUSION: Our work revealed the possible mechanism of lactate accumulation in colon cancer and explored a new potential treatment for colon cancer by cutting off aerobic glycolysis in tumor cells.

Circ_0004712 Silencing Suppresses the Aggressive Changes of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting miR-633/TRAF6 Axis.

Circular RNA_0004712 (circ_0004712) is reported to be up-regulated in rheumatoid arthritis (RA) patients. Nevertheless, its role and mechanism in RA pathology remain to be clarified. RNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, proliferation, apoptosis, migration, and inflammation were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-20-deoxyuridine assay, flow cytometry, scratch test, and enzyme-linked immunosorbent assay. The target correlation between microRNA-633 (miR-633) and circ_0004712 or TNF receptor associated factor 6 (TRAF6) was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0004712 was up-regulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0004712 silencing suppressed the viability, proliferation, migration and inflammatory response and facilitated the apoptosis of RA-FLSs. miR-633 was confirmed to be a direct target of circ_0004712, and miR-633 knockdown reversed circ_0004712 silencing-mediated protective effects on the dysfunction and inflammation of RA-FLSs. TRAF6 was a direct target of miR-633, and miR-633 overexpression suppressed the aggressive changes of RA-FLSs by down-regulating TRAF6. Circ_0004712 could up-regulate TRAF6 expression by sponging miR-633 in RA-FLSs. Circ_0004712 interference inactivated nuclear factor (NF)-κB signaling by targeting miR-633/TRAF6 axis. Circ_0004712 silencing inhibited the aggressive changes of RA-FLSs by targeting miR-633/TRAF6 axis and NF-κB signaling, which provided new targets for RA therapy.

A novel biodegradable polymer-coated sirolimus-eluting stent: 1-year results of the HELIOS registry / 中华医学杂志(英文版)

BACKGROUND@#The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.@*METHODS@#The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.@*RESULTS@#A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.@*CONCLUSION@#The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03916432.

Interventional treatment and early-stage follow-up of pulmonary atresia with intact ventricular septum / 中华儿科杂志

Objective: To explore the application value of percutaneous peripheral interventional therapy in pulmonary atresia with intact ventricular septal (PA-IVS). Methods: Retrospective case summary. The data was collected from 25 children who were hospitalized at the Children's Hospital,Zhejiang University School of Medicine from August 2019 to August 2022, had been diagnosed with PA-IVS by echocardiography, and underwent interventional treatment. The sex, age, weight, operation time, radiation exposure time, and radiation dose of the patients were collected. The patients were divided into the arterial duct stenting group and the non-stenting group. Preoperative tricuspid annular diameters and Z scores, right ventricular length diameters, and right ventricular/left ventricular length-diameter ratios were compared by paired t-tests. Right ventricular systolic pressure difference, oxygen saturation, lactic acid before and after the surgery were compared for 24 children who received percutaneous balloon pulmonary valvuloplasty. Right ventricular improvement in 25 children after operation was analyzed. The correlation between postoperative oxygen saturation and postoperative right ventricular systolic blood pressure difference, the degree of pulmonary valve opening and the Z value of tricuspid valve ring in the non-stenting group were analyzed. Results: A total of 25 patients with PA-IVS were enrolled in the study, of whom 19 were males and 6 females, with an age at surgery of 12 (6, 28) days and a weight of (3.7±0.5) kg. One of them underwent only stenting of the arterial duct; 20 children underwent only percutaneous pulmonary valve perforation and balloon angioplasty; 4 children underwent both procedures. The Z-value of the tricuspid ring was -1.5±1.2 in the group with arterial duct stenting, and -0.1±0.4 in the group without stenting (t=2.77, P=0.010). The tricuspid regurgitant flow rate 1 month after surgery was significantly lower than the preoperative ((3.4±0.6) vs. (4.8±0.9) m/s, t=6.62,P<0.001). In the 24 children with percutaneous pulmonary valve perforation and balloon angioplasty, the preoperative right ventricular systolic blood pressure was (110±32) mmHg, and the postoperative systolic blood pressure was (52±19) mmHg (1 mmHg=0.133 kPa) (F=59.55, P<0.001). The factors that may affect postoperative oxygen saturation in 20 cases of non-stenting group were analyzed. The results suggested that the pre and post-operative right ventricular systolic blood pressure differences (r=-0.11, P=0.649), and the pulmonary valve orifice opening (r=-0.31, P=0.201) and tricuspid annulus Z value (r=-0.18, P=0.452) at 1 month after the operation were not significantly correlated with the postoperative oxygen saturation. Conclusions: Interventional therapy can be used as the first choice for one-stage operation of PA-IVS. Percutaneous pulmonary valve perforation and balloon angioplasty are more suitable for children with well-developed right ventricles, tricuspid annulus, and pulmonary arteries. While the smaller the tricuspid annulus, the more dependent it is on the ductus arteriosus and thus patients are more suitable for arterial duct stenting.

Recent research on platelet-leukocyte aggregates and their role in the pathogenesis of Kawasaki disease / 中国当代儿科杂志

Activated platelets may interact with various types of leukocytes such as monocytes, neutrophils, dendritic cells, and lymphocytes, trigger intercellular signal transduction, and thus lead to thrombosis and synthesis of massive inflammatory mediators. Elevated levels of circulating platelet-leukocyte aggregates have been found in patients with thrombotic or inflammatory diseases. This article reviews the latest research on the formation, function, and detection methods of platelet-leukocyte aggregates and their role in the onset of Kawasaki disease, so as to provide new ideas for studying the pathogenesis of Kawasaki disease.

Phenotypic and genetic analysis of a child with partial trisomy 7q / 中华医学遗传学杂志

OBJECTIVE@#To define the nature and origin of a chromosomal aberration in a child with unexplained growth and development retardation, and to analyze its genotype-phenotype correlation.@*METHODS@#A child who had presented at the Affiliated Children's Hospital of Zhengzhou University on July 9, 2019 was selected as the study subject. Chromosomal karyotypes of the child and her parents were determined with routine G-banding analysis. Their genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array).@*RESULTS@#Karyotyping analysis combined with SNP array suggested that the chromosomal karyotype of the child was 46,XX,dup(7)(q34q36.3), whilst no karyotypic abnormality was found in either of her parents. SNP array has identified a de novo 20.6 Mb duplication at 7q34q36.3 [arr[hg19] 7q34q36.3(138335828_158923941)×3] in the child.@*CONCLUSION@#The partial trisomy 7q carried by the child was rated as a de novo pathogenic variant. SNP array can clarify the nature and origin of chromosomal aberrations. Analysis of the correlation between genotype and phenotype can facilitate the clinical diagnosis and genetic counseling.

Clinical characteristics and genetic variant analysis of a child with Snijders Blok-Campeau syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS).@*METHODS@#A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members.@*RESULTS@#The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing.@*CONCLUSION@#The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.

Rapid detection of zearalenone in Coicis Semen based on ELISA / 中国中药杂志

Zearalenone(ZEN) is a toxic metabolite produced by Fusarium culmorum, F. graminearum, F. tricinctum, and other fungi, with estrogenic characteristics. Exposure to or ingestion of ZEN during pregnancy can cause reproductive dysfunction, miscarriage, stillbirth, and malformation, and seriously endanger human life and health. The detection methods for ZEN in the Chinese Pharmacopoeia(2020 edition) are liquid chromatography(LC) and liquid chromatography-mass spectrometry(LC-MS), and it is stipulated that ZEN should not exceed 500 μg in 1 000 g of Coicis Semen. Although these detection methods by instruments can achieve the qualitative and quantitative analysis of ZEN in Coicis Semen, their high detection cost and long periods hinder the rapid screening of a large number of samples in the field. In this study, the synthesized ZEN hapten was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) to obtain the complete ZEN antigen. By virtue of antibody preparation techniques, ZEN monoclonal antibody 4F6 was prepared, which showed 177.5%, 137.1%, and 109.7% cross-reactivity with ZEN structural analogs zearalanol, zearalenone, and α-zearalenol, respectively, and no cross-reactivity with other fungal toxins such as aflatoxin. Direct competitive enzyme-linked immunosorbent assay(dcELISA) based on ZEN monoclonal antibody 4F6 was developed for the determination of ZEN in Coicis Semen with an IC_(50) of 1.3 μg·L~(-1) and a detection range of 0.22-21.92 μg·L~(-1). The recoveries were 83.91%-105.3% and the RSD was 4.4%-8.0%. The established dcELISA method was used to determine the ZEN residuals in nine batches of Coicis Semen samples, and the results were validated by LC-MS. The correlation between the two detection methods was found to be 0.993 9, indicating that the established dcELISA could be used for the rapid qualitative and quantitative detection of ZEN residuals in Coicis Semen.

Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

Effects of ICG-001 on autistic behaviors and the development of hippocampal dendritic spine morphology in rats / 中华实用儿科临床杂志

Objective:To explore the effects of the compound ICG-001 on autism-like behaviors and the morphological development of dendritic spines in hippocampal pyramidal neurons of rats.Methods:Healthy Wistar rats were mated.The offspring were divided into the saline-treated group, ICG-001 control group, Sodium valproate (VPA) group and ICG-001 treatment group by using the random number table method.Each group had 12 rats.Social interaction, repetitive, compulsive and anxiety-like behaviors in rodents were assessed by three-chambered social approach, marble burying, open-field and elevated plus maze tests.The number of neuronal nuclei (NeuN)-positive neurons in the hippocampal CA1 region was calculated by the immunofluorescence method.Golgi staining was carried out to detect the density and morphological changes of dendritic spines in hippocampal pyramidal neurons of rats.The expression of phosphorylated LIM kinase 1(LIMK1), phosphorylated actin binding protein(Cofilin), fibros actin (F-actin) and developmentally-regulated brain protein A (Drebrin A) was examined by Western blot.The univariate analysis was made to examine whether the difference was statistically significant, and the data between groups were compared by the Tukey method. Results:(1) In the three-chambered social approach test, the rats in the saline-treated group, ICG-001 control group, VPA group and ICG-001 treatment group spent (219.42±5.38) s, (218.67±10.12) s, (126.58±5.02) s, and (218.58±6.63) s in the chamber, respectively.The corresponding preference score of the said 4 groups were 0.43±0.05, 0.43±0.04, 0.22±0.01 and 0.42±0.04, respectively.Compared with the VPA group, the ICG-001 treatment group spent longer time in the chamber and had a higher preference score (all P<0.05). (2) In the marble burying experiment, the number of marbles buried in said 4 groups were 9.13±0.52, 9.08±0.64, 15.13±0.82 and 9.42±0.86, respectively.ICG-001-treated rats buried markedly less marbles than VPA-exposed rats ( P<0.05). (3) In the open-field test, the rats in the said 4 groups spent (82.33±1.83) s, (81.32±4.19) s, (45.51±3.02) s and (81.44±3.19) s in the center area, respectively.Administration of ICG-001 significantly increased the time that VPA-exposed rats spent in the center area ( P<0.05). (4)In the elevated plus maze trial, the rats in the said 4 groups spent (107.75±7.23) s, (106.08±7.50) s, (63.42±1.91) s and (106.67±7.07) s in open arms, respectively.ICG-001 treatment notably increased the time that VPA-exposed rats spent in open arms ( P<0.05). (5) Immunofluorescence analysis results revealed that the number of NeuN-positive cells in the hippocampal CA1 region of said 4 groups was (41.83±1.17)×10 4/μm 2, (41.00±0.77)×10 4/μm 2, (27.17±0.95)×10 4/μm 2 and (40.00±0.90)×10 4/μm 2, respectively.ICG-001 treatment normalized the alteration in the number of NeuN-containing neurons in VPA-exposed rats ( P<0.05). (6) Golgi staining showed that the density of dendritic spines in hippocampal CA1 pyramidal neurons of said 4 groups was (0.74±0.04)/μm, (0.73±0.03)/μm, (0.49±0.03)/μm and (0.70±0.02) /μm, respectively.Of all types of dendritic spines, mushroom spines accounted for (0.49±0.02)%, (0.49±0.02)%, (0.33±0.02)% and (0.43±0.02) % in said 4 groups.Thin spines accounted for (0.27±0.02)%, (0.26±0.02)%, (0.34±0.01)% and (0.26±0.01) % in said 4 groups, respectively.Compared with the VPA group, the ICG-001 treatment group showed a significant increase in the density of dendritic spines in hippocampal CA1 pyramidal neurons ( P<0.05). After ICG-001 treatment, the number of mushroom spines greatly increased and the number of thin spines sharply decreased in VPA-exposed rats (all P<0.05). (7) According to Western blot test results, the phosphorylated LIMK1/LIMK1 ratio of the hippocampus in said 4 groups were 100.33±2.30, 99.34±2.28, 57.76±4.10 and 99.13±1.90, respectively.The phosphorylated Cofilin /Cofilin ratio were 100.18±2.43, 100.18±1.70, 57.12±1.88 and 99.53±1.69, respectively.The F-actin/globular actin(G-actin) ratio were 100.07±0.86, 99.99±1.72, 51.19±1.23 and 99.28±3.17, respectively.The expression level of Drebrin A were 100.79±1.19, 100.12±2.04, 52.86±3.26 and 99.97±2.44, respectively.Administration of ICG-001 effectively prevented the decrease of phosphorylated LIMK1, phosphorylated Cofilin, F-actin and Drebrin A in the hippocampus of VPA-exposed rats (all P<0.05). Conclusions:ICG-001 regulates the LIMK1/Cofilin signaling pathway, promotes the generation of F-actin, increases the expression of Drebrin A, and thereby alleviates autistic-associated symptoms.

A case of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene shear variation and literature review / 中华神经科杂志

Objective:To summarize the clinical phenotype and genetic characteristics of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene variation. Methods:The clinical and genetic data of a child with Poirier-Bienvenu neurodevelopmental syndrome caused by shear variant of CSNK2B gene who was diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2022 were collected. Previous relevant literature at home and abroad was reviewed to summarize the clinical characteristics of the disease. Results:The child was a girl aged 13 months, mainly due to "intermittent convulsions for 2 months" for consultation. The clinical manifestations of the girl were normal face, generalized tonic-clonic seizures, low intelligence, language and motor retardation, and there was no abnormality in the long-range video electroencephalography and the head magnetic resonance imaging. No abnormality was found in chromosome karyotype analysis and chromosome coefficient of copy variation analysis. The whole exon gene sequencing test indicated that the child carried de novo heterozygous shear variant of CSNK2B gene c.291+5G>C, which had not been reported in the literature. According to the clinical manifestations and genetic examination results of the child, the diagnosis of Poirier-Bienvenu neurodevelopmental syndrome was clear. The CSNK2B gene of the proband′s parents and the twin sister was wild-type. The application of sodium valproate anti-seizure medication could effectively control the seizures of the child, and by giving rehabilitation function training, the child′s language and gross motor function was improved. Conclusions:The Poirier-Bienvenu neurodevelopmental syndrome is a rare autosomal dominant disorder caused by variants in the CSNK2B gene. The clinical manifestations are infancy-onset seizures, intellectual development disorders, language and motor development disorders, etc, and the video electroencephalogram and skull magnetic resonance are mostly normal. The CSNK2B gene shear variant is the genetic etiology of the proband.

Application of a comprehensive risk assessment method for occupational disease hazards of employers in occupational health classification management of wooden furniture manufacturing factories / 环境与职业医学

Background The contradiction between science and operability has always existed in the model of classified occupational health supervision and management. Comprehensive risk assessment method for occupational disease hazards of employers provides risk grading and classification for occupational health management, and it's a new attempt to explore classification supervision and law enforcement. Objective To apply a comprehensive risk assessment method for occupational disease hazards of employers to estimate health risk level of wood furniture enterprises, discuss its advantages and disadvantages, and provide a basis for improving the classified management of occupational health. Methods Seven typical factories were selected in counties with highly concentrated wooden furniture manufacturing. Occupational health field investigation and testing were carried out to estimate occupational disease hazard risk level (Ⅰ, Ⅱ, and Ⅲ). A self-rated checklist was applied to score occupational health management status by interviewing employers, one by one, and to determine occupational health management status grade (A, B, and C) by the score. Thus, a comprehensive risk level (Class A, Class B, and Class C) of a specific factory was obtained from a matrix of occupational disease hazard risk level and management status grade. Risk verification was carried out based on any abnormality reported by regular occupational physical examination in past 3 years. Results Defects in occupational health management were identified in all 7 factories, among which 6 were grade C with key nonconformities (poor), and 1 was grade B (medium). Disqualified occupational disease hazards were found in 6 of 7 factories, and the workstation-specific disqualified rates were 26.09% (12/46) for noise, 14.71% (5/34) for wood dust (hard), and 12.50% (1/8) for xylene. Level Ⅱ (medium) of occupational disease hazard risk was estimated in 5 of 7 factories, while level Ⅲ (high) in 2 factories. All 7 factories were class C (high risk) accessed by the comprehensive risk assessment method for occupational disease hazards. The occupational health surveillance documents showed 636 batches of regular occupational physical examination were ordered by the 7 employers, and a total of 37 workers from 5 factories reported abnormalities in physical examination, among which 3 workers reported dust exposure and 34 workers reported noise exposure. Conclusion The comprehensive risk assessment method for occupational disease hazards of employers is not able to perform with satisfaction in occupational health classification of wooden furniture manufacturing factories yet. It is necessary to expand the pilot to improve this assessment method and develop an efficient supervision mechanism to ensure the authenticity of the data before it is popularized and applied in classified occupational health management.

Effect of human urinary kallidinogenase on cognitive function of SAMP8 mouse model and its mechanism / 中国药理学通报

Aim To study the effect of human urinary kallidinogenase(HUK)on the cognitive function of SAMP8 mouse model and its mechanism. Methods SAMP8 mice were divided intofive groups:SAMP8 group,treatment group(giving 8.75×10-3,1.75×10-2,3.5×10-2,7.0×10-2 HUK),and the SAMR1 vehicle group was used as blank control. Each group was performed Morris water maze to detect spatial cognition. Afterwards the group with the most obvious cognitive improvement(HUK group)was selected for the follow-up experiments. Immunohistochemical detection of ChAT expression in CA3 area was further verified by RtPCR. Western blot was used to detect the expression of PSD95,SYN,BDNF,and pCREB protein. The activity of MPO and the content of IL-1β and IL-18 were determined. Results The passing times in the SAMP8 group was less than that of the SAMR1 group(P<0.05). The passing times of treatment group increased compared with the SAMP8 group(P<0.05 or P<0.01),and the spatial probe time of the target quadrant was shorter(P<0.05 or P<0.01). We conducted follow-up experiments with group d(HUK group). The expression of ChAT positive cells in CA3 area of SAMP8 group was significantly lower than that of SAMR1 group; the expression of positive cells in HUK group significantly increased; RtPCR showed that ChAT expression in SAMP8 group was lower than that in SAMR1 group,and ChAT expression was significantly higher than that in SAMP8 group after HUK treatment. Compared with the SAMR1 group,the levels of IL-1β,IL-18 and MPO activity in the CA3 area of SAMP8 group significantly increased,and the protein expressions of PSD95,SYN,BNDF and pCREB decreased. After HUK treatment,the content of IL-1β,IL-18 and MPO activity decreased,and the expression of PSD95,SYN,BNDF and pCREB increased. Conclusions HUK can improve the spatial cognition of SAMP8 mice. The mechanism may be achieved by promoting the expression of ChAT in CA3 area,reducing the oxidative stress and increasing synapse-related proteins.

An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

The Spike protein of SARS-CoV-2 impairs lipid metabolism and increases susceptibility to lipotoxicity: implication for a role of Nrf2

Background/objectivesCoronavirus disease 2019 (COVID-19) patients exhibit lipid metabolic alterations, but the mechanism remains unknown. In this study, we aimed to investigate whether the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs lipid metabolism in host cells. MethodsA Spike cell line in HEK293 was generated using the pcDNA vector carrying the Spike gene expression cassette. A control cell line was generated using the empty pcDNA vector. Gene expression profiles related to lipid metabolic, autophagic, and ferroptotic pathways were investigated. Palmitic acid (PA)-overload was used to assess lipotoxicity-induced necrosis. ResultsAs compared with controls, the Spike cells showed a significant increase in lipid depositions on cell membranes as well as dysregulation of expression of a panel of molecules involved lipid metabolism, autophagy, and ferroptosis. The Spike cells showed an upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a multifunctional transcriptional factor, in response to PA. Furthermore, the Spike cells exhibited increased necrosis in response to PA-induced lipotoxicity compared to control cells in a time- and dose-dependent manner via ferroptosis, which could be attenuated by the Nrf2 inhibitor trigonelline. ConclusionsThe Spike protein impairs lipid metabolic and autophagic pathways in host cells, leading to increased susceptibility to lipotoxicity via ferroptosis which can be suppressed by a Nrf2 inhibitor. This data also suggests a central role of Nrf2 in Spike-induced lipid metabolic impairments. HighlightsO_LIThe Spike protein increases lipid deposition in host cell membranes C_LIO_LIThe Spike protein impairs lipid metabolic and autophagic pathways C_LIO_LIThe Spike protein exaggerates PA-induced lipotoxicity in host cells via ferroptosis C_LIO_LINrf2 inhibitor Trigonelline can mitigate the Spike protein-induced necrosis C_LI

Influence of different levels of heparin and antithrombin Ⅲ on human coagulation factor Ⅸ activity / 中国输血杂志

【Objective】 To study the effect of different concentrations of heparin, ATⅢ or a mixture of heparin and antithrombin Ⅲ (ATⅢ) (1∶1)on the activity of human coagulation factor Ⅸ (FⅨ). 【Methods】 The heparin or heparin/ATⅢ with different concentrations were added into human coagulation Ⅸ products or human prothrombin complex (PCC) to prepare heparin or heparin/ATⅢ samples, containing 0, 0.1, 0.3, 0.5, 0.8, 1, 2 and 4 IU per unit. ATⅢ with different concentrations were added into FⅨ or PCC to prepare ATⅢ samples containing ATⅢ 0, 0.1, 0.5 and 1 IU per unit. The FⅨ activity of the samples prepared was tested by one-stage coagulation method. Then corresponding amount of protamine sulfate were added to neutralize heparin or heparin/ATⅢ to detect the FⅨ activity again. Their influence of heparin, ATⅢ and heparin/ATⅢ with different concentrations on the activity of FⅨ were analyzed. 【Results】 When the content of heparin or heparin/ATⅢ was 0, 0.1, 0.3 and 0.5 IU per unit of FⅨ, the detection results of FⅨ titer in samples were consistent. When the content of heparin or heparin/ATⅢ per unit of FⅨ was 0.8, 1, 2 and 4 IU, the detection results of FⅨ titer were all lower than those of samples without heparin. When the ATⅢ content was 0, 0.1, 0.5 and 1 IU, the FⅨ titer of the samples was consistent. 【Conclution】 When the content of heparin or heparin/ATⅢ in the product is less than or equal to 0.5 IU per IU of FⅨ, the step of protamine sulfate adding could be omitted as it has little effect on FⅨ activity. When >0.5 IU per IU of FⅨ, however, protamine sulfate adding, to neutralize heparin, is necessary before FⅨ activity testing.

Clinical phenotype and gene analysis of TSC2/PKD1 adjacency gene syndrome / 中华神经科杂志

Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.

Development of a set of indexes for the assessment of healthy older Chinese adults / 中华老年医学杂志

Objective:To develop a set of indexes for the assessment of healthy older adults in China, in order to provide a reference and basis for developing aging-related national policies, standardizing and guiding health management services for the elderly.Methods:A set of indexes for the assessment of healthy older adults in China was established based on a literature review, expert discussions, 2 rounds of Delphi surveys, expert consultations and a cross-sectional study assessing the indexes.Results:The positive coefficients for 2 rounds of expert consultations were 86.25%(69/80)and 94.52%(69/73), respectively.All surveyed experts(100%)specialized in the area of geriatric health and came from 22 provincial-level administrative regions in China.In the two rounds of consultations, the familiarity degree coefficients were 0.706-0.915 and 0.835-0.922, and the authority coefficients were 0.762-0.921 and 0.863-0.932, respectively.The mean importance scores of each index were 6.10-9.74 scores and 7.87-9.56 scores, with perfect score rates of 43%-99% and 75%-99%, respectively.The mean coefficients of variation(CV)were 0.19±0.05(0.07-0.34)and 0.16±0.03(0.10-0.21), respectively.The set of indexes for the assessment of healthy older Chinese adults covered multi-dimensions including physical health, mental health and social health, with 3 primary indexes, 11 secondary indexes and 17 tertiary indexes.Conclusions:The construction process of the set of indexes for the assessment of healthy Chinese adults was scientific and rigorous, and the panelists had a high level of agreement, strong authority and active participation.The set of indexes has comprehensive coverage and an inclusive framework, and indexes at each level are scientific and feasible.It can serve as a reference for the comprehensive assessment of health status of the elderly and for aging-related government policy formulation in the future.

A preliminary study on quantitative evaluation of thigh muscle fat content with IDEAL-IQ technique and correlation with muscle strength in the middle-aged and elderly volunteers / 中华放射学杂志

Objective:To explore the value of iterative decomposition of water and fat with asymmetry and least squares estimation-quantitative fat imaging (IDEAL-IQ) in quantitative evaluation of thigh muscle fat content and its correlation with muscle strength in middle-aged and elderly volunteers.Methods:From December 2020 to April 2021, 30 volunteers aged 45 to 70 were recruited prospectively, including 15 males and 15 females with 52.5 (49.0, 56.3) years old. All subjects were scanned at 3.0 T MR, including axial T 1WI, IDEAL-IQ and coronal T 2WI of the left thigh. The region of interest of the knee extensors (quadriceps femoris) and knee flexors (hamstrings) in the left mid-thigh were delineated, and muscle cross-sectional area (CSA), skeletal muscle index (SMI), intermuscular fat fraction (FF) and intramuscular FF were obtained. In addition, isokinetic muscle strength measurement was performed on the left knee joint of all subjects at angular speeds of 60°/s and 180°/s to obtain peak torque (PT) and total work (TW) of knee flexors and extensors. Independent sample t-test, paired t-test or Mann-Whitney U test were used to compare the differences of CSA, SMI, intermuscular FF, intramuscular FF, PT and TW between different genders and muscle groups. Pearson or Spearman correlation analysis, and multiple linear regression analysis were used to analyze the correlation between CSA, SMI, intermuscular FF, intramuscular FF and PT, TW of thigh muscles. Results:The CSA, PT and TW of thighs in males were higher than those in females ( P<0.05), while the intermuscular FF in males was lower than that in females ( P=0.005). The CSA, SMI and PT of the thigh extensors were higher than those of the flexors ( P<0.001), while the intramuscular FF and intermuscular FF were lower than those of the flexors ( P<0.001). Intramuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.635, P<0.001; r=-0.546, P<0.001), and highly, moderately negatively correlated with TW ( r=-0.718, P<0.001; r=-0.616, P<0.001). Intermuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.519, P=0.003; r=-0.443, P=0.014), and negatively correlated with TW ( r=-0.363, P=0.049; r=-0.552, P=0.002). There was no significant correlation between CSA, SMI and PT, TW in flexors and extensors of thigh ( P>0.05). Multiple linear regression analysis showed that intramuscular FF was still significantly correlated with PT and TW of flexors and extensors (flexors: R 2adj=0.505, P=0.001; R 2adj=0.540, P<0.001; extensors: R 2adj=0.351, P=0.006; R 2adj=0.470, P=0.002). Conclusion:FF based on IDEAL-IQ technology can accurately quantify the intramuscular and intermuscular fat content of thighs, and there are negative correlations between intramuscular FF, intermuscular FF and isokinetic muscle strength measurements including PT and TW. Among them, intramuscular FF is more significant.

Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular carcinoma / 医学前沿

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.