A family study of autosomal recessive primary familial brain calcification caused by JAM2 gene mutation and literature review / 中华神经科杂志

Objective:To improve the clinician′s recognition of the clinical and molecular characteristics of primary familial brain calcification (PFBC).Methods:The detailed clinical information, imaging and molecular characteristics were analyzed in proband and family members of a genetically confirmed autosomal recessive PFBC family. The clinical and imaging features of junctional adhesion molecule 2 (JAM2) gene related PFBC were analyzed in combination with the literature review.Results:The proband was a 32-year-old man, with slurred speech and paroxysmal limb twitch as the first symptoms, accompanied by cognitive dysfunction, and rigidity in the limbs, with epilepsy in the past. Brain CT showed extensive, symmetrical, and bilateral calcification involving the cerebellum, basal ganglia, thalamus, subcortex and cortex. Other family members showed no related clinical symptoms. Brain CT of the parents of the proband showed no calcification. Gene testing of the proband revealed a homozygous c.685C>T(p.R229*) mutation in JAM2 gene, which has been reported as a pathogenic variation abroad, whereas has not been reported in China. The proband′s parents and children were found with heterozygous c.685C>T (p.R229*) mutation.Conclusions:Autosomal recessive inherited PFBC is a rare disease, and JAM2 mutation is a newly discovered pathogenic gene of PFBC in 2020. Patients with intracranial calcification should be alert of JAM2 gene mutation.

Application of TACE combined with molecular targeted therapy and immunotherapy in BCLC B/C hepatocellular carcinoma / 国际肿瘤学杂志

Transcatheter arterial chemoembolization (TACE) is the standard treatment for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) . However, TACE has some limitations, TACE combined with systemic therapy may be more beneficial to patients with BCLC stage B/C HCC. To explore the efficacy and safety of TACE combined with molecular targeted therapy, immunotherapy and molecular targeted therapy + immunotherapy in the treatment of B/C stage HCC of BCLC will provide new ideas for the clinical treatment of HCC.

Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.

Clinical characteristics and risk factors for mortality in cancer patients with COVID-19 / 医学前沿

Patients with cancer are at increased risk of severe infections. From a cohort including 3060 patients with confirmed COVID-19, 109 (3.4%) cancer patients were included in this study. Among them, 23 (21.1%) patients died in the hospital. Cancer patients, especially those with hematological malignancies (41.6%), urinary carcinoma (35.7%), malignancies of the digestive system (33.3%), gynecological malignancies (20%), and lung cancer (14.3%), had a much higher mortality than patients without cancer. A total of 19 (17.4%) cancer patients were infected in the hospital. The clinical characteristics of deceased cancer patients were compared with those of recovered cancer patients. Multivariate Cox regression analysis indicated that a Nutritional Risk Screening (NRS2002) score ⩾ 3 (adjusted hazard ratio (HR) 11.00; 95% confidence interval (CI) 4.60-26.32; P < 0.001), high-risk type (adjusted HR 18.81; 95% CI 4.21-83.93; P < 0.001), tumor stage IV (adjusted HR 4.26; 95% CI 2.34-7.75; P < 0.001), and recent adjuvant therapy (< 1 month) (adjusted HR 3.16; 95% CI 1.75-5.70; P < 0.01) were independent risk factors for in-hospital death after adjusting for age, comorbidities, D-dimer, and lymphocyte count. In conclusion, cancer patients showed a higher risk of COVID-19 infection with a poorer prognosis than patients without cancer. Cancer patients with high-risk tumor, NRS2002 score ⩾ 3, advanced tumor stage, and recent adjuvant therapy (< 1 month) may have high risk of mortality.

UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway / 中华医学杂志(英文版)

BACKGROUND@#Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.@*METHODS@#BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.@*RESULTS@#In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.@*CONCLUSION@#UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.

Burden of Outpatient Visits Attributable to Ambient Temperature in Qingdao, China / 生物医学与环境科学（英文）

Climate change has been referred to as one of the greatest threats to human health, with reports citing likely increases in extreme meteorological events. In this study, we estimated the relationships between temperature and outpatients at a major hospital in Qingdao, China, during 2015-2017, and assessed the morbidity burden. The results showed that both low and high temperatures were associated with an increased risk of outpatient visits. High temperatures were responsible for more morbidity than low temperatures, with an attributed fraction (AF) of 16.86%. Most temperature-related burdens were attributed to moderate cold and hot temperatures, with AFs of 5.99% and 14.44%, respectively, with the young (0-17) and male showing greater susceptibility. The results suggest that governments should implement intervention measures to reduce the adverse effects of non-optimal temperatures on public health-especially in vulnerable groups.

6-Formylindolo3,2-bcarbazole alleviates lipopolysaccharide-induced acute lung injury via suppressing endoplasmic reticulum stress / 中华危重病急救医学

Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies: Characterization by Single-Unit Recording in Rats / 神经科学通报·英文版

The pain-relieving effect of acupuncture is known to involve primary afferent nerves (PANs) via their roles in signal transmission to the CNS. Using single-unit recording in rats, we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli. Acupuncture-like signals were elicited in PANs using three techniques: manual acupuncture (MAc), emulated acupuncture (EAc), and electro-acupuncture (EA)-like peripheral electrical stimulation (PES). The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz, respectively. The frequency of discharges in PANs was correlated with the frequency of PES. The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers. Therefore, EA in a dense-disperse mode (at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc. Frequencies of EA output >250 Hz appear to be obsolete for pain relief.

Anti-aging effect of Scutellaria baicalensis Georgi leaves based on 1H NMR serum and liver metabolomics / 药学学报

@#In this study a <italic>D</italic>-galactose-induced aging rat model combined with ¹H NMR of serum and liver metabolomics were used to explore the anti-aging effect and the potential metabolic regulatory mechanism of <italic>Scutellaria baicalensis</italic> Georgi leaves. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of Shanxi University. The results of physical characteristics, an open field test and serum biochemical indexes indicated that <italic>Scutellaria baicalensis</italic> Georgi leaves had an anti-aging effect that could ameliorate the characteristics of aging rats such as acquired hair loss and slow response, improve the spontaneous activity of aging rats, and decrease lipid peroxidation and glycosylation damage induced by <italic>D</italic>-galactose. Serum and liver metabolomics further revealed that <italic>Scutellaria baicalensis</italic> Georgi leaves could decrease serum and liver metabolism disturbances in aging rats, mainly through different metabolites and metabolic pathways. Specifically, 12 differential metabolites including glutamine and glutamate, 11 metabolic pathways including <italic>D</italic>-glutamine and <italic>D</italic>-glutamate metabolism and alanine, aspartate and glutamate metabolism in serum were significantly altered after the treatment. Simultaneously, five differential metabolites such as <italic>α</italic>-glucose and <italic>β</italic>-glucose, two metabolic pathways that are glycolysis or gluconeogenesis, and starch and sucrose metabolism in the liver were markedly altered.

Evidence for the Presence of Long-Lived Plasma Cells in Nasal Polyps

PURPOSE: Plasma cells and immunoglobulins (Igs) play a pivotal role in the induction and maintenance of chronic inflammation in nasal polyps. During secondary immune responses, plasma cell survival and Ig production are regulated by the local environment. The purpose of the present study was to investigate the presence of long-lived plasma cells (LLPCs) and specific survival niches for LLPCs in human nasal polyps.METHODS: Nasal mucosal samples were cultured with an air-liquid interface system and the Ig levels in culture supernatants were analyzed by enzyme-linked immunosorbent assay. The characteristics of LLPCs in nasal polyps were determined by immunohistochemistry and immunofluorescence. The expression of neurotrophins as well as their receptors was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting.RESULTS: The numbers of CD138⁺ total plasma cells and BCL2⁺ plasma cells were increased in both eosinophilic and non-eosinophilic nasal polyps compared with those in normal tissues. The production of IgG, IgA, and IgE was detected in culture supernatants even after a 32-day culture of nasal polyps. Although the total numbers of plasma cells were decreased in nasal polyps after culture, the numbers of BCL2⁺ plasma cells remained stable. The expression of nerve growth factor (NGF) as well as tropomyosin receptor kinase (Trk) A, a high-affinity receptor for NGF, was upregulated in both eosinophilic and non-eosinophilic nasal polyps. In addition, BCL2⁺ plasma cell numbers were positively correlated with NGF and TrkA mRNA expression in nasal mucosal tissues. Polyp plasma cells had the expression of TrkA.CONCLUSIONS: Human nasal polyps harbor a population of LLPCs and NGF may be involved in their prolonged survival. LLPCs may be a novel therapeutic target for suppressing the local Ig production in nasal polyps.

Based on Delphi method to build an assessment index system for standardized residency training of pulmonary and critical care medicine / 中华医学教育探索杂志

Objective:To establish a scientific and systematic department rotation examination and evaluation system adapted to the development of Pulmonary and Critical Care Medicine according to the clinical needs and the actual situation of the hospital.Methods:The literature analysis method and Delphi method were adopted to determine the index system after two rounds of consultation. The weight of the index was determined by the method of optimal sequence diagram.Results:The positive coefficients of the two rounds of consulting experts were 100% and 95.65%. The average value of the authoritative coefficients of the two consulting groups was 0.85. And the coordination coefficients of the two rounds of expert consultations were 0.513 and 0.516 respectively. Finally, five first-level indicators and 14 second-level indicators were established.Conclusion:The enthusiasm and coordination coefficient of experts are good, and the results are credible. The established index system can be used for standardized residency training assessment of residents in Department of Pulmonary and Critical Care Medicine.

Synergistic chemo-photothermal therapy of castration-resistant prostate cancer by single-walled carbon nanotube / 上海交通大学学报（医学版）

Objective : To study the synergistic effect of chemo-photothermal on castration-resistant prostate cancer (CRPC) for enhancing the efficacy of chemotherapy by single-walled carbon nanotubes (SWCNTs). Methods ¡¤ High-purity SWCNTs were used as the drug carrier. Firstly, SWCHTs were truncated (shorten SWCNTs, s-SWCNTs) by mixed acid solutions. At the same time, a large amount of -COOH were in-troduced onto the surface of s-SWCNTs. Secondly, the polyethylene glycol (PEG) with amino terminated was successfully modified onto s-SWCNTs through amido linkage in N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride solutions to endow s-SWCNTs with water solubility and biocompatibility. Finally, docetaxel (DTX) was successfully loaded through nano-deposition method and π-π stacking on the surface of s-SWCNTs. Thus a nanosystem with both chemotherapy and photothermal properties was established. The chemo-photothermal therapy synergistic inhibition on CRPC cell line C4-2 in vitro and the anti-tumor effect in vivo were evaluated. Results ¡¤ Fourier transform infrared spectrum and zeta potential test showed that -COOH was successfully introduced onto s-SWCNTs, and the amount of -COOH was 0.412 mol per gram of SWCNTs determined by automatic conduct metric titration. The UV absorption spectrum showed that DTX was successfully loaded onto the nanosystem. By monitoring the UV absorption of the dialysate, DTX could be loaded onto SWCNTs up to 1.35 mg per gram of s-SWCNTs. Under the stimulation of acidic conditions, DTX could be rapidly released from the surface of the nanosystem. The in vitro cell viability and in vivo anti-tumor experiment showed that DTX combined with photothermal had a synergetic effect on killing C4-2 cells than any single treatment model. Conclusion ¡¤ DTX-loaded s-SWCNTs nanosystem with high stability and photothermal effect can inhib-it the growth of CRPC cells and the tumor growth in mice bearing CRPC. The nanosystem with synergistic effect of chemotherapy and photo-thermal therapy could be used in the treatment of prostate cancer which is resistant to chemotherapy drugs.

Clinical, myopathological and genetic features of two Chinese families with paramyotonia congenita / 中华内科杂志

Objective:To investigate the clinical, myopathological and genetic mutation characteristics in two Chinese families with paramyotonia congenita (PMC).Methods:Clinical manifestations, electrophysiology, muscle pathology and gene sequencing of two Chinese families with PMC were analyzed retrospectively.Results:Family 1 involved 12 patients in 4 consecutive generations and family 2 involved only 1 patient in 3 generations. The onset of symptoms in all patients started at early childhood. Both probands presented with myotonia triggered by cold and paroxysmal weakness. However, the other 11 patients in family 1 only manifested cold-induced myotonia. Serum creatine kinase (CK) was slightly elevated between attacks of weakness in the 2 probands, and was even greater than 10 000 U/L during the episodes of weakness in the second proband, whose lower limb MRI revealed edema in bilateral medial gastrocnemius. Electromyography showed diffuse myotonia discharge and myogenic impairment in both probands, and myotonia discharge in the first proband′s mother. Muscle pathology of both probands showed mild myopathic changes, and tube aggregation was occasionally observed in the second one. Genetic testing revealed a maternally inherited heterozygous R1448H mutation of SCN4A gene in the first proband and part of his family. A novel heterozygous R1448G mutation of SCN4A gene was reported in the second proband.Conclusions:Cold-triggered myotonia with or without paroxysmal weakness are the common characteristics of PMC. Myotonic potential and myogenic impairment can be tested in electromyography. The p.R1448G mutation is a new missense mutation.

Comprehensive analysis of the functional role of lncRNA GAS5 in triple-negative breast cancer by bioinformatics / 中华内分泌外科杂志

Objective:To study the effect of long noncoding RNA growth arrest-specifific transcript 5 (lncRNA GAS5) on the occurrence and development of triple-negative breast cancer (TNBC) by analyzing the differential expression of lncrna GAS5 in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.Methods:The expression of GAS5 in each subtype and pathological stage of breast cancer was studied by the TCGA data. The correlation of GAS5 was analyzed by using TNBC data GSE76124 and GSE83937 from the GEO database of the United States. The elated genes were collected and take the intersection. The positive correlation genes were used to analyze the GO function and the enrichment of KEGG pathway. GSEA of GAS5 was analyzed with TCGA database and GEO76124 data. GSE40525 and GSE76250 were selected from GEO data set to screen different miRNA and mRNA of TNBC, and construct the ceRNA network of GAS5-mirna-mrna through prediction.Results:The expression of GAS5 in breast cancer was lower than that in the adjacent tissues. GAS5 was mainly involved in various metabolic processes, including organic metabolism, macromolecular metabolism, nitrogen metabolism, etc. In terms of pathway, GAS5 mainly affected the ribosome biogenesis in eukaryotes, Wnt signaling pathway. By constructing the regulatory network of GAS5 in TNBC, we found that GAS5 was most likely to regulate the expression of 25 genes including SLC7A2 and lLONRF2 by adsorbing hsa-mir-650 and has-mir-532-5p.Conclusion:lncrna GAS5 may play a role of tumor suppressor gene in breast cancer and provide a new therapeutic target for gene therapy of breast cancer.

A New Generation of Radiotherapy Technology-Flash Radiotherapy / 中国医疗器械杂志

Flash radiotherapy is a kind of radiotherapy method using ultra-high dose rate radiation. Compared with the traditional dose rate radiotherapy, it has unique radiobiological advantages. In this paper, the principle of flash radiotherapy, the process and results of biological experiments are summarized. At the same time, the advantages and challenges of flash radiotherapy are analyzed, and the future clinical application is prospected.

Analysis of a pedigree with autosomal dominant intermediate Charcot-Marie-Tooth disease type E and nephropathy / 中华医学遗传学杂志

OBJECTIVE@#To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy.@*METHODS@#Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband.@*RESULTS@#The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c.341G>A (p.G114D) mutation in exon 2 of the INF2 gene.@*CONCLUSION@#The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c.341G>A mutation of the INF2 gene.

Expression of transcription factor SOX12 in lung adenocarcinoma and its clinical significance / 南方医科大学学报

OBJECTIVE@#To explore the expression patterns of transcription factor SOX12 in lung adenocarcinoma and its significance in the diagnosis and prognosis of the malignancy.@*METHODS@#Large cancer genome databases were used to analyze SOX12 expression level in lung adenocarcinoma. Immunohistochemistry (IHC) and semiquantitative PCR were used to detect the expression of SOX12 in 36 specimens of lung adenocarcinoma tissues, 15 adjacent tissues and 21 normal lung tissues. The prognostic value of SOX12 in lung adenocarcinoma and lung squamous cell carcinoma were analyzed using Kaplan-Meier Plotter database, and the relationship between SOX12 expression and the overall survival (OS) and progression free survival (PPS) of the patients were analyzed.@*RESULTS@#Analysis of TCGA database and GEO (GSE40419) database showed that SOX12 expression levels were significantly higher in in lung adenocarcinoma than in normal lung tissues ( < 0.001). The results of IHC and semiquantitative PCR revealed that SOX12 was expressed at significantly higher levels in lung adenocarcinoma than in normal lung tissues ( < 0.001). Kaplan-Meier survival analysis showed that patients with lung adenocarcinoma positive for SOX12 had a significantly shorter OS and PPS time than those negative for SOX12 ( < 0.05), but SOX12 positivity did not significantly affect OS and PPS of patients with lung squamous cell carcinoma.@*CONCLUSIONS@#High expression levels of SOX12 in lung adenocarcinoma are significantly associated with a poor OS of the patients, suggesting the value of SOX12 to assist in early diagnosis and prognostic evaluation of lung adenocarcinoma.

Analysis of a pedigree with autosomal dominant intermediate Charcot-Marie-Tooth disease type E and nephropathy / 中华医学遗传学杂志

Objective@#To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy.@*Methods@#Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband.@*Results@#The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c. 341G>A (p.G114D) mutation in exon 2 of the INF2 gene.@*Conclusion@#The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c. 341G>A mutation of the INF2 gene.

Methylprednisolone alleviates LPS-induced acute lung injury by inhibiting STAT3-ERK1/2 signaling pathway / 中华急诊医学杂志

Objective@#To investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI).@*Methods@#The C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups: control group (control), LPS-induced endotoxemia model (LPS), only methylprednisolone (MP) administration group (MP), and intervention group with 2 mg/kg MP (LPS+MP) (n= 8 per group). The wet/dry (W/D) weight ratio of lung tissue, lung pathology by hematoxylin & eosin (HE) staining, serum and mRNA levels of TNF-α and IL-6 in lungs were determined. The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot. Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups.@*Results@#(1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17), P = 0.038]; (2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening; (3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±1.64) pg/mL vs (6.61±1.27) pg/mL, P = 0.003; (1.42±0.35) pg/mL vs (3.80±1.35) pg/mL, P = 0.008, respectively], and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05), P = 0.03; (1.62±1.00) vs (11.12±6.56), P=0.026; respectively]; (4) MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06), P < 0.001, (0.24±0.02) vs (1.34±0.32), P < 0.001].@*Conclusions@#Methylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression.

Methylprednisolone alleviates LPS-induced acute lung injury by inhibiting STAT3-ERK1/2 signaling pathway / 中华急诊医学杂志

Objective To investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods The C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups:control group (control),LPS-induced endotoxemia model (LPS),only methylprednisolone (MP) administration group (MP),and intervention group with 2 mg/kg MP (LPS+MP) (n=8 per group).The wet/dry (W/D) weight ratio of lung tissue,lung pathology by hematoxylin & eosin (HE) staining,serum and mRNA levels of TNF-α and IL-6 in lungs were determined.The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot.Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups.Results (1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17),P =0.038];(2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening;(3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±l.64) pg/mL vs (6.61±1.27) pg/mL,P =0.003;(1.42±0.35) pg/mL vs (3.80±1.35) pg/mL,P =0.008,respectively],and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05),P =0.03;(1.62±1.00) vs (11.12±6.56),P=0.026;respectively];(4)MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06),P ＜0.001,(0.24±0.02) vs (1.34±0.32),P ＜ 0.001].Conclusions Methylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression.