Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

Hemophagocytic Syndrome Secondary to Human Parvovirus B19 Infection in an Acquired Immunodeficiency Syndrome Patient:Report of One Case / 中国医学科学院学报

The acquired immunodeficiency syndrome patients with compromised immunity are prone to hemophagocytic syndrome secondary to opportunistic infections.This paper reports a rare case of hemophagocytic syndrome secondary to human parvovirus B19 infection in an acquired immunodeficiency syndrome patient,and analyzes the clinical characteristics,aiming to improve the diagnosis and treatment of the disease and prevent missed diagnosis and misdiagnosis.

Cloning and expression profile of ZFP36L1 gene in goat / 生物工程学报

The purpose of this study was to clone and characterize the ZFP36L1 (zinc finger protein 36-like 1) gene, clarify its expression characteristics, and elucidate its expression patterns in different tissues of goats. Samples of 15 tissues from Jianzhou big-eared goats, including heart, liver, spleen, lung and kidney were collected. Goat ZFP36L1 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR), then the gene and protein sequence were analyzed by online tools. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression level of ZFP36L1 in intramuscular preadipocytes in different tissues and adipocytes of goat at different differentiation stages. The results showed that the length of ZFR36L1 gene was 1 224 bp, and the coding sequence (CDS) region was 1 017 bp, encoding 338 amino acids, which was a non-secretory unstable protein mainly located in nucleus and cytoplasm. Tissue expression profile showed that ZFP36L1 gene was expressed in all selected tissues. In visceral tissues, the small intestine showed the highest expression level (P < 0.01). In muscle tissue, the highest expression level was presented in longissimus dorsi muscle (P < 0.01), whereas the expression level in subcutaneous adipose tissue was significantly higher than that in other tissues (P < 0.01). The results of induced differentiation showed that the expression of this gene was up-regulated during adipogenic differentiation of intramuscular precursor adipocytes (P < 0.01). These data may help to clarify the biological function of the ZFP36L1 gene in goat.

Inhibition of subicular seizure-labeled c-fos+ neurons alleviates cognitive deficit in epilepsy / 中国药理学与毒理学杂志

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Sarcopenia Before Concurrent Chemoradiotherapy May Develop Severe Adverse Reactions in Patients with Esophageal Squamous Cell Carcinoma / 肿瘤防治研究

Objective To investigate whether sarcopenia before concurrent chemoradiotherapy is prone to grade≥3 acute adverse reactions (AAR) and shorten survival in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods Data of advanced patients with pathologically diagnosed ESCC and CCRT (FP regimen) from August 2018 to July 2022 were reviewed retrospectively.Skeletal muscle mass and body composition were measured using pre-treatment CT images, and patients were divided into sarcopenia and non-sarcopenia groups.Grade≥3 AAR was diagnosed based on CTCAE5.0 and acute radiation injury criteria of the US RTOG.Risk factors for developing grade≥3 AAR were analyzed, and survival rates were calculated by Kaplan-Meier method. Results Among 132 patients with ESCC (87 in the sarcopenia group and 45 in the non-sarcopenia group), 23(17.4%) experienced grade≥3 AAR.In multivariate regression analysis, independent risk factors for grade ≥3 AAR included the following: sarcopenia (OR: 6.034, 95%CI: 1.206-30.190, P=0.029), decreased SMD (OR: 0.693, 95%CI: 0.492-0.976, P=0.036), decreased SMI (OR: 0.841, 95%CI: 0.721-0.982, P=0.028), and increased FMI (OR: 2.433, 95%CI: 1.194-4.958;P=0.014).The OS rates were 16.01 months (95%CI: 14.89-17.13) in the sarcopenia group and 19.27 months (95%CI: 14.45-24.09) in the non-sarcopenia group (χ2=5.326, P=0.021) as well as 14.86 months (95%CI: 11.30-18.42) for patients with grade≥3 AAR and 16.67 months (95%CI: 14.91-18.43) for patients with grade 0-2 AAR (χ2=5.47, P=0.019).Among patients with grade≥3 AAR, the OS rates were 12.13 months (95%CI: 10.15-14.11) in the sarcopenia group and 18.69 months (95%CI: 12.85-21.88) in the non-sarcopenia group (χ2=4.466, P=0.035). Conclusion Sarcopenia, decreased skeletal muscle density, and increased fat mass are important predictors of grade≥3 AAR.The OS of patients with sarcopenia and grade≥3 AAR may be reduced.

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Research on dynamic on-line monitoring method of moisture attribute in three honey-processed Chinese herbal slice based on in-situ general model / 药学学报

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R2pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

Traditional Chinese Medicine Treats Hepatic Fibrosis via NF-κB Signaling Pathway： A Review / 中国实验方剂学杂志

Hepatic fibrosis is a common complication of chronic liver disease， seriously affecting patients' quality of life and leading to severe consequences such as cirrhosis and liver cancer. Modern medicine has made progress in the treatment of hepatic fibrosis， while it still faces certain challenges and limitations. Therefore， seeking new therapeutic strategies is of great clinical significance. The nuclear factor-κB （NF-κB） signaling pathway plays a role in regulating inflammation and immune responses. Recent studies have shown that the NF-κB signaling pathway plays a key role in the occurrence and development of hepatic fibrosis. The abnormal activation of the NF-κB signaling pathway leads to the overexpression of genes related to liver inflammation and fibrosis， thereby promoting the development of hepatic fibrosis. Traditional Chinese medicine （TCM） is a traditional treatment method with unique advantages and potential. In recent years， increasing studies have proved that TCM can treat hepatic fibrosis by regulating the NF-κB signaling pathway. The active ingredients in Chinese herbal medicines can intervene in the activation of the NF-κB signaling pathway to inhibit inflammatory responses， thereby reducing the severity of hepatic fibrosis. This article reviews the mechanisms of TCM in treating hepatic fibrosis via the NF-κB signaling pathway and evaluates the efficacy and discusses the clinical application prospects of relevant Chinese herbs and formulae， aiming to provide references for further research and clinical practice.

Analysis of the ocular clinical features and pathogenic genes in patients with Alstr?m syndrome / 中华眼底病杂志

Objective:To observe and analyze the ocular clinical features and pathogenic genes of Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. From October 2020 to July 2022, 3 patients and 5 normal family members from 2 families affected with ALMS who visited in the Ophthalmology Department of Henan Children's Hospital were enrolled in the study. These 2 families were without blood relationship. The medical history and family history were inquired. Best corrected visual acuity (BCVA), fundus color photography, full-field electroretinogram (ERG), frequency domain optical coherence tomography (OCT) and systemic examination were performed. 3 ml peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. The second generation sequencing analysis was performed on these members. The suspected pathogenic mutation sites were verified by Sanger, and the pathogenicity of the gene mutation sites were determined by bioinformatics analysis.Results:Three patients from two families all developed nystagmus and photophobia in infancy. In the family 1, the BCVA of both eyes of the proband was no light perception. The fundus examination revealed vascular attenuation and retinal pigment abnormality. OCT showed retinal thinning, loss of photoreceptor layer and atrophy of the retinal pigment epithelium layer. ERG examination showed extinguished. The BCVA of the proband’s younger brother was 0.04 in the right eye and 0.02 in the left eye. The fundus examination revealed vascular attenuation but the pigment distribution was roughly normal. OCT showed blurred photoreceptor layers in both eyes. ERG examination showed extinguished. Two patients developed sensorineural deafness, obesity, acanthosis nigricans, insulin resistance/diabetes, and abnormal liver function. In addition, the proband also had left heart enlargement, hyperlipidemia and abnormal kidney function. The results of genetic testing showed that the proband and his younger brother had compound heterozygous mutations in exon 8 (c.1894C>T/p.Gln632*, M1) and exon 10 (c.9148_9149delCT/p.Leu 3050 Leufs*9, M2) of ALMS1, which were both known mutations. The father of the proband was a carrier of M1 and the mother of the proband was a carrier of M2. The proband of the family 2 had a normal fundus at 23 months old. The amplitude of ERG b wave under the stimulation of the dark adaptation 0.01 and a, b wave under the stimulation of dark adaptation 0.3 were all mild reduced. The amplitude of ERG a, b wave under the stimulation of the light adaptation 0.3 was severity decreased. At 4 years old, the BCVA was 0.01 in the right eye and 0.05 in the left eye. The fundus examination revealed vascular attenuation and bilateral blunted foveal reflex. In addition to severely diminished of a, b wave under the stimulation of dark adaptation 0.3, the rest showed extinguished. There were no systemic abnormalities. The results of genetic testing showed that the proband had compound heterozygous mutations in exon 11 (c.9627delT/p.Pro3210Glnfs*22, M3) and exon 5 (c.1089delT/p.Asp364Ilefs*13, M4) of ALMS1, which were both novel mutations. The father of the proband was a carrier of M3 and the mother of the proband was a carrier of M4. Conclusions:Nystagmus and photophobia are often the first clinical manifestations of ALMS. In the early stage, the fundus can be basically normal. As the disease progresses, the fundus examination reveals vascular attenuation and retinal pigment abnormality, and the reflection of the fovea is unclear. OCT shows the photoreceptor cell layers are blurred or even lost. The final ERG is extinguished. M1, M2, and M3, M4 compound heterozygous mutations may be the pathogeny for family 1 and family 2, respectively.

Mechanism of mesenchymal stem cell-derived exosome for alleviating hepatic ischemia-reperfusion injury / 中华器官移植杂志

The review focuses upon the mechanism of exosome derived from mesenchymal stem cells in hepatic ischemia-reperfusion injury(IRI)to provide references for clinical application of exosomes in alleviating hepatic IRI.

High-frequency ultrasonography-assisted evaluation of treatment outcomes of erysipelas: a prospective controlled study / 中华皮肤科杂志

Objective:To measure the skin thickness in patients with erysipelas by high-frequency ultrasonography (HF-USG), and to compare the clinical efficacy of systemic antibiotics alone versus their combination with glucocorticoids in the treatment of erysipelas.Methods:Hospitalized patients with erysipelas were enrolled from Zhongda Hospital, Southeast University from January to December in 2021, and randomly divided into the study group and control group according to the order of visits. The study group was treated with systemic cefathiamidine for 7 days followed by oral methylprednisolone at a dose of 0.4 mg·kg -1·d -1, while the control group was treated with cefathiamidine alone. Before and after the treatment for 10 days, the thicknesses of the epidermis-dermis layers and subcutaneous tissues were measured by HF-USG at the sites of the most severe skin lesions on the affected limbs and at the corresponding sites on the healthy limbs, and white blood cell (WBC) counts, neutrophil (NEU) counts, as well as C-reaction protein (CRP) levels were determined. The t test and non-parametric test were used to compare the efficacy between two groups. Results:A total of 23 patients with erysipelas were enrolled. Among the 12 patients in the study group, 8 were males and 4 were females, and their age was 71.4 ± 11.4 years. Among the 11 patients in the control group, 7 were males and 4 were females, and their age was 67.4 ± 11.1 years. Before treatment, the thicknesses of the epidermis-dermis layers (0.33 ± 0.12 cm) and subcutaneous tissues (1.08 ± 0.49 cm) in the study group were not significantly different from those in the control group (0.25 ± 0.09 cm, 0.98 ± 0.46 cm; t = -1.83, -0.49, P = 0.081, 0.626, respectively). After the 10-day treatment, the thicknesses of the epidermis-dermis layers and subcutaneous tissues of the skin lesions on the affected limbs significantly decreased in both groups compared with those before treatment (both P < 0.05), and the decrease in the thicknesses of subcutaneous tissues was significantly stronger in the study group (0.32 ± 0.33 cm) than in the control group (0.10 ± 0.07 cm; t = 2.20, P = 0.039). Before treatment, the WBC counts ([11.16 ± 4.42] × 10 9/L), NEU counts ([8.26 ± 4.16] × 10 9/L) and CRP levels (median [ Q1, Q3]: 72.20 [19.28, 140.50] mg/L) in the study group were not significantly different from those in the control group ([10.10 ± 4.53] × 10 9/L, [7.21 ± 3.00] × 10 9/L, 34.40 [8.00, 74.20] mg/L, respectively; t or Z = 0.60, 0.71, -0.85, P = 0.578, 0.496, 0.196, respectively). After the 10-day treatment, the WBC counts, NEU counts, and CRP levels significantly decreased in both groups compared with those before treatment (all P < 0.05) . Conclusion:The combined treatment with systemic antibiotics and glucocorticoids could effectively alleviate skin inflammation, and more rapidly reduce the thicknesses of inflamed subcutaneous tissues in patients with erysipelas compared with systemic antibiotics alone.

Relationship between preoperative serum albumin concentrations and postoperative delirium in patients undergoing total knee/hip arthroplasty / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative serum albumin concentrations and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:Five hundred patients of both sexes, aged 50-90 yr, with body mass index of 50-80 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective total knee or hip replacement under combined spinal-epidural anesthesia in our hospital from December 2021 to December 2022, were selected. Cerebrospinal fluid (CSF) samples were collected after successful subarachnoid puncture for determination of amyloid-beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) concentrations using enzyme-linked immunosorbent assay. Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence and severity of POD at 1-7 days after surgery (or before discharge), and the patients were divided into POD group and non-POD group (NPOD group). Logistic regression analysis was used to identify the risk factors for POD. The accuracy of plasma albumin concentration and CSF biomarker concentration in predicting POD was evaluated by the receiver operating characteristic (ROC) curve, and the mediating effect of CSF biomarker was analyzed.Results:A total of 343 patients were finally enrolled in the study, and the incidence of POD was 23.3%. There were statistically significant differences in age, preoperative plasma albumin concentration and Memorial Delirium Assessment Scale score in POD group as compared with NPOD group ( P<0.05). Before and after adjusting for confounding factors, decreased plasma albumin and increased concentrations of P-tau and T-tau in CSF before operation were the risk factors for POD, and increased concentrations of Aβ42, Aβ42/P-tau and Aβ42/T-tau ratio in CSF were protective factors for POD. The area under the ROC curve of preoperative plasma albumin concentrations in predicting POD was 0.668, and the area under the ROC curve of preoperative plasma albumin concentrations combined with CSF biomarker concentrations in predicting POD was 0.810 ( P<0.05). The direct effect of plasma albumin on POD was -0.009 869 2, the total effect was 0.029 443 7, and the mediating effect of P-tau accounted for 33.53% of the total effect. Conclusions:Decreased preoperative plasma albumin concentration is a risk factor for POD, and P-Tau in CSF serves as a key mediator in the relationship between serum albumin concentrations and postoperative delirium in the patients undergoing total knee/hip arthroplasty.

Progress of lipoxygenase in liver ischemia reperfusion injury / 中华肝胆外科杂志

Liver ischemia reperfusion injury (IRI) is one of the main causes of liver dysfunction or functional failure after liver transplantation or liver resection. As the main organ of lipid metabolism, liver is closely related to lipid metabolic balance. Lipoxygenase is a non-heme iron-containing oxidases that oxidizes polyunsaturated fatty acids to produce hydroxy-eicosanotetraenoic acid. Lipoxygenase is excessively expressed during liver ischemia, causing lipid metabolic disorders. High expression of several proinflammatory cytokines induced by lipoxygenase during liver reperfusion. Lipid peroxidation induced by lipoxygenase leads to the production of lipid oxygen free radicals, which induces iron death mainly characterized by lipid peroxidation, thus affecting apoptosis and tissue damage. This review mainly introduces the latest progress of lipoxygenase in liver IRI.

TRIM25 inhibits HBV replication by promoting HBx degradation and the RIG-I-mediated pgRNA recognition / 中华医学杂志(英文版)

BACKGROUND@#The hepatitis B virus (HBV) vaccine has been efficiently used for decades. However, hepatocellular carcinoma caused by HBV is still prevalent globally. We previously reported that interferon (IFN)-induced tripartite motif-containing 25 (TRIM25) inhibited HBV replication by increasing the IFN expression, and this study aimed to further clarify the anti-HBV mechanism of TRIM25.@*METHODS@#The TRIM25-mediated degradation of hepatitis B virus X (HBx) protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting. Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx, and colocalization of TRIM25 and HBx was identified via immunofluorescence; HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay (ELISA) kit from Kehua Biotech. TRIM25 mRNA, pregenomic RNA (pgRNA), and HBV DNA were detected by quantitative real-time polymerase chain reaction. The retinoic acid-inducible gene I (RIG-I) and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay.@*RESULTS@#We found that TRIM25 promoted HBx degradation, and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway. Interestingly, apart from the Really Interesting New Gene (RING) domain, the SPRY domain of TRIM25 was also indispensable for HBx degradation. In addition, we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I, which further increased the IFN production, and SPRY, but not the RING domain is critical in this process.@*CONCLUSIONS@#The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination, which led to HBx degradation. On the other hand, TRIM25 may function as an adaptor, which enhanced the recognition of pgRNA by RIG-I, thereby further promoting IFN production. Our study can contribute to a better understanding of host-virus interaction.

Peptic ulcer bleeding in the elderly and analysis of its correlation with Helicobacter pylori infection / 公共卫生与预防医学

Objective To analyze the risk factors of bleeding in elderly patients with peptic ulcer disease (PUD) and its correlation with Helicobacter pylori (Hp) infection, and to provide a theoretical basis for clinical diagnosis and treatment of elderly patients with PUD bleeding. Methods A total of 418 elderly PUD patients admitted to our hospital from June 2019 to June 2020 were selected. The 13C-urea breath test was used to determine HP infection. PUD patients were divided into observation group (n=87, bleeding) and control group (n=331, no bleeding). Age, sex, ulcer number, ulcer location, ulcer stage, ulcer diameter and other clinical data were collected. Univariate analysis and logistic regression were used to analyze the risk factors of bleeding in elderly PUD patients. The Forrest classification was used to evaluate the severity of PUD bleeding patients. Pearson correlation analysis was performed between Forrest classification and Hp infection in elderly PUD bleeding patients. Results There were statistically significant differences between the two groups in the course of disease, PUD history, NSAIDs application/ulcer number, ulcer diameter, ulcer location, ulcer stage, Hp infection and NSAIDs application (P<0.05). Multivariate logistic regression analysis showed that the use of NSAIDs, active ulcer, Hp infection and ulcer diameter ≥2 cm were risk factors for bleeding in elderly patients with PUD (P<0.05). The Hp positive rate in Forrest I patients was significantly higher than that in Forrest II and Forrest III patients (P<0.05). The positive rate of Hp in Forrest II patients was significantly higher than that in Forrest III patients. Pearson correlation analysis showed that Hp infection was positively correlated with the severity of peptic ulcer bleeding in the elderly (r=0.512, P<0.05). Conclusion The risk of bleeding from PUD is higher in the elderly, especially in patients with active ulcer, Hp infection and ulcer diameter ≥ 2 cm. In the treatment process of PUD patients, the eradication therapy of Hp should be emphasized, which can reduce the risk of bleeding.

Research Progress of Active Components of Traditional Chinese Medicine in Treatment of Hyperlipidemia by Activating PPARα Pathway / 中国实验方剂学杂志

Hyperlipidemia is a dyslipidemia caused by dyslipidemia of lipid metabolism， which can be divided into primary and secondary types. The current clinical diagnostic criteria are mainly changes in lipid levels， which are the inducers of high-risk cardiovascular diseases such as atherosclerosis， pancreatitis and coronary heart disease. As a key target in lipid metabolism， peroxisome proliferator-activated receptor α （PPARα） is involved in a variety of metabolic activities， including fatty acid degradation， synthesis， transport， storage， lipoprotein metabolism， etc. Activation of PPARα can maintain the balance of lipid metabolism through a variety of ways， which is an important way to treat hyperlipidemia. At present， chemical drugs such as statins and bettes are mainly used in the clinical treatment of hyperlipidemia. Although they can slow down the disease to a certain extent， there are many adverse reactions and drug resistance. By reviewing the literature in recent years， the author found that the activation of PPARα pathway by traditional Chinese medicine in the treatment of hyperlipidemia has significant effect and small adverse reactions. The lipid-lowering active ingredients include flavonoids， alkaloids， phenols， terpenoids and other compounds. These active components mainly affect the expression of downstream effectors through the activation of PPARα pathway， thereby inhibiting the synthesis of total cholesterol and promoting fatty acid oxidation， and play a role in the treatment of hyperlipidemia. In this paper， we systematically reviewed the structure types and mechanism of active components of traditional Chinese medicine that activate PPARα pathway， so as to provide guidance for the rational development and clinical application of lipid-lowering traditional Chinese medicine new drugs.

Pathogenesis of Bone Metastasis-caused Pain and Its Prevention and Treatment with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Bone metastasis-caused pain （BMP） is a common complication of cancer， and the incidence has been on the rise with the increase in the overall prevalence of cancer， threatening the survival and quality of life of patients. BMP is a kind of special pain with the characteristics of inflammatory pain and neuropathic pain， but is different from the two. Therefore， its pathogenesis is very complicated， and it is of great significance to understand the pathogenesis. The currently available studies mainly focused on osteoclast activation， changes in the bone microenvironment， glial cell activation， spinal cord neuron activation， and miRNA dysregulation. Modern therapies include the three-step analgesics， bisphosphonates， palliative radiotherapy， and interventional therapy for bone metastases， which show definite efficacy in short term. However， the long-term effect is unsatisfactory due to the adverse reactions， addiction， and drug resistance. Studies have shown that traditional Chinese medicine （TCM） has definite curative effect on BMP， which is safe， enhances efficacy， reduces toxicity， and boosts immunity. Moreover， it exerts the effect through multiple components， multiple targets， and multiple pathways. As a result， it has unique advantages in the prevention and treatment of BMP and has become a research focus. This paper summarizes the research on the pathogenesis of BMP， the intervention of TCM （compound Chinese medicine prescriptions， Chinese medicinals， and monomers from Chinese medicinals）， and the mechanisms of TCM， such as inhibiting osteoclast activation， glial cell activation， and spinal cord neuron activation， regulating pain mediators and abnormal expression of microRNA， and anti-tumor， which is expected to further clarify the pathogenesis of BMP and provide ideas and methods for the effective prevention and treatment of BMP with TCM.

Clinical study on the treatment of gastrointestinal neurosis with insomnia by combination of "stomach ten acupuncture" and domperidone tablets / 国际中医中药杂志

Objective:To study on the effect of "stomach ten acupuncture" combined with domperidone tablets on clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia based on the theory of "stomach harmonious leading to restless".Methods:Randomized controlled trial. From March 2020 to March 2021, 98 patients with gastrointestinal neurosis and insomnia in our hospital who met the inclusion criteria were randomly divided into two groups, with 49 patients in each group. The control group took domperidone tablets orally, and the observation group was treated with "stomach ten acupuncture" on the basis of the control group. Both groups were treated for 8 weeks. Before and after treatment, TCM syndromes were scored, the severity of gastrointestinal symptoms was assessed with Gastrointestinal Symptom Rating Scale (GSRS), anxiety and depression were assessed with Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), and sleep quality was assessed with Pittsburgh Sleep Quality Index Scale (PSQI).Results:After treatment, the scores and total scores of epigastric pain, belching, abdominal distension, anorexia, noisy acid regurgitation, tiredness and asthenia, constipation and loose stools in the observation group were significantly lower than those in the control group ( t values were 19.61, 19.30, 23.10, 22.05, 20.43, 21.81, 20.51, 16.38, respectively, P<0.01); the scores and total scores of typical symptoms, abdominal pain symptoms, reflux symptoms, diarrhea symptoms, constipation symptoms were significantly lower than those in the control group ( t values were 10.10, 11.14, 11.04, 9.31, 11.24, 5.30, respectively, P<0.01); HAMA and HAMD scores were significantly lower than those in the control group ( t values were 6.96 and 6.85, respectively, P<0.01). The scores of time to fall asleep (1.15 ± 0.56 vs. 2.11 ± 0.75, t=7.18), time to sleep (0.92 ± 0.63 vs. 1.52 ± 1.12, t=3.27), sleep quality (1.02 ± 0.66 vs. 1.96 ± 0.80, t=6.35), sleep efficiency (0.86 ± 0.62 vs. 1.68 ± 0.85, t=5.46), sleep disorders (0.92 ± 0.36 vs. 1.48 ± 0.55, t=5.96), daytime dysfunction (0.96 ± 0.42 vs. 1.97 ± 0.87, t=7.32), hypnotics (0.98 ± 0.45 vs. 1.81 ± 0.62, t=7.58) and total scores (6.85 ± 1.47 vs. 12.73 ± 2.95, t=12.49) were significantly lower than those in the control group ( P<0.01). Conclusion:The "stomach ten acupuncture" combined with domperidone tablets can improve the clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia.

Correlation between serum albumin and outcomes of successful recanalization after mechanical thrombectomy in patients with anterior circulation ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between serum albumin and hypoalbuminemia (HA) and the outcome after endovascular mechanical thrombectomy (EMT) in patients with stroke caused by acute anterior circulation large vessel occlusion.Methods:Stroke patients caused by acute anterior circulation large vessel occlusion received EMT treatment at the Department of Emergency Stroke, the Affiliated Hospital of Jining Medical University from June 2020 to August 2022 were retrospectively included. The demographic information, baseline clinical data, endovascular treatment parameters, and clinical outcomes of the patients were collected. HA was defined as serum albumin <35 g/L within 24 h of admission, and poor outcome was defined as the modified Rankin Scale score >2 at 90 d after onset. Multivariate logistic regression analysis was used to identify the independent influencing factors for poor outcomes. Results:A total of 177 patients were included, with a median age of 66 years, and 126 (71.19%) were males. Thirty-nine patients (22.03%) had HA, and 119 (67.23%) had poor outcomes. The proportion of pulmonary infection in the HA group was significantly higher than that in the non-HA group ( P<0.05). Multivariate logistic regression analysis showed that lower serum albumin (odds ratio [ OR] 4.102, 95% confidence interval [ CI] 1.316-16.451; P=0.028), postprocedural neurological deterioration ( OR 6.326, 95% CI 1.263-48.318; P=0.042) and pulmonary infection ( OR 5.873, 95% CI 1.028-24.452; P=0.018) were significantly independently associated with the poor outcomes. Conclusions:The HA group has a higher incidence of postprocedural pulmonary infection. Lower serum albumin, postprocedural neurological deterioration and pulmonary infection are the independent risk factors for the poor outcomes in patients with anterior circulation ischemic stroke who had successful recanalization after EMT.

A multicenter clinical study of the impact of COVID-19 pandemic on hospitalization of children with bronchiolitis / 国际儿科学杂志

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.