From the perspective of state differentiation and treatment， it is believed that the pathogenesis of acute respiratory distress syndrome （ARDS） is that evil poisons injured the lungs， and the lung qi suddenly collapsed， then blocked and exhausted， and the qi failure to control blood and liquid， then the fluids overflow outside the vessels， and damp phlegm， stasis， and toxins became knotted up in the body， which ultimately leads to qi dysfunction， and a series of symptom arise， so qi impairment is the principal mechanism of ARDS. A combination of Chinese and Western medicine was proposed to treat ARDS by combining tangible qi and intangible qi， using Chinese herbal medicine to boost qi and relieve collapse， percolate and drain dampness with bland medicinals， resolve toxins and dissolve stasis， and regulate qi， and combining with Western medicine to assist qi circulation to improve qi's consolidation， propulsion， and transformation， so as to make the evil qi go away， the positive qi restored， the viscera qi circulated， qi， blood， yin， and yang connected， and the activities of life maintained， and thus to achieve the goal of treating ARDS by integrated Chinese medicine and Western medicine.

ObjectiveTo classify subtypes among middle-aged and elderly type 2 diabetes mellitus (T2DM) patients aged between 35‒74 years in Shanghai suburbs, to compare their characteristics and analyze incidence risk for cerebrovascular disease among these subtypes, so as to promote personalized and precise treatment of T2DM. MethodsA total of 7 792 patients with T2DM who completed a baseline survey from 2016 and 2019 were selected as the research subjects, based on the data from a natural population cohort and biobank in Shanghai suburbs. Patients were stratified by gender and clustered into subtypes using k-means method based on baseline parameters including the age at T2DM diagnosis, body mass index (BMI), fasting blood glucose, and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Patients were followed up until March 31, 2023. Multivariate Cox regression models were used to analyze the association between subtypes and incidence risk for cerebrovascular disease, and those with cerebrovascular disease within 1 year of follow-up survey were excluded from sensitivity analysis. ResultsAmong the 7 792 patients with T2DM, 3 615 were males and 4 177 were females. Stratified by gender, 4 subgroups were identified through k-means clustering analysis, namely poor blood glucose control subgroup, severe insulin-resistant subgroup, younger onset subgroup, and older onset subgroup. The median follow-up time was 4.30 years, during which 1 960 cerebrovascular disease events were observed (844 in males, 1 116 in females). After adjusting for smoking, alcohol consumption, weekly exercise, family history of diabetes mellitus, and duration of diabetes mellitus, among male patients, the incidence risk for cerebrovascular disease was lower in the younger onset subgroup (HR=0.59, 95%CI: 0.48‒0.73, P<0.001), poor blood glucose control subgroup (HR=0.81, 95%CI: 0.65‒1.00, P=0.046), and severe insulin-resistant subgroup (HR=0.61, 95%CI: 0.50‒0.75, P<0.001), compared to the older onset subgroup. While among female patients, the incidence risk for cerebrovascular disease was also lower in the younger onset subgroup (HR=0.68, 95%CI: 0.57‒0.80, P<0.001), poor blood glucose control subgroup (HR=0.73, 95%CI: 0.60‒0.89, P=0.002), and severe insulin-resistant subgroup (HR=0.72, 95%CI: 0.61‒0.85, P<0.001), compared to the older onset subgroup. Results of the sensitivity analysis were consistent with the main findings. ConclusionAmong middle-aged and elderly T2DM patients in suburban Shanghai, both male and female patients have the highest incidence risk for cerebrovascular disease in the older onset subgroup. Subtyping of T2DM patients can help to identify the high-risk populations of cerebrovascular disease.

Objective To investigate the protective effect of berberine (BBR) against ionizing radiation injury in rats and its mechanism of action. Methods Sprague-Dawley rats were divided into seven groups: normal control group, 1-Gy radiation group, 1-Gy radiation plus low-dose BBR (50 mg/kg) group, 1-Gy radiation plus high-dose BBR (150 mg/kg) group, 3-Gy radiation group, 3-Gy radiation plus low-dose BBR (50 mg/kg) group, and 3-Gy radiation plus high-dose BBR (150 mg/kg) group. All the groups except the normal control group were exposed to external irradiation with a medical electron linear accelerator, followed by BBR administration by gavage for consecutive ten days. The serum levels of superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) were measured by using the micromethod. The pathological changes of the bone marrow and small intestine were observed with HE staining. Results Compared with the normal control group, the radiation groups showed significantly increased MDA levels (P < 0.05), significantly decreased SOD and GSH levels (P < 0.05), and more severe pathological damage of the bone marrow and small intestine. Compared with the radiation groups, the BBR groups showed significantly decreased MDA levels (P < 0.05), significantly increased SOD and GSH levels (P < 0.05), and reduced pathological damage to the bone marrow and small intestine, which were more marked in the high-dose BBR group. Conclusion BBR has a certain protective effect against radiation injury in rats, which may be through increasing the activity of antioxidant substances, enhancing free radical clearance, and thereby alleviating free radicals-caused oxidative damage.

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.
Animals ; Imaging, Three-Dimensional ; Mice ; Neural Networks, Computer ; Spinal Cord/diagnostic imaging* ; Synchrotrons ; X-Ray Microtomography

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
A549 Cells ; Animals ; Apoptosis Regulatory Proteins/immunology* ; DEAD Box Protein 58/immunology* ; Dogs ; HEK293 Cells ; Humans ; Influenza A Virus, H1N1 Subtype/immunology* ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/pathology* ; Proteolysis ; RAW 264.7 Cells ; Signal Transduction/immunology* ; THP-1 Cells ; TNF Receptor-Associated Factor 3/immunology* ; Ubiquitination/immunology* ; Viral Proteins/immunology*

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)uclear factor erythroid 2-related factor 2 (Nrf2) axis.Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSEmediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)uclear factor erythroid 2-related factor 2 (Nrf2) axis.Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSEmediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

The concentrations and distributions of trace metals and rare earth elements (REE) in sediment and mussel samples collected from the India Ocean hydrothermal area were analyzed.The metal correlation between organisms and sediments was investigated, and the ecological and chemical characteristics of REE were also explored.The results showed that, the trace metals in sediments were mainly Fe (96.6 mg/kg), Mn (1.14 mg/kg) and Zn (322.6 μg/kg), and Fe had high ratio of 98.15% by normalized calculation, which indicated that the available sediments in this studying hydrothermal area mainly consisted of iron ore substances.Trace metals and REE distributions all had good correlation between deep-sea sediments and deep-sea mussels, and the correlation coefficients were 0.991 for trace metals and 0.996 for REE.The contents and distributions of metal elements in deep-sea mussels were different from those in offshore mussels.The REE distributions in sediments and mussels showed obvious fractionation phenomenon, and the enrichment of LREE in mussels was significant.Through the REE patterns, Eu and Gd in sediments and mussels all showed anomalies, and Eu had a significant abnormal phenomenon in deep-sea sediments and deep-sea mussels.Besides, δEu values were 9.50, 10.68 and 0.23 in deep-sea sediments, deep-sea mussels and offshore mussels, respectively, and δCe were 2.21, 2.71 and 4.38, which showed that the enrichment sources of REE in offshore mussels and deep-sea mussels were different, and the REE in sediments and mussels from the India Ocean were homologous.

Objective:To investigate the relationship between the distance from the upper and lower resection margin and the gastric cancer patients with R0 resection and no distant metastasis.Methods:Retrospective analysis of 281 patients with gastric cancer in our hospital,the relationship between the age,sex,tumor size,tumor size,vascular invasion,lymph node metastasis,TNM stage,type of gastric cancer,tumor location and operation mode was analyzed.To compare the survival time of patients with different upper and lower margins.Results:The increase of the distance from upper resection margin was significantly related to the tumor size＞5 cm,TNM stage,type of gastric cancer,tumor location,and the difference was statistically significant(P＜0.05);The distance of lower resection margin was significantly correlated with tumor size＞5cm,vascular invasion,lymph node metastasis and TNM stage,type of gastric cancer,and the difference was statistically significant (P＜0.05);Themedian survival timein patientsof upper resection marginr□3cm with 48 months of the 5-year follow-up period was significantly higher than that in patients of the resection margin＞3cmwith 46 months (P＜0.001).Themedian survival timein patientsof lower resection margin□3cm with 45 months of the 5-year follow-up period was significantly higher than that in patients of the resection margin＞3cm with 44 months (P＜0.001).Conclusion:Gastric cancer postoperative upper and lower resection margin was significantly related with tumor size,TNM staging factors,and the median survival time of upper and lower resection margin＞5 cm was significantly lower than that of the resection margin3 cm.