Combinatorial Bionic Hierarchical Flexible Strain Sensor for Sign Language Recognition with Machine Learning.

Flexible strain sensors have been widely researched in fields such as smart wearables, human health monitoring, and biomedical applications. However, achieving a wide sensing range and high sensitivity of flexible strain sensors simultaneously remains a challenge, limiting their further applications. To address these issues, a cross-scale combinatorial bionic hierarchical design featuring microscale morphology combined with a macroscale base to balance the sensing range and sensitivity is presented. Inspired by the combination of serpentine and butterfly wing structures, this study employs three-dimensional printing, prestretching, and mold transfer processes to construct a combinatorial bionic hierarchical flexible strain sensor (CBH-sensor) with serpentine-shaped inverted-V-groove/wrinkling-cracking structures. The CBH-sensor has a high wide sensing range of 150% and high sensitivity with a gauge factor of up to 2416.67. In addition, it demonstrates the application of the CBH-sensor array in sign language gesture recognition, successfully identifying nine different sign language gestures with an impressive accuracy of 100% with the assistance of machine learning. The CBH-sensor exhibits considerable promise for use in enabling unobstructed communication between individuals who use sign language and those who do not. Furthermore, it has wide-ranging possibilities for use in the field of gesture-driven interactions in human-computer interfaces.

Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease.

Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis, consistent with nonalcoholic fatty liver disease (NAFLD). RNA sequencing analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Fasted Acss1K635Q/K635Q mouse livers showed increased fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1), both associated with NAFLD, and increased carbohydrate response element-binding protein binding to Fasn and Scd1 enhancer regions. Last, liver lipidomics showed elevated ceramide, lysophosphatidylethanolamine, and lysophosphatidylcholine, all associated with NAFLD. Thus, we propose that ACSS1-K635-Ac dysregulation leads to aberrant lipid metabolism, cellular senescence, and NAFLD.

Ketogenic diet induces p53-dependent cellular senescence in multiple organs.

A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.

Intermittent hypoxic pretreatment exacerbates house dust mite-induced asthma airway inflammation.

BACKGROUND: Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. METHODS: Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF-κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. RESULT: Compared to the RA and IH groups, HDM-treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF-κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). CONCLUSION: IHP treatment potentially exacerbates HDM-induced airway inflammation in asthma, with the involvement of NF-κB, particularly under high-dose allergen stimulation.

Female Protection Against Diabetic Kidney Disease Is Regulated by Kidney-Specific AMPK Activity.

Reduced kidney AMPK activity is associated with nutrient stress-induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress-induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes was evaluated in diabetic kidney tubule-specific AMPKγ2KO (KTAMPKγ2ΚΟ) male and female mice. In wild-type (WT) males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKγ2ΚΟ. Whereas WT females had protection against diabetes-induced kidney injury, KTAMPKγ2ΚΟ led to loss of female protection against kidney disease. The hormone 17ß-estradiol ameliorated high glucose-induced AMPK inactivation, p70S6K phosphorylation, and matrix protein accumulation in kidney tubule cells. The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA sequencing and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges.

[Analysis of Delphain lymph node detection rate, metastasis rate and risk factors for metastasis in papillary thyroid adenocarcinoma patients].

Objective:To investigate the detection rate and metastasis rate of delphain lymph node （DLN）in thyroid papillary adenocarcinoma（PTC） and to analyze the risk factors for DLN metastasis. Methods:The clinicopathological data of 200 PTC patients admitted to the from January 2018 to June 2020 were retrospectively analyzed, and the detection of DLN was clearly recorded in the pathological reports of all patients. The number of DLN detected, the number of metastasis, the detection rate and the metastasis rate were counted. The clinicopathological factors that might affect DLN metastasis were analyzed by univariate analysis and multivariate Logistic regression analysis, including gender, age, tumor size and tumor location. Results:DLN was detected in 121 of 200 PTC patients, with a detection rate of 60.50% （121/200）. DLN metastasis was found in 46 of the 121 patients with a metastasis rate of 38.02% （46/121）.Univariate analysis showed that tumor diameter, multiple foci, capsular invasion, extradandular invasion, lymphatic vascular invasion, lymph node metastasis in central region （excluding DLN）, and lateral cervical lymph node metastasis were the risk factors for DLN metastasis of PTC （P<0.05）. Gender, age, tumor location, bilateral tumors, Hashimoto's thyroiditis and BRAFV600E mutation were not significantly correlated with DLN metastasis of PTC（P>0.05）. The 7 variables with statistically significant differences in univariate analysis were incorporated into Logistic regression model for multivariate analysis, and the results showed that, Tumor diameter ≥1.0 cm, capsule invasion, lymphatic vascular invasion, lymph node metastasis in central region （excluding DLN）, and lateral cervical lymph node metastasis were independent risk factors for DLN metastasis of PTC （OR= 3.386-9.186, P<0.05）. The sensitivity and specificity of DLN metastasis in predicting central lymph node （excluding DLN） metastasis in PTC patients were 36.79% and 92.55%, respectively, while the sensitivity and specificity of DLN metastasis in predicting lateral cervical lymph node metastasis were 41.03% and 81.37%, respectively.The incidence of central lymph node metastasis （excluding DLN） in DLN-positive patients were was 4.94 times higher than that in DLN-negative patients, and the incidence of lateral neck lymph node metastasis in DLN-positive patients were 2.20 times higher than that in DLN-negative patients. Conclusion:The detection rate and metastasis rate of DLN in PTC patients were higher, DLN metastasis predicts more extensive lymph node metastasis, and DLN metastasis was related to multiple factors,among which tumor diameter ≥ 1.0 cm, capsule invasion, lymphatic vascular infiltration, lymph node metastasis in the central region （excluding DLN）, and lateral cervical lymph node metastasis were independent risk factors for DLN metastasis of PTC. Therefore, PTC patients with the above characteristics should actively explore DLN and formulate appropriate surgical strategies.

Hypoxia-inducible PRMT2 addiction in glioblastomas.

Hypoxia-inducible transcription factors (HIFs) are key transcription factors for cellular response to low oxygen levels. However, the specific mediators responsible for activating downstream transcription are not well characterized. We previously identified Protein Arginine methyltransferase 2 (PRMT2), a highly expressed methyltransferase in glioblastoma multiforme, as a transcription co-activator. And we established a connection between PRMT2-mediated histone H3R8 asymmetric methylation (H3R8me2a) and transcription activation. Here we find that PRMT2 is activated by HIF1α under hypoxic conditions. And we demonstrate that PRMT2 and its H3R8me2a activity are required for the transcription activation of a significant subset of hypoxia-induced genes. Consequently, the inactivation of PRMT2 suppresses hypoxia-induced glioblastoma cell migration, attenuates tumor progression, and enhances chemotherapeutic sensitivity in mouse xenograft models. In addition, our analysis of clinical glioma specimens reveals a correlation between PRMT2 protein levels, HIF1α abundance, and an unfavorable prognosis. Our study establishes HIF1α-induced PRMT2 as a critical modulator in the activation of hypoxia-related transcriptional programs, ultimately driving malignant progression.

Investigation of the shared gene signatures and molecular mechanisms between obstructive sleep apnea syndrome and asthma.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is highly related with asthma from the epidemiology to pathogenesis, while the underlying mechanism is still unclear. Herein, we aimed to reveal the shared gene signatures and molecular mechanisms underlying the coexistence of OSAS and asthma and verified relating pathway in mouse models. We downloaded GSE75097 of OSAS and GSE165934 of asthma from GEO database and performed differential expression analysis and functional enrichment analysis to screen differentially expressed genes (DEGs) and potential pathogenic pathway. PPI network was constructed with the STRING database. Hub genes were identified with cytoHubba and immune infiltration analysis was performed with cibersort for further verification. Potential drugs were screened with Comparative Toxicogenomics Database and miRNA-gene network was constructed. Besides, to test the pulmonary function and inflammatory cytokine, mouse models with OSAS and asthma were constructed, followed by validating the involvement of NOD1/NOD2-RIPK2-NF-κB-MCPIP-1 pathway in associated diseases. RESULTS: In total, 104 DEGs were identified, in which PLAUR, RIPK2, PELI1, ZC3H12A, and TNFAIP8 are the hub genes, while NOD-like receptor signaling pathway and apoptosis signaling pathway were the potential influential pathways. Increased γδT cells and neutrophils were detected in asthma patients through immune infiltration analysis. Significant difference was detected among genders in OSAS, and acetaminophen is a potential drug in the comorbidity by screening the drugs in the Comparative Toxicogenomics Database. Mice with OSAS and asthma presented with worse pulmonary function and higher levels of inflammatory cytokines. The relative proteins, including NOD1, NOD2, RIPK2, NF-κB, and MCPIP-1, were up-regulated in mice with the OSAS and asthma. CONCLUSIONS: This research firstly elucidates NOD1/NOD2-RIPK2-NF-κB-MCPIP-1 pathway as the shared pathway in the development of OSAS and asthma through bioinformatics and experimental methods. There is an interactive deterioration model between OSAS and asthma. This study may provide some potential biomarkers in the future research of the underlying pathogenesis and treatment of comorbidity of OSAS and asthma.

Complications analysis of Ilizarov bone transport technique in the treatment of tibial bone defects-a retrospective study of 199 cases.

BACKGROUND: The clinical treatment of long bone defets in the extremities caused by trauma, infection, tumours, and nonunion has been a challenge for orthopaedic surgeons. Bone transport techniques have become the only way to treat such bone defects. However, inevitable difficulties and complications related to bone transport techniques have been reported in many studies. AIM: The purpose of this study was to investigate the risk factors for complications and the effectiveness of the Ilizarov bone transport technique in the treatment of tibial bone defects. METHODS: The study was conducted in 199 patients who underwent treatment with the Ilizarov bone transport technique at our institution from May 2012 to September 2019. Patient demographic data, complications and clinical outcomes after a minimum of 2 years of follow-up were collected and retrospectively analysed. Additionally, a risk factor analysis was performed for the top three major complications. The clinical outcomes were evaluated using the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria at the last clinical follow-up. RESULTS: A total of 199 patients underwent follow-up for 12-40 months, with an average of 23.5 months, and all achieved bone healing. A total of 310 complications occurred, with an average of 1.04 minor complications and 0.48 major complications per patient. The top three complications were pin tract infection in 48 cases (61.3%), axial deviation in 86 cases (43.2%), and delayed union in 50 cases (25.13%). Multivariate analysis showed that the bone defect length (P = 0.02, OR = 5.489), the number of previous surgeries (P = 0.003, OR = 2.204), and the external fixation index (P = 0.01, OR = 1.202) were significantly correlated with pin tract infection. Bone defects of the middle 1/3 (P < 0.001, OR = 23.769), the bone defect length (P < 0.001, OR = 2.776), and the external fixation index (P < 0.001, OR = 1.154) were significantly correlated with axial deviation. The bone defect length (P = 0.003, OR = 1.242), soft tissue defects (P = 0.013, OR = 0.312) and bone defects of the distal 1/3 (P = 0.023, OR = 4.257) were significantly correlated with delayed healing. The ASAMI bone score at the last follow-up showed a rate of excellent and good bone results of 95.48% and a rate of excellent functional results of 87.94%. CONCLUSION: The Ilizarov bone transfer technique is an effective method for treating tibial bone defects, and shortening the treatment period can reduce the incidence of complications. Older patients and those with longer bone defects, a higher external fixation index, more previous operations, and defects of the middle and distal 1/3 had a higher incidence of complications.

Safety and Risk Factors of Needle Thoracentesis Decompression in Tension Pneumothorax in Patients over 75 Years Old.

Background: There are very few professional recommendations or guidelines on the needle thoracentesis decompression (NTD) for the tension pneumothorax in the elderly. This study aimed to investigate the safety and risk factors of tension pneumothorax NTD in patients over 75 years old based on CT evaluation of the chest wall thickness (CWT). Methods: The retrospective study was conducted among 136 in-patients over 75 years old. The CWT and closest depth to vital structure of the second intercostal space at the midclavicular line (second ICS-MCL) and the fifth intercostal space at the midaxillary line (fifth ICS-MAL) were compared as well as the expected failure rates and the incidence of severe complications of different needles. We also analyzed the influence of age, sex, presence or absence of chronic obstructive pulmonary disease (COPD), and body mass index (BMI) on CWT. Results: The CWT of the second ICS-MCL was smaller than the fifth ICS-MAL both on the left and the right side (P < 0.05). The success rate associated with a 7 cm needle was significantly higher than a 5 cm needle (P < 0.05), and the incidence of severe complications with a 7 cm needle was significantly less than an 8 cm needle (P < 0.05). The CWT of the second ICS-MCL was significantly correlated with age, sex, presence or absence of COPD, and BMI (P < 0.05), whereas the CWT of the fifth ICS-MAL was significantly correlated with sex and BMI (P < 0.05). Conclusion: The second ICS-MCL was recommended as the primary thoracentesis site and a 7 cm needle was advised as preferred needle length for the older patients. Factors such as age, sex, presence or absence of COPD, and BMI should be considered when choosing the appropriate needle length.

Features of transbronchial lung cryobiopsy-diagnosed fibrotic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is a common type among all the interstitial lung diseases, and transbronchial lung cryobiopsy is an alternative diagnostic technique for interstitial lung diseases. In this study, we describe the clinical and pathological features of fibrotic hypersensitivity pneumonitis diagnosed with transbronchial lung cryobiopsy (TBLC). METHODS: A total of 46 diffused parenchyma lung disease (DPLD) patients received TBLC were included in this study. Medical records including medical history spirometry examinations, 6-min walk test (6MWT) results, high resolution computed tomographic (HRCT) scans, BAL, and histopathology were collected. Results of HRCT and histopathology were compared and classified, especially. RESULTS: Sixteen patients were diagnosed with fibrotic HP, the mean age of whom was 56.3 ± 12.1 years, and 62.5% of them were male. Three of the 16 patients had been misdiagnosed as tuberculosis and received antituberculosis medications, five patients had been diagnosed as unclassifiable pulmonary fibrosis, and five patients had been diagnosed as idiopathic pulmonary fibrosis (IPF). Thirteen (81.3%) patients had a normal lymphocyte count in BAL. The pathological features of usual interstitial pneumonia (UIP) were detected in 11 (68.8%) of the cases, poor defined granulomatous was detected in nine (56.3%) of the cases, and bronchiolocentric fibrosis was detected in two (12.5%) of the 16 cases. CONCLUSIONS: Fibrotic hypersensitivity pneumonitis should be included in differential diagnosis of pulmonary fibrosis. Pathological characteristics of fibrotic hypersensitivity pneumonitis could be demonstrated from cryobiopsy lung tissue. TBLC is recommended as an alternative diagnostic technique, which may improve the specificity of hypersensitivity pneumonia detection, and UIP is the most frequent pathological finding.

Prevalence of sarcopenia under different diagnostic criteria and the changes in muscle mass, muscle strength, and physical function with age in Chinese old adults.

BACKGROUND: At present, there are several diagnostic criteria of sarcopenia were used in China, and the diagnostic criteria were not unified. This study aims to investigate the consistency between the latest sarcopenia diagnostic criteria Asian Working Group for Sarcopenia(AWGS 2019) and other common diagnostic criteria. The changes of muscle mass, muscle strength and physical function with age and their effects on the diagnosis of sarcopenia were also analyzed. METHODS: A total of 1009 men aged ≥60 years were enrolled from multiple communities. Skeletal muscle mass index, grip strength and 6 m gait speed were measured. The consistency of AWGS 2019 with other diagnostic criteria was analyzed and the trends of these three indicators were observed. The differences of muscle mass, muscle strength and function among different diagnostic criteria and age groups were evaluated. In addition, the change trends of these three indicators with age were observed. RESULTS: According to AWGS 2019 diagnostic criteria, the incidence of sarcopenia in male aged 60-69 years, 70-79 years and over 80 years was 1.5%, 9.6% and 33.1%, respectively. AWGS 2019 was highly consistent with other diagnostic criteria (Kappa = 0.66-0.80, P < 0.01), except the Foundation for the National Institutes of Health(FNIH) (Kappa = 0.32, P < 0.01). When AWGSA2019 diagnostic criteria are applied, the prevalence of decreased muscle strength (39.1%) and physical function (46.4%) was significantly higher than that of low muscle mass (35.9%) in the men over 80 years old. Muscle strength (P < 0.01) and function (P < 0.01) decreased at the same rate with age, both of which were more significant than muscle mass (P < 0.01). CONCLUSION: AWGS 2019 was highly consistent with other criteria. Maintaining muscle mass should be the focus of attention before age 80, while improving muscle strength and function should be focused after age 80 to prevent disability.

SLC8A1 antisense RNA 1 suppresses papillary thyroid cancer malignant progression via the FUS RNA binding protein (FUS)/NUMB like endocytic adaptor protein (Numbl) axis.

Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies and is associated with severe morbidity and high mortality. This study aimed to explore the role of long non-coding RNA (lncRNA) SLC8A1 antisense RNA 1 (SLC8A1-AS1) in the pathogenesis of PTC. In this study, we explored the function of SLC8A1-AS1 in PTC progression. We observed that the expression of SLC8A1-AS1 was downregulated in clinical PTC samples and PTC cell lines compared to that in normal controls. Cell counting kit (CCK)-8 assays demonstrated that the overexpression of SLC8A1-AS1 significantly reduced the proliferation of PTC cells. Consistently, apoptosis of PTC cells was enhanced by SLC8A1-AS1 overexpression. SLC8A1-AS1 overexpression attenuated the invasion and migration of PTC cells. Mechanistically, SLC8A1-AS1 maintained NUMB like endocytic adaptor protein (Numbl) mRNA stability by interacting with FUS RNA Binding Protein (FUS) in PTC cells. Depletion of Numbl reversed the inhibitory effect of SLC8A1-AS1 overexpression on PTC. Thus, we concluded that SLC8A1-AS1 suppresses PTC progression via the FUS/Numbl axis. Our findings provide novel insights into the mechanism underlying SLC8A1-AS1 attenuation of the malignant development of PTC, improving our understanding of the association between lncRNAs and PTC. SLC8A1-AS1 and FUS may be potential targets for PTC treatment.

Comparative analysis and influencing factors of hospitalization expenses of three single diseases in a tertiary Class A general hospital.

OBJECTIVE: To compare the hospitalization expenses among three single diseases in The First Affiliated Hospital of Hebei North University (a tertiary Class A general hospital), and analyze the factors affecting hospitalization costs, so as to provide some basis for controlling the unreasonable increase of hospitalization expenses as well as to render references for medical management. METHODS: By retrospective investigation, we selected the basic information of inpatient medical records and detailed billing of patients hospitalized in our hospital from Jan. 1, 2016 to Dec. 31, 2018. The collected data were sorted based on the International Classification of Diseases (ICD-10). Finally, 1,199 cases of frequently-occurring diseases and common illnesses such as rectal cancer (RC), nodular goiter (NG) and chronic renal failure (hemodialysis, HD) (CRF) were selected to conduct descriptive statistics on influencing factors and cost structure. The influencing factors of hospitalization expenses were identified by one-way analysis of variance (ANOVA) and multiple linear regression analysis. RESULTS: The hospitalization cost of inpatients with RC or CRF (HD) mainly spent on drugs, diagnosis and materials. As to NG, the cost of surgery, diagnosis and materials were the main components of hospitalization costs. Occupation and length of stay (LOS) were identified as the main influencing factors of hospitalization expenses for RC patients. While age and LOS were the main influencing factors of hospitalization cost for NG patients, and LOS alone for patients with CRF (HD). A across-sectional study was conducted on the CRF (HD) patients over 60 years old. CONCLUSIONS: In order to reasonably control inpatient medical expenses, comprehensive intervention should be carried out in clinical work, from rational drug use and selection of consumables, to shorten the hospitalization days to an appropriate level and reduce the waste of medical resources.

Receptor-Interacting Protein Kinase 3 Suppresses Mitophagy Activation via the Yes-Associated Protein/Transcription Factor EB Pathways in Septic Cardiomyopathy.

Mitophagy, known as the main mechanism of mitochondrial quality control, determines the pathophysiology of septic cardiomyopathy, although the precise regulatory mechanisms remain elusive. Data from the present study suggested that receptor-interacting protein kinase 3 (RIPK3) expression could be enhanced in response to lipopolysaccharide (LPS) challenge. Upregulated RIPK3 expression was accompanied by severe cardiac injury and cardiac dysfunction. Further examination revealed that elevated RIPK3 expression subsequently inhibited the Yes-associated protein (YAP) pathway, which was accompanied by reduced transcription factor EB (TFEB) expression. Inhibition of TFEB would reduce mitophagy, which ultimately induced cardiomyocyte death under LPS challenge. In contrast, loss of RIPK3 induced the YAP/TFEB/mitophagy pathway alleviated the sensitivity of cardiomyocytes to LPS-induced cytotoxicity. Collectively, the RIPK3/YAP/TFEB axis was confirmed to be responsible for the pathogenesis of septic cardiomyopathy by inhibiting mitophagy. These findings have potential significance for the progression of new approaches to the treatment of septic cardiomyopathy.

NR4A1 Promotes LPS-Induced Acute Lung Injury through Inhibition of Opa1-Mediated Mitochondrial Fusion and Activation of PGAM5-Related Necroptosis.

Mitochondrial dysfunction and necroptosis have been perceived as the primary molecular mechanisms underscoring acute lung injury. Meanwhile, nuclear receptor subfamily 4 group A member 1 (NR4A1) is considered a regulator of inflammation-related endothelial injury in lung tissue although the downstream molecular events remain elusive. In this study, we employed NR4A1-/- mice to decipher the role of NR4A1 in the onset and progression of acute lung injury with a focus on mitochondrial damage and necroptosis. Our results demonstrated that NR4A1 was significantly upregulated in lipopolysaccharide- (LPS-) treated lung tissues. Knockout of NR4A1 overtly improved lung tissue morphology, inhibited inflammation, and reduced oxidative stress in LPS-treated lung tissue. A cell signaling study suggested that NR4A1 deletion repressed levels of PGAM5 and attenuated LPS-mediated necroptosis in primary murine alveolar epithelial type II (ATII) cells, the effects of which were mitigated by PGAM5 overexpression. Moreover, LPS-mediated mitochondrial injury including mitochondrial membrane potential collapse and mitochondrial oxidative stress was drastically improved by NR4A1 deletion. Furthermore, NR4A1 deletion preserved mitochondrial homeostasis through activation of Opa1-related mitochondrial fusion. Silencing of Opa1 triggered mitochondrial dysfunction in NR4A1-deleted ATII cells. Taken together, our data identified NR4A1 as a novel regulator of LPS-related acute lung injury through regulation of mitochondrial fusion and necroptosis, indicating therapeutic promises of targeting NR4A1 in the treatment of acute lung injury in clinical practice.

The Diagnosis and Management of Allergic Reactions Caused by Chinese Materia Medica.

Traditional Chinese medicines (TCM) have been used in China for thousands of years. Although TCM has been generally perceived to be safe, adverse reactions to Chinese materia medica (CMM) have been reported. Most of the adverse reactions are allergic in nature, but other mechanisms may play a role. This review focuses on the mechanism and clinical presentation of these allergic reactions. Allergic reactions can occur as a result of the active and inactive ingredients of CMM. Impurities and chemicals generated during the production process can also lead to allergic or adverse reactions. Environmental factors such as temperature, humidity, and light can cause changes in the allergenicity of drugs. Human error in formulating CMM drugs also contributes to adverse drug reactions. The management of allergic reactions to CMM includes taking a good history, avoidance of medications in the same class as those which caused prior reactions, the proper training of staff, adherence to manufacturer guidelines and expiration dates, evaluation of benefit and risk balance, and the formulation of a risk management strategy for the use of CMM. A small test dose of a considered drug before using, improvements in drug purification technology, and proper storage and clinical administration help reduce allergic reactions due to CMM.

Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality.

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1ß and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.

Prognostic Significance of Ultrasound Findings of Acute Acalculous Cholecystitis for Elderly Long-Term Bedridden Patients.

Background: Acute acalculous cholecystitis (AAC) is characterized by the development of cholecystitis in the gallbladder without gallstones or with small gallstones unrelated to inflammatory diseases. This disease is not rare in the elderly bedridden patients with co-morbidities and prone to develop life-threatening gangrene or perforation of gallbladder. Early imaging is essential for detecting and effectively treating AAC. This study aimed to evaluate the use of ultrasound diagnostic criteria for the diagnosis and prognosis of elderly long-term bedridden patients with suspected AAC. Methods: We retrospectively studied 374 elderly bedridden patients with clinical manifestations of AC at the acute stage of the disease. Gallbladder anomalies were found in 92 patients by ultrasound examination, which correlated with the duration time of clinical manifestations, complications, as well as therapeutic prognosis. The major and minor ultrasound criteria of AAC were made according to the Tokyo Guidelines 2018. Ultrasound results were thought to be AAC positive when they met two major criteria or one major and two minor criteria. Results: Forty-three (46.7%) of the 92 patients presented with AAC (+) test results based on the ultrasound criteria, with a higher incidence of complications (27.9%) than AAC (-) patients (0%; P < 0.001). The median length of symptoms (8 vs. 4 days, P < 0.001) and duration of antibiotic therapy (13 vs. 5 days, P < 0.001) were longer in the AAC (+) group. Conclusions: The ultrasound-based AAC (+) group often had a worse prognosis than the AAC (-) group. Therefore, patients from the AAC (+) group should receive a follow-up ultrasound examination to detect disease progression early.