An orexin-receptor-2-mediated heart-brain axis in cardiac pain.

Orexin is a neuropeptide released from hypothalamus regulating feeding, sleeping, arousal, and cardiovascular activity. Past research has demonstrated that orexin receptor 2 (OX2R) agonist infusion in the brain results in sympathoexcitatory responses. Here, we found that epicardial administration of OX2R agonism leads to opposite responses. We proved that OX2R is expressed mainly in DRG neurons and transported to sensory nerve endings innervating the heart. In a capsaicin-induced cardiac sympathetic afferent reflex (CSAR) model, we recorded the calcium influx in DRG neurons, measured heart rate variability, and examined the PVN c-Fos activity to prove that epicardial OX2R agonism administration could attenuate capsaicin-induced CSAR. We further showed that OX2R agonism could partially rescue acute myocardial infarction by reducing sympathetic overactivation. Our data indicate that epicardial application of OX2R agonist exerts a cardioprotective effect by attenuating CSAR. This OX2R-mediated heart-brain axis may provide therapeutic targets for acute cardiovascular diseases.

Intermedin alleviates diabetic vascular calcification by inhibiting GLUT1 through activation of the cAMP/PKA signaling pathway.

BACKGROUND AND AIMS: Vascular calcification (VC) is regarded as an independent risk factor for cardiovascular events in type 2 diabetic patients. Glucose transporter 1 (GLUT1) involves VC. Intermedin/Adrenomedullin-2 (IMD/ADM2) is a cardiovascular protective peptide that can inhibit multiple disease-associated VC. However, the role and mechanism of IMD in diabetic VC remain unclear. Here, we investigated whether IMD inhibits diabetic VC by inhibiting GLUT1. METHODS AND RESULTS: It was found that plasma IMD concentration was significantly decreased in type 2 diabetic patients and in fructose-induced diabetic rats compared with that in controls. Plasma IMD content was inversely correlated with fasting blood glucose level and VC severity. IMD alleviated VC in fructose-induced diabetic rats. Deficiency of Adm2 aggravated and Adm2 overexpression attenuated VC in high-fat diet-induced diabetic mice. In vitro, IMD mitigated high glucose-induced calcification of vascular smooth muscle cells (VSMCs). Mechanistically, IMD reduced advanced glycation end products (AGEs) content and the level of receptor for AGEs (RAGE). IMD decreased glucose transporter 1 (GLUT1) levels. The inhibitory effect of IMD on RAGE protein level was blocked by GLUT1 knockdown. GLUT1 knockdown abolished the effect of IMD on alleviating VSMC calcification. IMD receptor antagonist IMD17-47 and cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) inhibitor H89 abolished the inhibitory effects of IMD on GLUT1 and VSMC calcification. CONCLUSIONS: These findings revealed that IMD exerted its anti-calcification effect by inhibiting GLUT1, providing a novel therapeutic target for diabetic VC.

Microstructure and Biomechanical Properties in Selective Laser Melting of Porous Metal Implants.

Two kinds of porous structure design strategies, ring-support (RS) and column-support (CS), are proposed for human implants. The accurate design of porosity is realized by adjusting the pore characteristics, such as strut diameter, pore diameter, and unit size. Porous specimens with porosity of 50%, 60%, 70%, and 80% were prepared by selective laser melting. The three-dimensional pore structure is basically consistent with the design characteristics, and the measured porosity is slightly lower than design value. The microstructure, microhardness, and friction and wear properties of the samples were studied. The results show that the performance along the scanning orientation is slightly better than that along the forming orientation. The compression and dynamic elastic modulus of porous specimens with different structures and porosities were analyzed. The CS porous with 60-80% porosity has suitable compressive strength and elastic modulus, which is close to that of human tissue, and effectively avoids the stress shielding phenomenon.

Construction and effectiveness evaluation of a knowledge-based infectious disease monitoring and decision support system.

To improve the hospital's ability to proactively detect infectious diseases, a knowledge-based infectious disease monitoring and decision support system was established based on real medical records and knowledge rules. The effectiveness of the system was evaluated using interrupted time series analysis. In the system, a monitoring and alert rule library for infectious diseases was generated by combining infectious disease diagnosis guidelines with literature and a real medical record knowledge map. The system was integrated with the electronic medical record system, and doctors were provided with various types of real-time warning prompts when writing medical records. The effectiveness of the system's alerts was analyzed from the perspectives of false positive rates, rule accuracy, alert effectiveness, and missed case rates using interrupted time series analysis. Over a period of 12 months, the system analyzed 4,497,091 medical records, triggering a total of 12,027 monitoring alerts. Of these, 98.43% were clinically effective, while 1.56% were invalid alerts, mainly owing to the relatively rough rules generated by the guidelines leading to several false alarms. In addition, the effectiveness of the system's alerts, distribution of diagnosis times, and reporting efficiency of doctors were analyzed. 89.26% of infectious disease cases could be confirmed and reported by doctors within 5 min of receiving the alert, and 77.6% of doctors could complete the filling of 33 items of information within 2 min, which is a reduction in time compared to the past. The timely reminders from the system reduced the rate of missed cases by doctors; the analysis using interrupted time series method showed an average reduction of 4.4037% in the missed-case rate. This study proposed a knowledge-based infectious disease decision support system based on real medical records and knowledge rules, and its effectiveness was verified. The system improved the management of infectious diseases, increased the reliability of decision-making, and reduced the rate of underreporting.

Method and application of information sharing throughout the emergency rescue process based on 5G and AR wearable devices.

The 2022 Winter Olympics were held in the three competition zones of Beijing, Yanqing and Zhangjiakou, China. The venues of this Winter Olympics were scattered and the terrain was complex. Moreover, the medical resources of Hebei and Beijing were relatively unbalanced. In the medical security of major events, the connection between first aid and in-hospital processes is of the utmost importance to rescue quality. 5th generation mobile network (5G) applications in medical scenarios are on the rise. It would be of great relevance to fully use 5G's low-latency and high-speed features to share the process information of patients, ambulance personnel, and the destination hospital's rescue team at emergency scenes and in transportation, improving rescue efficiency. This paper proposes a system scheme of cross-institutional emergency health information sharing based on 5G and augmented reality wearable devices. It also integrates the construction method of monitoring and other sign data sharing, in addition to testing the proposed scheme's service quality in 5G environments. In the deployment area of the 5G emergency medical rescue information sharing scheme for the Beijing Winter Olympic Games, we selected two designated medical support institutions for testing. The test adopted a combination of fixed-point and driving tests to experiment on the service data, voice service, and streaming media indicators. The 5G signal's coverage rate was close to 100%, the standalone connection's success rate was 100%, and the drop rate was 0. The average downlink rate of multiple scenarios was 620mbps, and the average uplink rate of 5G was over 71.8mbps, which is higher than the average 5G level in China. The downlink rate was more than 20 times larger than the 4th generation mobile network (4G) rate. This study's proposed scheme demonstrates the importance of 5G applications in emergency response and support, in addition to providing a suitable scheme for the integration of 5G networks in the medical scene.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Effect of Linggui Zhugan Decoction on myocardial infarction induced heart failure in rats based on Nrf2/BNIP3 pathway and its mechanism / 中国药理学通报

Aim To investigate whether Linggui Zhugan Decoction ( LGZGD) can inhibit ventricular remodeling and prevent heart failure in rats after myocardial infarction by regulating Nrf2/BNIP3 pathway. Methods The model of heart failure after myocardial infarction was established by left coronary artery ligation in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme -linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detected by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunofluorescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3, protecting mitochondrial function, and reducing cardiomyocyte apoptosis.

Intermedin Alleviates Vascular Calcification in CKD through Sirtuin 3-Mediated Inhibition of Mitochondrial Oxidative Stress.

Vascular calcification (VC) is a common pathophysiological process of chronic kidney disease (CKD). Sirtuin 3 (Sirt3), a major NAD+-dependent protein deacetylase predominantly in mitochondria, is involved in the pathogenesis of VC. We previously reported that intermedin (IMD) could protect against VC. In this study, we investigated whether IMD attenuates VC by Sirt3-mediated inhibition of mitochondrial oxidative stress. A rat VC with CKD model was induced by the 5/6 nephrectomy plus vitamin D3. Vascular smooth muscle cell (VSMC) calcification was induced by CaCl2 and ß-glycerophosphate. IMD1-53 treatment attenuated VC in vitro and in vivo, rescued the depressed mitochondrial membrane potential (MMP) level and decreased mitochondrial ROS levels in calcified VSMCs. IMD1-53 treatment recovered the reduced protein level of Sirt3 in calcified rat aortas and VSMCs. Inhibition of VSMC calcification by IMD1-53 disappeared when the cells were Sirt3 absent or pretreated with the Sirt3 inhibitor 3-TYP. Furthermore, 3-TYP pretreatment blocked IMD1-53-mediated restoration of the MMP level and inhibition of mitochondrial oxidative stress in calcified VSMCs. The attenuation of VSMC calcification by IMD1-53 through upregulation of Sirt3 might be achieved through activation of the IMD receptor and post-receptor signaling pathway AMPK, as indicated by pretreatment with an IMD receptor antagonist or AMPK inhibitor blocking the inhibition of VSMC calcification and upregulation of Sirt3 by IMD1-53. AMPK inhibitor treatment reversed the effects of IMD1-53 on restoring the MMP level and inhibiting mitochondrial oxidative stress in calcified VSMCs. In conclusion, IMD attenuates VC by improving mitochondrial function and inhibiting mitochondrial oxidative stress through upregulating Sirt3.

Maximum Likelihood Reconstruction of Water Cherenkov Events With Deep Generative Neural Networks.

Large water Cherenkov detectors have shaped our current knowledge of neutrino physics and nucleon decay, and will continue to do so in the foreseeable future. These highly capable detectors allow for directional and topological, as well as calorimetric information to be extracted from signals on their photosensors. The current state-of-the-art approach to water Cherenkov reconstruction relies on maximum-likelihood estimation, with several simplifying assumptions employed to make the problem tractable. In this paper, we describe neural networks that produce probability density functions for the signals at each photosensor, given a set of inputs that characterizes a particle in the detector. The neural networks we propose allow for likelihood-based approaches to event reconstruction with significantly fewer assumptions compared to traditional methods, and are thus expected to improve on the current performance of water Cherenkov detectors.

Orexin receptor type 2 agonism inhibits thermogenesis in brown adipose tissue by attenuating afferent innervation.

Orexin signaling has been associated with energy expenditure and brown adipose tissue (BAT) function. However, conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis. In this study, we show that a specific orexin receptor type 2 (OX2R) agonist [Ala11, D-Leu15]-OxB (OB-Ala) inhibited intrascapular brown adipose tissue (iBAT) thermogenesis by reducing sympathetic output to iBAT. This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself. Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus. Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop. Our study uncovers a novel primary action site of orexin in the regulation of energy balance.

Intelligent virtual case learning system based on real medical records and natural language processing.

BACKGROUND: Modernizing medical education by using artificial intelligence and other new technologies to improve the clinical thinking ability of medical students is an important research topic in recent years. Prominent medical universities are actively conducting research and exploration in this area. In particular, given the shortage of human resources, the need to maintain social distancing to prevent the spread of the epidemics, and the increase in the cost of medical education, it is critical to harness online learning to promote medical education. A virtual case learning system that uses natural language processing technology to process and present a hospital's real medical records and evaluate student responses can effectively improve medical students' clinical thinking abilities. OBJECTIVE: The purpose of this study is to develop a virtual case system, AIteach, based on actual complete hospital medical records and natural language processing technology, and achieve clinical thinking ability improvement through a contactless, self-service, trial-and-error system application. METHODS: Case extraction is performed on a hospital's case data center and the best-matching cases are produced through natural language processing, word segmentation, synonym conversion, and sorting. A standard clinical questioning data module, virtual case data module, and student learning difficulty module are established to achieve simulation. Students can view the objective examination and inspection data of actual cases, including details of the consultation and physical examination, and automatically provide their learning response via a multi-dimensional evaluation system. In order to assess the changes in students' clinical thinking after using AIteach, 15 medical graduate students were subjected to two simulation tests before and after learning through the virtual case system. The tests, which included the full-process case examination of cases having the same difficulty level, examined core clinical thinking test points such as consultation, physical examination, and disposal, and generated multi-dimensional evaluation indicators (rigor, logic, system, agility, and knowledge expansion). Thus, a complete and credible evaluation system is developed. RESULTS: The AIteach system used an internal and external double-cycle learning model. Students collect case information through online inquiries, physical examinations, and other means, analyze the information for feedback verification, and generate their detailed multi-dimensional clinical thinking after learning. The feedback report can be evaluated and its knowledge gaps analyzed. Such learning based on real cases is in line with traditional methods of disease diagnosis and treatment, and addresses the practical difficulties in reflecting actual disease progression while keeping pace with recent research. Test results regarding short-term learning showed that the average score (P < 0.01) increased from 69.87 to 85.6, the five indicators of clinical thinking evaluation improved, and there was obvious logical improvement, reaching 47%. CONCLUSION: By combining real cases and natural language processing technology, AIteach can provide medical students (including undergraduates and postgraduates) with an online learning tool for clinical thinking training. Virtual case learning helps students to cultivate clinical thinking abilities even in the absence of clinical tutor, such as during pandemics or natural disasters.

SARS-CoV-2 Survival in Common Non-Alcoholic and Alcoholic Beverages.

SARS-CoV-2, the causative agent of COVID-19, is known to be transmitted by respiratory droplets and aerosols. Since the virus is shed at high concentrations in respiratory secretions and saliva, SARS-CoV-2 would also be expected to be transmitted through activities that involve the transfer of saliva from one individual to another, such as kissing or sharing beverages. To assess the survival of infectious SARS-CoV-2 in common beverages, we quantified infectious virus by plaque assays one hour after inoculation into 18 non-alcoholic and 16 alcoholic beverages, plus saliva, and also 7 days later for 5 of these beverages. SARS-CoV-2 remains infectious with minimal reductions in several common beverages, including milk and beer. However, cocoa, coffee, tea, fruit juices, and wine contain antiviral compounds that inactivate SARS-CoV-2. Although hard liquors containing 40% alcohol immediately inactivate SARS-CoV-2, mixing with non-alcoholic beverages reduces the antiviral effects. In summary, SARS-CoV-2 can be recovered from commonly consumed beverages in a beverage type and time-dependent manner. Although aerosol or droplet transmission remains the most likely mode of transmission, our findings combined with others suggest that beverages contaminated with SARS-CoV-2 during handling, serving, or through sharing of drinks should be considered as a potential vehicle for virus transmission.

Intermedin1-53 Inhibits NLRP3 Inflammasome Activation by Targeting IRE1α in Cardiac Fibrosis.

Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to cardiac fibrosis. In this study, we aimed to investigate whether IMD mitigated cardiac fibrosis by inhibiting NLRP3. Cardiac fibrosis was induced by angiotensin II (Ang II) infusion for 2 weeks in rats. Western blot, real-time PCR, histological staining, immunofluorescence assay, RNA sequencing, echocardiography, and hemodynamics were used to detect the role and the mechanism of IMD in cardiac fibrosis. Ang II infusion resulted in rat cardiac fibrosis, shown as over-deposition of myocardial interstitial collagen and cardiac dysfunction. Importantly, NLRP3 activation and endoplasmic reticulum stress (ERS) were found in Ang II-treated rat myocardium. Ang II infusion decreased the expression of IMD and increased the expression of the receptor system of IMD in the fibrotic rat myocardium. IMD treatment attenuated the cardiac fibrosis and improved cardiac function. In addition, IMD inhibited the upregulation of NLRP3 markers and ERS markers induced by Ang II. In vitro, IMD knockdown by small interfering RNA significantly promoted the Ang II-induced cardiac fibroblast and NLRP3 activation. Moreover, silencing of inositol requiring enzyme 1 α (IRE1α) blocked the effects of IMD inhibiting fibroblast and NLRP3 activation. Pre-incubation with PKA pathway inhibitor H89 blocked the effects of IMD on the anti-ERS, anti-NLRP3, and anti-fibrotic response. In conclusion, IMD alleviated cardiac fibrosis by inhibiting NLRP3 inflammasome activation through suppressing IRE1α via the cAMP/PKA pathway.

Deep learning model for multi-classification of infectious diseases from unstructured electronic medical records.

PURPOSE: Predictively diagnosing infectious diseases helps in providing better treatment and enhances the prevention and control of such diseases. This study uses actual data from a hospital. A multiple infectious disease diagnostic model (MIDDM) is designed for conducting multi-classification of infectious diseases so as to assist in clinical infectious-disease decision-making. METHODS: Based on actual hospital medical records of infectious diseases from December 2012 to December 2020, a deep learning model for multi-classification research on infectious diseases is constructed. The data includes 20,620 cases covering seven types of infectious diseases, including outpatients and inpatients, of which training data accounted for 80%, i.e., 16,496 cases, and test data accounted for 20%, i.e., 4124 cases. Through the auto-encoder, data normalization and sparse data densification processing are carried out to improve the model training effect. A residual network and attention mechanism are introduced into the MIDDM model to improve the performance of the model. RESULT: MIDDM achieved improved prediction results in diagnosing seven kinds of infectious diseases. In the case of similar disease diagnosis characteristics and similar interference factors, the prediction accuracy of disease classification with more sample data is significantly higher than the prediction accuracy of disease classification with fewer sample data. For instance, the training data for viral hepatitis, influenza, and hand foot and mouth disease were 2954, 3924, and 3015 respectively and the corresponding test accuracy rates were 99.86%, 98.47%, and 97.31%. There is less training data for syphilis, infectious diarrhea, and measles, i.e., 1208, 575, and 190 respectively and the corresponding test accuracy rates were noticeably lower, i.e., 83.03%, 87.30%, and42.11%. We also compared the MIDDM model with the models used in other studies. Using the same input data, taking viral hepatitis as an example, the accuracy of MIDDM is 99.44%, which is significantly higher than that of XGBoost (96.19%), Decision tree (90.13%), Bayesian method (85.19%), and logistic regression (91.26%). Other diseases were also significantly better predicted by MIDDM than by these three models. CONCLUSION: The application of the MIDDM model to multi-class diagnosis and prediction of infectious diseases can improve the accuracy of infectious-disease diagnosis. However, these results need to be further confirmed via clinical randomized controlled trials.

SARS-CoV-2 Remains Infectious on Refrigerated Deli Food, Meats, and Fresh Produce for up to 21 Days.

SARS-CoV-2, the virus that causes COVID-19, has been detected on foods and food packaging and the virus can infect oral cavity and intestinal cells, suggesting that infection could potentially occur following ingestion of virus-contaminated foods. To determine the relative risk of infection from different types of foods, we assessed survival of SARS-CoV-2 on refrigerated ready-to-eat deli items, fresh produce, and meats (including seafood). Deli items and meats with high protein, fat, and moisture maintained infectivity of SARS-CoV-2 for up to 21 days. However, processed meat, such as salami, and some fresh produce exhibited antiviral effects. SARS-CoV-2 also remained infectious in ground beef cooked rare or medium, but not well-done. Although infectious SARS-CoV-2 was inactivated on the foods over time, viral RNA was not degraded in similar trends, regardless of food type; thus, PCR-based assays for detection of pathogens on foods only indicate the presence of viral RNA, but do not correlate with presence or quantity of infectious virus. The survival and high recovery of SARS-CoV-2 on certain foods support the possibility that food contaminated with SARS-CoV-2 could potentially be a source of infection, highlighting the importance of proper food handling and cooking to inactivate any contaminating virus prior to consumption.

Occurrence of Intracranial Hemorrhage and Associated Risk Factors in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy:A Systematic Review and Meta-Analysis

Background@#and Purpose Intracranial hemorrhage (ICH) is thought to be a rare but probably underestimated presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We conducted a systematic review and meta-analysis with the aim of comprehensively revealing the occurrence of ICH in patients with CADASIL. @*Methods@#English-language studies published up to September 30, 2021 were searched for in the MEDLINE (PubMed), Web of Science, and Cochrane Library databases. The design, patient characteristics, occurrence rate of ICH, and associated risk factors were retrieved for each identified relevant study. @*Results@#We enrolled 13 studies in the final meta-analysis, which included 1,310 patients with CADASIL. The probability of ICH occurrence in patients with CADASIL was 10.1% (95% confidence interval [CI]=5.6%–18.0%, I2 =85.1%). When stratified by geographic region, the occurrence rate of ICH was much higher in Asians (17.7%; 95% CI=11.0%–28.5%, I2 =76.3%) than in Europeans (2.0%; 95% CI=0.4%–10.8%, I2 =82.8%). A higher burden of cerebral microbleeds (CMBs) and a history of hypertension were the most commonly recorded risk factors for ICH, which were available for three and two of the included studies, respectively. @*Conclusions@#Our study suggests that ICH is an important clinical manifestation of CADASIL, especially in Asians. A higher burden of CMBs and the existence of hypertension were found to be associated with a higher probability of ICH occurrence in patients with CADASIL.

Quality value transfer of substance benchmarks in Sanpian Decoction / 中国中药杂志

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

Analysis of Bacterial Biofilm Formation in Patients with Malignancy Undergoing Double J Stent Indwelling and Its Influencing Factors.

OBJECTIVE: To analyze the bacterial biofilm (BF) formation in patients with malignancy undergoing double J stent indwelling and its influencing factors. METHODS: A total of 167 patients with malignant tumors who received double J stent indwelling in the hospital from January 2018 to January 2021 were included in the study. The urine and double J stent samples were collected for bacterial identification and observed for BF formation on the surface of the urinary catheter under a scanning electron microscope (SEM). Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of BF. RESULTS: The BF formation rate was 34.73% (58/167). The BF formation rate of positive specimens cultured in urine and double J stent was significantly higher than that of negative ones (P<0.05). Staphylococcus was the main BF bacteria in double J stent and urine culture specimens, followed by Enterococcus, Pseudomonas, Enterobacter, and Acinetobacter. Compared with the non-BF group, the number of viable bacteria in the double J stent and urine and the catheterization time in the BF group rose markedly (P<0.05). Advanced age, chemotherapy, anemia, indwelling time ≥90d, and urinary tract infection were risk factors for BF formation in patients with malignancy undergoing double J stent indwelling (P<0.05). CONCLUSION: There is a high rate of BF formation in patients with malignancy undergoing double J stent indwelling, with Staphylococcus as the dominant species. Treatment requires enhanced urinary catheter management and nutritional status to inhibit BF formation and lower the rate of urinary catheter-related infections.

Survival of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Herpes Simplex Virus 1 (HSV-1) on Foods Stored at Refrigerated Temperature.

Outbreaks of coronavirus infectious disease 2019 (COVID-19) in meat processing plants and media reports of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection on foods have raised concerns of a public health risk from contaminated foods. We used herpes simplex virus 1, a non-Biosafety Level 3 (non-BSL3) enveloped virus, as a surrogate to develop and validate methods before assessing the survival of infectious SARS-CoV-2 on foods. Several food types, including chicken, seafood, and produce, were held at 4 °C and assessed for infectious virus survival (herpes simplex virus 1 (HSV-1) and SARS-CoV-2) at 0 h, 1 h, and 24 h post-inoculation (hpi) by plaque assay. At all three time points, recovery of SARS-CoV-2 was similar from chicken, salmon, shrimp, and spinach, ranging from 3.4 to 4.3 log PFU/mL. However, initial (0 h) virus recovery from apples and mushrooms was significantly lower than that from poultry and seafood, and infectious virus decreased over time, with recovery from mushrooms becoming undetectable by 24 hpi. Comparing infectious virus titers with viral genome copies confirmed that PCR-based tests only indicate presence of viral nucleic acid, which does not necessarily correlate with the quantity of infectious virus. The survival and high recovery of SARS-CoV-2 on certain foods highlight the importance of safe food handling practices in mitigating any public health concerns related to potentially contaminated foods.

Intestinal expression of ACE2 in mice with high-fat diet-induced obesity and neonates exposed to maternal high-fat diet.

OBJECTIVE: The 2019 novel coronavirus disease (COVID-19) is threatening global health and is especially pronounced in patients with chronic metabolic syndromes. Meanwhile, a significant proportion of patients present with digestive symptoms since angiotensin-converting enzyme 2 (ACE2), which is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the intestine. The aim of this study was to evaluate the effects of a high-fat diet (HFD) and a maternal HFD on the intestinal ACE2 levels in adults and neonates. METHODS: We examined intestinal ACE2 protein levels in mice with diet-induced obesity (DIO) and neonatal mice exposed to a maternal HFD. We also investigated Ace2 mRNA expression in intestinal macrophages. RESULTS: Intestinal ACE2 protein levels were increased in DIO mice but decreased in offspring exposed to a maternal HFD compared with chow-fed controls. Ace2 mRNA expression in intestinal macrophages was detected and downregulated in DIO mice. Additionally, higher intestinal ACE2 protein levels were observed in neonates than in adult mice. CONCLUSIONS: The influence of an HFD on intestinal ACE2 protein levels is opposite in adults and neonates. Macrophages might also be involved in SARS-CoV-2 intestinal infection. These findings provide some clues for the outcomes of patients with COVID-19 with metabolic syndromes.