Dynamin-related protein 1 is a critical regulator of mitochondrial calcium homeostasis during myocardial ischemia/reperfusion injury.

Dynamin-related protein 1 (Drp1) is a cytosolic GTPase protein that when activated translocates to the mitochondria, meditating mitochondrial fission and increasing reactive oxygen species (ROS) in cardiomyocytes. Drp1 has shown promise as a therapeutic target for reducing cardiac ischemia/reperfusion (IR) injury; however, the lack of specificity of some small molecule Drp1 inhibitors and the reliance on the use of Drp1 haploinsufficient hearts from older mice have left the role of Drp1 in IR in question. Here, we address these concerns using two approaches, using: (a) short-term (3 weeks), conditional, cardiomyocyte-specific, Drp1 knockout (KO) and (b) a novel, highly specific Drp1 GTPase inhibitor, Drpitor1a. Short-term Drp1 KO mice exhibited preserved exercise capacity and cardiac contractility, and their isolated cardiac mitochondria demonstrated increased mitochondrial complex 1 activity, respiratory coupling, and calcium retention capacity compared to controls. When exposed to IR injury in a Langendorff perfusion system, Drp1 KO hearts had preserved contractility, decreased reactive oxygen species (ROS), enhanced mitochondrial calcium capacity, and increased resistance to mitochondrial permeability transition pore (MPTP) opening. Pharmacological inhibition of Drp1 with Drpitor1a following ischemia, but before reperfusion, was as protective as Drp1 KO for cardiac function and mitochondrial calcium homeostasis. In contrast to the benefits of short-term Drp1 inhibition, prolonged Drp1 ablation (6 weeks) resulted in cardiomyopathy. Drp1 KO hearts were also associated with decreased ryanodine receptor 2 (RyR2) protein expression and pharmacological inhibition of the RyR2 receptor decreased ROS in post-IR hearts suggesting that changes in RyR2 may have a role in Drp1 KO mediated cardioprotection. We conclude that Drp1-mediated increases in myocardial ROS production and impairment of mitochondrial calcium handling are key mechanisms of IR injury. Short-term inhibition of Drp1 is a promising strategy to limit early myocardial IR injury which is relevant for the therapy of acute myocardial infarction, cardiac arrest, and heart transplantation.

Integrated analysis of potential biomarkers associated with diabetic periodontitis development based on bioinformatics: An observational study.

Based on the importance of chronic inflammation in the pathogenesis of periodontitis and diabetes, the bidirectional relationship between these 2 diseases has been widely confirmed. However, the molecular mechanisms of bidirectional relationship still need to be studied further. In this study, gene expression profile data for diabetes and periodontitis were obtained from Gene Expression Omnibus (GEO) database. Integrative analytical platform were constructed, including common differentially expressed genes (cDEGs), Gene Ontology-Kyoto Encyclopedia of Genes and Genomes (GO-KEGG), and protein-protein interaction. Hub genes and essential modules were detected via Cytoscape. Key hub genes and signaling pathway that mediate chronic inflammation were validated by qPCR and Western blot. Eleven cDEGs were identified. Function analysis showed that cDEGs plays an important role in inflammatory response, cytokine receptor binding, TNF signaling pathway. As hub genes, CXCR4, IL1B, IL6, CXCL2, and MMP9 were detected based on the protein-protein interactions network. IL1B, CXCR4 mRNA were up-regulated in gingivitis samples compared with normal tissues (P < .05). Western blot indicated that the levels of TNF were enhanced in gingivitis of type 2 diabetes compared with normal tissues (P < .01). Hub gene and TNF signaling pathway are helpful to elucidate the molecular mechanism of the bidirectional relationship between periodontitis and diabetes.

Blood-spinal cord barrier disruption in degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is the most prevalent cause of spinal cord dysfunction in the aging population. Significant neurological deficits may result from a delayed diagnosis as well as inadequate neurological recovery following surgical decompression. Here, we review the pathophysiology of DCM with an emphasis on how blood-spinal cord barrier (BSCB) disruption is a critical yet neglected pathological feature affecting prognosis. In patients suffering from DCM, compromise of the BSCB is evidenced by elevated cerebrospinal fluid (CSF) to serum protein ratios and abnormal contrast-enhancement upon magnetic resonance imaging (MRI). In animal model correlates, there is histological evidence of increased extravasation of tissue dyes and serum contents, and pathological changes to the neurovascular unit. BSCB dysfunction is the likely culprit for ischemia-reperfusion injury following surgical decompression, which can result in devastating neurological sequelae. As there are currently no therapeutic approaches specifically targeting BSCB reconstitution, we conclude the review by discussing potential interventions harnessed for this purpose.

Development of a New Sex Attractant via the Peripheral Coding of Pheromones in Mythimna loreyi.

Sex pheromones play an essential role when moths are searching for mates. Male olfactory receptor neurons (ORNs) are the primary determinant during peripheral pheromone recognition. Here, we identified the sex pheromones of a global agricultural pest, Mythimna loreyi, using gas chromatography coupled with mass spectrometry and electroantennographic detection. Nine pheromone components were identified, including (Z)-9-tetradecen-1-yl acetate (Z9-14:OAc), (Z)-7-dodecen-1-yl acetate (Z7-12:OAc), and (Z)-11-hexadecen-1-yl acetate (Z11-16:OAc), and the first two elicited electrophysiological activities in the male antennae. Trichoid sensilla were classified into four functional types on the basis of neuronal responses to pheromones by single sensillum recording. Five functional ORNs were involved in recognizing pheromones and pheromone analogues. Finally, a field bioassay revealed that a blend of Z9-14:OAc, Z7-12:OAc, and Z11-16:OAc at a ratio of 100:8.8:19.7 was highly efficient for trapping males. Our results uncover the pheromone recognition mechanism in M. loreyi and provide a novel angle for developing efficient sex attractants of pests on the basis of screening the peripheral olfactory neurons.

Ionizable drug delivery systems for efficient and selective gene therapy.

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.

Comparative study of medical common data models for FAIR data sharing / 中华流行病学杂志

The common data model (CDM) is an important tool to facilitate the standardized integration of multi-source heterogeneous healthcare big data, enhance the consistency of data semantic understanding, and promote multi-party collaborative analysis. The data collections standardized by CDM can provide powerful support for observational studies, such as large-scale population cohort study. This paper provides an in-depth comparative analysis of the data storage structure, term mapping pattern, and auxiliary tools development of the three international typical CDMs, then analyzes the advantages and limitations of each CDM and summarizes the challenges and opportunities faced in the CDM application in China. It is expected that exploring the advanced technical concepts and practical patterns of foreign countries in data management and sharing will provide references for promoting FAIR (findable, accessible, interoperable, reusable) construction of healthcare big data in China and solving the current practical problems, such as the poor quality of data resources, the low degree of semantization, and the inabilities of data sharing and reuse.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis / 亚洲男科学杂志(英文版)

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

Development and present situation of occupational health grading and classification supervision methods of employers in China / 环境与职业医学

In the face of a serious occupational disease prevention and control situation, the lack of efficient supervision and regulation methods has become a prominent contradiction. This paper reviewed the progress and application of occupational health grading and classification supervision methods for employers in China in recent years, and analyzed the characteristics and limitations of selected methods. The grading and classification supervision methods have gradually developed from considering only inherent health risk of occupational disease hazards, to considering both inherent attributes of occupational disease hazards and exposure duration. Some regional authorities introduced trial measures for grading and classification of occupational health supervision by embracing exposure level of an occupational disease hazard of interest, associated outcome severity, and occupational health management situation of targeted employers. In October 2022, the National Disease Control and Prevention Bureau issued the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which further promoted the establishment of a differentiated occupational health supervision model. Grading and classification of occupational health supervision can improve the supervision efficiency of public health administration departments and promote employers to fulfill the main responsibility of occupational disease prevention and control.

Determination of the ELISA kits for screening convalescence plasma with high potency of SARS-CoV-2 IgG / 中国输血杂志

【Objective】 To determine the ELISA kit for screening convalescence plasma with high potency of SARS-CoV-2 IgG by comparing and analyzing the plasma detection results of convalescent plasma collected in different periods via ELISA kits from two manufacturers and the results of mixed plasma with different potency via pseudovirus neutralization experiments. 【Methods】 Two ELISA kits from different manufacturers(named A, B) were used to detect the plasma of 269 convalescent patients collected from Feb.2020~Jan.2022. The correlation and concordance rate of the two results were analyzed to determine the kit preliminarily. According to the titers of diluted series of standard of the preliminary selected kit, 5 mixed plasma samples (G4-G128) with different potency were prepared. The correlation of ELISA IgG results of product A/B, as well as the pseudovirus neutralization test of the original strain, Omicron mutant BA.1 and BA.2 strains were analyzed. Combined with the outside-well dilution mode of the strongly positive samples, the kit for high potency of SARS-CoV-2 IgG screening was determined. 【Results】 When the internal control reference B2 was used as the standard, the detection sensitivity of product A and B was 1∶32 vs 1∶8; the detection sensitivity of product A was 4 times that of product B. The correlation Pearson r between the results given by two kits was 0.944 1(P<0.000 1). Product B with low sensitivity was primarily selected as an alternative kit. The ELISA IgG results of samples from mixed plasma showed that the order of correlation r between product A and B was 0.988. The correlation r between product A and neutralization antibody potency of the three viruses was original strain (0.978)>BA.2(0.970)>BA.1(0.799); the order of correlation r between ELISA IgG results of product B and neutralization antibody potency of the three viruses was original strain(0.994)>BA.2(0.968)>BA.1(0.804). If twice-diluted B2 was taken as the excellent standard, 55.4% of product B met the criterion, while 47.2% of product A met.For positive plasma with high IgG potency, the product B kit required a lower dilution of the sample, which was more convenient to operate. 【Conclusion】 Both of the ELISA IgG kit from product A and B can be used to screen IgG antibodies of SARS-CoV-2, while product B is more suitable for screening positive plasma with high IgG potency.

Changes and distribution of antibodies in plasma before and after infection of SARS-CoV-2 Omicron strain / 中国输血杂志

【Objective】 To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test. 【Methods】 An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified. SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection, two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results, and pseudovirus neutralization experiments with different virus strain (prototype strain, BA. 1,BA.2, BA.4/5, BF.7, BQ.1.1) were carried out to determine the distribution of neutralizing antibodies against different virus strain. SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected, including Omicron convalescent plasma (OP) collected from different plasma stations from December 2022 to May 2023 and normal pool plasma (VN) feed in March 2023 which collected from March 2022 to December 2022. According to the results, the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed. 【Results】 The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL, the accuracy in-batch ranged from 81.793% to 106.985%, the precision in-batch ranged from 1. 100% to 13.000%, and the total error in-batch ranged from 2.988% to 22.679%. The accuracy between batches ranged from 90.788%to 96.893%, the precision between batches ranged from 4.870% to 6.272%, and the total error between batches ranged from 9.192% to 15.399%. The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype strain>BA.2>BA.4/5>BF.7≈ BQ.1.1>BA.1 and the correlation between WP1 and WP2 was high (Pearson r=0. 931 1, P=0.002 3) which indicated that the potency distribution of neutralizing antibodies of different virus strain in Omicron convalescent plasma was basically stable. Compared with the mixed convalescent plasma sample G128 collected in June 2022, the potency of Omicron neutralizing antibodies of WP series were significantly higher, the ratio of BA.2 antibody to prototype antibody increased from 26.9% (before infection) to 82.6%-87.5% (after infection). The results of VN series before Omicron infection were < 100 EIU/mL, and the results of OP series after Omicron infection showed that the plasma collected from the beginning of December 2022 was the peak of antibody in the same month,and then dropped sharply, entering a short plateau in February-March 2023 (potency was about 40% of the peak value),and then dropped sharply again in April (potency was about 20% of the peak value). 【Conclusion】 The potency and proportion of neutralizing antibody against Omicron subtype in convalescent plasma after COVID-19 Omicron strain infection increased significantly. IgG antibody of plasma donors in different regions reached its peak in the month of infection, then continued to dropped sharply. The best collection period of plasma that can be used for human COVID-19 immunoglobulin for intravenous injection was 1 to 2 months after infection.

Expert consensus on platelet-rich plasma treatment for osteochondral lesion of talus (version 2023) / 中华创伤杂志

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Novel management indications for conservative treatment of chylous ascites after gastric cancer surgery.

BACKGROUND: Chylous ascites (CA) presents a challenge as a relatively common postoperative complication in gastric cancer (GC). Primary conservative therapy involved total parenteral nutrition, continuous low-pressure drainage, somatostatin, and a low-fat diet. Drainage tube (DT) clamping has been presented as a potential alternative conservative treatment for GC patients with CA. AIM: To propose novel conservative treatment strategies for CA following GC surgery. METHODS: The data of patients with CA after GC surgery performed at the Fudan University Shanghai Cancer Center between 2006 and 2021 were evaluated retrospectively. RESULTS: 53 patients underwent surgery for GC and exhibited postoperative CA during the study period. Postoperative hospitalization and time of DT removal showed a significant positive association (R 2 = 0.979, P < 0.001). We further observed that delayed DT removal significantly extended the total and postoperative hospitalization, antibiotic usage duration, and hospitalization cost (postoperative hospitalization: 25.8 d vs 15.5 d, P < 0.001; total hospitalization: 33.2 d vs 24.7 d, P < 0.01; antibiotic usage duration: 10.8 d vs 6.2 d, P < 0.01; hospitalization cost: ¥9.2 × 104 vs ¥6.5 × 104, P < 0.01). Multivariate analysis demonstrated that postoperative infection and antibiotic usage were independent factors for delayed DT removal. Furthermore, DT removal times were shorter in seven patients who underwent DT clamping (clamped DT vs normal group, 11.8 d vs 13.6 d, P = 0.047; clamped DT vs delayed group, 13.6 d vs 27.4 d, P < 0.001). In addition, our results indicated that removal of the DT may be possible after three consecutive days of drainage volumes less than 300 mL in GC patients with CA. CONCLUSION: Infection and antibiotic usage were vital independent factors that influenced delayed DT removal in patients with CA. Appropriate standards for DT removal can significantly reduce the duration of hospitalization. Furthermore, DT clamping might be a recommended option for conservative treatment of postoperative CA.

Lyophilized mRNA-lipid nanoparticles vaccine with long-term stability and high antigenicity against SARS-CoV-2

Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, due to their poor stability, most current mRNA delivery platforms need to be stored at -20{degrees}C or -70{degrees}C, which severely limits their distribution. Herein, we present lyophilized SARS-CoV-2 mRNA-lipid nanoparticle vaccines, which can be stored at room temperature with long-term thermostability. In the in vivo Delta virus challenge experiment, lyophilized Delta variant mRNA vaccine successfully protected mice from infection and cleared the virus. Lyophilized omicron mRNA vaccine enabled to elicit both potent humoral and cellular immunity. In booster immunization experiments in mice and old monkeys, lyophilized omicron mRNA vaccine could effectively increase the titers of neutralizing antibodies against wild-type coronavirus and omicron variants. In humans, lyophilized omicron mRNA vaccine as a booster shot could also engender excellent immunity and had less severe adverse events. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity, and significantly improved their accessibility, particularly in remote regions.

Microglial Activation and Neurological Outcomes in a Murine Model of Cardiac Arrest.

BACKGROUND: Neurological injury following successful resuscitation from sudden cardiac arrest (CA) is common. The pathophysiological basis of this injury remains poorly understood, and treatment options are limited. Microglial activation and neuroinflammation are established contributors to many neuropathologies, such as Alzheimer disease and traumatic brain injury, but their potential role in post-CA injury has only recently been recognized. Here, we hypothesize that microglial activation that occurs following brief asystolic CA is associated with neurological injury and represents a potential therapeutic target. METHODS: Adult C57BL/6 male and female mice were randomly assigned to 12-min, KCl-induced asystolic CA, under anesthesia and ventilation, followed by successful cardiopulmonary resuscitation (n = 19) or sham intervention (n = 11). Neurological assessments of mice were performed using standardized neurological scoring, video motion tracking, and sensory/motor testing. Mice were killed at 72 h for histological studies; neuronal degeneration was assessed using Fluoro-Jade C staining. Microglial characteristics were assessed by immunohistochemistry using the marker of ionized calcium binding adaptor molecule 1, followed by ImageJ analyses for cell integrity density and skeletal analyses. RESULTS: Neurological injury in post-cardiopulmonary-resuscitation mice vs. sham mice was evident by poorer neurological scores (difference of 3.626 ± 0.4921, 95% confidence interval 2.618-4.634), sensory and motor functions (worsened by sixfold and sevenfold, respectively, compared with baseline), and locomotion (75% slower with a 76% decrease in total distance traveled). Post-CA brains demonstrated evidence of neurodegeneration and neuroinflammatory microglial activation. CONCLUSIONS: Extensive microglial activation and neurodegeneration in the CA1 region and the dentate gyrus of the hippocampus are evident following brief asystolic CA and are associated with severe neurological injury.

High-flow nasal cannula therapy: A multicentred survey of the practices among physicians and respiratory therapists in Singapore.

BACKGROUND: Use of high-flow nasal cannula (HFNC) has become a regular intervention in the intensive care units especially in patients coming in with hypoxaemic respiratory failure. Clinical practices may differ from published literature. OBJECTIVES: The objective of this study was to determine the clinical practices of physicians and respiratory therapists (RTs) on the use of HFNC. METHODS: A retrospective observational study looking at medical records on HFNC usage from January 2015 to September 2017 was performed and was followed by a series of questions related to HFNC practices. The survey involved physicians and RTs in intensive care units from multiple centres in Singapore from January to April 2018. Indications and thresholds for HFNC usage with titration and weaning practices were compared with the retrospective observational study data. RESULTS: One hundred twenty-three recipients (69.9%) responded to the survey and reported postextubation (87.8%), pneumonia in nonimmunocompromised (65.9%), and pneumonia in immunocompromised (61.8%) patients as the top three indications for HFNC. Of all, 39.8% of respondents wanted to use HFNC for palliative intent. Similar practices were observed in the retrospective study with the large cohort of 63% patients (483 of the total 768 patients) where HFNC was used for acute hypoxaemic respiratory failure and 274 (35.7%) patients to facilitate extubation. The survey suggested that respondents would initiate HFNC at a lower fraction of inspired oxygen (FiO2), higher partial pressure of oxygen to FiO2 ratio, and higher oxygen saturation to FiO2 ratio for nonpneumonia patients than patients with pneumonia. RTs were less likely to start HFNC for patients suffering from pneumonia and interstitial lung disease than physicians. RTs also preferred adjustment of FiO2 to improve oxygen saturations and noninvasive ventilation for rescue. CONCLUSIONS: Among the different intensive care units surveyed, the indications and thresholds for the initiation of HFNC differed in the clinical practices of physicians and RTs.

Effects of oxidative stress, PSMB5, TFEB, and lysosomes on sodium arsenite-induced liver injury in rats / 环境与职业医学

Background Liver damage presented in endemic arsenic poisoning is usually serious. Studies have shown that oxidative stress, proteasome beta 5 subunit (PSMB5), regulatory transcription factor EB (TFEB), and lysosomes are associated with liver injury, but their specific links to arsenic-induced liver injury remain unclear. Objective Using a sodium arsenite (NaAsO2)-induced rat liver injury model established earlier by the research group, the expressions of PSMB5, TFEB, and lysosomal associated membrane protein 1 (LAMP1) in liver tissues were detected. Methods Twenty-four SPF Wistar rats were randomly divided into control group, and low, medium, and high dose groups, with 6 rats in each group, half male and half female. The exposure concentrations were 0, 25, 50, and 100 mg·L−1 NaAsO2 solutions for 24 weeks. At the end of the experiment, liver was dissected after rats were anesthetized. The levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bile acid (TBA), and catalase (CAT) in liver tissues were detected by chemical colorimetry, and the levels of lipid peroxide (LPO), 4-hydroxynonenal (4-HNE), LAMP1, and cathepsin D (CTSD) in liver tissues were detected by enzyme-linked immunosorbent assay (ELISA); the transcriptional expression levels of PSMB5 and TFEB in liver tissues were detected by real-time fluorescence quantitative PCR (RT-qPCR), and the protein expressions of PSMB5, TFEB, and phosphorylated TFEB (p-TFEB) in liver tissues were detected by immunohistochemistry. Results The results of chemical colorimetry and ELISA showed that compared with the control group, the liver homogenate levels of ALP, TBA, and LAMP1 of each arsenic-exposed group, the ALT and LPO in the medium and high concentration groups, the 4-HNE and CTSD in the high concentration group were increased, while the CAT activity of each arsenic-exposed group was decreased (P<0.05). The results of real-time fluorescence quantitative PCR showed that the transcription levels of PSMB5 and TFEB in the liver tissues of each arsenic-exposed group were decreased compared with those of the control group (P<0.05). The results of immunohistochemistry showed that compared with the control group, the expression of PSMB5 of each arsenic-exposed group were decreased, the expression of TFEB in the medium and high concentration groups was decreased, while the expression of p-TFEB of each arsenic-exposed group was increased (P<0.05). The expression of TFEB protein gradually decreased in the nucleus, while the expression of p-TFEB protein gradually increased in the cytoplasm, but no expression of p-TFEB was found in the nucleus. The results of Pearson correlation analysis showed that PSMB5 in liver tissues was positively correlated with CAT (r=0.818, P＜0.05), and negatively correlated with 4-HNE and p-TFEB (r=−0.582, r=−0.899; P＜0.05); TFEB was negatively correlated with CTSD and LAMP1 (r=−0.457, r=−0.564; P＜0.05); CTSD was positively correlated with ALT and ALP (r=0.529, r=0.485; P＜0.05). Conclusion Long-term exposure to NaAsO2 can induce oxidative stress, inhibit the expression of PSMB5 and TFEB, promote the accumulation of p-TFEB in the cytoplasm, decrease the nuclear entry of active TFEB, damage the lysosome, and cause liver damage.

Measuring method of occupational non-Gaussian noise exposure based on kurtosis adjustment / 环境与职业医学

The existing measuring methods of noise exposure on the basis of equal energy hypothesis are applicable to Gaussian noise while not fully applicable to non-Gaussian noise. Studies have shown that temporal structure (kurtosis) combined with noise energy has the potential to quantify non-Gaussian noise exposure effectively. However, there is no unified measuring method adopting this joint metric. In this paper, the measuring method of non-Gaussian noise exposure based on kurtosis adjustment was introduced, detailing measurement indicators, adjustment schemes, applicable objects, instrument requirements, and measurement steps. Adjusting the exposure duration of cumulative noise exposure (CNE) by kurtosis or adjusting the equivalent continuous A-weighted sound pressure level (LAeq) by an adjustment coefficient based on animal or population studies can more accurately quantify workers' exposure to non-Gaussian noise and improve the underestimation of hearing loss caused by non-Gaussian noise. A large number of population studies are warranted in the future to verify the effectiveness of these two adjustment schemes.

Dendrobium nobile protects against ovalbumin-induced allergic rhinitis by regulating intestinal flora and suppressing lung inflammation / 中国天然药物

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.

The Gut Microbiota and Traditional Chinese Medicine: A New Clinical Frontier on Cancer.

Gut microbiota is a complex microecosystem, which is called the second genome of the human body. Herbal medicine can balance tumor-suppressing bacteria and tumor-promoting bacteria and exert its anti-cancer effect by regulating gut microbiota. Traditional Chinese medicine (TCM) has a history of thousands of years in prevention and treatment of diseases in China. In recent decades, TCM has been shown to have an obvious advantage in prolonging the survival time and improving the living quality of patients with cancer. Notably, gut microbiota has become a new pathway to understanding TCM. In this review, we will focus on gut microbiota and tumor progression, especially the diversity, functionality and metabolites of gut microbiota affected by TCM in various cancer. We will also discuss the potential mechanism of gut microbiota for exploring TCM in anti-cancer effect. This article aims to comprehensively review the anti-cancer research of TCM by regulating gut microbiota, and address future perspectives and challenges of gut microbiota in TCM intervention for cancer.

Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.