A biomimetic ion channel shortens the QT interval of type 2 long QT syndrome through efficient transmembrane transport of potassium ions.

Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K+ (BICK) with the highest transport activity among them. The selected BICK can restore potassium ion transport and increase transmembrane potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BICK does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic ion channels, such as BICK, will show great potential in treating diseases related to ion transport blockade. STATEMENT OF SIGNIFICANCE: Type 2 long QT syndrome (LQT2) is a disease caused by K+ transport disorder, which can cause malignant arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K+ transmembrane transport. In this study, we report that a small-molecule biomimetic ion channel BICK can efficiently simulate natural K+ channel proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K+ transport function for the first time. This study found that the potassium transmembrane transport by BICK significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease.

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3 years (1.8-6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.

Tensile Strain-Mediated Bimetallene Nanozyme for Enhanced Photothermal Tumor Catalytic Therapy.

Nanozymes have demonstrated significant potential in combating malignant tumor proliferation through catalytic therapy. However, the therapeutic effect is often limited by insufficient catalytic performance. In this study, we propose the utilization of strain engineering in metallenes to fully expose the active regions due to their ultrathin nature. Here, we present the first report on a novel tensile strain-mediated local amorphous RhRu (la-RhRu) bimetallene with exceptional intrinsic photothermal effect and photo-enhanced multiple enzyme-like activities. Through geometric phase analysis, electron diffraction profile, and X-ray diffraction, it is revealed that crystalline-amorphous heterophase boundaries can generate approximately 2 % tensile strain in the bimetallene. The ultrathin structure and in-plane strain of the bimetallene induce an amplified strain effect. Both experimental and theoretical evidence support the notion that tensile strain promotes multiple enzyme-like activities. Functioning as a tumor microenvironment (TME)-responsive nanozyme, la-RhRu exhibits remarkable therapeutic efficacy both in vitro and in vivo. This work highlights the tremendous potential of atomic-scale tensile strain engineering strategy in enhancing tumor catalytic therapy.

NMAAP1 regulated macrophage polarizion into M1 type through glycolysis stimulated with BCG.

Bacillus Calmette Guerin (BCG) perfusion is widely used as cancer adjuvant therapy, in which macrophages play an important role. Novel macrophage activated associated protein 1 (NMAAP1), upregulated after BCG's activation, was proved to promote macrophage polarization to the M1 type. We found that BCG could stimulate mice BMDM to the M1 type and kill tumor cells. After the deletion of NMAAP1, the tumor volume of mice became larger, and the number of M1 type macrophages in the tumor decreased significantly. When macrophages were induced into the M1 type, aerobic glycolysis, the Warburg effect manifested in the increased uptake of glucose and the conversion of pyruvate to lactic acid. NMAAP1 could bind with IP3R and regulate macrophage polarization to the M1 type. However, the specific mechanism of how NMAAP1 regulates macrophage polarization towards the M1 type and plays an antitumor role must be clarified. NMAAP1 could promote the release of lactic acid and pyruvate, enhance the glycolysis of macrophages, and affect the expression of HIF-1α. After inhibition of glycolysis by 2-DG and lactic acid generation by FX11, the effects of NMAAP1 promoting macrophage polarization to the antitumor M1 type were weakened. Furthermore, NMAAP1 upregulated the expression of HIF-1α, which is associated with glycolysis. Moreover, the Ca2+/NF-κB pathway regulated HIF-1α expression by NMAAP1 in the macrophages. NMAAP1 promotes the polarization of macrophages towards the M1 type by affecting the Warburg effect stimulated by BCG.

PEN-coated superparamagnetic iron-mediated delivery of siSnail2 to inhibit metastasis and promote ferroptosis in the treatment of cancer.

Cancer represents a significant global public health challenge, and conventional cancer therapies such as surgery and chemoradiotherapy are not enough due to the increased complexity of cancer. Nanotechnology has the potential to revolutionize tumor treatments by integrating gene therapy, tumor targeting, and drug delivery. In this study, we demonstrated that Snail2 plays a crucial role in the migration and invasion of lung and liver carcinoma. We proposed a novel approach to synergize the aminated crosslinking dextran coat of superparamagnetic iron oxide nano worms (CLIO-NH2, CN) with small interfering Snail2 RNA (siSnail2). The efficiency of siSnail2 delivery was significantly improved by coating CN with N-Isopropylacrylamide-modified polyethylenimine (CNP). In vitro, experiments revealed that CNP@siSnail2 effectively inhibited cancer cell EMT, migration, and invasion. Moreover, CNP@ siSnail2 promoted cancer cell death through various mechanisms, including apoptosis and ferroptosis. The combination of CNP@ siSnail2 and cisplatin significantly improved the anti-tumor effect of the treatment. Animal models demonstrated that the combined treatment of CNP@ siSnail2 and cisplatin resulted in excellent tumor inhibition effects. Our findings provide a potential combined treatment strategy for cancer therapy.

Clinical and Epidemiological Characteristics of Rhabdomyolysis: A Retrospective Study.

Background: Rhabdomyolysis (RM) refers to a clinical syndrome in which muscle cells are damaged by various causes and the clinical manifestations are mainly muscle pain, weakness, and dark urine. Acute kidney injury (AKI) is a serious complication of RM with complex mechanisms and high mortality. Therefore, understanding the pathogenesis and clinical manifestations, early diagnosis and treatment of RM are crucial to improve its prognosis. Method: Analysis of medical records of RM patients admitted to Tianjin Medical University General Hospital from October 2019 to October 2022. Statistical software SPSS 25.0 was used to analyze the data. The risk factors of RM-complicated AKI were analyzed by logistic regression. The receiver operating characteristic (ROC) curve was plotted, the area under the curve (AUC) was calculated, and the optimal cutoff value was determined by the Youden index. P < 0.05 indicates a statistically significant difference between the groups. Result: Among the 71 patients, the median age of the patients was 53.0 (30.0, 71.0) years and was 2.5 times higher in men than in women. Infection was the most common etiology. History of alcohol consumption, CK, and creatinine were independent influencing factors for AKI due to RM. Logistic regression analysis showed that CK combined with creatinine had a better predictive value than the single index. Conclusion: Our study revealed the clinical and laboratory characteristics of RM in the population attending the Tianjin Medical University General Hospital in the last three years, which is a reference for future multicenter, prospective studies.

Neutralization against Omicron subvariants after BA.5/BF.7 breakthrough infection weakened as virus evolution and aging despite repeated prototype-based vaccination1.

BACKGROUND: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it's urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sub-lineages among existing vaccination strategies and the elders. METHOD: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. RESULTS: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5 while booster dose against the prototype prior-breakthrough would not further significantly enhance individual's humoral responses against the latest Omicron subvariants. CONCLUSIONS: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.

Tolyporphins-Exotic Tetrapyrrole Pigments in a Cyanobacterium-A Review.

Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium-microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known-each is a free base tetrapyrrole macrocycle with a dioxobacteriochlorin (14), oxochlorin (3), or porphyrin (1) chromophore. Each compound displays two, three, or four open ß-pyrrole positions and two, one, or zero appended C-glycoside (or -OH or -OAc) groups, respectively; the appended groups form part of a geminal disubstitution motif flanking the oxo moiety in the pyrroline ring. The distinct structures and repertoire of tolyporphins stand alone in the large pigments-of-life family. Efforts to understand the cyanobacterial origin, biosynthetic pathways, structural diversity, physiological roles, and potential pharmacological properties of tolyporphins have attracted a broad spectrum of researchers from diverse scientific areas. The identification of putative biosynthetic gene clusters in the HT-58-2 cyanobacterial genome and accompanying studies suggest a new biosynthetic paradigm in the tetrapyrrole arena. The present review provides a comprehensive treatment of the rich science concerning tolyporphins.

Genomic tracking and precise control of Klebsiella pneumoniae transmission in a newly established hospital: a prospective molecular epidemiological study.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose an emerging clinical threat. We investigated its introduction and transmission in a new hospital, evaluating the effect of whole-genome sequencing (WGS) as an infection control measure. METHODS: Based on WGS of identified K. pneumoniae (Kpn) strains, a prospective molecular epidemiological study of nosocomial transmission of CRKP in a newly established Chinese hospital was conducted. RESULTS: Between September 2018 and August 2020, 206 Kpn strains were isolated, including 180 CRKP, from 152 patients. The first imported and nosocomial transmission cases were recorded in December 2018 and April 2019, respectively. Overall, 22 nosocomial transmission clusters involving 85 patients were identified, among which 5 were large-size clusters comprising 5-18 patients. Index cases of the large-size clusters were more likely associated with lower Glasgow Coma Scale scores than those of small-size clusters. Furthermore, results of multivariable logistic regression indicated that Kpn tended to transmit more among patients in the ICU [adjusted odds ratio (aOR) = 4.96, 95% confidence interval (CI) 1.97-13.47] and those infected with a ST11 strain (aOR = 8.04, 95% CI 2.51-29.53) or tetracycline-resistant strains (aOR = 17.63, 95% CI 6.32-57.32). However, transmission was less likely in strains bearing the rmpA gene (aOR = 0.12, 95% CI 0.03-0.37). The rate of nosocomial CRKP cases decreased by 2.25 with the intervention of WGS-based infection control. CONCLUSIONS: Kpn transmission in the newly established hospital originated from several imported cases. Rates of nosocomial CRKP infection were reduced considerably through precise infection control measures.

The roles of interleukin-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury.

BACKGROUND: The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). METHODS: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. RESULTS: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. CONCLUSION: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

Tethered Indoxyl-Glucuronides for Enzymatically Triggered Cross-Linking.

Indoxyl-glucuronides, upon treatment with ß-glucuronidase under physiological conditions, are well known to afford the corresponding indigoid dye via oxidative dimerization. Here, seven indoxyl-glucuronide target compounds have been prepared along with 22 intermediates. Of the target compounds, four contain a conjugatable handle (azido-PEG, hydroxy-PEG, or BCN) attached to the indoxyl moiety, while three are isomers that include a PEG-ethynyl group at the 5-, 6-, or 7-position. All seven target compounds have been examined in indigoid-forming reactions upon treatment with ß-glucuronidase from two different sources and rat liver tritosomes. Taken together, the results suggest the utility of tethered indoxyl-glucuronides for use in bioconjugation chemistry with a chromogenic readout under physiological conditions.

A case of pulmonary infection with Prevotella melanogenica having the paving stone symptom.

Prevotella melanogenica is a typical organism present in the human oral cavity and female reproductive tract, which is responsible for causing periodontal disease and the inflammation of the female reproductive tract. The present report discusses the case of a young female patient who presented with cough and fever as the main clinical symptoms. Computed Tomography (CT) revealed multiple clusters of ground glass density shadows in both lungs, with network-like and paving stone-like changes. The alveolar lavage fluid was collected for next-generation sequencing, which revealed the presence of Prevotella melanogenica. The patient received treatments, CT revealed that the density of multiple flakes of ground glass density in both lungs was lower than the previously observed density. Prevotella melanogenica pneumonia is rare, and the paving stone symptom observed in CT is not specific. Therefore, the case reported here provides a novel perspective regarding the diagnosis of pneumonia.

Realization of high-dynamic-range broadband magnetic-field sensing with ensemble nitrogen-vacancy centers in diamond.

We present a new magnetometry method integrating an ensemble of nitrogen-vacancy (NV) centers in a single-crystal diamond with an extended dynamic range for monitoring a fast changing magnetic-field. The NV-center spin resonance frequency is tracked using a closed-loop frequency locked technique with fast frequency hopping to achieve a 10 kHz measurement bandwidth, thus allowing for the detection of fast changing magnetic signals up to 0.723 T/s. This technique exhibits an extended dynamic range subjected to the working bandwidth of the microwave source. This extended dynamic range can reach up to 4.3 mT, which is 86 times broader than the intrinsic dynamic range. The essential components for NV spin control and signal processing, such as signal generation, microwave frequency control, data processing, and readout, are integrated in a board-level system. With this platform, we demonstrate a broadband magnetometry with an optimized sensitivity of 4.2 nT Hz-1/2. This magnetometry method has the potential to be implemented in a multichannel frequency locked vector magnetometer suitable for a wide range of practical applications, such as magnetocardiography and high-precision current sensors.

Microfabricated sensor device for CW and pulsed laser power measurements.

On-line measurement is a trend of development toward laser-based applications. We present a fiber-integrated force sensor device for laser power measurement with both CW mode and pulse mode based on laser radiometric heat and radiation force sensing simultaneously. The sensor device is fabricated using a standard microfabrication process. Laser intensity is determined through the displacement of a movable mirror measured by an integrated Fabry-Perot interferometer. Compared with the performance of the device in the ambient condition, a non-linearity error of 0.02% and measurement uncertainty of 2.06% is observed in the quasi-vacuum condition for CW laser illumination. This device can measure a CW laser power with a 46.4 µW/Hz1/2 noise floor and a minimum detection limit of 0.125 mW. For a pulsed laser, a non-linearity error of 0.37% and measurement uncertainty of 2.08% is achieved with a noise floor of 1.3 µJ/Hz1/2 and a minimum detection limit of 3 µJ.

Multifunctional Au Modified Ti3C2-MXene for Photothermal/Enzyme Dynamic/Immune Synergistic Therapy.

Ti3C2-MXene-based composites provide multifunctional interfaces in diagnosis and treatment of tumors. Herein, we proposed a multifunctional nanoplatform based on Ti3C2-MXene-Au nanocomposites, which combines photothermal properties and peroxidase-like activity, accomplishing synergistic photothermal therapy (PTT) and enzyme dynamic therapy (EDT) accompanied by photoacoustic (PA) and thermal dual-mode imaging in vivo. Furthermore, PTT induces immunogenic cell death, and EDT promotes cell apoptosis, facilitating dendritic cell (DC) maturation and T cell infiltration into the tumor. On this basis, the antibody OX40 (αOX40) was utilized to further contribute immune therapy for reversing the immunosuppressive tumor microenvironment by activating CD4+ and CD8+ T cells. In summary, a triune of PTT/EDT/antitumor immune therapy is achieved by combining Ti3C2-MXene-Au nanocomposites and αOX40, which possesses several strong features of good biocompatibility, NIR-controlled targeting, significant cancer cell killing, and satisfactory biosafety in vitro and in vivo. Our work might highlight the promising application of MXene-based nanoplatforms for cancer therapy.

miR-351 promotes atherosclerosis in diabetes by inhibiting the ITGB3/PIK3R1/Akt pathway and induces endothelial cell injury and lipid accumulation.

BACKGROUND: The miR-351 gene is significantly upregulated in diabetic mice with atherosclerosis. However, the mechanism by which its presence is important for the overall disease has not been elucidated. Therefore, this study will investigate the mechanism of miR-351 in the process of diabetes mellitus with atherosclerosis through miR-351 gene knockout mice. METHODS: In this study, miR-351-/- C57BL/6 mice were first induced to form a type 2 diabetes mellitus model with atherosclerosis by STZ injection and a high-fat diet. Pathological tests (oil red O, HE, and Masson staining) combined with biochemical indices (TC, TG, LDL-C, HDL-C, TNF-α, hs-CRP, NO, SOD, MDA, CAT, and GSH-Px) were performed to evaluate the pathological degree of atherosclerosis in each group. Mouse aortic endothelial cells were treated with oxidized low-density lipoprotein (ox-LDL) and 30 mM glucose to establish a diabetic atherosclerosis cell model. Combined with cell oil red O staining and flow cytometry, the effects of silencing miR-351 on lipid accumulation and cell apoptosis in the diabetic atherosclerosis cell model were determined. Fluorescence in situ hybridization was used to detect the localization and transcription levels of miR-351 in cells. The target genes of miR-351 were predicted by bioinformatics and verified by dual-luciferase activity reporting. Western blotting was used to detect the expression levels of phosphorylated inosine 3-kinase regulatory subunit 1 (PIK3R1)/serine/threonine kinase 1 (Akt) and apoptosis-related proteins after transfection with integrin subunit ß3 (ITGB3) small interfering ribonucleic acid (siRNA). RESULTS: The expression of the miR-351 gene was significantly increased in the high-fat wild-type (HWT) group, and its expression was significantly decreased in the knockout mice. Silencing miR-351 effectively alleviated atherosclerosis in mice. The levels of miR-351 expression, apoptosis, lipid accumulation, and oxidative stress in ox-LDL + high glucose-induced endothelial cells were significantly increased. These phenomena were effectively inhibited in lentivirus-infected miR-351-silenced cell lines. Bioinformatics predicted that miR-351-5p could directly target the ITGB3 gene. Transfection of ITGB3 siRNA reversed the downregulation of apoptosis, decreased oil accumulation, and decreased oxidative stress levels induced by miR-351 silencing. In addition, it inhibited the activation of the PIK3R1/Akt pathway. CONCLUSION: Silencing miR-351 upregulates ITGB3 and activates the PIK3R1/Akt pathway, thereby exerting anti-apoptosis and protective effects on endothelial cells.

Comprehensive Surveillance and Sampling Reveal Carbapenem-Resistant Organism Spreading in Tertiary Hospitals in China.

Purpose: Carbapenem-resistant organisms (CROs) have posed a great threat to antibiotic use and induce multi-drug resistance. Contamination of the hospital environment and infection of healthcare workers (HCWs) are reported as sources of nosocomial infections. Here, we performed a comprehensive environment sampling and timely epidemiological investigation during outbreaks to investigate the role of the environment and HCWs in CRO transmission. Patients and Methods: We enrolled carbapenem-resistant organism outbreaks in ICU-1 of Huashan Hospital from January 2019 to March 2019, and ICU-2 located at west branch of Huashan Hospital from October 2019 to November 2019. Carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates were collected from the patients. We performed a real-time comprehensive environmental and HCW sampling in the two ICUs. Isolated strains from patients and the positive colonies from the screening were sent for whole-genome sequencing. Finally, phylogenetic trees were constructed. Results: CRAB and CRKP outbreaks simultaneously occurred in ICU-1; the outbreak involved 13 patients. Meanwhile, the CRKP outbreak in ICU-2 included 11 patients. Twelve out of 146 environment and HCWs samples in ICU-1 were carbapenem-resistant bacteria, including six CRKP and six CRAB strains. For ICU-2, hospital surfaces and HCWs were negative for CRKP. Phylogenetic analyses showed that CRKP strains in ICU-1 were classified into two clades: Clade 1 and Clade 2, sharing a high similarity of isolates from the environment and HCWs. The same phenomenon was observed in CRAB. Conclusion: A timely comprehensive sampling combined with genome-based investigation may aid in tracking the transmission route of and controlling the infections. The environment and HCWs could be contaminated during CRO transmission, which calls for strengthened prevention and control measures.

Dynamic changes of emergency visits: a retrospective observational study.

BACKGROUND: With more emergency visits, there is increasing pressure to provide emergency medical services globally and locally. This study aimed to investigate the epidemiological characteristics and the disease spectrum of patients presenting in the last three years to the Department of Emergency Medicine of Tianjin Medical University General Hospital, a tertiary hospital in Tianjin, China, to improve the services of the emergency medicine department. METHODS: A retrospective study was conducted on all patients in the Department of Emergency Medicine of Tianjin Medical University General Hospital from Jan 1, 2017, 00:00:00 to Dec 31, 2020, 23:59:59, including variables like medical record number, gender, age, date of admission, principal diagnosis. The data were analyzed by SPSS statistical software; statistical charts were prepared by GraphPad Prism9.0 and SPSS 20.0; statistical tables were made by Microsoft Excel. RESULTS: A total of 1,314,916 patients presented to the Department of Emergency Medicine of Tianjin Medical University General Hospital from Jan 1, 2017, 00:00:00 to Dec 31, 2020, 23:59:59. In terms of gender distribution, the male-female ratio was 0.78∶1. As for age distribution, patients aged 60-69 were the most (23.47%), and patients younger than 20 years were the least (2.80%). Concerning monthly data, the number of visits peaked during January and December. The distribution of daily visits showed the feature of three highs and a low. The top three prevalence diseases in the emergency disease spectrum were respiratory, cardiovascular, and digestive diseases. The respiratory system was the most common in patients with infectious diseases (200,912, accounting for 86.97%). Among the patients suffering from infectious diseases, the number of patients with respiratory infections peaked in 2019 (73,530) and was the lowest in 2020 (20,078). CONCLUSIONS: From 2017 to 2019, the demand for emergency services in Tianjin Medical University General Hospital continued to increase, but it was greatly affected by COVID-19 in 2020. This emergency department is mainly for patients with respiratory system, circulatory system and digestive system diseases, and its treatment time is relatively centralized. The prevention of diseases for people of all ages, especially female patients and the elderly, should be strengthened, and emergency medical resources should be allocated reasonably according to the peak months and crowed periods of patients.

IL-1ß-activated mTORC2 promotes accumulation of IFN-γ+ γδ T cells by upregulating CXCR3 to restrict hepatic fibrosis.

Liver fibrosis represents a severe stage of liver damage, with hallmarks of inflammation, hepatic stellate cell activation, and extracellular matrix accumulation. Although previous studies demonstrated γδ T cells are involved in liver fibrosis, the precise role and mechanisms of γδ T cells migrating to fibrotic liver have not been elucidated. Here, we aim to investigate the functional subsets of γδ T cells in hepatic fibrosis and to further explore the underlying causes and drivers of migration. In this study, we observed that γδ T cells accumulate in fibrotic liver. Adoptive transfer of γδ T, especially Vγ4 γδ T subset, can significantly alleviate liver fibrosis. In addition, CCl4 treatment also leads to activation of mTOR signaling in γδ T cells. Genetic deletion of the Rictor gene, but not Raptor, in γδ T cells markedly exacerbated liver fibrosis. Mechanistically, CCl4-induced liver injury causes macrophage accumulation in the liver, and IL-1ß produced by macrophages promotes mTORC2 signaling activation in γδ T cells, which upregulates T-bet expression and eventually promotes CXCR3 transcription to drive γδ T cell migration. Moreover, hepatic γδ T cells ameliorated liver fibrosis by cytotoxicity against activated hepatic stellate cells in FasL-dependent manner, and secrete IFN-γ to inhibit the differentiation of pro-fibrotic Th17 cells. Thus, IL-1ß-activated mTORC2 signaling in γδ T cells upregulates CXCR3 expression, which is critical for IFN-γ+ γδ T cells migration into the liver and amelioration of liver fibrosis. Our findings indicate that targeting the mTORC2 or CXCR3 in γδ T cells could be considered as a promising approach for γδ T cell immunotherapy against liver fibrosis.

A diagnostic accuracy study comparing RNA LAMP, direct LAMP, and rapid antigen testing from nasopharyngeal swabs.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, the early detection and isolation of individuals infected with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) through mass testing can effectively prevent disease transmission. SARS-CoV-2 nucleic acid rapid detection based on loop-mediated isothermal amplification (LAMP) may be appropriate to include in testing procedures. Methods: We used 860 nasopharyngeal specimens from healthcare workers of Huashan Hospital and COVID-19 patients collected from April 7th to 21st, 2022, to assess the clinical diagnostic performance of the LAMP assay marketed by Shanghai GeneSc Biotech and compared it to the result of a rapid antigen test (RAT) head-to-head. Results: Overall, the diagnostic performance of LAMP assay and RAT were as follows. The LAMP assay represented higher sensitivity and specificity than RAT, especially in the extracted RNA samples. The sensitivity was 70.92% and 92.91% for direct LAMP and RNA-LAMP assay, respectively, while the specificity was 99.86% and 98.33%. The LAMP assay had overall better diagnostic performance on the specimens with relatively lower C t values or collected in the early phase (≤7 days) of COVID-19. The combination of LAMP assay and RAT improved diagnostic efficiency, providing new strategies for rapidly detecting SARS-CoV-2. Conclusion: The LAMP assay are suitable for mass screenings of SARS-CoV-2 infections in the general population.