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Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS. Methods We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching. Results Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p

Background: Scrub typhus, an acute febrile disease caused by Orientia tsutsugamushi, is transmitted to humans through infected chigger mites. We present a case of scrub typhus in a previously healthy man from Shandong Province diagnosed using next-generation sequencing (NGS) and PCR and review recent literature on NGS for scrub typhus diagnosis. Methods: NGS was utilized for testing whole blood collected on admission. Confirmatory testing was done by detecting IgM and IgG antibodies to Orientia in acute and convalescent sera by ELISA. Orientia 47-kDa protein gene TaqMan and standard PCR of the 56-kDa protein gene and Sanger sequencing were performed on eschar scab DNA. Results: The NGS diagnosis was confirmed by 47-kDa protein gene TaqMan and sequencing of a fragment of the O. tsutsugamushi 56-kDa protein gene from the eschar scab. Analysis of this sequence and the NGS data indicated O. tsutsugamushi strain Cheeloo2020 is a novel genotype. Mapping of the NGS data against the O. tsutsugamushi Gilliam strain genome sequence identified 304 reads with high similarity. Conclusions: NGS is not only useful for multiplex diagnosis of scrub typhus, but also provides insight into the genetic diversity of O. tsutsugamushi. The common failure to submit sequences to databases makes it difficult to determine the minimal quantity and quality of NGS data being used for the positive identification of Orientia DNA in clinical specimens.

In this study, the regeneration of waste activated carbon by the synergic combination of ultrasonication and persulfate treatment was explored. The regeneration efficiencies achieved with sonication and persulfate, both in combination and separately, were assessed from a sample’s ability to adsorb ofloxacin before and after regeneration. The introduction of persulfate increased the regeneration rate by 4–5% over that of ultrasound alone, and the regeneration rate increased from 40.95 % to 45.71 % upon increasing the persulfate dosage from 1 to 10 mmol/L. Furthermore, the regeneration rate was found to be largely unaffected by pH. The specific surface area of the activated carbon regenerated by the combined technology was 527 m2/g, which was 37 m2/g higher than that for ultrasonic regeneration alone, further demonstrating the utility of the combined approach. In summary, combined ultrasonication/persulfate regeneration provides a practical and cost-effective method for the reuse of waste activated carbon.

Abstract Background Timely and accurate identification of pathogens is crucial for appropriate treatment and prognosis of infectious diseases. As an increasingly popular pathogen detection method, the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens in febrile patients with suspected infection requires further exploration. Methods This study included 368 febrile patients with suspected infections who were admitted to the Infectious Disease Department of Qilu Hospital, Shandong University between January 5, 2021 and April 14, 2023. Both mNGS testing and conventional culture were performed in all patients. Clinical data of enrolled patients were collected, and the diagnostic performances of mNGS and culture were compared. Results Of the 368 enrolled patients, 231 were finally diagnosed with infection and 137 were with diseases other than infection. The sensitivity (58.01% vs. 21.65%, p

Abstract Background Talaromyces marneffei is endemic to eastern India, Southeast Asia, and Guangdong and Guangxi provinces in China. It is common in immunocompromised individuals, especially in HIV-infected patients. Case presentation A 66-year-old male who had a history of hypertension and resided in Shandong Province (Northern China) was admitted for recurrent fever for one month. The patient had recurrent fever, multiple lymphadenopathies, hepatosplenomegaly, a back rash, and a progressive decrease in white blood cells and platelets. Talaromyces marneffei was isolated from peripheral blood and bone marrow after admission, and suspected fungal cells were found via lymph node pathology. The patient’s infection secondary to haemophagocytic syndrome continued to worsen despite antifungal, anti-inflammatory, and symptomatic treatment, leading to death due to multiple-organ failure. Conclusion Although rare, infection due to Talaromyces marneffei in HIV-negative patients has been increasing in recent years, and we should be vigilant about “new” infections in nonendemic areas.

China is not considered as an endemic area of Rickettsia conorii, so there is no routine clinical way to diagnose this infection. This study aims to determine whether 2 febrile patients who had a tick bite in East China were indeed infected with R. conorii. The citrate synthase gene (gltA) was amplified with universal rickettsial primers by real-time fluorescent PCR from the patients’ blood samples. Nested PCR was used to amplify the outer membrane protein A gene (ompA) for positive specimens. PCR products were further identified and analyzed through nucleic acid sequencing. Positive amplification of the gltA and ompA genes was found in both patients. The nucleotide sequences (303 bp) of the ompA gene of the 2 patients had high homology (99%) with the R. conorii Indian tick typhus strain in GenBank. A more than 4-fold increase in IgG against R. conorii provided supportive evidence of SFG Rickettsia infection. And the rapid recovery after doxycycline treatment also supported a rickettsial cause for the disease. Physicians in East China should be aware of human infections with R. conorii. PCR-based diagnostic methods offer a rapid and precise way to diagnose rickettsiosis, improving patient identification and management.

The contradiction between charging stations (CSs) and electric vehicles (EVs) is a “chicken-and-egg” problem. Multiple factors and stakeholders, including the goals of the government's industry planning, CS operators' profits, and EV consumers' charging demand, influence the CS layout. Using multisource open data, this study proposes a time series optimization layout model based on the supply-demand balance by constructing EV customers' urban travel dynamics index and CS adaptability index. The results show that: the supply-demand imbalance is widespread in Shenzhen, a Chinese city. The “mismatch”, “unmatch” and “overmatch” of CSs are prevalent. Addressing this supply-demand imbalance will help reduce consumer concerns regarding “range anxiety”. Facing potential future power supply constraints, the government needs to expand the existing CS development strategy to include battery swap stations (BSs) and mobile charging stations (MCSs).

Electrospinning as a versatile, simple, and cost-effective method to engineer a variety of micro or nanofibrous materials, has contributed to significant developments in the biomedical field. However, the traditional electrospinning of single material only can produce homogeneous fibrous assemblies with limited functional properties, which oftentimes fails to meet the ever-increasing requirements of biomedical applications. Thus, multi-material electrospinning referring to engineering two or more kinds of materials, has been recently developed to enable the fabrication of diversified complex fibrous structures with advanced performance for greatly promoting biomedical development. This review firstly gives an overview of multi-material electrospinning modalities, with a highlight on their features and accessibility for constructing different complex fibrous structures. A perspective of how multi-material electrospinning opens up new opportunities for specific biomedical applications, i.e., tissue engineering and drug delivery, is also offered.

ObjectivesPositive antiphospholipid antibodies (aPLs) and chronic hypertension (CH) in pregnancy are important causes of maternal and neonatal morbidity and mortality. However, there are no relevant studies on the treatment of aPL-positive pregnant women with CH. This study aimed to determine the effect of low-dose aspirin (LDA) plus low-molecular-weight heparin (LMWH) on maternal and perinatal outcomes in persistently aPL-positive pregnant women with CH.MethodsThis study was performed at the First Affiliated Hospital of Dalian Medical University in Liaoning, China, from January 2018 to December 2021. Pregnant women diagnosed CH and persistently positive aPL who had no autoimmune disease such as systemic lupus erythematosus, antiphospholipid syndrome were recruited and divided into control group (LDA and LWMH were not used), LDA group (LDA was used) and LDA plus LMWH group (both LDA and LMWH were used) according to whether they use LDA and/or LMWH. A total of 81 patients were enrolled, including 40 patients in the control group, 19 patients in the LDA group, and 22 patients in the LDA plus LMWH group. The maternal and perinatal outcomes of LDA plus LMWH therapy were analysed.ResultsCompared with control group, the rate of severe preeclampsia in LDA group (65.00% vs. 31.58%, p = 0.016) and LDA plus LMWH group (65.00% vs. 36.36%, p = 0.030) had a statistically significant reduction. Compared with control group, the rate of fetal loss in LDA group (35.00% vs. 10.53%, p = 0.014) and LDA plus LMWH group (35.00% vs. 0.00%, p = 0.002) had a statistically significant reduction. Compared with control group, the rate of live birth in LDA group (65.00% vs. 89.74%, p = 0.048) and LDA plus LMWH group (65.00% vs. 100.00%, p = 0.002) had a statistically significant increased. Compared withcontrol group, the incidence of early-onset preeclampsia (47.50% vs. 36.84%, p = 0.008) and early-onset severe preeclampsia (47.50% vs. 13.64%, p = 0.001) in the LDA plus LMWH group decreased and were statistically different. Furthermore, we also found that LDA or LDA plus LMWH hadn't increase the rate of blood loss and placental abruption.ConclusionBoth LDA and LDA combined with LMWH could decrease the incidence of severe preeclampsia, decrease the rate of foetal loss, increase the rate of live birth. However, LDA plus LWMH could reduce and delay the onset of severe preeclampsia, prolong the gestational age and increase the rate of full-term delivery, improve the maternal and perinatal outcomes.

BackgroundThis study aims to evaluate the efficacy of the standard agglutination test (SAT), the Brucellacapt test and enzyme-linked immunosorbent assay (ELISA) in clinical specimens collected from patients with suspected brucellosis.MethodsA prospective study was conducted from December 2020 to December 2021. Brucellosis was diagnosed on the basis of clinical evidence, and confirmed by isolation of Brucella or a four-fold rise in SAT titer. All samples were tested by the SAT, ELISA and the Brucellacapt test. Titers ≥1:100 were considered as SAT positive; ELISA was considered positive when an index greater than 11 was detected, while titers ≥1/160 indicated positivity on the Brucellacapt test. The specificity, sensitivity, and positive (PPVs) and negative predictive values (NPVs) of the three different methods were calculated.ResultsA total of 149 samples were collected from patients with suspected brucellosis. The sensitivities for the SAT, IgG, and IgM detection were 74.42%, 88.37% and 74.42%, respectively. The specificities were 95.24%, 93.65%, and 88.89%, respectively. The simultaneous measurement of IgG and IgM improved the sensitivity (98.84%) but reduced the specificity (84.13%) compared to each antibody test separately. The Brucellacapt test had excellent specificity (100%) and a high PPV (100%); however, the sensitivity and NPV were 88.37% and 86.30%, respectively. The combination of IgG detection by ELISA and the Brucellacapt test had excellent diagnostic performance, with 98.84% sensitivity and 93.65% specificity.ConclusionThis study showed that the simultaneous performance of IgG detection by ELISA and the Brucellacapt test has the potential to overcome the current limitations of detection.

The burden of cancer is increasing, being widely recognized as one of the main reasons for deaths among humans. Despite the tremendous efforts that have been made worldwide to stem the progression and metastasis of cancer, morbidity and mortality in malignant tumors have been clearly rising and threatening human health. In recent years, nanomedicine has come to occupy an increasingly important position in precision oncotherapy, which improves the diagnosis, treatment, and long-term prognosis of cancer. In particular, LDNs with distinctive physicochemical capabilities have provided great potential for advanced biomedical applications, attributed to their large surface area, abundant surface binding sites, and good cellular permeation properties. In addition, LDNs can integrate CT/MR/US/PAI and PTT/PDT/CDT/NDDS into a multimodal theranostic nanoplatform, enabling targeted therapy and efficacy assessments for cancer. This review attempts to concisely summarize the classification and major properties of LDNs. Simultaneously, we particularly emphasize their applications in the imaging, diagnosis, and treatment of cancerous diseases.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. A 73-year-old woman presented to the hospital with fever after being bitten by ticks and was diagnosed with SFTS. Three days after treatment with high-flow oxygen and supportive therapy, her condition deteriorated to septic shock and multiple organ failure. Ruxolitinib, a JAK1/2 inhibitor, was used for the treatment of cytokine release syndrome, and the patient finally recovered. Ruxolitinib and other host-based immunomodulatory drugs may be potential treatments for fatal SFTS.

Information diffusion in social media has attracted the wide attention of scholars from diverse disciplines. In real life, many offline events can cause online diffusion of relevant information, and the relation between the characteristics of information diffusion and offline events, as well as the diffusion differences corresponding to different phases of offline events have been studied. However, the effects of offline events on information diffusion are not well explored. In this paper, we study the influence of a popular and multi-phase talent show with elimination mechanism on relevant information diffusion. We find that elimination mechanism has significant influence on the features of information diffusion, and elimination results have a negative effect on followers’ emotional tendency. Elimination results also significantly affect the topics discussed by users. Besides elimination results have a negative effect on participants’ popularity, but do not affect the followers’ loyalty to program participants. This study not only reveals the effects of offline events on online information diffusion, but also provides approaches for studying the online diffusion of similar offline events.

Human brucellosis is one of the most prevalent zoonoses. There are many similarities between the pathogenesis of Mycobacterium tuberculosis (MTB) infection and that of brucellosis. Immune reconstitution inflammatory syndrome (IRIS) may occur during the treatment of MTB infection, but it has not been reported in brucellosis cases thus far. We report the case of a 40-year-old male whose condition initially improved after adequate anti-Brucella therapy. However, 3 weeks later, the patient presented with exacerbation of symptoms and development of a paravertebral abscess. After exclusion of other possible causes of clinical deterioration, immune reconstitution inflammatory syndrome (IRIS) with brucellosis was presumed. After supplementation with anti-Brucella treatment with corticosteroids, the abscess disappeared, and the symptoms completely resolved. Our case suggests that it is necessary to be aware of the possible occurrence of IRIS in patients with brucellosis in clinical practice.

Nanomaterials integrating a variety of excellent properties (such as controllable/suitable size, surface modifier, and multifunctionality) have attracted increasing attention in the biomedical field and have been considered a new generation of magnetic resonance imaging (MRI) contrast agents (CAs). In recent years, stimuli-responsive nanomaterials with specifically responsive ability have been synthesized as MRI CAs, which can significantly improve the diagnostic sensitivity and accuracy depending on their outstanding performance. Furthermore, the inherent tumor microenvironment (TME) of malignant tumor is considered to possess several unique features, such as low extracellular pH, redox condition, hypoxia, and high interstitial pressure, that are significantly different from healthy tissues. Hence, constructing nanomaterials for TME-responsive MRI as an emerging strategy is expected to overcome the current obstacles to precise diagnosis. This review focuses on recent advances of nanomaterials in their application of TME-responsive MRI that trigger the diagnostic function in response to various endogenous stimulations, including pH, redox, enzyme, and hypoxia. Moreover, the future challenges and trends in the development of nanomaterials serving as TME-responsive MRI CAs are discussed.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Recent studies have shown that n6-methyladenosine (m6A) plays a major role in cardiovascular homeostasis and pathophysiology. These studies have confirmed that m6A methylation affects the pathophysiology of cardiovascular diseases by regulating cellular processes such as differentiation, proliferation, inflammation, autophagy, and apoptosis. Moreover, plenty of research has confirmed that m6A modification can delay the progression of CVD via the post-transcriptional regulation of RNA. However, there are few available summaries of m6A modification regarding CVD. In this review, we highlight advances in CVD-specific research concerning m6A modification, summarize the mechanisms underlying the involvement of m6A modification during the development of CVD, and discuss the potential of m6A modification as a therapeutic target of CVD.

Background: Doxorubicin (DOX)-induced cardiotoxicity is a highly concerning issue, and the mechanism by which DOX induces cardiotoxicity is likely to be multifactorial. NADPH oxidase (NOX) is associated with DOX-induced cardiotoxicity. Setanaxib (GKT137831), a preferential direct inhibitor of NOX1 and NOX4, can delay or prevent the progression of many cardiovascular disorders by inhibiting reactive oxygen species (ROS) generation. In this study, we investigated the role of GKT137831 in ameliorating DOX-induced cardiotoxicity and the potential mechanisms of its action.Methods and Results: The mice model of cardiotoxicity induced by DOX was established, and GKT137831 treatment was performed at the same time. Neonatal rat cardiomyocytes (NRCMs) were treated with DOX or GKT137831 for in vitro experiments. We found that DOX administration impaired cardiac function in vivo, reflected by decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS%). DOX also impaired the viability of NRCMs in vitro. In addition, DOX increased the levels of NOX1 and NOX4 expression and ROS production and the cardiomyocyte apoptosis rate, both in vivo and in vitro. GKT137831 improved cardiac function, as indicated by the increased LVEF and FS%. In vitro, GKT137831 improved NRCM viability. It also decreased ROS production and the cardiomyocyte apoptosis rate. Apoptotic indices, such as cleaved PARP (c-PARP), cleaved caspase 3 (CC3) and BAX expression levels, were decreased, and the antiapoptotic index of Bcl-2 expression was increased. DOX markedly activated phosphorylated JNK, ERK and p38 proteins in NRCMs. Specific inhibitors of JNK (SP600125), ERK (PD98059) or p38 (SB203580) inhibited DOX-induced apoptosis of NRCMs. GKT137831 pretreatment inhibited excessive DOX-induced MAPK pathway activation.Conclusion: This study revealed that GKT137831 can alleviate DOX-induced cardiomyocyte apoptosis by inhibiting NOX1/4-driven ROS production. The upregulation of MAPK pathway induced by NOX1/4-derived ROS production may be the potential mechanism of GKT137831 action. GKT137831 may be a potential drug candidate to ameliorate DOX-induced cardiotoxicity.

Difficulty in emotional regulation is significantly correlated with depression. Depression is a psychological disease that seriously affects the physical and mental health of college students. Therefore, it is of great importance to develop diversified preventive interventions such as group impromptu music therapy (GIMT). The main purpose of this study was to evaluate the effect of GIMT on the improvement of emotional regulation ability and the reduction of depressive symptoms in college students. A 71 college students (36 in the experimental group and 35 in the control group) were recruited to carry out randomized controlled trial was used. The experimental group was intervened by GIMT. After the 4th week of intervention, follow-up and scale measurement were carried out. In the experimental group, emotional regulation difficulty scales (DERS) showed significant difference before and after GIMT, implying the improvement in the emotional regulation. But there was no significant improvement in the control group. In addition, the depressive symptoms of experimental group were relieved. All findings showed that GIMT can effectively improve college students’ emotional regulation and reduce depressive symptoms.

Abundant research findings have proved the value of two-dimensional (2D) materials in the study of nonlinear optics in fiber lasers. However, there remains two problems: how to reduce the start-up threshold, and how to improve the damage threshold, of fiber lasers based on 2D materials. A 15.1 mW low-threshold mode-locked fiber laser, based on a Cr2Si2Te6 saturable absorber (SA) prepared by the liquid-phase exfoliation method, is demonstrated successfully in this work. This provides a useful and economical method to produce SAs with low insertion loss and low saturation intensity. Besides, multiple high-order harmonics, from the fundamental frequency (12.6 MHz) to the 49th-order harmonic (617.6 MHz), mode-locked operations are recorded. The experimental results indicate the excellent potential of Cr2Si2Te6 as an optical modulator in exploring the soliton dynamics, harmonic mode locking, and other nonlinear effects in fiber lasers.

In different kinds of sports, the balance control ability plays an important role for every athlete. Therefore, coaches and athletes need accurate and efficient assessments of the balance control ability to improve the athletes’ training performance scientifically. With the fast growth of sport technology and training devices, intelligent and automatic assessment methods have been in high demand in the past years. This paper proposes a deep-learning-based method for a balance control ability assessment involving an analysis of the time-series signals from the athletes. The proposed method directly processes the raw data and provides the assessment results, with an end-to-end structure. This straight-forward structure facilitates its practical application. A deep learning model is employed to explore the target features with a multi-headed self-attention mechanism, which is a new approach to sports assessments. In the experiments, the real athletes’ balance control ability assessment data are utilized for the validation of the proposed method. Through comparisons with different existing methods, the accuracy rate of the proposed method is shown to be more than 95% for all four tasks, which is higher than the other compared methods for tasks containing more than one athlete of each level. The results show that the proposed method works effectively and efficiently in real scenarios for athlete balance control ability evaluations. However, reducing the proposed method’s calculation costs is an important task for future studies.

Background: Many publications have reported that acute COVID-19 infection can cause autonomic dysfunction. In this series, we described seven patients who had recurrent fever after acute COVID-19 infection, and the possible pathophysiological basis is autonomic dysfunction., Patients: This was a retrospective study conducted at the Qilu Hospital of Shandong University from January 2023 to March 2023. Patients who were hospitalized in the Department of Infectious Diseases with a diagnosis of fever of unknown origin., Results: Between January and March 2023, a total of seven patients with autonomic dysfunction in post-COVID condition, who had recurrent fever accompanied by electrolyte imbalances and other manifestations of autonomic dysfunction. The median age of these patients was relatively high, and they were mostly indoor workers with comorbidities such as diabetes and chronic hypertension. Physical cooling and correction of electrolyte imbalances with medication were effective treatments., Conclusions: The COVID-19 infection can lead to autonomic dysfunction, which manifests not only as tachycardia and blood pressure abnormalities, but may also be the pathophysiological mechanism underlying recurrent fever in post-COVID cases.