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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

Pancreatitis caused by a fish bone penetrating the posterior wall of the stomach and entering the pancreas is rare. We herein report a case involving a woman in her late 30s with an approximately 1-month history of recurrent upper abdominal pain. Initial evaluation at another hospital failed to identify the cause but raised suspicion of pancreatic cancer. Computed tomography, magnetic resonance imaging, and a detailed consultation led us to suspect that the patient’s pain had been caused by inadvertent ingestion of a fish bone. We used three-dimensional visualization technology to determine the location of the fish bone and informed the patient of the lesion and surgical plan through a simulated surgical demonstration. During surgery, we applied augmented reality navigation technology to remove the fish bone by a minimally invasive approach. The patient was discharged on postoperative day 3. She was followed up by telephone 24 hours after discharge. Outpatient follow-up was performed 1 week after discharge and on day 30. The patient recovered well and developed no complications. This case shows that digital medical technology can be applied in patients undergoing surgical removal of a pancreatic foreign body. Such technology assists with preoperative evaluation, patient education, and intraoperative trauma reduction.

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.

Integrin Alpha v Beta 6 is expressed primarily in solid epithelial tumors, such as cholangiocarcinoma, pancreatic cancer, and colorectal cancer. It has been considered a potential and promising molecular marker for the early diagnosis and treatment of cancer. Cholangiocarcinoma and pancreatic ductal adenocarcinoma share genetic, histological, and pathophysiological similarities due to the shared embryonic origin of the bile duct and pancreas. These cancers share numerous clinicopathological characteristics, including growth pattern, poor response to conventional radiotherapy and chemotherapy, and poor prognosis. This review focuses on the role of integrin Alpha v Beta 6 in cancer progression. It addition, it reviews how the marker can be used in molecular imaging and therapeutic targets. We propose further research explorations and questions that need to be addressed. We conclude that integrin Alpha v Beta 6 may serve as a potential biomarker for cancer disease progression and prognosis.

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.

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.

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.

Selenium (Se) is an essential nutrient element in human physiological metabolism and immune function. Supplementation of bioavailable Se will confer benefit on human life, especially when intake of this nutrient is inadequate. The edible and medicinal mushroom Antrodia camphorata is a unique fungus endemic to Taiwan, which has shown high therapeutic and nutritive value. This study is the first to demonstrate that A. camphorata can assimilate and transform sodium selenite into organic selenium. With an initial concentration of Se (IV) at 10 mg/L in 100 mL of the medium at 25 °C, the total selenium content in Se-enriched A. camphorata mycelia was 1281.3 ± 79.2 µg/g, in which the organic selenium content accounted for 88.1%. Further analysis demonstrated that selenium-enriched polysaccharide was the main form of Se present in A. camphorata (61.5% of the organic selenium). Four water-soluble Se-polysaccharide fractions were separated from A. camphorata, and ACP II was the major fraction of Se-polysaccharide. The scavenging efficiency of Se-polysaccharides on DPPH and ABTS radicals was determined, proving that selenium enrichment dramatically improved the in vitro antioxidant capacity of A. camphorata polysaccharide. Therefore, the selenium accumulation and transformation ability of A. camphorata provides an opportunity for developing this beneficent fungus into a novel selenium-enriched dietary or medicinal supplement.

Lysozymes are hydrolytic enzymes characterized by their ability to cleave the β-(1,4)-glycosidic bonds in peptidoglycan, a major structural component of the bacterial cell wall. This hydrolysis action compromises the integrity of the cell wall, causing the lysis of bacteria. For more than 80 years, its role of antibacterial defense in animals has been renowned, and it is also used as a preservative in foods and pharmaceuticals. In order to improve the antimicrobial efficacy of lysozyme, extensive research has been intended for its modifications. This manuscript reviews the natural antibiotic compound lysozyme with reference to its catalytic and non-catalytic mode of antibacterial action, lysozyme types, susceptibility and resistance of bacteria, modification of lysozyme molecules, and its applications in the food industry.

Purpose: To establish a valid prediction model to prognose the occurrence of microvascular invasion (MVI), and to compare the efficacy of anatomic resection (AR) or non-anatomic resection (NAR) for hepatocellular carcinoma (HCC).Methods: Two hundred twenty-eight patients with HCC who underwent surgical treatment were enrolled. Their hematological indicators, MRI imaging features, and outcome data were acquired.Result: In the multivariable analysis, alpha-fetoprotein >15 ng/mL, neutrophil to lymphocyte ratio >3.8, corona enhancement, and peritumoral hypointensity on hepatobiliary phase were associated with MVI. According on these factors, the AUROC of the predictive model in the primary and validation cohorts was 0.884 (95% CI: 0.829, 0.938) and 0.899 (95% CI: 0.821, 0.967), respectively. Patients with high risk of MVI or those with low risk of MVI but tumor size >5 cm in the AR group were associated with a lower rate of recurrence and death than patients in the NAR group; however, when patients are in the state of low-risk MVI with tumor size >5 cm, there is no difference in the rate of recurrence and death between AR and NAR.Conclusion: Our predictive model for HCC with MVI is convenient and accurate. Patients with high-risk of MVI or low-risk of MVI but tumor size >5 cm executing AR is of great necessity.

A short self-assembly peptide A6K (H2N−AAAAAAK−OH) with unmodified N− and C−terminus was designed, and the charge distribution model of this short peptide at different pH was established by computer simulation. The pH of the solution was adjusted according to the model and the corresponding self-assembled structure was observed using a transmission electron microscope (TEM). As the pH changes, the peptide will assemble into blocks or nanoribbons, which indicates that the A6K peptide is a pH-responsive peptide. Circular dichroism (CD) and molecular dynamics (MD) simulation showed that the block structure was formed by random coils, while the increase in β-turn content contributes to the formation of intact nanoribbons. A reasonable explanation of the self-assembling structure was made according to the electrostatic distribution model and the effect of electrostatic interaction on self-assembly was investigated. This study laid the foundation for further design of nanomaterials based on pH-responsive peptides.

BACKGROUNDIn preclinical murine and early clinical studies of hematopoietic cell transplantation, engineering of donor grafts with defined ratios of CD4+CD25+FoxP3+ Tregs to conventional T cells (Tcons) results in the prevention of graft-versus-host disease and improved immune reconstitution. The use of highly purified primary graft Tregs for direct cell infusion has potential advantages over impure immunomagnetic selection or culture expansion, but has not been tested clinically. We performed a phase I study of the timed addition of CD34-selected hematopoietic stem cells and Tregs, followed by Tcons for the treatment of patients with high-risk hematological malignancies.METHODSWe present interim evaluation of a single-center open phase I/II study of administration of human leukocyte-matched Tregs and CD34-selected hematopoietic cells, followed by infusion of an equal ratio of Tcons in adult patients undergoing myeloablative hematopoietic stem cell transplantation (HCT) for high-risk or active hematological malignancies. Tregs were purified by immunomagnetic selection and high-speed cell sorting.RESULTSHere we report results for the first 12 patients who received Tregs of between 91% and 96% purity. Greater than grade II GVHD was noted in 2 patients in the first cohort of 5 patients, who received cryopreserved Tregs, but neither acute nor chronic GVHD was noted in the second cohort of 7 patients, who received fresh Tregs and single-agent GVHD prophylaxis. Patients in the second cohort appeared to have normal immune reconstitution compared with patients who underwent transplantation and did not develop GVHD.CONCLUSIONOur study shows that the use of highly purified fresh Tregs is clinically feasible and supports continued investigation of the strategy.TRIAL REGISTRATIONClinicalTrials.gov NCT01660607.FUNDINGNIH NHBLI R01 HL114591 and K08HL119590.

Knockdown or gene disruption of the ubiquitously expressed cell surface receptor CD47 protects non-malignant cells from genotoxic stress caused by ionizing radiation or cytotoxic chemotherapy but sensitizes tumors in an immune competent host to genotoxic stress. The selective radioprotection of non-malignant cells is mediated in part by enhanced autophagy and protection of anabolic metabolism pathways, but differential H2AX activation kinetics suggested that the DNA damage response is also CD47-dependent. A high throughput screen of drug sensitivities indicated that CD47 expression selectively sensitizes Jurkat T cells to inhibitors of topoisomerases, which are known targets of Schlafen-11 (SLFN11). CD47 mRNA expression positively correlated with schlafen-11 mRNA expression in a subset of human cancers but not the corresponding non-malignant tissues. CD47 mRNA expression was also negatively correlated with SLFN11 promoter methylation in some cancers. CD47 knockdown, gene disruption, or treatment with a CD47 function-blocking antibody decreased SLFN11 expression in Jurkat cells. The CD47 signaling ligand thrombospondin-1 also suppressed schlafen-11 expression in wild type but not CD47-deficient T cells. Re-expressing SLFN11 restored radiosensitivity to a CD47-deficient Jurkat cells. Disruption of CD47 in PC3 prostate cancer cells similarly decreased schlafen-11 expression and was associated with a CD47-dependent decrease in acetylation and increased methylation of histone H3 in the SLFN11 promoter region. The ability of histone deacetylase or topoisomerase inhibitors to induce SLFN11 expression in PC3 cells was lost when CD47 was targeted in these cells. Disrupting CD47 in PC3 cells increased resistance to etoposide but, in contrast to Jurkat cells, not to ionizing radiation. These data identify CD47 as a context-dependent regulator of SLFN11 expression and suggest an approach to improve radiotherapy and chemotherapy responses by combining with CD47-targeted therapeutics.