Tree frogs Polypedates Dennysi landing on horizontal perches: the effects of perch diameters.

Secure landing is indispensable for both leaping animals and robotics. Tree frogs, renowned for their adhesive capabilities, can effectively jump across intricate 3D terrain and land safely. Compared to jumping, the mechanisms underlying their landing technique, particularly in arboreal environments, have remained largely unknown. In this study, we focused on the landing patterns of the tree frogs Polypedates Dennysi on horizontally placed perches, explicitly emphasizing the impact of perch diameters. Tree frogs demonstrated diverse landing postures, including the utilization of (1) single front foot, (2) double front feet, (3) anterior bellies, (4) middle bellies, (5) posterior bellies, (6) single hind foot, or (5) double hind feet. Generally, tree frogs favour bellies on slimmer targets but double front feet on large perches. Analysis of limb-trunk relationships revealed their adaptability to modifying postures, including body positions and limb orientations, for successful landing. The variations in the initial landing postures affect the succeeding landing procedures and, consequently, the dynamics. As the initial contact position was switched from front foot to hind foot, the stabilization time decreased first, reaching the minimum in middle belly landings, and then increased. The maximum vertical forces changed in an inverse trend, whereas the maximum fore-aft forces continuously increased as the initial contact position switched. As the perch diameter rose, the time expenses dropped, whereas the maximum impact increased. These findings not only added to our understanding of frog landings but also highlighted the necessity of considering perch diameters and landing styles when studying the biomechanics of arboreal locomotion.

Improved diagnostic markers for invasive pulmonary aspergillosis in COPD patients.

Background: The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection. Methods: This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients. Results: The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration. Conclusion: Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.

Integrating serum pharmacochemistry and network pharmacology to explore the molecular mechanisms of Acanthopanax senticosus (Rupr. & Maxim.) Harms on attenuating doxorubicin-induced myocardial injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. or Siberian ginseng, has a rich history of use as an adaptogen, a substance believed to increase the body's resistance to stress, fatigue, and infectious diseases. As a traditional Chinese medicine, AS is popular for its cardioprotective effects which can protect the cardiovascular system from hazardous conditions. Doxorubicin (DOX), on the other hand, is a first-line chemotherapeutic agent against a variety of cancers, including breast cancer, lung cancer, gastric cancer, and leukemia, etc. Despite its effectiveness, the clinical use of DOX is limited by its side effects, the most serious of which is cardiotoxicity. Considering AS could be applied as an adjuvant to anticancer agents, the combination of AS and DOX might exert synergistic effects on certain malignancies with mitigated cardiotoxicity. Given this, it is necessary and meaningful to confirm whether AS would neutralize the DOX-induced cardiotoxicity and its underlying molecular mechanisms. AIM OF THE STUDY: This paper aims to validate the cardioprotective effects of AS against DOX-induced myocardial injury (MI) while deciphering the molecular mechanisms underlying such effects. MATERIALS AND METHODS: Firstly, the cardioprotective effects of AS against DOX-induced MI were confirmed both in vitro and in vivo. Secondly, serum pharmacochemistry and network pharmacology were orchestrated to explore the in vivo active compounds of AS and predict their ways of functioning in the treatment of DOX-induced MI. Finally, the predicted mechanisms were validated by Western blot analysis during in vivo experiments. RESULTS: The results demonstrated that AS possessed excellent antioxidative ability, and could alleviate the apoptosis of H9C2 cells and the damage to mitochondria induced by DOX. In vivo experiments indicated that AS could restore the conduction abnormalities and ameliorate histopathological changes according to the electrocardiogram and cardiac morphology. Meanwhile, it markedly downregulated the inflammatory factors (TNF-α, IL-6, and IL-1ß), decreased plasma ALT, AST, LDH, CK, CK-MB, and MDA levels, as well as increased SOD and GSH levels compared to the model group, which collectively substantiate the effectiveness of AS. Afterward, 14 compounds were identified from different batches of AS-dosed serum and selected for mechanism prediction through HPLC-HRMS analysis and network pharmacology. Consequently, the MAPKs and caspase cascade were confirmed as primary targets among which the interplay between the JNK/Caspase 3 feedback loop and the phosphorylation of ERK1/2 were highlighted. CONCLUSIONS: In conclusion, the integrated approach employed in this paper illuminated the molecular mechanism of AS against DOX-induced MI, whilst providing a valuable strategy to elucidate the therapeutic effects of complicated TCM systems more reliably and efficiently.

Impact of macrophage differentiation on hematopoietic function enhancement by Shenzhu ErKang Syrup.

Shenzhu Erkang Syrup (SZEK) is a traditional Chinese medicine that improves spleen and stomach function, tonifying the Qi and activating the blood; however, its therapeutic effects in hematopoietic dysfunction and their underlying mechanism remain unexplored. In this study, mice were given cyclophosphamide (100 mg/kg) by intraperitoneal injections for three days to produce hematopoietic dysfunction model. We investigated the hematopoietic effect and mechanism of SZEK in mice with hematopoietic dysfunction via histopathological examination, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting combined with intestinal flora and serum metabolomics analysis. In mice with hematopoietic dysfunction, SZEK (gavage, 0.3 mL/25 g) alleviated pathological damage to the bone marrow and spleen; increased the number of naïve cells (Lin-), hematopoietic stem cells (Lin-Sca-1+c-Kit+), long-term self-renewing hematopoietic stem cells (Lin-Sca-1+c-Kit+CD48-CD150+), B lymphocytes (CD45+CD19+), and macrophages (CD11b+F4/80+) in the bone marrow; and reduced inflammation. Preliminary intestinal flora and serum metabolome analyses indicated that the pro-hematopoietic mechanism of SZEK was associated with macrophage differentiation. Further validation revealed that SZEK promoted hematopoiesis by decreasing the number of M2 macrophages and inhibiting the secretion of negative hematopoietic regulatory factors in mice with hematopoietic dysfunction.

Pulmonary cryptococcosis complicated with pulmonary aspergillosis: a series of studies and a literature review.

BACKGROUND/OBJECTIVE: With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals. METHODS: A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review. RESULT: The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%). CONCLUSION: Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.

Gentiana Scabra Bge Extract (GSE) Protects Against Alcoholic Liver Disease by Regulating the TLR4/NF-κB Pathway in Mice.

BACKGROUND: Alcohol abuse leads to alcoholic liver disease (ALD), for which no effective treatment is yet known. Gentiana Scabra Bge is a traditional Chinese medicine; its extract has a significant liver protection effect, but its effects on the mechanism of improving alcohol-induced toxicity remain unclear. Therefore, this study used cell and mouse models to investigate how Gentiana Scabra Bge extract (GSE) might affect the TLT4/NF-κB inflammation pathway in ALD. METHODS: In mice, we induced the alcoholic liver injury model by applying alcohol and induced the inflammatory cell model by lipopolysaccharide (LPS)-induced macrophages. Using an enzyme-linked immunosorbent assay (ELISA) kit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured in liver tissue; we also performed histological analysis of liver tissue sections to assess the hepatoprotective effect of GSE on alcohol. Using real-time fluorescence quantification, we determined the expression of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA levels; we used Western blotting to detect the expression of TLR4/NF-κB signaling pathway-related proteins. RESULTS: We demonstrate that GSE decreased AST and ALT activity, ameliorated liver dysfunction, decreased cytokine levels, and reduced LPS-induced cellular inflammation. In addition, GSE protected mouse liver cells from the inflammatory response by reducing alcohol-induced liver pathological damage and downregulating genes and proteins such as nuclear factors. CONCLUSIONS: GSE can attenuate liver injury in mice through the TLR4/NF-κB pathway by inhibiting the activation of nuclear factors.

VIGA: a one-stop tool for eukaryotic virus identification and genome assembly from next-generation-sequencing data.

Identification of viruses and further assembly of viral genomes from the next-generation-sequencing data are essential steps in virome studies. This study presented a one-stop tool named VIGA (available at https://github.com/viralInformatics/VIGA) for eukaryotic virus identification and genome assembly from NGS data. It was composed of four modules, namely, identification, taxonomic annotation, assembly and novel virus discovery, which integrated several third-party tools such as BLAST, Trinity, MetaCompass and RagTag. Evaluation on multiple simulated and real virome datasets showed that VIGA assembled more complete virus genomes than its competitors on both the metatranscriptomic and metagenomic data and performed well in assembling virus genomes at the strain level. Finally, VIGA was used to investigate the virome in metatranscriptomic data from the Human Microbiome Project and revealed different composition and positive rate of viromes in diseases of prediabetes, Crohn's disease and ulcerative colitis. Overall, VIGA would help much in identification and characterization of viromes, especially the known viruses, in future studies.

Clinical characteristics of tracheobronchial Talaromyces marneffei infection in non-HIV-infected patients in South China.

OBJECTIVES: Tracheobronchial Talaromyces marneffei (T. marneffei) infections among non-HIV-infected patients are rare. To improve understanding, we analysed the clinical features, immune mechanisms, treatment, and prognosis. METHODS: Data on hospitalized patients with tracheobronchial T. marneffei infections from September 2013 to May 2022 were collected. The clinical and imaging features were analysed. RESULTS: Nineteen patients were enrolled, with a median age of 52 years (45-62 years). The most common symptoms were cough, expectoration, fever, weight loss, and anaemia. The total white blood cell and neutrophil counts, erythrocyte sedimentation rate, C-reactive protein, procalcitonin and globulin were increased, and the serum albumin levels were decreased. Chest CT manifestations included patchy shadows, masses, obstructive atelectasis, cavities, pleural effusion, and hilar and mediastinal lymphadenopathy. The fibreoptic bronchoscopy findings included masses, polyps or nodules with mucosal oedema, hypertrophic bulges, lumen stenosis or obstruction, and purulent secretions. T. marneffei infection was confirmed in 10 patients by positive culture, in five by both culture and metagenomic next-generation sequencing (mNGS), in two by mNGS, in one by culture and pathology and in 1 by histopathology. BALF (15/19, 78.9%) had the highest culture positive rate, followed by sputum (3/19), bronchial mucosa (1/1), lung biopsy (1/2); 36.8% of the patients were coinfected with other pathogens. For induction therapy, 7, 6, 2, and 4 patients received voriconazole, amphotericin B, voriconazole combined with amphotericin B, and fluconazole therapy, respectively, and 26.3% received treatment combined with nebulization and/or administration of amphotericin B under fibreoptic bronchoscopy. Four patients were treated for underlying diseases or coinfection, 31.6% were cured, 42.1% improved, and 26.3% died. CONCLUSIONS: T. marneffei infection is common in the tracheobronchial airway tissue or secretions, and bronchoscopy has important diagnostic and treatment value. Antifungal therapy, including systemic therapy, involves triazoles and amphotericin administration, and aerosol inhalation and administration of amphotericin B under bronchoscopy are important.

T. marneffei infection involving the tracheobronchial region in airway tissue or secretions is high, and bronchoscopy has important value in diagnosing and treating these patientsThe use of triazoles and amphotericin and the aerosol inhalation and instillation of amphotericin B under bronchoscopy are essential to antifungal therapy.

Subacute infective endocarditis due to Lodderomyces elongisporus: a case report and review of the literature.

Lodderomyces elongisporus, a rare emerging pathogen, can cause fungemia often related to immunosuppression or intravenous devices. Herein, we report the case of a 58-year-old woman with subacute infective endocarditis due to Lodderomyces elongisporus identified by blood fungal culture and whole-genome sequencing, who was treated with antifungals, mitral replacement and endocardial vegetation removal surgery.

Mitigating the impact of bisphenol A exposure on mortality: Is diet the key? A cohort study based on NHANES.

Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal.

Hyperoside Nanomicelles Alleviate Atherosclerosis by Modulating the Lipid Profile and Intestinal Flora Structure in High-Fat-Diet-Fed Apolipoprotein-E-Deficient Mice.

Atherosclerosis (AS) is a serious threat to human health and the main pathological basis of cardiovascular disease. Hyperoside (Hyp), a flavonoid found mainly in traditional Chinese herbs, can exert antitumor, anti-inflammatory, antioxidant, and cardiovascular-protective effects. Herein, we prepared hybrid nanomicelles (HFT) comprising Hyp loaded into pluronic F-127 and polyethylene glycol 1000 vitamin E succinate and assessed their effects on AS. To establish an AS model, apolipoprotein-E-deficient (ApoE-/-) mice were fed a high-fat diet. We then analyzed the effects of HFT on AS-induced changes in aortic tissues and metabolic markers, simultaneously assessing changes in gut flora community structure. In mice with AS, HFT significantly reduced the aortic plaque area; decreased levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, inflammatory factors, and inducible nitric oxide synthase (NOS); increased high-density lipoprotein cholesterol, endothelial NOS, superoxide dismutase, catalase, and glutathione levels; and promoted the proliferation of beneficial gut bacteria. HFT could regulate intestinal flora structure and lipid metabolism and inhibit inflammatory responses. These beneficial effects may be mediated by inhibiting nuclear factor kappa B signal activation, reducing inflammatory factor expression and improving gut microflora structure and dyslipidemia. The present study provides an empirical basis for the development and clinical application of new dosage forms of Hyp.

Sulfated Glycomimetic α-Helical Polypeptides for Antiviral Activity.

In this work, we developed a library of sulfated glycomimetic polypeptides with a high sulfated degree (up to 99%) via a click reaction and sulfation modification, enabling control over the helicity, molecular weight, rigidity, and side-chain structure. Their potentials as the inhibitors of SARS-CoV-2 and common enterovirus were investigated, and the structure-activity relationship was explored in detail. The in vitro results revealed the crucial role of α-helical conformation and sulfated sugar since all the sulfated glycopolypeptides exhibited outperformed activity in suppressing SARS-CoV-2 infection with the inhibition efficiency up to 85%. Other structural properties, including the rigid chain structure and a moderate molecular weight, also contributed to blocking the viral entry into host cells. Among the sulfated glycopolypeptides, L60-SG-POB showed the highest inhibition efficiency with an IC50 of 0.71 µg/mL. Furthermore, these optimized sulfated glycopolypeptides were also capable of preventing enterovirus infection with the inhibition efficiency of up to 86%. This work opens new avenues for the development of synthetic polypeptides bearing sulfated sugars against SARS-CoV-2 and other viruses.

Multicentric Castleman disease of hyaline­vascular variant with paraneoplastic pemphigus results in abnormal lung function: Report of 3 cases.

Castleman disease (CD) is clinically divided into unicentric CD (UCD) and multicentric CD (MCD). Hyaline-vascular variant (HV) is the most common pathological type of UCD, while the plasma cell type (PC) is the most common type of MCD and thus, hyaline-vascular variant multicentric CD (HV-MCD) is a rare type of CD. In addition, its etiology has remained elusive. The present study retrospectively analyzed the medical records of 3 patients diagnosed as HV-MCD admitted to The First Affiliated Hospital of Guangxi Medical University (Guangxi, China) between January 2007 and September 2020. A total of 2 males and 1 female were admitted. The areas involved varied considerably. Respiratory symptoms were seen in 3 cases, along with fever, weight loss and splenomegaly. Damage to the skin and mucous membranes resulted in oral ulcers when accompanied by paraneoplastic pemphigus (PNP). Dry and wet rales were found in all patients. All 3 cases were complicated with PNP and had hypoxemia and obstructive ventilation dysfunction. In accordance with PC-MCD, it manifested as lymph node enlargement and may involve several lymph nodes. Computed tomography mainly indicated bronchiectasis and mediastinal lymph node enlargement. In 1 case, chemotherapy failed after local mass excision, 1 case remitted after chemotherapy but the lung lesion was irreversible and 1 case was untreated and soon died of respiratory failure. The cases of HV-MCD with pulmonary involvement were induced by small airway lesions and associated with poor prognosis. Respiratory symptoms along with systemic symptoms were common.

The anticancer mechanism of Terpenoid-based drug candi-dates: focus on tumor microenvironment.

Cancer is considered to be the most lethal threat to human life globally. Although, versatile strategies have been established in the field of surgery, chemotherapy, radiotherapy and im-munotherapy against cancer, discovery of new therapeutic drugs from natural products still un-derlays anticancer remedy due to their unique functional mechanisms and potential low side ef-fects. Terpenoids are among the most diversified and enormous natural products which have been proved promising in cancer treatment. Some terpenoids have been through multiple stages of clinical trials and some even approved as anticancer agent, but most of these studies empha-sized the direct effects on tumor cells while paying less attention to their systemic effects on tu-mor microenvironment (TME) Therefore, we recruited the patent drugs and investigated drug candidates of terpenoids in this review and summarized their general anti-tumor mechanisms among which the regulation on TME was highlighted. Finally, the prospect on the drug ability of terpenoids and their potential benefits in immunotherapy were discussed to illuminate fur-ther researches on these natural products. Keywords.

Effect of Composite Edible Coatings Combined with Modified Atmosphere Packaging on the Storage Quality and Microbiological Properties of Fresh-Cut Pineapple.

This study investigated the effect of edible coating (EC), modified atmosphere packaging (MAP), and edible coating + modified atmosphere packaging (EC + MAP) treatments on the quality of fresh-cut pineapples during storage at 4 °C. The quality differences were analyzed by measuring the quality, physiological indicators, and total microbial counts. After 8 d of storage, the brightness (L*) values of the EC + MAP and control samples were 72.76 and 60.83, respectively. The water loss and respiratory rate of the EC + MAP were significantly inhibited from 0% and 29.33 mg CO2 kg-1 h-1 to 4.13% and 43.84 mg CO2 kg-1 h-1, respectively. Furthermore, the fresh-cut pineapples treated with EC + MAP presented a good appearance, with lower total soluble solids (TSS) and relative conductivity and higher titratable acid (TA), ascorbic acid (AA), total phenol content, and firmness compared to the other treatment groups. At the end of storage, the EC + MAP samples exhibited the lowest polyphenol oxidase (PPO) activity, peroxidase (POD) activity, and malondialdehyde (MDA) content at 28.53 U, 60.37 U, and 1.47 nmol·g-1, respectively. Furthermore, the efficiency of EC + MAP treatment exceeded that of EC or MAP alone, preventing key problems involving the surface browning and microbiological safety of the fresh-cut pineapples. The results showed that EC + MAP treatment was more successful in maintaining the storage quality and extending the shelf life of fresh-cut pineapples.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Non-inferior efficacy of non-surgical treatment to surgical treatment in patients with nonmetastatic head and neck rhabdomyosarcoma: a SEER-based study.

PURPOSE: Head and neck rhabdomyosarcoma (HNRMS) is a rare but aggressive malignant neoplasm. Given the young patient age and critical anatomy of the head and neck, performing surgery on the primary tumor still remains debatable. This study aimed to evaluate the impact of the non-surgery-based treatment versus surgery-based treatment on patients with nonmetastatic HNRMS. METHODS: Patients diagnosed with nonmetastatic HNRMS between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in our study. Inverse probability treatment weighting (IPTW) method was employed to balance confounding factors between surgery and non-surgery groups. Kaplan-Meier methods and COX regression analyses were used to analyze survival outcomes of overall survival (OS) and cancer-specific survival (CSS). Prognostic nomogram was established to predict survival. RESULTS: A total of 260 eligible patients were extracted from the SEER database. Kaplan-Meier survival curves revealed that there was no significant difference in OS and CSS between the surgery and non-surgery groups both before and after IPTW (p > 0.05). Cox regression analyses and IPTW-adjusted Cox regression analyses for both OS and CSS showed similar survival between the two groups. Prognostic factors were explored and a nomogram for patients in the surgery group was constructed. Risk stratification based on the nomogram indicated that patients in surgery-high-risk group did not benefit from primary surgery. While those in surgery-low-risk group had an equal survival outcome to those in non-surgery group. CONCLUSIONS: Our study revealed that compared to patients receiving surgery, those not receiving surgery had similar survival outcomes for nonmetastatic HNRMS. Our established nomogram may serve as a practical tool for individual prognostic evaluations.

Clinical features of rare disseminated Mycobacterium colombiense infection in nine patients who are HIV-negative in Guangxi, China.

OBJECTIVES: Localized or disseminated infection caused by different nontuberculous mycobacteria (NTM) species has been increasingly reported in recent years, but reports of Mycobacterium colombiense infection are extremely rare. Herein, we analyzed the clinical features of patients with disseminated M. colombiense infection. METHODS: Patients diagnosed with disseminated M. colombiense infection between February 4, 2016 and August 25, 2021 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. RESULTS: NTM infection was diagnosed in 248 HIV-negative patients. Of these, nine patients with disseminated M. colombiense infection were enrolled. Five of these patients were positive for anti-interferon-γ autoantibodies. The lung, lymph nodes, bones, and joints were the most commonly involved organs. Anemia, fever, lymphadenopathy, cough and expectoration, and ostealgia were the most common symptoms. The levels of white blood cells and neutrophils were increased in eight patients. M. colombiense was detected by both metagenomic next-generation sequencing (mNGS) and culture in four patients and only by mNGS in the remaining five patients. All patients received combination anti-NTM therapy; five underwent surgery. The condition of eight patients improved, and one died during the treatment. CONCLUSION: Patients infected with M. colombiense can present as disseminated infections, easily involving multiple organs, such as the lung, lymph nodes, bone, and joints, with fever, lymphadenopathy, and increased white blood cell and neutrophil counts. mNGS plays a crucial role in the early diagnosis of M. colombiense infection. Once diagnosed, timely and effective anti-NTM therapy, combined with local surgery if necessary, can improve the prognosis of patients with this condition.

Cryptotanshinone inhibits oral squamous cell carcinoma through the autophagic pathway.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients, it is urgent to find new and efficient drugs with good safety for clinical treatment. This study aimed to identify potential anticancer drugs starting from the traditional Chinese medicine Salvia miltiorrhiza extract. Cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, was found to significantly induce apoptosis and inhibit proliferation in OSCC. By electron microscopy, autophagosomes were found. Confocal fluorescence microscopy data showed that cryptotanshinone significantly induced autophagy in OSCC cells. Mechanistically, the western blot assay indicated that cryptotanshinone induced cell autophagy through the activation of the LC3 pathway, whereas the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, we demonstrated that cryptotanshinone had a significant antitumor effect in a tumor xenograft model, and no damage to vital organs was observed. Our findings provide evidence that cryptotanshinone may be a novel therapeutic strategy for the treatment of OSCC.

Construction of IMMS Containing Multi-site Liposomes for Dynamic Monitoring of Blood CTC in Patients with Osimertinib-resistant Non-small-cell Lung Cancer and its Mechanism.

OBJECTIVE: This article aims to establish a liquid biopsy system for gene detection of circulating tumor cells (CTC) in lung cancer, systematically analyze the significance of osimertinib resistance, and formulate an individualized diagnosis and treatment plan. METHODS: Liposome-contained magnetic microspheres coated with Fe3O4 nanoparticles were synthesized by microemulsion, and the surface was modified with EGFR antibody to form EGFR/EpCAM multi-site liposome-contained immunomagnetic microspheres (IMMSs). The CTCs were isolated and identified from peripheral blood samples and the cell lines of lung cancer patients collected by the multi-site liposome-contained IMMSs. To investigate the effects of the order of use of IMMSs sequence at different sites on the sorting and trapping efficiency of non-small-cell lung cancer (NSCLC) cells . The preliminary verification of drug-resistant gene function and dynamic monitoring of CTCs in 20 patients with EGFR-positive NSCLC were screened and statistically analyzed before and after osimertinib treatment. Sensitivity analysis and drug resistance evaluation of oxitidine were detected in vitro. RESULTS: Results showed the prepared multi-site liposome-contained IMMSs had high stability and specificity. The number of CTCs in blood samples of the patients with NSCLC was detected, revealing high sorting efficiency, and positive sorting rate reaching more than 90%. We investigated the effect of osimertinib on the HER-2 expression on the EGFR-mutated NSCLC cells and found that osimertinib increased the expression of HER-2 on the cell surface of NSCLC cell lines., And further explored the therapeutic potential of osimertinib combined with T-DM1 at different dosing times. CONCLUSION: Our results demonstrate that the prepared multi-site liposome-contained IMMSs can efficiently isolate CTCs from the peripheral blood in lung cancer. Combined with the experimental data about osimertinib can be effectively identified, the resistant genes of NSCLC including EGFR, which will provide a new scientific basis for guiding clinical medication and formulating individualized treatment plans.