mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases.

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

Bioactive compounds and biological functions of medicinal plant-derived extracellular vesicles.

Extracellular vesicles (EVs) are tiny lipid bilayer-enclosed membrane particles released from a variety of cell types into the surrounding environment. These EVs have massive participated in cell-to-cell communication and interspecies communication. In recent years, plant-derived extracellular vesicles (PDEVs) and "exosome-like" EVs populations found in distinct plants have attracted widespread attention. Especially, research on medicinal plant-derived extracellular vesicles (MPDEVs) are increasing, which are considered a kind of promising natural compound. This review summarizes current knowledge on MPDEVs in terms of bioactive compounds, including small RNA, protein, lipid, and metabolite, have been found on the surface and/or in the lumen of MPDEVs. Moreover, both in vitro and in vivo experiments have shown that MPDEVs exert broad biomedical functions, such as anti-inflammatory, anticancer, antioxidant, modulate microbiota, etc. MPDEVs may be a better substitute than animal-derived extracellular vesicles (ADEVs) because of safety and biocompatibility in the future.

CO2 electrocatalytic reduction to ethylene and its application outlook in food science.

The efficient conversion of CO2 is considered to be an important step toward carbon emissions peak and carbon neutrality. Presently, great efforts have been devoted to the study of efficient nanocatalysts, electrolytic cell, and electrolytes to achieve high reactivity and selectivity in the electrochemical reduction of CO2 to mono- and multi-carbon (C2+) compounds. However, there are very few reviews focusing on highly reactive and selective ethylene production and application in the field of electrochemical carbon dioxide reduction reaction (CO2RR). Ethylene is a class of multi-carbon compounds that are widely applied in industrial, ecological, and agricultural fields. This review focuses especially on the convertibility of CO2 reduction to generate ethylene technology in practical applications and provides a detailed summary of the latest technologies for the efficient production of ethylene by CO2RR and suggests the potential application of CO2RR systems in food science to further expand the application market of CO2RR for ethylene production.

ZNF671 methylation test in cervical scrapings for cervical intraepithelial neoplasia grade 3 and cervical cancer detection.

Effective triage of high-risk human papillomavirus (hrHPV)+ women is warranted to avoid unnecessary referral and overtreatment. Molecular triage tests have recently begun to impact cervical intraepithelial neoplasia grade 3 (CIN3) or cervical cancer (CC), termed CIN3+, detection. We find that zinc finger protein 671 methylation (ZNF671m) test has superior performance for CIN3+ detection in all single molecular triage tests, including HPV16/18 genotyping, paired box gene 1 methylation (PAX1m), and ZNF671m, in the training set. Using ZNF671m test instead of Thinprep cytologic test (TCT) as a single triage strategy or as a combined triage strategy with HPV16/18 genotyping has achieved comparable sensitivity but higher specificity for CIN3+ detection among 391 hrHPV+ women in the validation set. Little attention has been paid to the women with hrHPV- status but detected CIN3+. We find that the CIN3+ risk after a negative result could be reduced further by triage using ZNF671m in hrHPV- patients.

Advances in biomimetic hydrogels for organoid culture.

An organoid is a 3-dimensional (3D) cell culture system that mimics the structural and functional characteristics of organs, and it has promising applications in regenerative medicine, precision drug screening and personalised therapy. However, current culture techniques of organoids usually use mouse tumour-derived scaffolds (Matrigel) or other animal-derived decellularised extracellular matrices as culture systems with poorly defined components and undefined chemical and physical properties, which limit the growth of organoids and the reproducibility of culture conditions. In contrast, some synthetic culture materials have emerged in recent years with well-defined compositions, and flexible adjustment and optimisation of physical and chemical properties, which can effectively support organoid growth and development and prolong survival time of organoid in vitro. In this review, we will introduce the challenge of animal-derived decellularised extracellular matrices in organoid culture, and summarise the categories of biomimetic hydrogels currently used for organoid culture, and then discuss the future opportunities and perspectives in the development of advanced hydrogels in organoids. We hope that this review can promote academic communication in the field of organoid research and provide some assistance in advancing the development of organoid cultivation technology.

MFNG is an independent prognostic marker for osteosarcoma.

BACKGROUND: Osteosarcoma (OS) has been the most common malignancy of the bone in children and adolescents, and the unsatisfactory prognosis of OS sufferers has long been a hard nut. Here, we delved into the markers with a prognostic value for predicting the prognosis of OS patients. METHODS: The messenger RNA (mRNA) sequencing data and clinical data of OS were retrieved from a Gene Expression Omnibus (GEO) dataset (GSE39058). Next, prognosis-related genes (PRGs) were filtered with the aid of Kaplan-Meier (K-M) curves and Cox regression analysis (CRA). Later, Gene Ontology (GO) biological process analysis was used in verifying the function of different genes. CCK-8 and cell apoptosis assay were performed to evaluate the function of MFNG in U2OS cells. RESULTS: Among the obtained genes, Manic Fringe (MFNG) had the closest relevance to prognosis and clinical traits, thus becoming the research object herein. In light of the expression level of MFNG, patients fell into high- and low-MFNG groups. Patients with elevated MFNG expression had a worse prognosis, according to the survival analysis. It was unveiled by the univariate and multivariate analyses that MFNG expression was an independent adverse prognostic factor for disease-free survival in OS patients (p = 0.006). Meanwhile, MFNG expression was linked to gender and tumor recurrence, and it was higher in patients with OS recurrence. Moreover, overexpression of MFNG promoted the cell proliferation and inhibited the cell apoptosis of U2OS cells. CONCLUSIONS: The expression level of MFNG negatively correlated with OS progression, and as an independent adverse prognostic factor for disease-free survival in OS patients. Moreover, MFNG regulated the cell proliferation and apoptosis of OS cells.

Efficacy of endoscopic ultrasound and endoscopic resection for esophageal schwannoma.

BACKGROUND: Esophageal schwannoma (ES) is a rare submucosal tumor, and its complete and safe resection is a topic that deserves special attention. AIM: This study aimed to investigate the clinical value of endoscopic ultrasound (EUS) in the diagnosis of ES and the clinical efficacy of endoscopic resection for ES. METHODS: The clinical data, endoscopic characteristics, endoscopic treatment, postoperative complications, immunohistochemical results, and follow-up records of patients with ES admitted to the Tianjin Medical University General Hospital from January 2012 to January 2022 were retrospectively analyzed. RESULTS: Under white-light endoscopy, 81.8% (9/11) of lesions were submucosal elevations, covering the normal esophageal epithelium. Two of the lesions with redness and erosive surface. Eight lesions (72.7%) appear on EUS originating from the muscularis propria were homogeneous or inhomogeneous hypoechoic signals. Two lesions were inhomogeneous hyperechoic originating from the submucosa or muscularis propria, respectively. One lesion was homogeneous hypoechoic originating from the submucosa. All lesions had no blood flow signals, cystic changes, or calcification, and were completely removed by submucosal tunnel endoscopic resection (STER) or endoscopic submucosal dissection (ESD). All patients did not experience serious adverse events as well as recurrence, metastasis, or cicatricial esophageal stenosis during the follow-up period. CONCLUSION: ES is a rare submucosal lesion, which endoscopic characteristics are difficult to distinguish from other esophageal submucosal tumors. Endoscopic resection can provide a minimally invasive and alternative treatment for ES.

Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion.

Cervical cancer (CC) remains one of the leading causes of cancer-related deaths worldwide. However, cervical cancer is preceded by the pre-malignant cervical intraepithelial neoplasia (CIN) that can last for up to 20 years before becoming malignant. Therefore, early screening is the key to prevent the progression of cervical lesions into invasive cervical cancer and decrease the incidence. The genes, down-regulated and hypermethylated in cancers, may provide potential drug targets for cervical cancer. In our current study, using the datasets from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, we found that endothelin 3 (EDN3) was downregulated and hypermethylated in cervical squamous cell carcinoma (CSCC). The further analysis in GSE63514 (n=128) dataset and in our samples (n=221) found that the expression of EDN3 was decreased with the degree of cervical lesions. Pyrosequencing was performed to evaluate 4 CpG sites of the EDN3 promoter region in our samples (n=469). The data indicated that the methylation level of EDN3 was increased with the degree of cervical lesions. EDN3 silencing mediated by methylation can be blocked by 5-Azacytidine (5-Aza), a DNA methyltransferase 1 (DNMT1) inhibitor, treatment in cervical cancer cell lines. Ethynyldeoxyuridine (EdU) assay, would-healing assay, clone formation assay and transwell assay were conducted to investigate the biological function of EDN3 in cervical cancer cell lines. The results of these experiments confirmed that overexpression of EDN3 could inhibit the proliferation, clone formation, migration and invasion of cervical cancer cells. EDN3 may provide potential biomarker and therapeutic target for CSCC.

Long-term exposure to PM2.5 and PM10 and chronic kidney disease: the Beijing Health Management Cohort, from 2013 to 2018.

Long-term exposure to ambient particulate pollutants (PM2.5 and PM10) may increase the risk of chronic kidney disease (CKD), but the results of previous research were limited and inconsistent. The purpose of this study was to assess the relationships of PM2.5 and PM10 with CKD. This study was a cohort study based on the physical examination data of 2082 Beijing residents from 2013 to 2018 in the Beijing Health Management Cohort (BHMC). A land-use regression model was used to estimate the individual exposure concentration of air pollution based on the address provided by each participant. CKD events were identified based on self-report or medical evaluation (estimated glomerular filtration rate, eGFR less than 60 ml/min/1.73 m2). Finally, the associations of PM2.5 and PM10 with CKD were calculated using univariate and multivariate logistic regression models. During the research period, we collected potentially confounding information. After adjusting for confounders, each 10 µg/m3 increase in PM2.5 and PM10 exposure was associated with an 84% (OR: 1.84; 95% CI: 1.45, 2.33) and 37% (OR: 1.37; 95% CI: 1.15, 1.63) increased risk of CKD. Adjusting for the four common gaseous air pollutants (CO, NO2, SO2, O3), the effect of PM2.5 and PM10 on CKD was significantly enhanced, but the effect of PM10 was no longer significant in the multi-pollutant model. The results of the stratified analysis showed that PM2.5 and PM10 were more significant in males, middle-aged and elderly people over 45 years old, smokers, drinkers, BMI ≥ 24 kg/m2, and abnormal metabolic components. In conclusion, long-term exposure to ambient PM2.5 and PM10 was associated with an increased risk of CKD.

Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function.

Adiponectin, an adipokine secreted by adipocytes, has anti-atherosclerotic and antithrombotic activities. AdipoRon is synthetic small molecule adiponectin receptor agonist. In this study, we investigated the effect of AdipoRon on platelet activation and thrombus formation. Washed human platelets were prepared from the peripheral blood of healthy donors. In a series of in vitro platelet functional assays, pre-treatment with AdipoRon (10, 20, 40 µg/mL) dose-dependently inhibited the aggregation, granule secretion and spreading of washed human platelets. We showed that AdipoRon (20, 40 µg/mL) significantly inhibited AMPK, Syk, PLCγ2, PI3K, Akt, p38-MAPK and ERK1/2 signalling pathways in washed human platelets. In addition, we demonstrated that the phosphorylation of CKII at Tyr255 was an important mechanism of the integrin αIIbß3-mediated platelet activation. Meanwhile, AdipoR1 deficiency impaired the inhibitory effect of AdipoRon on mouse platelets. In ferric chloride-induced carotid injury model, injection of AdipoRon (5 or 12.5 mg/kg, iv) significantly attenuated arterial thrombosis. In conclusion, AdipoRon attenuates platelet function via the AdipoR1/AMPK/CKII/PI3K/AKT signalling pathways, while exerting a protective effect against arterial thrombosis. This study offers new insights into the fields of cardiovascular disease and antiplatelet drug discovery.Schematic model of AdipoRon regulating platelet activation. (BioRender.com).

Endoscopic resection in the treatment of intramural esophageal bronchogenic cysts: A retrospective analysis of 17 cases.

BACKGROUND: Intramural esophageal bronchogenic cysts (EBCs) are rare congenital malformations. Differences in reports on the clinical features of intramural EBCs and some controversies about the treatment strategy for intramural EBCs exist. OBJECTIVES: To investigate the clinical characteristics of intramural EBCs and evaluate the safety and efficacy of endoscopic resection. METHODS: The clinical and endoscopic features, endoscopic resection treatment, postoperative adverse events, and follow-up results of 17 patients with intramural EBCs were retrospectively studied. RESULTS: Intramural EBCs exhibited male predominance with a male/female ratio of 58.8% (10/7) and were predominantly found in the distal esophagus. Approximately 94.1% of patients presented with gastrointestinal symptoms. All lesions were protruding masses covered by intact mucosal epithelium. The morphologies of intramural EBCs were diverse under white light endoscopy. On endoscopic ultrasonography, intramural EBCs presented as homogeneous or inhomogeneous hypoechoic or anechoic lesions. Eleven lesions originated from the muscularis propria, which underwent submucosal tunnel endoscopic resection (STER), and six lesions were from the submucosa, which underwent endoscopic submucosal dissection (ESD). Approximately 88.2% of patients underwent complete endoscopic resection. No serious pneumothorax, bleeding, pleural effusion, esophagotracheal fistula, or other adverse events occurred in all patients after endoscopic resection, and no cyst recurrence, metastasis, or esophageal scar stenosis was observed during the follow-up period. CONCLUSIONS: Intramural EBCs can be treated by digestive endoscopic surgery. STER and ESD are safe, effective, and minimally invasive resection methods.

Role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors.

BACKGROUND AND AIM: Diagnosis and complete resection of esophageal granular cell tumors (GCTs) is an area of concern. However, articles on endoscopic ultrasound (EUS) and endoscopic resection of esophageal granular cell tumors are few. To evaluate the role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors. METHODS: A retrospective analysis of 15 patients with esophageal granular cell tumors who underwent endoscopic ultrasound examination and endoscopic resection in our hospital was conducted. The clinical data, endoscopic ultrasound images, endoscopic treatment, pathological characteristics, postoperative complications and follow-up status of all patients were evaluated. Ten board-certified endoscopists independently evaluated the white light endoscopic images of the 15 patients (Test 1) and the endoscopic ultrasound images together with white light endoscopic images of the same patient set (Test 2). RESULT: Female patients accounted for 53.4% of the participants. The average age at the time of diagnosis was 49.13 ± 9.31 years old. Ten lesions (66.67%) showed hypoechoic signal, four lesions (26.67%) showed hyperechoic signal and one lesion showed medium signal. The diagnostic accuracy was significantly higher with Test 2(65.3% vs. 92.0%, p < .001). Complete endoscopic resection was performed in all the patients. No complications occurred in any of the patients. No esophageal stenosis, recurrence, or metastases was found in all patients during the follow-up period. CONCLUSION: The endoscopic ultrasound images of esophageal granular cell tumors have certain characteristics that help diagnose esophageal granular cell tumors. Endoscopic resection of esophageal granular cell tumors is an effective, safe and feasible treatment method.

Cinnamic Acid Improved Lipopolysaccharide-Induced Depressive-Like Behaviors by Inhibiting Neuroinflammation and Oxidative Stress in Mice.

AIM: Recent evidence indicates that neuroinflammation and oxidative stress play vital roles in the pathological process of major depressive disorder (MDD). Cinnamic acid (CA), a naturally occurring organic acid, has been reported to ameliorate neuroinflammation and oxidative stress for treatment of diabetes-related memory deficits. Here, we explored whether CA pretreatment ameliorated lipopolysaccharide (LPS)-induced depressive-like behaviors in mice by suppressing neuroinflammation and by improving oxidative stress status. METHODS: The mice were treated with CA, vehicle, or fluoxetine as a positive control. After 14 days, LPS (1 mg/kg, i.p.) or saline was administered. The depression-like behaviors were examined by the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). Furthermore, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex of mice were assayed. RESULTS: Our results demonstrated that CA pretreatment at the doses of 100 and 200 mg/kg significantly attenuated depressive-like behaviors in the TST, FST, and SPT. In addition, not only the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) but also oxidative stress parameters including SOD, GSH, and MDA in the hippocampus and cortex of mice treated with LPS were dramatically improved by CA pretreatment. Finally, CA pretreatment strikingly ameliorated the downregulation of BDNF induced by LPS in the hippocampus and cortex of mice. CONCLUSION: Our results indicated that CA may have therapeutic potential for MDD treatment through attenuating the LPS-induced inflammation and oxidative stress along with significant improvement of BDNF impairment.

Extracellular ATP and cAMP signaling promote Piezo2-dependent mechanical allodynia after trigeminal nerve compression injury.

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, a mechanically gated ion channel that mediates tactile allodynia in neuropathic pain, can be potentiated by a cyclic adenosine monophosphate (cAMP)-dependent signaling pathway that involves the exchange protein directly activated by cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization in a rat model of TN after trigeminal nerve compression injury, the expression of Piezo2 and activation of cAMP signal-related molecules in the trigeminal ganglion (TG) were detected. Changes in purinergic P2 receptors in the TG were also studied by RNA-seq. The expression of Piezo2, cAMP, and Epac1 in the TG of the TN animals increased after chronic compression of the trigeminal nerve root (CCT) for 21 days, but Piezo2 knockdown by shRNA in the TG attenuated orofacial mechanical allodynia. Purinergic P2 receptors P2X4, P2X7, P2Y1, and P2Y2 were significantly up-regulated after CCT injury. In vitro, Piezo2 expression in TG neurons was significantly increased by exogenous adenosine 5'-triphosphate (ATP) and Ca2+ ionophore ionomycin. ATP pre-treated TG neurons displayed elevated [Ca2+ ]i and faster increase in responding to blockage of Na+ /Ca2+ exchanger by KB-R7943. Furthermore, mechanical stimulation of cultured TG neurons led to sustained elevation in [Ca2+ ]i in ATP pre-treated TG neurons, which is much less in naïve TG neurons, or is significantly reduced by Piezo2 inhibitor GsMTx4. These results indicated a pivotal role of Piezo2 in peripheral mechanical allodynia in the rat CCT model. Extracellular ATP, Ca2+ influx, and the cAMP-to-Epac1 signaling pathway synergistically contribute to the pathogenesis and the persistence of mechanical allodynia.

Therapeutic Potential of Exosomal circRNA Derived from Synovial Mesenchymal Cells via Targeting circEDIL3/miR-485-3p/PIAS3/STAT3/VEGF Functional Module in Rheumatoid Arthritis.

BACKGROUND: Synovial inflammation and its associated activation of angiogenesis play critical roles in rheumatoid arthritis (RA). Exosomes, as carriers of genetic information including circular RNAs (circRNAs), have been explored as delivery vehicles for therapeutic molecules. However, the effects of synovial mesenchymal stem cells (SMSCs)-derived exosomal circRNAs and their mechanisms of action in RA progression remain unclear. METHODS: SMSCs-derived exosomes (SMSCs-Exos) were administered to a co-culture of RA fibroblast-like synoviocytes (RA-FLS) and human dermal microvascular endothelial cells (HDMECs) in vitro as well as to a collagen-induced arthritis (CIA) mouse model in vivo. Their effects on VEGF expression and angiogenic activity in vitro and the therapeutic efficacy in vivo were evaluated. Exosomes from circEDIL3-overexpressing SMSCs (Ad-circEDIL3-SMSCs-Exos) were used to further determine the role of circEDIL3 in SMSCs-Exo-based therapy. RESULTS: Both SMSCs-Exos and Ad-circEDIL3-SMSCs-Exos significantly downregulated the expression of VEGF induced by the IL-6/sIL-6R complex in the supernatants of RA-FLS and HDMECs co-culture as well as in the cell lysate of co-cultured RA-FLS, and the extent of reduction was more pronounced in the latter. Subsequent experiments showed that angiogenic activity was significantly downregulated by SMSCs-Exos and Ad-circEDIL3-SMSCs-Exos due to reduced VEGF expression. CircEDIL3 functioned as a sponge for miR-485-3p, which targeted PIAS3. PIAS3 is known to suppress STAT3 activity and reduce downstream VEGF. Injection of SMSCs-Exos or Ad-circEDIL3-SMSCs-Exos reduced synovial VEGF and consequently ameliorated arthritis severity in the CIA mouse model. CONCLUSION: The intracellular transfer of circEDIL3 by SMSCs-Exos may be a potential novel therapeutic strategy for RA.

Co-occurrence of TCF3-PBX1 gene fusion, and chromosomal aberration in a pediatric pre-B cell acute lymphoblastic leukemia with clitoris swelling: A case report and literature review.

RATIONALE: Clitoris swelling as the initial clinical presentation of acute lymphoblastic leukemia (ALL) is extremely rare. These patients may be misdiagnosed with acute myeloid leukemia or solid tumor, and the main treatment can also be delayed. PATIENT CONCERNS: A 2.10-year-old girl was referred to the pediatric surgery clinic with a worsening onset of clitoris swellings. The patient was afebrile and well appearing. Multiple retroperitoneal mass were confirmed by computed tomography (CT) and high serum neuron-specific enolase level was high. She was scheduled for an abdominal biopsy from the retroperitoneal mass suspicious of neuroblastoma. DIAGNOSES: The child was eventually diagnosed as having precursor B cell ALL with central nervous system involved, with TCF3-PBX1 fusion gene and additional chromosomal aberrations, based on examinations of the bone marrow and brain magnetic resonance imaging. INTERVENTIONS: Before the diagnosis of leukemia, the patient was given symptomatic treatment for 1 week. She was treated with chemotherapy in accordance with the Chinese Children's Cancer Group protocol 2015 after confirmed diagnosis. OUTCOMES: After induction chemotherapy for ALL, although the girl had transiently clinical remission, the bone marrow aspirate indicated a poor outcome. Our patient discontinued treatment and discharged. From literature review, there was only 1 case of in acute myeloid leukemia with clitoris swelling as the initial symptom. LESSONS: The clinical symptoms of ALL with clitoris swelling are not typical, with a high rate of misdiagnosis. When the cause of clitoris swelling is unknown, ALL should be considered. Bone marrow aspiration must be done before doing a more invasive investigation like biopsy.

Anlotinib Alone or in Combination With Temozolomide in the Treatment of Recurrent High-Grade Glioma: A Retrospective Analysis.

Background: Anlotinib is a multi-target anti-angiogenic agent. This retrospective study aimed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide for the treatment of recurrent high-grade glioma. Materials and Methods: The clinical data of patients with recurrent high-grade glioma treated with anlotinib alone or in combination with temozolomide in our cancer center were collected and analyzed. Treatment response was evaluated according to the response assessment for neuro-oncology criteria. Progression-free survival, progression-free survival at 6 months, overall survival, and overall survival at 12 months were evaluated by Kaplan-Meier method and compared by log-rank test. Results: Between August 2019 and December 2020, 31 patients with recurrent high-grade glioma (21 of grade 4 and 10 of grade 3) were enrolled in this study. Seventeen patients received anlotinib alone and 14 received anlotinib plus temozolomide. All patients were heavily treated, the median lines of previous treatments were 2, and the median Karnofsky score was 60. At the data cutoff date, the median progression-free survival was 4.5 months and the progression-free survival at 6 months was 43.5%. The median overall survival was 7.7 months, and the overall survival at 12 months was 26.7%. The progression-free survival at 6 months and the overall survival at 12 months for 21 patients with grade 4 glioma was 40.2 and 27.9%, respectively. The tumor objective response rate was 41.9% in all patients and 33.3% in patients with grade 4 glioma. No grade 3 or worse treatment-related adverse events were recorded during the treatment. Conclusion: Anlotinib alone or in combination with temozolomide showed encouraging efficacy and favorable tolerability in patients with recurrent high-grade glioma who had been heavily treated.

Identification and Verification on Prognostic Index of Lower-Grade Glioma Immune-Related LncRNAs.

Previous studies have shown that the prognosis of patients with lower-grade glioma (LGG) is closely related to the infiltration of immune cells and the expression of long non-coding RNAs (lncRNAs). In this paper, we applied single-sample gene set enrichment analysis (ssGSEA) algorithm to evaluate the expression level of immune genes from tumor tissues in The Cancer Genome Atlas (TCGA) database, and divided patients into the high immune group and the low immune group, which were separately analyzed for differential expression. Venn analysis was taken to select 36 immune-related lncRNAs. To construct a prognostic model of LGG based on immune-related lncRNAs, we divided patients into a training set and a verification set at a ratio of 2:1. Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to select 11 immune-related lncRNAs associated with the prognosis of LGG, and based on these selected lncRNAs, the risk scoring model was constructed. Through Kaplan-Meier analysis, the overall survival (OS) of patients in the high-risk group was significantly lower than that of the low-risk group. Then, established a nomogram including age, gender, neoplasm histologic grade, and risk score. Meanwhile, the predictive performance of the model was evaluated by calculating the C-index, drawing the calibration chart, the clinical decision curve as well as the Receiver Operating Characteristic (ROC) curve. Similar results were obtained by utilizing the validation data to verify the above consequences. Based on the TIMER database, the correlation analysis showed that the 11 immune-related lncRNAs risk score of LGG were in connection with the infiltration of the subtypes of immune cells. Subsequently, we performed enrichment analysis, whose results showed that these immune-related lncRNAs played important roles in the progress of LGG. In conclusion, these 11 immune-related lncRNAs have the potential to predict the prognosis of patients with LGG, which may play a key role in the development of LGG.

Thrombocytopenia and thrombosis in hospitalized patients with COVID-19.

As our understanding on coronavirus disease 2019 (COVID-19) deepens, it is increasingly recognized that COVID-19 is more than a respiratory condition. Thrombocytopenia and thromboembolic complications are a composite factor associated with critical COVID-19 and increased mortality. Immune-inflammation-mediated destruction, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per se and increased consumption are proposed to be responsible for thrombocytopenia. Multiple concomitant conditions or results caused by SARS-CoV-2 infection are high risk factors for thrombosis. Recently, platelet activation and platelet-mediated immune inflammation induced by SARS-CoV-2 infection were also found to be the contributors to the thrombosis in COVID-19 patients. In addition to thrombus scoring system, D-dimer is an excellent indicator for monitoring thrombosis. COVID-19 patients with high risk for thrombosis should be subjected to early thromboprophylaxis, and prolonged activated partial-thromboplastin time should not be a barrier to the use of anticoagulation therapies in the control of thrombosis in COVID-19 patients.

STAT3-PTTG11 abrogation inhibits proliferation and induces apoptosis in malignant glioma cells.

Pituitary tumor transforming gene 1 (PTTG11) is abundantly expressed in glioma. Our previous study demonstrated that the downregulation of PTTG11 gene expression significantly inhibited the proliferation, migration and invasion ability, and increased the apoptosis of SHG44 glioma cells. However, the molecular mechanisms that regulate PTTG11 and its actions remain elusive. In the present study, CCK-8 and flow cytometry assays were used to assess the proliferation/viability and apoptosis, respectively, of the human glioma U251 cell line. STAT3-PTTG1 signals were further evaluated by western blotting. The findings of the present study revealed that STAT3 induced PTTG11 expression, which subsequently induced downstream c-Myc and Bcl-2 expression while inhibiting Bax expression, thereby promoting cell viability and inhibiting apoptosis. PTTG11 suppression via siRNA inhibited the viability and increased the apoptosis of glioma cells induced by the STAT3 activator S3I-201. c-Myc and Bcl-2 expression was suppressed by PTTG11 inhibition. The findings of the present study suggest that the STAT3-PTTG11 signaling pathway may play an important role in glioma progression by regulating cell proliferation and apoptosis.