LncRNA PVT1 facilitates the growth and metastasis of colorectal cancer by sponging with miR-3619-5p to regulate TRIM29 expression.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis. METHODS: Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo. RESULTS: PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells. CONCLUSIONS: We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.

The Efficacy and Safety of Minocycline-Containing Quadruple Therapies Against Helicobacter pylori Infection: A Retrospective Cohort Study.

Background: Minocycline, a derivative of tetracycline, has anti-Helicobacter pylori (H. pylori) properties and can be used to treat H. pylori infection. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of minocycline-containing quadruple therapy (MCQT) in treating H. pylori infection. This study aimed to determine the efficacy and safety of MCQT and investigate the factors influencing both aspects. Methods: This was a retrospective cohort study. Patients diagnosed with H. pylori infection between January 1, 2022, and July 31, 2023 at. The primary outcome was the eradication rate of H. pylori, and the secondary outcome was the number and type of adverse events. Results: A total of 828 patients were included in this study. The overall H. pylori eradication rate among the included patients at 95% confidence interval (CI) (Range 0.864 to 0.907) was 88.53%. The H. pylori eradication rate for patients who received MCQT regimen as the primary therapy was 92.28% (95% CI: 0.901-0.945), significantly higher than that of patients who received MCQT as rescue therapy (80.81%; 95% CI: 0.761-0.855, P=0.003). Adverse events, including dizziness, abdominal distension, diarrhea, nausea, abdominal discomfort, constipation, headache, rash, sleep disorder, palpitation, backache, and anorexia, occurred in 185 (22.34%) patients, with dizziness being the most common (75/828, 9.06%). Compliance with MCQT therapy was an independent factor influencing H. pylori eradication in patients receiving MCQT as a primary therapy. Compliance and presence or absence of H. pylori infection symptoms at the time of screening were independent factors influencing H. Pylori eradication in patients receiving MCQT as rescue therapy. Factors that influenced the occurrence of adverse events included reasons for H. pylori infection screening, residence, treatment compliance, and the use of acid-suppressant regimens. Conclusion: MCQT regimens were effective in H. pylori infection eradication, and the treatment resulted only in fewer adverse events when used as primary or rescue therapies for H. pylori infection treatment. Future prospective studies with larger sample sizes and more comprehensive data are needed to validate our findings.

In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia.

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.

Global burden of disease study analysis of thyroid cancer burden across 204 countries and territories from 1990 to 2019.

Background: The purpose of this study is to assess the burden of thyroid cancer over the course of 30 years in 204 countries and territories. Methods: Data from the Global Burden of Disease (GBD) 2019 database was analyzed to extract information on prevalence, deaths, DALYs(disability-adjusted life-years), YLL(years of life los), YLD(years lived with disability), and their corresponding age-standardized rates at global, regional, and national levels. The primary focus of the study was to examine trends in thyroid cancer from 1990 to 2019, specifically looking at the Estimated Annual Percentage Change (EAPC) for ASPR, ASDR, and ASDR. Additionally, the study investigated the relationship between cancer burden and the Socio-Demographic Index (SDI). Results: Globally, there will be approximately 18.3 million thyroid cancer (TC) cases in 2019; China and the USA are projected to be the most significant with 310,327 and 220,711 cases (16.17 and 14.82 cases per 100,000 people, respectively).Over the period from 1990 to 2019, age-standardized prevalence rates exhibited a global rise, whereas deaths and DALYs saw a decrease(EAPC:1.63, -0.15- -0.14, respectively). Significantly, the age-standardized prevalence rate increased in 21 GBD regions, affecting 195 out of 204 countries or territories. Over the studied period, thyroid cancer cases, deaths, and DALYs were consistently higher among females than males. Furthermore, a higher Socio-demographic Index was associated with increased age-standardized prevalence rates.

Developmental toxicity and potential mechanisms exposed to polystyrene microplastics and polybrominated diphenyl ethers during early life stages of fat greenling (Hexagrammos otakii).

The occurrence of microplastics (MPs) in aquatic ecosystems and their ability to absorb hydrophobic pollutants, such as persistent organic pollutants (POPs), is currently a significant concern. MPs, which are the main breakdown product of plastics, have been frequently detected in the environment, posing serious threats to organisms' health. One particular pollutant, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), is a dominant congener of PBDEs and is highly toxic to organisms. However, there is limited knowledge regarding the exposure of marine fishes to PBDEs through MPs and their combined toxic effects. In this study, the embryo toxicity of Hexagrammos otakii was conducted to investigate the combined effects of MPs and BDE-47. The results showed that MPs and BDE-47 co-exposure had detrimental effects on embryonic development, such as reduced hatchability, increased mortality, decreased heart rate, and body malformation. Moreover, the combined toxicity of these substances appeared more pronounced harmful effects compared to exposure to BDE-47 alone. Histopathological examination revealed that co-exposure can cause greater damage to hatching glands and yolk. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included phagosome, metabolism of xenobiotics by cytochrome P450, TCA cycle, and Wnt signaling pathway, which are closely related to embryonic growth. BDE-47 and MPs may activate the Wnt signaling pathway to affect the normal development of embryos. Our results suggest that MPs and BDE-47 exposure may cause growth disorders in the early life stages of H.otakii, leading to abnormal embryonic development. All these results will contribute to the further study of the ecological risk assessment and toxicity of MPs and organic pollutant mixtures in marine fish.

The effects and mechanisms of natural products on Helicobacter pylori eradication.

Helicobacter pylori (H. pylori) eradication is pivotal for alleviating gastric mucosal inflammation and preventing the progression of gastric diseases. While antibiotic-based therapies have achieved significant success in H. pylori eradication, challenges such as antibiotic resistance, drug toxicity, side effects, nonadherence, inapplicability, and disruption of gastrointestinal microflora have emerged. Updated therapies are urgently needed to suppress H. pylori. Nature has provided multitudinous therapeutic agents since ancient times. Natural products can be a potential therapy endowed with H. pylori eradication efficacy. We summarize the basic information, possible mechanisms, and the latest research progress of some representative natural products in H. pylori eradication, highlighting their safety, accessibility, efficiency, and ability to overcome limitations associated with antibiotic application. This review highlights the potential therapeutic advantages of incorporating ethnomedicine into anti-H. pylori regimens. The findings of this review may provide insights into the development of novel natural products and expand the therapeutic options available for H. pylori eradication.

1q21+ is associated with poor prognosis in newly diagnosed multiple myeloma patients with extramedullary disease: a retrospective study.

1q21+ is a common cytogenetic abnormality in multiple myeloma (MM) and is considered an independent predictor of poor prognosis; however, its impact on extramedullary disease (EMD) remains unknown. Our study reviewed the clinical relevance and prognostic value of 1q21+ status in 92 patients with NDMM and EMD. 1q21+ was detected in 23.9% (22/92) of patients. Patients with 1q21+ presented with advanced International Staging System stages (P = 0.006), lower level of hemoglobin (P = 0.004), higher percentage of plasma cells in the bone marrow (P < 0.001), higher level of serum ß2-microglobulin (7.24 g/L vs. 3.85 g/L, P = 0.003), and higher levels of lactic dehydrogenase (LDH) (206.5 U/L vs. 177 U/L, P = 0.019). The prevalence of soft tissue-related EMD (EMD-S) (54.5% vs. 18.6%, P < 0.001), renal dysfunction (50.5% vs. 17.7%, P = 0.002), and hypercalcemia (27.3% vs. 7.1%, P = 0.011) was also higher. 1q21+ was strongly associated with other high-risk cytogenetic abnormalities, including IgH/FGFR3 (22.7% vs. 4.3%, P = 0.007) and IgH/MAF translocations (22.7% vs. 1.4%, P < 0.001). 1q21+ patients had significantly shorter overall survival (OS) and progression-free survival (PFS) (OS: 24 months vs. 47 months, P = 0.002; PFS: 14 months vs. 38 months, P < 0.001); the poor survival outcomes could not be reversed by autologous hematopoietic stem cell transplantation. Multivariate analysis suggested that 1q21+ , EMD-S, elevated lactate dehydrogenase (LDH) levels, and P53 deletion were independent risk factors for poor prognosis in patients with EMD. In patients with 1q21+ EMD, hypercalcemia, elevated LDH levels, and P53 deletion were independent adverse risk prognostic factors.

Setup margins based on the inter- and intrafractional setup error of left-sided breast cancer radiotherapy using deep inspiration breath-hold technique (DIBH) and surface guided radiotherapy (SGRT).

PURPOSE: The use of volumetric modulated arc therapy (VMAT), simultaneous integrated boost (SIB), and hypofractionated regimen requires adequate patient setup accuracy to achieve an optimal outcome. The purpose of this study was to assess the setup accuracy of patients receiving left-sided breast cancer radiotherapy using deep inspiration breath-hold technique (DIBH) and surface guided radiotherapy (SGRT) and to calculate the corresponding setup margins. METHODS: The patient setup accuracy between and within radiotherapy fractions was measured by comparing the 6DOF shifts made by the SGRT system AlignRT with the shifts made by kV-CBCT. Three hundred and three radiotherapy fractions of 23 left-sided breast cancer patients using DIBH and SGRT were used for the analysis. All patients received pre-treatment DIBH training and visual feedback during DIBH. An analysis of variance (ANOVA) was used to test patient setup differences for statistical significance. The corresponding setup margins were calculated using the van Herk's formula. RESULTS: The intrafractional patient setup accuracy was significantly better than the interfractional setup accuracy (p < 0.001). The setup margin for the combined inter- and intrafractional setup error was 4, 6, and 4 mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1 mm to the calculated setup margins. CONCLUSION: With SGRT, excellent intrafractional and acceptable interfractional patient setup accuracy can be achieved for the radiotherapy of left-sided breast cancer using DIBH and modern radiation techniques. This allows for reducing the frequency of kV-CBCTs, thereby saving treatment time and radiation exposure.

Relationship Between Liver Fibrosis and Increased Risk of Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients Undergoing Mechanical Thrombectomy.

Background: Liver fibrosis has been reported to be associated with hematoma expansion and mortality in patients with intracerebral hemorrhage. This study aimed to detect the association between liver fibrosis and symptomatic intracranial hemorrhage (sICH) in ischemic stroke after mechanical thrombectomy (MT). Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated with MT at a single stroke center. The fibrosis-4 index (FIB-4) was used to assess the severity of liver fibrosis. sICH was diagnosed according to the Heidelberg Bleeding Classification criteria. Multivariate logistic regression and restricted cubic spline analysis were conducted to examine the relationship between liver fibrosis and sICH. Results: Among the 578 patients (mean age, 70.1 years; 58.5% male) included in the study, 65 (11.2%) individuals were diagnosed with sICH. After adjusting for demographic characteristics and other potential confounders, a higher FIB-4 index was found to be independently associated with an increased risk of sICH (odds ratio: 1.306, 95% confidence interval: 1.127-1.512, P=0.001). Similar results were obtained when analyzing FIB-4 as a categorical variable. Conclusion: This study demonstrated that there is a significant association between FIB-4 and the risk of sICH in patients with acute ischemic stroke who underwent MT. Therefore, liver fibrosis could serve as a valuable parameter in monitoring the risk of sICH following MT.

Mucous cell histopathology and label-free quantitative proteomic analysis of skin mucus in fat greenling (Hexagrammos otakii) infected with Vibrio harveyi.

Hexagrammos otakii is favored by consumers and aquaculture practitioners because of its strong adaptability and fast growth. However, recently, frequent outbreaks of diseases in the breeding of H. otakii have led to significant economic losses, especially due to bacterial diseases, which limit the healthy breeding of H. otakii. As a luminescent Gram-negative bacterium, Vibrio harveyi is the main pathogenic bacteria of H. otakii. In this study, the histopathology and label-free quantitative proteomics analysis were performed to reveal the changes of skin mucus proteins in H. otakii after infection with V. harveyi. The histopathological changes in the skin of H. otakii showed that when the bacteria were injected into the epithelial cells, it caused an increase in the number of mucous cells and a certain degree of damage and deformation in skin. Moreover, the quantitative proteomics analysis revealed a total of 364 differentially expressed proteins (DEPs), and these DEPs were found to be involved in environmental information processing, metabolism, infectious diseases: bacteria, replication and repair. More importantly, the enrichment analysis of the DEPs revealed that these different proteins were mainly targeted immune-related pathways. After infection of bacteria, the host's immune ability will be weakened, causing V. harveyi to enter the organism more easily, resulting in increased mucus in H. otakii, which will eventually lead to a decline in its physical function. These results provided an insight into a series of physiological changes after the bacterial infection of fish at the proteomic level and basic data for further exploration of the potential mechanism of skin mucus. Taken together, the results indicated more opportunities for the future designs and discoveries of effective antibacterial vaccines and antibacterial drugs for H. otakii.

Effects of interventions on the screening behavior in female first-degree relatives of breast cancer patients: A systematic review.

BACKGROUND: Women are more likely to develop breast cancer if their first-degree relatives (FDRs) have the disease, but they are often unaware of their individual risk and conduct screening behaviors. OBJECTIVE: This study aimed to evaluate the effectiveness of interventions in increasing breast self-examination, clinical breast examination, and mammography rates in FDRs of breast cancer patients. METHODS: We selected randomized clinical trials and quasi-experimental studies in eight databases. Interventions in each study were categorized as "promising", or "non-promising" according to whether they led to a positive change in screening behaviors. Interventions were also coded using the Behavioral Change Techniques (BCTs) Taxonomy and a promise ratio calculated for each. BCTs with a promise ratio ≥2 was classified as "promising". RESULTS: Thirteen studies with 21 different BCTs were included. The most frequent BCTs were "Prompts/cues", "Credible source", and "Instructions on how to perform the behavior". Seven BCTs had a promise ratio of ≥2 and the four most promising were "Information about health consequences" (promise ratio = 6), "Problem solving" (promise ratio = 4), "Demonstration of the behavior" (promise ratio = 4), and "Adding objects to the environment" (promise ratio = 4). CONCLUSIONS: This review indicated an overall weak use of theory, and an insufficient description of several interventions to support the assessment of how specific BCTs were activated.

Association of Chinese visceral adiposity index with clinical outcome in patients after endovascular thrombectomy.

BACKGROUND AND PURPOSE: The Chinese Visceral Adiposity Index (CVAI) is a reliable indicator of visceral adiposity dysfunction in the Chinese population. We aimed to evaluate the association between CVAI and clinical outcome in Chinese ischemic stroke patients who received endovascular thrombectomy (EVT). METHODS: This study retrospectively included patients with large vessel occlusive stroke receiving EVT treatment in 2 China stroke centers. Baseline CVAI was calculated after admission. Patients with a modified Rankin scale score ≥ 3 at 3 months after ischemic stroke were defined as poor outcome. Binary multivariate logistic regression models were utilized to explore the association between CVAI and the risk of 90-day unfavorable outcome. RESULTS: A total of 453 patients (mean age, 70.4  ± 12.1 years; 280 male) were included. During the 90-day follow-up, 236 (52.1 %) patients experienced poor outcome. After multivariable adjustment for potential confounders, increasing CVAI was associated with an increased risk of 90-day poor outcome (odds ratios, per-standard deviation increase: 1.521; 95 % confidence interval, 1.127-2.052; P = 0.006). Similar significant results were observed when the CVAI was analyzed as a categorical variable. Furthermore, the multiple-adjusted spline regression model showed an inverted J-shape association between CVAI and risk of unfavorable outcome (P = 0.048 for non-linearity). CONCLUSIONS: This study demonstrated that CVAI is positively correlated with 90-day poor outcome in Chinese ischemic stroke patients after EVT.

Setup accuracy and margins for surface-guided radiotherapy (SGRT) of head, thorax, abdomen, and pelvic target volumes.

The goal of the study was to evaluate the inter- and intrafractional patient setup accuracy of target volumes located in the head, thoracic, abdominal, and pelvic regions when using SGRT, by comparing it with that of laser alignment using patient skin marks, and to calculate the corresponding setup margins. A total of 2303 radiotherapy fractions of 183 patients were analyzed. All patients received daily kilovoltage cone-beam computed tomography scans (kV-CBCT) for online verification. From November 2019 until September 2020, patient setup was performed using laser alignment with patient skin marks, and since October 2020, using SGRT. The setup accuracy was measured by the six degrees of freedom (6DOF) corrections based on the kV-CBCT. The corresponding setup margins were calculated using the van Herk formula. Analysis of variance (ANOVA) was used to evaluate the impact of multiple factors on the setup accuracy. The inter-fractional patient setup accuracy was significantly better using SGRT compared to laser alignment with skin marks. The mean three-dimensional vector of the translational setup deviation of tumors located in the thorax, abdomen, and pelvis using SGRT was 3.6 mm (95% confidence interval (CI) 3.3 mm to 3.9 mm) and 4.5 mm using laser alignment with skin marks (95% CI 3.9 mm to 5.2 mm; p = 0.001). Calculation of setup margins for the combined inter- and intra-fractional setup error revealed similar setup margins using SGRT and kV-CBCT once a week compared to laser alignment with skin marks and kV-CBCT every other day. Furthermore, comparable setup margins were found for open-face thermoplastic masks with AlignRT compared to closed-face thermoplastic masks with laser alignment and mask marks. SGRT opens the possibility to reduce the number of CBCTs while maintaining sufficient setup accuracy. The advantage is a reduction of imaging dose and overall treatment time. Open-face thermoplastic masks may be used instead of closed-face thermoplastic masks to increase the patient's comfort.

Effectiveness of telemedicine-based psychosocial intervention for breast cancer patients: a systematic review and meta-analysis.

OBJECTIVES: This review aimed to synthesize the available evidence on the effectiveness of telemedicine-based psychosocial interventions among breast cancer (BC) patients regarding quality of life (QOL), depression, anxiety, distress, fatigue, sleep disorders, sexual function, and fear of cancer recurrence (FCR). METHODS: A search of 10 databases was conducted to identify RCTs of the effects of telemedicine-based psychosocial interventions on outcomes. Selection of studies, quality appraisal, and data extraction were performed by two reviewers independently. GRADE and Cochrane risk of bias assessment tools were used for quality appraisal. Heterogeneity was determined by I2, standardized mean differences (SMD) were used to determine intervention effects, and meta-analyses, subgroup analysis, and sensitivity analysis were performed. RESULTS: In total, 29 RCTs were included. Telemedicine-based psychosocial interventions improved the primary outcomes of QOL (SMD = 0.32), distress (SMD = - 0.22), and anxiety (SMD = - 0.16) in BC patients with moderate effect size. There were some improvements in the secondary outcomes of sleep disorders (SMD = - 056), sexual function (SMD = 0.19), and FCR (SMD = - 0.41). After sensitivity analysis, the effect size of fatigue was moderate (SMD = - 0.24). CONCLUSION: Telemedicine-based psychosocial interventions are superior to usual care in BC patients with improved QOL, sexual function, and less distress, anxiety, fatigue, sleep disorders, and FCR. Due to the heterogeneity of the results for QOL, anxiety, fatigue, sleep disturbance, and FCR, these results should be interpreted cautiously. In the future, more rigorous RCTs need to be designed to identify better delivery models and intervention times to further test their effectiveness.

Risk Investigation and Analysis of Risk Factors for Malnutrition in Patients with Advanced Kidney Cancer: A Single-Centre Retrospective Study.

OBJECTIVE: To investigate the nutritional status of patients with advanced kidney cancer and analyse the risk factors for malnutrition in such patients. METHODS: The study selected the clinical data of 103 patients with advanced kidney cancer who were admitted to Qingdao Jiaozhou Central Hospital from February 2020 to February 2022 for a retrospective analysis. The Subjective Global Assessment of Nutrition scale was used to evaluate the nutritional status of all research subjects. Patients' baseline data, such as gender, age and clinical classifications, and laboratory indicators, such as albumin and C-reactive protein (CRP), were collected, and multivariate logistic regression was used to screen the independent risk factors for malnutrition in patients with advanced kidney cancer. RESULTS: A total of 78 (76.00%) individuals among the 103 patients with advanced kidney cancer had malnutrition. The results of univariate analysis showed marked differences in the age, body mass index (BMI), albumin, haemoglobin, CRP, diabetes, anorexia and family monthly income of patients of the good nutrition and malnutrition groups (p < 0.05). The results of logistic regression showed that age ≥65 years old (odds ratio (OR) = 29.187), albumin <40 g/L (OR = 0.025), haemoglobin <110 g/L (OR = 0.049), the presence of diabetes (OR = 28.138), the presence of anorexia (OR = 98.739), BMI <18.5 kg/m2 (OR = 0.024) and CRP <3 mg/L (OR = 24.819) were independent influencing factors of malnutrition in the patients with advanced kidney cancer (all p < 0.05). CONCLUSIONS: The incidence of malnutrition in patients with advanced kidney cancer is relatively high. Therefore, the understanding of malnutrition in such patients in clinical work must be fortified, and attention should be paid to screening the above risk factors and implementing active measures in nutrition therapy to reduce the risk of malnutrition in patients with advanced kidney cancer and prolong their survival time.

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs). METHODS: The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort. RESULTS: A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7-51.2] in the MTX cohort and 24.3 months (95% CI: 16.6-32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8-35.2) in the MTX cohort and 32 months (95% CI: 27.6-36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts. CONCLUSIONS: This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate - based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.

Dietary artemisinin boosts intestinal immunity and healthy in fat greenling (Hexagrammos otakii).

Introduction: Artemisinin (ART) is very common as a diet additive due to its immunoregulatory activities. Nonetheless, the immunoregulatory mechanism of ART in marine fish remains unknown. This study comprehensively examined the effects and explored the potential mechanism of ART ameliorating intestinal immune disease (IID) in fat greenlings (Hexagrammos otakii). Methods and results: The targets of ART were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Here, eight putative targets of ART were collected and identified with the Uniprot database, and 1419 IID-associated target proteins were filtered through the Drugbank, Genecards, OMIM, and PHARMGKB Databases. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways point out that ART may have immunoprotective effects by regulating cellular responses to stress, hypoxia, inflammation, and vascular endothelial growth factor stimulus through the hypoxia-inducible factor 1 (HIF-1) signaling pathway. The findings of molecular docking indicated that ART contains one active ingredient and three cross-targets, which showed a kind combination with hypoxia-inducible factor 1-alpha (HIF1-a), transcription factor p65 (RELA), and vascular endothelial growth factor A (VEGF-A), respectively. Furthermore, an ART feeding model was established to assess the ART's immunoprotect effect on the intestine of H.otakii in vivo. The D48 group showed smaller intestinal structural changes after being challenged by Edwardsiella tarda. The supplementation of ART to the diet improved total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced the malondialdehyde (MDA) in intestine of H. otakii. The expression of transcription factor p65, HIF1-α, VEGF-A, cyclin D1, matrix metalloprotease 9 (MMP9), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) was decreased after dietary ART in the intestinal of H. otakii. Discussion: The present results demonstrated that dietary ART improved antioxidants and immunity, optimized the intestinal structure, and increased resistance to E. tarda through the SOD2/nuclear-factor-kappa- B (NFkB)/HIF1-a/VEGF-A pathway in the intestinal tract of H.otakii. This study integrated pharmacological analysis and experimental validation and revealed the mechanism of ART on IID, which provides insight into the improvement of IID in H. otakii.

Risk Investigation and Analysis of Risk Factors for Malnutrition in Patients with Advanced Kidney Cancer: A Single-Centre Retrospective Study

Objective: To investigate the nutritional status of patients with advanced kidney cancer and analyse the risk factors for malnutrition in such patients. Methods: The study selected the clinical data of 103 patients with advanced kidney cancer who were admitted to Qingdao Jiaozhou Central Hospital from February 2020 to February 2022 for a retrospective analysis. The Subjective Global Assessment of Nutrition scale was used to evaluate the nutritional status of all research subjects. Patients’ baseline data, such as gender, age and clinical classifications, and laboratory indicators, such as albumin and C-reactive protein (CRP), were collected, and multivariate logistic regression was used to screen the independent risk factors for malnutrition in patients with advanced kidney cancer. Results: A total of 78 (76.00%) individuals among the 103 patients with advanced kidney cancer had malnutrition. The results of univariate analysis showed marked differences in the age, body mass index (BMI), albumin, haemoglobin, CRP, diabetes, anorexia and family monthly income of patients of the good nutrition and malnutrition groups (p < 0.05). The results of logistic regression showed that age ≥65 years old (odds ratio (OR) = 29.187), albumin <40 g/L (OR = 0.025), haemoglobin <110 g/L (OR = 0.049), the presence of diabetes (OR = 28.138), the presence of anorexia (OR = 98.739), BMI <18.5 kg/m2 (OR = 0.024) and CRP <3 mg/L (OR = 24.819) were independent influencing factors of malnutrition in the patients with advanced kidney cancer (all p < 0.05). Conclusions: The incidence of malnutrition in patients with advanced kidney cancer is relatively high. Therefore, the understanding of malnutrition in such patients in clinical work must be fortified, and attention should be paid to screening the above risk factors and implementing active measures in nutrition therapy to reduce the risk of malnutrition in patients with advanced kidney cancer and prolong their survival time (AU)

Multi-granularity knowledge distillation and prototype consistency regularization for class-incremental learning.

Deep neural networks (DNNs) are prone to the notorious catastrophic forgetting problem when learning new tasks incrementally. Class-incremental learning (CIL) is a promising solution to tackle the challenge and learn new classes while not forgetting old ones. Existing CIL approaches adopted stored representative exemplars or complex generative models to achieve good performance. However, storing data from previous tasks causes memory or privacy issues, and the training of generative models is unstable and inefficient. This paper proposes a method based on multi-granularity knowledge distillation and prototype consistency regularization (MDPCR) that performs well even when the previous training data is unavailable. First, we propose to design knowledge distillation losses in the deep feature space to constrain the incremental model trained on the new data. Thereby, multi-granularity is captured from three aspects: by distilling multi-scale self-attentive features, the feature similarity probability, and global features to maximize the retention of previous knowledge, effectively alleviating catastrophic forgetting. Conversely, we preserve the prototype of each old class and employ prototype consistency regularization (PCR) to ensure that the old prototypes and semantically enhanced prototypes produce consistent prediction, which excels in enhancing the robustness of old prototypes and reduces the classification bias. Extensive experiments on three CIL benchmark datasets confirm that MDPCR performs significantly better over exemplar-free methods and outperforms typical exemplar-based approaches.

Persistent symptoms and risk factors predicting prolonged time to symptom-free after SARS­CoV­2 infection: an analysis of the baseline examination of the German COVIDOM/NAPKON-POP cohort.

PURPOSE: We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free. METHODS: COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled ≥ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan-Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free. RESULTS: Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49-59 years compared to < 49 years (aHR 0.70, 95% CI 0.56-0.87), female sex (aHR 0.78, 95% CI 0.65-0.93), lower educational level (aHR 0.77, 95% CI 0.64-0.93), living with a partner (aHR 0.81, 95% CI 0.66-0.99), low resilience (aHR 0.65, 95% CI 0.47-0.90), steroid treatment (aHR 0.22, 95% CI 0.05-0.90) and no medication (aHR 0.74, 95% CI 0.62-0.89) during acute infection. CONCLUSION: In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant's characteristics that are difficult to modify.