Multi-center study of COVID-19 infection in elderly patients with lymphoma: on behalf of Jiangsu Cooperative Lymphoma Group (JCLG).

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.

Anti-lymphangiogenesis for boosting drug accumulation in tumors.

The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for nanomedicines. Various strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies, with a primary focus on vascular regulation and stromal reduction. However, these methods may trigger or facilitate tumor metastasis as a tradeoff. Therefore, there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment outcomes. As another important factor affecting drug tumor accumulation besides vasculature and stroma, the impact of tumor-associated lymphatic vessels (LVs) has not been widely considered. In the current research, we verified that anlotinib, a tyrosine kinase inhibitor with anti-lymphangiogenesis activity, and SAR131675, a selective VEGFR-3 inhibitor, effectively decreased the density of tumor lymphatic vessels in mouse cancer models, further enhancing drug accumulation in tumor tissue. By combining anlotinib with therapeutic drugs, including doxorubicin (Dox), liposomal doxorubicin (Lip-Dox), and anti-PD-L1 antibody, we observed improved anti-tumor efficacy in comparison with monotherapy regimens. Meanwhile, this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses. Our work describes a new, clinically transferrable approach to augmenting intratumoral drug accumulation, which shows great potential to address the current, unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Starter molds and multi-enzyme catalysis in koji fermentation of soy sauce brewing: A review.

Soy sauce is a traditional fermented food produced from soybean and wheat under the action of microorganisms. The soy sauce brewing process mainly involves two steps, namely koji fermentation and moromi fermentation. In the koji fermentation process, enzymes from starter molds, such as protease, aminopeptidase, carboxypeptidase, l-glutaminase, amylase, and cellulase, hydrolyze the protein and starch in the raw ingredients to produce short-chain substances. However, the enzymatic reactions may be diminished after being subjected to moromi fermentation due to its high NaCl concentration. These enzymatically hydrolyzed products are further metabolized by lactic acid bacteria and yeasts during the moromi fermentation process into organic acids and aromatic compounds, giving soy sauce a unique flavor. Thus, the starter molds, such as Aspergillus oryzae, Aspergillus sojae, and Aspergillus niger, and their secreted enzymes play crucial roles in soy sauce brewing. This review comprehensively covers the characteristics of the starter molds mainly used in soy sauce brewing, the enzymes produced by starter molds, and the roles of enzymes in the degradation of raw material. We also enumerate current problems in the production of soy sauce, aiming to offer some directions for the improvement of soy sauce taste.

The structural characterization of a novel Chinese yam polysaccharide and its hypolipidemic activity in HFD-induced obese C57BL/6J mice.

Obesity was considered as a rapidly growing chronic disease that influences human health worldwide. In this study, we investigated the primary structure characteristics of Chinese yam polysaccharide (CYP) and its role in regulating lipid metabolism in a high-fat diet (HFD)-fed obese mice. The molecular weight of CYP was determined to be 3.16 × 103 kDa. Periodic acid oxidation & smith degradation and nuclear magnetic resonance results suggested that CYP consists of 1 → 2, 1 â†’ 2, 6, 1 â†’ 4, 1 â†’ 4, 6, 1→, or 1 â†’ 6 glycoside bonds. The in vivo experiment results suggested that the biochemical indices, tissue sections, and protein regulation associated with lipid metabolism were changed after administering CYP in obese mice. In addition, the abundances of short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Lachnospiraceae_NK4A136_group, and Ruminococcaceae_UCG-014 were increased, and the abundances of bacteria Desulfovibrionaceae and Ruminococcus and metabolites of arginine, propionylcarnitine, and alloisoleucine were decreased after CYP intervention in obese mice. Spearman's correlation analysis of intestinal flora, metabolites, and lipid metabolism parameters showed that CYP may affect lipid metabolism in obese mice by regulating the intestinal environment. Therefore, CYP may be used as a promising nutritional intervention agent for lipid metabolism.

Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades' progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

Risk Factors of Hidden Blood Loss in Unilateral Biportal Endoscopic Surgery for Patients with Lumbar Spinal Stenosis.

OBJECTIVE: Unilateral biportal endoscopic (UBE) surgery has recently been used as a minimally invasive procedure for the treatment of lumbar spinal stenosis and is associated with less perioperative blood loss. However, perioperative hidden blood loss (HBL) may be neglected during UBE. This study aimed to examine the volume of HBL and discuss the influential risk factors for HBL during unilateral biportal endoscopic surgery. METHODS: From January 2022 to August 2022, 51 patients underwent percutaneous unilateral biportal endoscopic surgery for lumbar spinal stenosis at the Department of Spinal Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and were enrolled in this study. The data included general indicators (age, sex and body mass index [BMI]), underlying disease (hypertension and diabetes), laboratory test results (prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [Fbg]), and preoperative and postoperative hematocrit and hemoglobin), related imaging parameters (severity of intervertebral disc [IVD] degeneration and soft tissue thickness of the interlaminar approach), number of operated vertebrae and operation time. Total blood loss (TBL) and HBL during surgical procedures were measured via the Gross formula. Influential factors were further analyzed by multivariate linear regression analysis and t-tests. RESULTS: The mean HBL was 257.89 ± 190.66 mL for single-operation patients and 296.58 ± 269.75 mL for two-operation patients. Patients with lower PT (p = 0.044), deeper tissue thickness (p = 0.047), and diabetes mellitus were determined to have more HBL during UBE. The operation time might also be an important factor (p = 0.047). However, sex (p = 0.265), age (p = 0.771/0.624), BMI (p = 0.655/0.664), APTT (p = 0.545/0.751), degree of degenerated IVD (p = 0.932/0.477), and hypertension (p = 0.356/0.896) were not related to HBL. CONCLUSION: This study determined the different influential factors of HBL during UBE. PT, tissue thickness, and diabetes mellitus are the independent risk factors that affect HBL incidence. Long PT may decrease the volume of HBL within a certain range. Tissue thickness and diabetes mellitus can lead to an increased volume of HBL.

[Real-World Efficacy and Safety of China-Made Flumatinib Mesylate in the Treatment of Chronic Myeloid Leukemia in Chronic Phase].

OBJECTIVE: To evaluate the efficacy and safty of China-made flumatinib mesylate in the treatment of chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 42 CML-CP patients treated with Chinese produced flumatinib (oral, 600 mg, 1/d) were included in the study, including 14 newly diagnosed patients and 28 patients underwent conversion therapy. The hematological, cytogenetic and molecular response and safety were observed and evaluated after 3, 6 and 12 months of treatment. RESULTS: 35 patients were treated for more than 3 months, among which 31 patients were treated for more than 6 months and 17 patients were treated for more than 12 months. After 3 months of treatment, 33 patients underwent hematological, cytogenetic and molecular examination. Of these, 32 patients achieved complete hematological response (CHR), 13 patients achieved complete cytogenetic response (CCyR), 20 patients showed BCR-ABLIS≤10% and 7 patients reached major molecular response (MMR). After 6 months of treatment, all 30 patients who could evaluate efficacy achieved CHR, of which 17 patients achieved CCyR, 18 patients showed BCR-ABLIS≤1% and 16 patients reached MMR. After 12 months of treatment, all 17 patients were evaluated for efficacy, all achieved CHR, 10 patients obtained CCyR, 7 patients reached MMR. Grade III or IV thrombocytopenia, leukopenia and anemia occurred in 7, 2 and 1 patients, respectively. The non-hematological adverse reactions were diarrhea in 6 cases, renal function damage in 4 cases, rash and pruritus in 3 cases, liver function damage in 3 cases, nausea in 1 case, fever in 1 case, bone/joint or muscle pain in 1 case. CONCLUSION: In the real world, China-made flumatinib mesylate has a positive short-term efficacy and reliable safety in the treatment of CML-CP patients, whether as first-line treatment or second- and third-line conversion therapy.

Characterization of two CYP80 enzymes provides insights into aporphine alkaloid skeleton formation in Aristolochia contorta.

Aporphine alkaloids are a large group of natural compounds with extensive pharmaceutical application prospects. The biosynthesis of aporphine alkaloids has been paid attentions in the past decades. Here, we determined the contents of four 1-benzylisoquinoline alkaloids and five aporphine alkaloids in root, stem, leaf, and flower of Aristolochia contorta Bunge, which belongs to magnoliids. Two CYP80 enzymes were identified and characterized from A. contorta. Both of them catalyze the unusual C-C phenol coupling reactions and directly form the aporphine alkaloid skeleton. AcCYP80G7 catalyzed the formation of hexacyclic aporphine corytuberine. AcCYP80Q8 catalyzed the formation of pentacyclic proaporphine glaziovine. Kingdom-wide phylogenetic analysis of the CYP80 family suggested that CYP80 first appeared in Nymphaeales. The functional divergence of hydroxylation and C-C (or C-O) phenol coupling preceded the divergence of magnoliids and eudicots. Probable crucial residues of AcCYP80Q8 were selected through sequence alignment and molecular docking. Site-directed mutagenesis revealed two crucial residues E284 and Y106 for the catalytic reaction. Identification and characterization of two aporphine skeleton-forming enzymes provide insights into the biosynthesis of aporphine alkaloids.

Glycolysis Induced by METTL14 Is Essential for Macrophage Phagocytosis and Phenotype in Cervical Cancer.

N 6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and it plays a vital role in various biological processes. However, the roles of m6A on cervical cancer tumorigenesis, especially macrophages infiltrated in the tumor microenvironment of cervical cancer, are still unclear. We analyzed the abnormal m6A methylation in cervical cancer, using CaSki and THP-1 cell lines, that might influence macrophage polarization and/or function in the tumor microenvironment. In addition, C57BL/6J and BALB/c nude mice were used for validation in vivo. In this study, m6A methylated RNA immunoprecipitation sequencing analysis revealed the m6A profiles in cervical cancer. Then, we discovered that the high expression of METTL14 (methyltransferase 14, N6-adenosine-methyltransferase subunit) in cervical cancer tissues can promote the proportion of programmed cell death protein 1 (PD-1)-positive tumor-associated macrophages, which have an obstacle to devour tumor cells. Functionally, changes of METTL14 in cervical cancer inhibit the recognition and phagocytosis of macrophages to tumor cells. Mechanistically, the abnormality of METTL14 could target the glycolysis of tumors in vivo and vitro. Moreover, lactate acid produced by tumor glycolysis has an important role in the PD-1 expression of tumor-associated macrophages as a proinflammatory and immunosuppressive mediator. In this study, we revealed the effect of glycolysis regulated by METTL14 on the expression of PD-1 and phagocytosis of macrophages, which showed that METTL14 was a potential therapeutic target for treating advanced human cancers.

The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients.

To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.19 mg/L. The optimal cut-off of serum B2M was 8.73 mg/L, and the cases with serum B2M level >8.73 mg/L were older and had a more advanced stage, lower levels of platelets, albumin, and fibrinogen, and higher creatinine level. The serum B2M >8.73 mg/L, creatinine ≥133 µmol/L, fibrinogen ≤1.5 g/L, agranulocytosis (<0.5 × 109/L), severe thrombocytopenia (<50 × 109/L), and high Epstein-Barr virus DNA copy number were found to have independent prognostic values in all patients, and the serum B2M >8.73 mg/L was also an independent prognostic factor in patients with creatinine <133 µmol/L. Finally, a prognostic scoring system was established based on independent prognostic factors of all patients and categorized the patients into three groups with significant prognostic differences. This study confirmed that the serum B2M level can be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.

Promoting nonsymmetric C-C coupling to valuable oxygenates without metal catalysts in alkali aqueous medium.

Efficient conversion of C1 molecules into multicarbon oxygenates is a promising avenue for energy storage. Herein, we synthesize adjustable alkanoic acids/alcohols from formate C1 molecules via a hydrothermal reaction without any metal catalyst participation. This is achieved via HCO* and HCOO- nonsymmetric C-C coupling by alkali catalysis in aqueous medium.

Development and validation of a nomogram to predict cardiac death after radiotherapy for esophageal cancer.

Background: Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision-making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods: A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5- and 10-year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C-index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan-Meier (K-M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five- and ten-year survival rates for the two groups were shown using K-M curves. Results: The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C-indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5- and 10-year risk of cardiac death. The model exhibited moderate predictive power for 5- and 10-year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions: Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Assessment of knowledge, attitudes, and practices of CML patients and their families toward TKI therapy in China.

The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized chronic myeloid leukemia (CML) treatment. The knowledge, attitude, and practice (KAP) of patients and their families play a significant role in treatment adherence and effectiveness. This study aimed to investigate the KAP of CML patients and their families regarding TKI therapy in China. From November 1 to December 31, 2022, a cross-sectional study was conducted at the Affiliated Huai'an No. 1 People's Hospital in China. A total of 313 CML patients and 268 family caregivers were selected using convenience sampling. Participants answered a self-designed questionnaire. The questionnaire contained demographic/clinical data and assessed KAP toward CML and TKI therapy. Participants exhibited mean KAP scores of 8.91 (55.7%), 33.10 (73.6%), and 2.20 (73.3%), respectively. Family members had higher knowledge and practice scores than patients (both P < .05), with factors such as younger age, urban residency, higher education, employment, higher income, and interaction with peers correlating with better knowledge scores (P < .001). Although participants were well-informed about their diagnosis and medication (>80%), understanding of disease causes (<30%) and treatment prognosis and side effects (<50%) was limited, and cost concerns affected 80.55%. Anxiety and depression were reported more among caregivers (46.64% and 13.8%) than patients (29.71% and 11.51%). While 84.85% adhered to the doctor's instructions, only 68.50% actively sought more CML information. Positive correlations were observed among KAP scores, indicating their interdependence (knowledge-attitude: R = 0.397; knowledge-practice: R = 0.598; attitude-practice: R = 0.353; all P < .001). The findings underscore the importance of tailored education to fill knowledge gaps about CML and the need to address financial concerns and provide psychological support. The positive correlations among knowledge, attitudes, and practices emphasize the need for comprehensive interventions. In conclusion, this study highlights the importance of tailored education, addresses financial concerns, and provides emotional support for CML patients and caregivers in China, despite limitations such as convenience sampling and questionnaire design. Future research should evaluate the effectiveness of educational interventions and long-term outcomes to further enhance the overall well-being of this population.

Flow field and sediment removal in a stormwater sump utilizing internal structures.

This study investigated the hydraulic characteristics of stormwater sumps and their design optimization for sediment retention using physical experiments. Particle image velocimetry was utilized to measure the flow field, and the use of internal structures was investigated for improving solids retention. Results indicate that these internal structures can significantly improve the sediment removal efficiency of suspended solids with an average size of 125 µm, resulting in an efficiency improvement of 20-30%. Additionally, a modified Péclet number was proposed to more accurately evaluate the sediment removal efficiency of stormwater sumps, and recommendations were provided for further improving and optimizing sump design. This study provides insights into the hydraulic characteristics of stormwater sumps and has important implications for optimizing and designing particle removal systems for various industrial and environmental applications.

Pan-Genome Analyses of the Genus Cohnella and Proposal of the Novel Species Cohnella silvisoli sp. nov., Isolated from Forest Soil.

Two strains, designated NL03-T5T and NL03-T5-1, were isolated from a soil sample collected from the Nanling National Forests, Guangdong Province, PR China. The two strains were Gram-stain-positive, aerobic, rod-shaped and had lophotrichous flagellation. Strain NL03-T5T could secrete extracellular mucus whereas NL03-T5-1 could not. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the two strains belong to the genus Cohnella, were most closely related to Cohnella lupini LMG 27416T (95.9% and 96.1% similarities), and both showed 94.0% similarity with Cohnella arctica NRRL B-59459T, respectively. The two strains showed 99.8% 16S rRNA gene sequence similarity between them. The draft genome size of strain NL03-T5T was 7.44 Mbp with a DNA G+C content of 49.2 mol%. The average nucleotide identities (ANI) and the digital DNA-DNA hybridization (dDDH) values between NL03-T5T and NL03-T5-1 were 99.98% and 100%, indicating the two strains were of the same species. Additionally, the ANI and dDDH values between NL03-T5T and C. lupini LMG 27416T were 76.1% and 20.4%, respectively. The major cellular fatty acids of strain NL03-T5T included anteiso-C15:0 and iso-C16:0. The major polar lipids and predominant respiratory quinone were diphosphatidylglycerol (DPG) and menaquinone-7 (MK-7). Based on phylogenetic analysis, phenotypic and chemotaxonomic characterization, genomic DNA G+C content, and ANI and dDDH values, strains NL03-T5T and NL03-T5-1 represent novel species in the genus Cohnella, for which the name Cohnella silvisoli is proposed. The type strain is NL03-T5T (=GDMCC 1.2294T = JCM 34999T). Furthermore, comparative genomics revealed that the genus Cohnella had an open pan-genome. The pan-genome of 29 Cohnella strains contained 41,356 gene families, and the number of strain-specific genes ranged from 6 to 1649. The results may explain the good adaptability of the Cohnella strains to different habitats at the genetic level.

Study on the Prediction Model of Wound Infection After Spinal Fusion and Internal Fixation Based on Logistic Regression.

With the development of the times, spinal problems are not only one of the diseases that older people pay close attention to, but also gradually spread among teenagers. Therefore, it is very important to predict the possibility of wound infection in patients after spinal fusion and internal fixation. The method is to statistically analyze the clinical data of patients with clinical spinal disease, and to propose individualized treatment and recovery plan for each patient's pathological characteristics and postoperative recovery, so as to realize humanized service and minimize the possibility of wound infection. In this paper, Logistic logistic regression, SMOTE algorithm and confusion matrix are used to model the probability of infection after spinal fusion and internal fixation. In the positive confirmation analysis part, the information data of 449 clinical cases were selected for analysis, and 14 variables such as gender, age, number of internal fusion fixation segments, past medical history, intraoperative blood transfusion and bleeding volume were selected as research indicators to explore the related factors of postoperative infection. The classification method adopts two classifications. The two types of data are 'postoperative infection' and 'postoperative non-infection'. In the statistical description of the data, it is found that age, selection of internal fusion fixation segments, preoperative hospitalization days, cerebrospinal fluid leakage, and preoperative ASA score are all important factors affecting the incidence of postoperative infection.

Aerobic Exercise Ameliorates Liver Injury in Db/Db Mice by Attenuating Oxidative Stress, Apoptosis and Inflammation Through the Nrf2 and JAK2/STAT3 Signalling Pathways.

Objective: Diabetes mellitus (DM) implicates oxidative stress, apoptosis, and inflammation, all of which may contribute liver injury. Aerobic exercise is assured to positively regulate metabolism in the liver. This project was designed to investigate whether and how aerobic exercise improves DM-induced liver injury. Methods: Seven-week-old male db/db mice and age-matched m/m mice were randomly divided into a rest control group or a group that received 12 weeks of aerobic exercise by treadmill training (10 m/min). Haematoxylin and eosin (HE) staining, electron microscopy, Oil Red O staining and TUNEL assays were used to evaluate the histopathological changes in mouse liver. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TRIG), cholesterol (CHOL) were analyzed by serum biochemical analysis. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed via ELISA. Nuclear factor E2-associated factor-2 (Nrf2), nuclear factor κB (NF-κB) and JAK2/STAT3 pathway-related proteins were measured by immunofluorescence, Western blotting and q-PCR. F4/80 expression in liver tissues was assessed by immunohistochemistry. Results: In diabetic mice, exercise training significantly decreased the levels of serum TRIG, CHOL, IL-6, TNF-α, ALT and AST; prevented weight gain, hyperglycaemia, and impaired glucose and insulin tolerance. Morphologically, exercise mitigated the diabetes-induced increase in liver tissue microvesicles, inflammatory cells, F4/80 (macrophage marker) levels, and TUNEL-positive cells. In addition, exercise reduced the apoptosis index, which is consistent with the results for caspase-3 and Bax. Additionally, exercise significantly increased SOD activity, decreased MDA levels, activated Nrf2 and decreased the expression of NF-kB, phosphorylated JAK2 and STAT3 proteins in the livers of diabetic mice. Conclusion: This study demonstrated that aerobic exercise reversed liver dysfunction in db/db mice with T2DM by reducing oxidative stress, apoptosis and inflammation, possibly by enhancing Nrf2 expression and inhibiting the JAK2/STAT3 cascade response.

Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer.

The primary cause of mortality in esophageal cancer survivors is cardiac death. Early identification of cardiac mortality risk during chemotherapy for esophageal cancer is crucial for improving the prognosis. We developed and validated a nomogram model to identify patients with high cardiac mortality risk after chemotherapy for esophageal cancer for early screening and clinical decision-making. We randomly allocated 37,994 patients with chemotherapy-treated esophageal cancer into two groups using a 7:3 split ratio: model training (n = 26,598) and validation (n = 11,396). 5- and 10-year survival rates were used as endpoints for model training and validation. Decision curve analysis and the consistency index (C-index) were used to evaluate the model's net clinical advantage. Model performance was evaluated using receiver operating characteristic curves and computing the area under the curve (AUC). Kaplan-Meier survival analysis based on the prognostic index was performed. Patient risk was stratified according to the death probability. Age, surgery, sex, and year were most closely related to cardiac death and used to plot the nomograms. The C-index for the training and validation datasets were 0.669 and 0.698, respectively, indicating the nomogram's net clinical advantage in predicting cardiac death risk at 5 and 10 years. The 5- and 10-year AUCs were 0.753 and 0.772 for the training dataset and 0.778 and 0.789 for the validation dataset, respectively. The accuracy of the model in predicting cardiac death risk was moderate. This nomogram can identify patients at risk of cardiac death after chemotherapy for esophageal cancer at an early stage.

Emerging nanotechnological approaches to regulating tumor vasculature for cancer therapy.

Abnormal angiogenesis stands for one of the most striking manifestations of malignant tumor. The pathologically and structurally abnormal tumor vasculature facilitates a hostile tumor microenvironment, providing an ideal refuge exclusively for cancer cells. The emergence of vascular regulation drugs has introduced a distinctive class of therapeutics capable of influencing nutrition supply and drug delivery efficacy without the need to penetrate a series of physical barriers to reach tumor cells. Nanomedicines have been further developed for more precise regulation of tumor vasculature with the capacity of co-delivering multiple active pharmaceutical ingredients, which overall reduces the systemic toxicity and boosts the therapeutic efficacy of free drugs. Additionally, precise structure design enables the integration of specific functional motifs, such as surface-targeting ligands, droppable shells, degradable framework, or stimuli-responsive components into nanomedicines, which can improve tissue-specific accumulation, enhance tissue penetration, and realize the controlled and stimulus-triggered release of the loaded cargo. This review describes the morphological and functional characteristics of tumor blood vessels and summarizes the pivotal molecular targets commonly used in nanomedicine design, and then highlights the recent cutting-edge advancements utilizing nanotechnologies for precise regulation of tumor vasculature. Finally, the challenges and future directions of this field are discussed.