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Abstract Background Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced, inoperable non-small cell lung cancer (NSCLC). Previous studies have mainly focused on examining local failure and recurrence patterns after surgery and the principles of lymph node metastasis (LNM) in surgical candidates with NSCLC. However, these studies were just only able to guide postoperative radiotherapy (PORT) and the patterns of LNM in patients with resected NSCLC was inadequate to represent that in locally advanced inoperable NSCLC patients for guiding target volume delineation of CCRT. In this study, we aimed to analyze the metastasis regularities and establish the correlations between different lymph node levels in NSCLC patients without any intervention using positron emission tomography/computed tomography (PET/CT) images. Methods Overall, 358 patients with N1–N3 NSCLC admitted in our hospital between 2018 and 2022 were retrospectively analyzed. The diagnosis of metastatic lymph nodes was reviewed and determined using the European Organization for Research and Treatment of Cancer standard and the standardized value of the PET/CT examination. Univariate and multivariate analysis were performed to investigate the correlations between the different levels were evaluated by using of the chi-square test and logistic regression model. Results The lymph nodes with the highest metastasis rates in patients with left lung cancer were in order as follows: 10L, 4L, 5, 4R, and 7; while in those with right lung cancer they were 10R, 4R, 7, 2R, and 1R. Notably, we found left lung patients were more likely to have contralateral hilar, mediastinal and supraclavicular lymph nodes involved, and the right lung group exhibited a higher propensity for ipsilateral mediastinum and supraclavicular lymph node invasion. Furthermore, correlation analysis revealed there were significant correlative patterns in the LNM across different levels. Conclusions This study elucidated the patterns of primary LNM in patients with NSCLC who had not undergone surgery (without any treatment interventions) and the correlations between lymph node levels. These findings were expected to provide useful reference for target volume delineation in definitive concurrent chemoradiotherapy in locally advanced NSCLC patients.

Electrocatalytic oxygen evolution reaction (OER) is not only a half-reaction of water-splitting to produce hydrogen, but also an important half-reaction of electrocatalytic carbon dioxide reduction, nitrogen reduction, nitrate reduction, organic small molecule reduction, and metal-air batteries. The OER process is driven by a four-electron mechanism. Due to the slow and complex kinetics of the electrocatalytic OER and its strong oxidation characteristics, studying the oxidative reconstruction rules and catalytic mechanisms of electrode materials in the OER process is of great significance to improve the efficiency of the OER. As a kind of metal-free electrode materials, carbon materials are widely used in electrocatalysis, which has become a potential electrocatalyst for OER due to their low price, abundant reserves, and high activity stability. At present, oxygen-containing functional groups on the surface of carbon materials have been proven to be active sites for OER. However, the deactivation mechanism of carbon materials at higher oxidation potentials during the OER process remains unclear due to a lack of understanding of the active site evolution mechanism. Correctly identifying the active sites of carbon materials under oxygen evolution conditions has become a research hotspot in the field. However, ex-situ characterization techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM) are difficult to reflect the catalytic behavior of carbon materials under working conditions. In this study, differential electrochemical mass spectrometry (DEMS) was used to monitor the structural changes of carbon material during the OER process with graphite as the model material. The effects of applied voltage and pH value of electrolyte on graphite oxidation were investigated respectively. By changing the applied potential and the pH value of the electrolyte, we found that graphite firstly oxidizes itself to form oxygen-containing functional groups under acidic (pH 0), neutral (pH 7), and alkaline (pH 14) conditions. As the potential increases, the graphite begins to produce CO2 and CO at 1.6 V vs. RHE over the full pH value range, and the content of CO2 gradually augments as the potential increases. The generation potential of O2 is higher than that of CO2 under acidic condition, and the opposite is true under alkaline condition. Therefore, graphite can be used as an OER catalyst under alkaline condition in a certain potential range. This work not only reveals the structural transformation rules and corresponding evolution products of carbon materials in the full pH value range under electrochemical oxidation conditions, but also proposes a feasible potential operating range when carbon materials are used as OER catalysts.

Background: Radiotherapy (RT) for breast cancer (BC) may raise the risk of second primary cancers (SPCs), a relationship inadequately studied. Methods: We analyzed 248268 female BC patients from 9 SEER registries, 1988–2018, identifying SPCs >5 years after initial treatment, comparing SPC risks between RT and non-RT cohorts using Fine-Gray and Poisson regressions. Results: Of all participants, 55.4 % received surgery and RT. The RT group had a higher SPC incidence, with excess incidence significantly dropped from 6.9 % in 1990 to 0.2 % in 2012. The 30-year SPC incidence was 24.69 % in the RT cohort and 18.11 % in the NRT cohort. RT increased the risk of SPCs(HR, 1.29 [95%CI,1.26–1.33]; P

Dispersive soil is a common problem soil in engineering projects, which has the potential risk of causing serious engineering failures. In this paper, calcined waste phosphorus slag (CPS) was chosen to enhance the mechanical properties and reduce soil dispersivity. Dispersive soil samples with 1 % to 10 % CPS content were prepared and cured for 0 to 28 days. The dispersivity identification test was used to assess soil sample dispersivity. The compressive and tensile strength, conductivity, and pH were determined for the soil. Microstructural and mineral composition were analyzed using SEM/EDS, TG/DTG, and XRD analysis. The natural dispersive soil was selected to verify the effect of CPS in improving soil. Experiments show that the CPS inhibits soil dispersivity and converts it into non-dispersive soil. Both compressive and tensile strength increases significantly with the increase in the content of CPS and curing time. The tensile strength of the soil samples cured for 28 days increased by about 76 % and the compressive strength by about 61 % as the mixed content of CPS was increased from 1 % to 10 %. Results show that CPS can improve the strength and modify the dispersivity of soil, its optimal mixing content is 5 %. In addition, using CPS in dispersive soil could also solve the disposal problem of phosphate slag, which is a win-to-win solution.

Abstract Background Cervical mullerian adenosarcoma is a rare uterine sarcoma, especially in young women. Its pathological features are low-grade malignant tumors with bidirectional differentiation, and the degree of malignancy is similar to that of low-grade endometrial stromal sarcoma. This paper reports the case of a young asexual patient who has been closely followed up after tumor resection and has not had any recurrences. Case presentation A 20-year-old, young asexual woman was diagnosed with cervical mullerian adenosarcoma with sarcomatous overgrowth (MASO). Cervical tumor resection was performed after admission, and the resection margin was negative. After the operation, she refused to undergo secondary surgery due to fertility requirements and did not receive adjuvant treatment. The patient was closely followed up after the operation and has not yet relapsed. Conclusion A young woman with cervical MASO did not receive adjuvant treatment after cervical tumor resection. For women with fertility requirements, close follow-ups should be conducted after the operation to guard against tumor recurrence and radical tumor resection should be performed as early as possible after the patient no longer requires their fertility.

Background: Acute acquired comitant esotropia (AACE) is a rare subtype of esotropia that occurs after infancy. The exact pathogenesis of AACE remains unknown with aetiologies ranging from benign conditions to serious underlying neurological diseases being reported. Given the elusive characteristic of AACE, diagnostic and management guidelines remain unclear. This systematic review aims to contribute to this field by summarising the risk factors for AACE reported thus far. Methods: A systematic review was conducted with papers found in CINAHL, MEDLINE, Cochrane library, PubMed databases and other sources. Eligible studies investigating the risk factors for, and clinical features of, AACE in children and young adults were critically appraised before relevant data were extracted and discussed via a narrative summary. Results: Twelve studies were included in the final review, of which six and eight papers reported on benign and non-benign risk factors for AACE respectively. Identified benign risk factors varied among studies, while non-benign risk factors were associated with intracranial pathologies, multiple sclerosis and head trauma. Conclusion: Given the low generalisability of study findings, no definitive conclusions can be drawn on the significance of each risk factor on AACE development. Further prospective research with more objective measurements of ‘near work’, larger sample sizes and control groups is required to better ascertain any cause-effect relationship, refine the diagnostic criteria for each AACE subtype and advise on appropriate management guidelines for AACE.

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown. Design: Retrospective cohort study. Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations. Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p

ObjectiveThis study aimed to investigate the status quo of readiness for hospital discharge in patients with brain tumours after surgery and to analyse its influencing factors.MethodA total of 300 patients with brain tumours who were admitted to the neurosurgery ward of our hospital between September 2020 and December 2022 were selected as the study participants using the convenient sampling method. The readiness for hospital discharge in patients with brain tumours after surgery was investigated using a general information questionnaire, the Readiness for Hospital Discharge Scale (RHDS), the Quality of Discharge Teaching Scale (QDTS), the University of Washington Quality of Life Questionnaire (UW-QOL), and the Social Support Rating Scale (SSRS), and its influencing factors were analysed.ResultsThe total RHDS score of patients with brain tumours was (155.02 ± 14.67), which was at a medium level. There was a positive correlation between readiness for hospital discharge in patients with brain tumours after surgery and the UW-QOL score (r = 0.459, p = 0.001), SSRS score (r = 0.322, p = 0.000), and QDTS score (r = 0.407, p = 0.001). The influencing factors of readiness for hospital discharge in patients with brain tumours included the content actually obtained by patients (health guidance) before discharge (p = 0.001), discharge teaching skills (p = 0.001), age (p = 0.006), swallowing status (p = 0.021), education level (p = 0.016), and objective support (p = 0.022).ConclusionThe readiness for hospital discharge in patients with brain tumours is at a medium level. Medical staff should give inpatients more targeted knowledge and implement personalised health education according to the patient’s age, education level, swallowing status, and objective support to improve the patient’s readiness for hospital discharge.

Abstract Background The activation of hepatic stellate cells (HSCs) has been emphasized as a leading event of the pathogenesis of liver cirrhosis, while the exact mechanism of its activation is largely unknown. Furthermore, the novel non-invasive predictors of prognosis in cirrhotic patients warrant more exploration. miR-541 has been identified as a tumor suppressor in hepatocellular carcinoma and a regulator of fibrotic disease, such as lung fibrosis and renal fibrosis. However, its role in liver cirrhosis has not been reported. Methods Real-time PCR was used to detect miR-541 expression in the liver tissues and sera of liver cirrhosis patients and in the human LX-2. Gain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the activation of LX-2. Bioinformatics analysis and a luciferase reporter assay were conducted to investigate the target gene of miR-541. Results miR-541 was downregulated in the tissues and sera of patients with liver cirrhosis, which was exacerbated by deteriorating disease severity. Importantly, the lower expression of miR-541 was associated with more episodes of complications including ascites and hepatic encephalopathy, a shorter overall lifespan, and decompensation-free survival. Moreover, multivariate Cox’s regression analysis verified lower serum miR-541 as an independent risk factor for liver-related death in cirrhotic patients (HR = 0.394; 95% CI: 0.164–0.947; P = 0.037). miR-541 was also decreased in LX-2 cells activated by TGF-β and the overexpression of miR-541 inhibited the proliferation, activation and hydroxyproline secretion of LX-2 cells. JAG2 is an important ligand of Notch signaling and was identified as a direct target gene of miR-541. The expression of JAG2 was upregulated in the liver tissues of cirrhotic patients and was inversely correlated with miR-541 levels. A rescue assay further confirmed that JAG2 was involved in the function of miR-541 when regulating LX-2 activation and Notch signaling. Conclusions Dysregulation of miR-541/JAG2 axis might be a as a new mechanism of liver fibrosis, and miR-541 could serve as a novel non-invasive biomarker and therapeutic targets for liver cirrhosis.

To evaluate the effects of varying proportions of yak meat in feed on the growth of rats and provide a theoretical basis for selecting the optimal feed proportion suitable for rats. This study was designed as a one-variable experiment. Fifty male rats were divided into five groups. The ratios of yak meat to basal feed of rats in four dietary treatment groups were 2:8, 4:6, 6:4, and 8:2, respectively, while those in the control group were only provided a basal diet. In the feeding experiment, the body weights of the rats were recorded on Day 0 and subsequently in the first, second, third, and fourth weeks, along with quantities of feed intake. The body and tail lengths, as well as the waist circumference of the rats, were measured, and blood samples were collected in the fourth week for routine blood and biochemistry investigations. The rats in the 4:6 feed group had the best body condition. They had normal body and tail lengths, smaller waist circumferences, good posture, and were in better overall health than rats in the other groups. The results indicate that the 4:6 diet was optimal for enhancing rats’ growth performance compared to the other diets.

Abstract Purpose Local primary-recurrence of esophageal squamous cell carcinoma (ESCC) after definitive treatment has the potential for increasing overall survival with re-irradiation (Re-RT), especially with advanced technique. This study aimed to evaluate the efficacy and toxicities of Re-RT using intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) for local primary-recurrence of ESCC. Materials and methods A total of 130 ESCC patients with local primary-recurrence from Xijing hospital between 2008 and 2021 were enrolled and 30 patients underwent IMRT/VMAT based salvage Re-RT. Cox regression analysis was used to analyze the prognostic factors for overall survival (OS) and after recurrence survival (ARS). The toxicities of 30 patients receiving Re-RT were also assessed. Results The median OS and ARS of the 130 recurrent patients were 21 months (1−164 months) and 6 months (1−142 months). The 1-, 2-, and 3-year OS rates were 81.5%, 39.2%, and 23.8%, respectively. Besides, the 1-, 2-, and 3-year ARS rates were 30.0%, 10%, and 6.2%. Multivariate analysis showed that Re-RT ± chemotherapy (p = 0.043) and chemotherapy alone (p 12 months) and initial radiation dose (> 60 Gy) were significantly associated with improved OS. Radiation esophagitis (Grade 1–2) occurred in 16 patients and myelosuppression (Grade1−2) occurred in 10 patients. Grade 3 toxicities (radiation esophagitis and myelosuppression) were only 13.3%. There were no grade 4 toxicities. Conclusion Our results demonstrated that IMRT/VMAT-based Re-RT was an effective therapeutic option for ESCC patients with local primary-recurrence compared with chemotherapy alone or without any treatment. Re-RT had improved OS but unfavorable ARS.

Abstract The application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs), such as gefitinib, has shifted lung cancer treatment from empirical chemotherapy to targeted molecular therapy. However, acquired drug resistance is inevitable in almost all non‐small cell lung cancer (NSCLC) patients treated with gefitinib. Combined treatment with dihydroartemisinin (DHA) and gefitinib produced a better inhibitory effect on lung adenocarcinoma than gefitinib treatment alone; however, the specific mechanism remains unclear. In this study, we aimed to assess the underlying mechanism of this combination treatment. We prepared gefitinib‐resistant A549 cells and investigated whether apoptosis and ferroptosis were involved in the sensitizing effect of DHA. Treatment with 5 μM gefitinib resulted in rupturing and floatation of A549 cells in the medium, while A549‐GR cells were found to be insusceptible to gefitinib. However, treatment with DHA substantially inhibited the proliferation of A549‐GR cells in a dose‐dependent manner accompanied by increased apoptosis and ferroptosis. The accumulated reactive oxygen species (ROS) was crucial for the inhibitory effect of DHA on A549‐GR cells. Moreover, cellular autophagy was significantly upregulated post‐DHA treatment. The combined treatment of DHA and gefitinib resulted in inhibition of proliferation of A549, H1975, and HCC827 cells, and ROS accumulation and a remarkable induction of apoptosis was observed in A549‐GR cells. DHA significantly induced apoptosis and ferroptosis in a dose‐dependent manner and exhibited high cellular toxicity on A549‐GR cells when combined with gefitinib.

Abstract This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early‐stage extranodal nasal‐type natural killer (NK)/T‐cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM‐free survival (DMFS) and overall survival (OS). The 5‐year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis — distant LN, SST, extracutaneous site, and lymphoma‐associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late‐onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early‐stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

Abstract Background Filamentous fungi are extensively exploited as important enzyme producers due to the superior secretory capability. However, the complexity of their secretomes greatly impairs the titer and purity of heterologous enzymes. Meanwhile, high-efficient evaluation and production of bulk enzymes, such as biomass-degrading enzymes, necessitate constructing powerful expression systems for bio-refinery applications. Results A novel sucrose-inducible expression system based on the host strain Aspergillus niger ATCC 20611 and the β-fructofuranosidase promoter (PfopA) was constructed. A. niger ATCC 20611 preferentially utilized sucrose for rapid growth and β-fructofuranosidase production. Its secretory background was relatively clean because β-fructofuranosidase, the key enzyme responsible for sucrose utilization, was essentially not secreted into the medium and the extracellular protease activity was low. Furthermore, the PfopA promoter showed a sucrose concentration-dependent induction pattern and was not subject to glucose repression. Moreover, the strength of PfopA was 7.68-fold higher than that of the commonly used glyceraldehyde-3-phosphate dehydrogenase promoter (PgpdA) with enhanced green fluorescence protein (EGFP) as a reporter. Thus, A. niger ATCC 20611 coupled with the PfopA promoter was used as an expression system to express a β-glucosidase gene (bgla) from A. niger C112, allowing the production of β-glucosidase at a titer of 17.84 U/mL. The crude β-glucosidase preparation could remarkably improve glucose yield in the saccharification of pretreated corncob residues when added to the cellulase mixture of Trichoderma reesei QM9414. The efficacy of this expression system was further demonstrated by co-expressing the T. reesei-derived chitinase Chi46 and β-N-acetylglucosaminidase Nag1 to obtain an efficient chitin-degrading enzyme cocktail, which could achieve the production of N-acetyl-D-glucosamine from colloidal chitin with a conversion ratio of 91.83%. Besides, the purity of the above-secreted biomass-degrading enzymes in the crude culture supernatant was over 86%. Conclusions This PfopA-driven expression system expands the genetic toolbox of A. niger and broadens the application field of the traditional fructo-oligosaccharides-producing strain A. niger ATCC 20611, advancing it to become a high-performing enzyme-producing cell factory. In particular, the sucrose-inducible expression system possessed the capacity to produce biomass-degrading enzymes at a high level and evade endogenous protein interference, providing a potential purification-free enzyme production platform for bio-refinery applications.

Purpose: To assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT). Methods: We retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes. Results: The median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association 0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P 50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS. Conclusions: Age was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.

The cellular mechanisms mediating norepinephrine (NE) functions in brain to result in behaviors are unknown. We identified the L-type Ca2+ channel (LTCC) CaV1.2 as a principal target for Gq-coupled α1-adrenergic receptors (ARs). α1AR signaling increased LTCC activity in hippocampal neurons. This regulation required protein kinase C (PKC)-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with CaV1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of CaV1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by α1AR and formation of a signaling complex with PKC, Pyk2, and Src suggests that CaV1.2 is a central conduit for signaling by NE. Indeed, a form of hippocampal long-term potentiation (LTP) in young mice requires both the LTCC and α1AR stimulation. Inhibition of Pyk2 and Src blocked this LTP, indicating that enhancement of CaV1.2 activity via α1AR–Pyk2–Src signaling regulates synaptic strength.

Abstract Background The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI‐ENKTL). Methods The clinical data of GI‐ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. Results A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty‐nine patients received chemotherapy, of whom 15 patients received asparaginase‐based (ASP‐based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP‐based regimens, and 50.0% and 25.0% for those treated with non‐ASP‐based regimens, respectively. The median follow‐up was 12.9 months and the 1‐year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP‐based regimens resulted in a superior 1‐year progression‐free survival rate compared to non‐ASP‐based regimens (100.0% vs. 36.0%, p = .07). However, ASP‐based regimens did not improve survival in patients at an advanced stage. Conclusion GI‐ENKTL still has a poor prognosis, even in the era of modern asparaginase‐based treatment strategies.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs. [ABSTRACT FROM AUTHOR]

Background: Recurrent miscarriage (RM) affects an estimated 1-3% of couples attempting to conceive, and its molecular components stay ineffectively caught on. This study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM models. Meanwhile, explore relevant traditional Chinese medicine (TCM) components targeting potential therapeutic targets. Methods: We utilized the GSE211251 mouse and the GSE26787 human datasets, employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched pathways. Single-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target intelligence. We employed molecular docking strategies to assess the affinity of TCM components for key proteins. Results: In the mouse model, genes such as Ly6f1 and Gpr26 were upregulated, while Stc5a and Galca exhibited downregulation. Gene set enrichment analysis identified key pathways, including the tumor necrosis factor-mediated signaling pathway. In human samples, Gene Ontology analysis highlighted processes such as apoptosis and cell adhesion. Single-cell RNA analysis revealed distinct cellular populations between normal and RM samples. Systems pharmacology identified C-X-C motif chemokine receptor 4 (CXCR4) and endothelin 1 (EDN1) as potential key targets, and molecular docking confirmed that stearic acid from TCM appears to regulate these proteins. Conclusion: This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM, identifying CXCR4 and EDN1 as promising therapeutic targets. Stearic acid from TCM could provide targeted treatment by modulating these key proteins, paving the way for new RM treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: To clarify the effect of postmastectomy radiotherapy (PMRT) on pT1-2N1 breast cancer patients with different molecular subtypes. Methods: We retrospectively analyzed the data of 5442 patients with pT1-2N1 breast cancer treated using modified radical mastectomy in 11 hospitals in China. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of PMRT on locoregional recurrence (LRR). Results: With a median follow-up duration of 63.8 months, the 5-year LRR rates were 4.0% and 7.7% among patients treated with and without PMRT, respectively (p

ObjectiveTo examine changing trend and regional disparity in the insufficiency of government predominance in maternal health care financing and the maternal mortality ratio (MMR) in Beijing and Shanghai during 2000 to 2017 for exploring a rational government predominance in maternal health care financing. Methods Documents and literatures about maternal health care financing in Beijing and Shanghai published from 1995 through 2017 were searched; from which, the information on government predominance financing was extracted and the insufficiency of government predominance in maternal health care financing was evaluated with a severity score. Spearman correlation and linear regression analysis were used to analyze the relationship between the insufficiency of government predominance financing and MMR in the two municipalities. Results The severity score for the insufficiency of government predominance in maternal health care financing decreased from 3.58 in 2000 to 2.82 in 2017 in Beijing municipality; while in Shanghai the severity score decreased from 3.72 to 1.44. A significant correlation between the MMR and the severity score was observed in Shanghai municipality (r = 0.723, P < 0.01). Conclusion The government predominance in maternal health care financing increased during 2000 – 2017 in Beijing and Shanghai municipality and the government predominance financing has a more obvious influence on the reduction of maternal mortality ratio in Shanghai municipality.

This study investigated cold plasmas for multiple biological applications. Our previous work has found dielectric barrier discharge plasma improves chicken sperm quality. The number of Sertoli cells (SCs) decides spermatogenesis. However, whether cold plasma can regulate SC proliferation remains unclear. This study explored the effects of cold plasma on immature chicken SC proliferation and the regulation mechanism. Results showed that cold plasma exposure at 2.4 W for 30 s twice with an interval of 6 h produced (P

Myeloperoxidase is an important inflammatory factor in the myeloid system, primarily expressed in neutrophils and microglia. Myeloperoxidase and its active products participate in the occurrence and development of hemorrhagic and ischemic stroke, including damage to the blood-brain barrier and brain. As a specific inflammatory marker, myeloperoxidase can be used in the evaluation of vascular disease occurrence and development in stroke, and a large amount of experimental and clinical data has indicated that the inhibition or lack of myeloperoxidase has positive impacts on stroke prognosis. Many studies have also shown that there is a correlation between the overexpression of myeloperoxidase and the risk of stroke. The occurrence of stroke not only refers to the first occurrence but also includes recurrence. Therefore, myeloperoxidase is significant for the clinical evaluation and prognosis of stroke. This paper reviews the potential role played by myeloperoxidase in the development of vascular injury and secondary brain injury after stroke and explores the effects of inhibiting myeloperoxidase on stroke prognosis. This paper also analyzes the significance of myeloperoxidase etiology in the occurrence and development of stroke and discusses whether myeloperoxidase can be used as a target for the treatment and prediction of stroke.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered “cured” of the disease. We aimed to evaluate the statistical “cure” of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients’ perspective.

Cellulose degradation results from the synergistic effect of different enzymes, but which enzyme is involved in the initial stage of cellulose degradation is still not well understood. Cellobiohydrolase 2 (CBH2) attached to the conidial surface is possibly associated with the initial stage. However, its specific mechanism is still incompletely known. This study explored the potential role of CBH2 in initiating cellulose degradation using a constitutive overexpression strategy. First, the CBH2-overexpression Trichoderma reesei strains Qgc2–5 and Qrc2–40 were constructed using the constitutive promoters Pgpd1 and PrpS30, respectively. It was found that cbh2 was expressed at a high level under the glucose conditions and was significantly higher than that of the parental strain QM9414 at the early stage of 29 h when cellulose was used as the carbon source. Particularly, the constitutive overexpression of cbh2 caused the strong expression of major cellulase-encoding genes (cbh1, eg1, and eg2) and the rapid decomposition of cellulosic material. Meanwhile, the scanning electron microscope showed that the groove-like structure of the cellulose surface was eroded seriously owing to CBH2 overexpression, which caused the cellulose surface to be smooth. These results showed that the overexpression of CHB2 caused the major cellulase enzymes to be expressed and contributed to cellulose degradation, showing the potential role of CBH2 in the initial stage of the cellulose hydrolytic process.

GoalsTo assess the efficacy and safety of Chinese Medicine Prescription “W-LHIT” in subjects with simple obesity, and to explore its potential mechanism of action.MethodsThirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the “W-LHIT” capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding.Results72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment.ConclusionW-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

The standard of care for locally advanced cervical cancer is concurrent chemoradiotherapy, which is associated with significant toxicity, especially hematologic toxicity. To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during radical chemoradiotherapy for cervical cancer, 40 patients receiving prophylaxis from February 2018 to July 2019 were randomly divided into two arms in a 1:1 ratio. Patients in the study arm (N = 21) received PEG-rhG-CSF, while patients in the control arm (N = 19) received short-acting rhG-CSF. The primary endpoint was the incidence of grade 3–4 neutropenia, and the secondary endpoints were the incidence of febrile neutropenia, chemotherapy delay, and radiotherapy interruption. In addition, dynamic changes in absolute neutrophil count during radical chemoradiotherapy and adverse events were compared between the two groups. There were 0 and 4 cycles of grade 3–4 neutropenia in the PEG-rhG-CSF and rhG-CSF groups, respectively. The incidence of neutropenia of all grades was lower in patients on PEG-rhG-CSF than on rhG-CSF [24.05% (19/79) vs. 56.94% (41/72); p < 0.001]. No patient developed neutropenic fever. The lowest values of neutropenia during concurrent chemoradiotherapy cycles were 2.73 ± 1.02 and 1.91 ± 0.79 × 10 9/ml in the PEG-rhG-CSF and rhG-CSF groups, respectively (p < 0.001). In the PEG-rhG-CSF and rhG-CSF groups, 0 and 8 (11.11%) cycles of chemotherapy were delayed due to neutropenia, respectively (p = 0.01). There was no delay of radiotherapy by more than one week in either group. Prophylactic use of PEG-rhG-CSF during chemoradiotherapy for cervical cancer can effectively prevent neutropenia and associated adverse events. PEG-rhG-CSF may be an effective strategy to provide uninterrupted radical chemoradiotherapy for cervical cancer.