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AbstractContext Traditional Chinese Medicine (TCM) is effective as a cancer treatment modality. However, this is the first bibliometric analysis of TCM in lymphoma treatment.Objective This study explores the current trends and research topics of TCM in treating lymphoma from 2000 to 2023.Materials and methods We searched within the Web of Science Core Collection (WoSCC) for publications on TCM in lymphoma treatment, spanning 2000 to 2023. Subsequently, we employed a comprehensive approach utilizing CiteSpace software and VOSviewer to visually analyze research trends, authors, institutions, co-cited references, and keywords.Results From January 1, 2000, to August 31, 2023, annual scientific publications on TCM for lymphoma treatment have steadily increased. Among the leading institutions in this field, the Beijing University of Chinese Medicine and the Fujian Medical University occupied the top positions. Regarding the authors, Jun Peng, Jiumao Lin, and Hongwei Chen emerged as the top three contributors. In the co-citation analysis of references, the top three co-cited references were authored by Hanahan D, Elmore S, and Livak KJ with citations numbered 13, 14, and 17, respectively. In particular, keywords reflecting current emerging trends included ‘pathway’, ‘traditional Chinese medicine’, ‘oxidative stress’, and ‘macrophage polarization’.Discussion and conclusions This bibliometric analysis provides a comprehensive overview of TCM for lymphoma treatment. This analysis identified the predominant trends and research topics in the field. The findings are expected to be of significant value for researchers who focus on TCM in lymphoma treatment, helping them better understand the development of this field.

Abstract Background Recurrent gliomas rapidly progress and have high mortality and poor prognosis in the central nervous system. Therefore, further investigation of prognostic and therapeutic markers is needed. Methods The mRNA expression, clinical data, and coagulation-related genes (CRGs) associated with recurrent glioma were obtained and calculated from the Chinese Glioma Genome Atlas and Kyoto Encyclopedia of Genes and Genomes databases. The significant CRGs were calculated by Weighted gene co-expression network analysis and PPI network. A prediction model was constructed using the least absolute shrinkage and selection operator regression analysis. Recurrent gliomas were stratified into high and low-risk groups based on the median risk score (RS). The Kaplan–Meier curve was used to analyze the difference in overall survival (OS) between these groups, while the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of the gene model at 1-, 3-, and 5-years. Clinical factors, including age, gender, MGMT methylation status, radiotherapy, chemotherapy, and RS, were included in the univariate and multivariate regression analysis. A prognostic nomogram and calibration curve were established based on these factors. Results Overall, seven CRGs associated with the prognosis were identified, including BTK, ITGB1, GNAI3, CFH, LYN, CFI, and F3. OS and survival rates were lower in the high-risk group compared with the low-risk group. The ROC curve demonstrated the area under the curve values >0.65 at 1-, 3-, and 5-years, confirming the reliability of the prognostic model. The univariate regression analysis indicated that tumor grade (grades 2, 3, and 4), histopathology (GBM or not), chemotherapy, IDH mutation, and 1p19q co-deletion status were independent prognostic indicators. Univariate and multivariate regression analyses indicated that RS was an independent prognostic factor for patients with recurrent glioma. Immune analysis revealed low infiltration of resting dendritic cells and high expression of programmed death receptor 1 in the high-risk group. Conclusion This study comprehensively investigated the correlation between CRGs and recurrent glioma prognosis, offering crucial insights for further research into glioma recurrence mechanisms and treatment strategies.

In order to explore the feasibility of combining near-infrared (NIR) spectroscopy and deep learning network for quantitative moisture detection, the dried Porphyra was divided into 479 groups, which detected the NIR spectra and moisture content. Four traditional quantitative moisture prediction models and a convolution neural networks (CNN) deep-learning moisture prediction model were finally established at full spectrum by preprocessing and analyzing the experimental data. After comparing the prediction results of the five models, it was found that the CNN model established by the preprocessing method of S-G smoothing combined with the second derivative had the best prediction effect. Its root-mean-square error of prediction (RMSEP) value was 0.456 and the coefficient of determination of prediction (Rp2) value was 0.990. After optimization, the RMSEP value of the model was reduced to 0.342 and the Rp2 value could reach 0.994 (>0.8). At the same time, the ratio of performance to deviation for validation (RPD) was 6.155 (>3), which proved the possibility of practical application of the model in agriculture and food industry. The CNN model could predict the moisture content quickly, accurately, and non-destructive, improve the efficiency and accuracy of moisture detection, and provide an important reference for the quality control of related dry aquatic products.

Through hot compression and subsequent heat treatment experiments on GH4079 superalloy, the influence of different hot deformation and heat treatment conditions on the evolution of GH4079 superalloy microstructure was studied. The evolution of grains and γ′ phases under different thermomechanical conditions was investigated. The results indicate that at deformation temperatures above 1100 °C and strain rates ranging from 0.01 to 0.1 s−1, the primary mechanism of dynamic softening in the alloy is discontinuous dynamic recrystallization (DDRX). When the deformation temperature is below 1100 °C and strain rates range from 0.01 to 0.1 s−1, both continuous dynamic recrystallization (CDRX) and DDRX are the main dynamic softening mechanisms. Due to high strain energy accumulation, the samples deformed at lower temperatures (below 1100 °C) and then solution-treated at 1120 °C for 8 h exhibit significant increases in recrystallization volume fraction and recrystallization grain size. Conversely, the samples deformed at higher temperatures (above 1100 °C) and then solution-treated at 1120 °C for 8 h show minimal changes in recrystallization volume fraction and recrystallization grain size. After solution treatment at 1140 °C, the grain size of the alloy significantly increases. The samples deformed at higher strain rates exhibit the evolution of fine γ′ phases into elongated rod shapes during solution treatment, while larger γ′ phases undergo splitting processes.

Abstract Both anaesthesiologists and surgeons experience challenges in managing airway stenosis and scar contracture in the face and neck. Herein, we report the case of a 38-year-old woman (BMI 23.1 kg/m2, third-degree burns covering 40% of her body, an American Society of Anaesthesiologists physical status III) with an unusual case of airway constriction. This patient had a predictable difficult airway (mouth opening of 2 cm, bilateral nostril scar hyperplasia, Mallampatti score III, scarring of the head and neck, and severe tracheal stenosis). Tracheal stenosis measuring 5.5 mm in width as observed 8 cm below the glottis, and the bronchoscope could not pass through it. After two failed attempts at laryngeal mask insertion, we decided to instead insert a custom-made tracheal tube under the guidance of a fiberoptic bronchoscope. The operation was successful, and the patient was transferred to the intensive care unit (ICU).

This work systematically investigated the coarsening, dissolution, and morphological evolution behavior of γ′ precipitates in GH4742 superalloy through carefully designed heat treatment experiments. During long-term aging processes at 650 °C, 750 °C, and 850 °C, the coarsening model of γ′ precipitates followed the classic function of r3 vs. t, consistent with the classical Lifshitz-Slyozov-Wagner (LSW) coarsening model (diffusion-controlled). Due to higher diffusion coefficients of γ′ forming elements at higher temperatures, the coarsening rate K increased with aging temperature. The dynamical models for the dissolution of primary γ′ precipitates were established during sub-solvus (1080 °C) and super-solvus (1120 °C) heat treatment processes. The results indicated rapid dissolution of primary γ′ precipitates in the initial stages of solution heat treatment, with the dissolution rate gradually decreasing as the treatment time extended, approaching the γ′ precipitate size at thermodynamic equilibrium. During subsequent slow cooling at 14 °C/min after super-solvus (1120 °C) heat treatment, irregular-shaped γ′ precipitates formed through “aggregation” of adjacent γ′ precipitates, followed by “splitting” into smaller γ′ precipitates during growing up. Conversely, during subsequent slow cooling at 14 °C/min after sub-solvus (1080 °C) heat treatment, irregular-shaped γ′ precipitates were mainly controlled by unstable growth and “splitting” of cubic-shaped γ′ precipitates. For individual γ′ precipitates, the portion undergoing unstable growth (protrusions) did not undergo further splitting.

Abstract Background Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. Purpose This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. Methods C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. Results The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. Conclusions Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin. Graphical abstract

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639–0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882–0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60–80%, >40–60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51–0.97) to 0.48 (95% CI, 0.36–0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

Abstract Background To explore the clinical characteristics of ovarian Brenner tumors and provide some basis for the treatment regimen of ovarian Brenner tumors. Methods A retrospective analysis of the pathology database of surgical specimens at the Huzhou Maternal and Child Health Hospital from September 2008 to February 2023 was conducted. Patients who were pathologically diagnosed with ovarian Brenner tumors were included. Clinical data of patients was collected, and their diagnostic and treatment characteristics were summarized and analyzed. Results A total of 20 cases were included in this study, all of which were histologically confirmed by surgical pathology. Among them, 8 cases (40%) were combined with serous, mucinous cystadenoma, or simple cyst. One case presented with a benign ovarian Brenner tumor combined with mucinous cystadenoma, underwent right adnexectomy, and relapsed 5 years later as a malignant Brenner tumor (MBT) coexisting with ovarian squamous cell carcinoma. Multiple tumor markers were elevated malignantly, with CA199 being the most significant. Treatments included unilateral adnexectomy in 7 cases, bilateral adnexectomy in 3 cases, total hysterectomy with bilateral adnexectomy in 7 cases, radical hysterectomy in 1 case, and 2 cases underwent ovarian staging surgery. MBT patients received three cycles of postoperative chemotherapy with the carboplatin-paclitaxel (TC) regimen. Follow-up: One case with concomitant cervical cancer was lost to follow-up after surgery in an external hospital; one case with concomitant ovarian cancer received no further treatment after surgery and was lost to follow-up after 2 years; one case with concomitant endometrial cancer received no further treatment after surgery, and had no recurrence after 4 years of follow-up. Regular follow-up for MBT patients continued for 5 years without recurrence. The remaining 16 cases were followed up for a period ranging from 6 months to 7 years, with no reported recurrences. Conclusion Clinical manifestations and auxiliary examinations of ovarian Brenner tumors lack obvious specificity. When necessary, a combination of tumor markers and imaging examinations can aid in diagnosis. Surgical strategies should be selected according to the patient's menopausal status. Trial registration Not applicable.

Abstract Human trophoblastic cell surface antigen 2 (Trop2) is a glycoprotein, a cellular marker of trophoblastic and stem cells, and a calcium signaling transducer involved in several signaling pathways, leading to the proliferation, invasion, and metastasis of tumors. It is expressed at a low level in normal epithelial cells, but at a high level in many tumors, making it an ideal target for cancer therapy. According to previous literature, Trop2 is broadly expressed in all breast cancer subtypes, especially in triple negative breast cancer (TNBC). Several clinical trials have demonstrated the effectiveness of Trop2-targeted therapy in breast cancer. Sacituzumab govitecan (SG) is a Trop2-targeted antibody-drug conjugate (ADC) that has been approved for the treatment of metastatic TNBC and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This article reviews the structure and function of Trop2, several major Trop2-targeted ADCs, other appealing novel Trop2-targeted agents and relevant clinical trials to provide a landscape of how Trop2-targeted treatments will develop in the future.

Abstract Background We described a case of abdominal aortic aneurysm complicated by type B thoracic aortic dissection, in whom molecular analysis revealed a pathogenic TGFBR1 missense mutation. Case presentation A 36-year-old woman was admitted to our hospital with sudden onset of back pain. Computed tomography angiogram demonstrated descending aortic dissection extending into the abdominal aorta aneurysm. Whole-exome sequencing and subsequent Sanger sequencing confirmed a pathogenic mutation in the TGFBRI gene (NM_004612.4: c.605C > T; p.Ala202Val). She refused to receive surgery and died one month later. Conclusion To our knowledge, this is the first documented case of the TGFBR1 gene mutation who suffered from abdominal aortic aneurysm complicated by descending thoracic aortic dissection. Her rapid death underscores the importance of timely intervention in TGFBR1 mutation-positive patients.

Background: The application of traditional Chinese medicine (TCM) therapy to acute leukemia has been intensively investigated. However, the bibliometric analysis in this field has not been performed. This bibliometric study aimed to comprehensively analyze the research trends and active areas of TCM therapy for acute leukemia from 2000 to 2023.Methods: We searched articles and reviews published between 2000 and 2023 that discussed TCM in acute leukemia from the Web of Science Core Collection (WoSCC). Knowledge mapping and bibliometric analysis were conducted using VOSviewer, CiteSpace software, and R-bibliometrix.Results: A total of 1,099 articles were included, with China, the United States, and Korea contributing the most papers. Most papers were published in the Journal of Ethnopharmacology. Meanwhile, China saw a steady increase in the number of publications. The three leading institutions that made outstanding contributions were the China Medical University, the Chinese Academy of Sciences, and the China Academy of Chinese Medical Sciences. Efferth Thomas, Liu Wei, and Liu Jie were the top three productive authors, with Efferth T receiving the most co-citations. The most frequently cited reference was Shen ZX (1997). In the analysis of keywords co-occurrence, ‘survival,’ ‘risk factors,’ ‘nanoparticles,’ and ‘metabolism’ are the active research topics.Conclusion: This bibliometric study provides researchers with a comprehensive overview and significant value in understanding the development of TCM in acute leukemia treatment.

The edible flower buds of Hemerocallis citrina Baroni are used both as a vegetable and functional food. It has various health benefits due to the diversity of natural products. However, the establishment of functional components in the edible flower bud remains to be studied. We conducted a high-resolution metabolomic analysis of flower buds at three developmental stages, 1–2 cm, 4–6 cm, and edible (10–15 cm). Our analysis revealed 157 differential accumulated metabolites, including flavonoids (49), fatty acids (17) and terpenoids (13) while most of them decreased during flower bud development. Among them, 2 flavonoids, 2 long-chain fatty acids and 1 triterpene saponin are highly accumulated in edible flower buds. Furthermore, the expression levels of catalytic genes mirrored the changes in metabolite levels detected. These results track the dynamics of functional component accumulation during edible flower bud development, laying the theoretical basis for nutrition formation in H. citrina.

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague–Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFβ1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFβ1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro, peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.

Background Sepsis-associated acute kidney injury (S-AKI) is a critical illness and is often associated with high morbidity and mortality rates. The soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator and is involved in kidney injury. However, its diagnostic value in S-AKI patients remains unclear. Therefore, we assessed the early predictive value of suPAR for S-AKI patients.Methods We prospectively enrolled adult patients, immediately after fulfilling the sepsis-3 criteria. Plasma suPAR levels at 0-, 12-, 24-, and 48-h post-sepsis diagnosis were measured. S-AKI development was the primary outcome. S-AKI risk factors were analyzed using logistic regression, and the value of plasma suPAR for early S-AKI diagnosis was assessed using receiver operating characteristic (ROC) curves.Results Of 179 sepsis patients, 63 (35.2%) developed AKI during hospitalization. At 12-, 24-, and 48-h post-sepsis diagnosis, plasma suPAR levels were significantly higher in patients with S-AKI than in patients without S-AKI (p

Abstract Background Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and is often accompanied by mild cognitive impairment (MCI). The detrimental effects of T2DM and IR on the hippocampus have been extensively demonstrated. Few studies have examined the effects of IR on structure and function of hippocampal subfields in T2DM‐MCI patients. Method A total of 104 T2DM patients were recruited in this prospective study and divided into four groups (T2DM‐MCI‐higherIR, n = 17; T2DM‐MCI‐lowerIR, n = 32; T2DM‐nonMCI‐higherIR, n = 19; T2DM‐nonMCI‐lowerIR, n = 36). Structure and function MRI data were captured. Clinical variables and neuropsychological scores were determined for all participants. Hippocampal subfield volume and functional connectivity were compared among four groups. Partial correlation analysis was performed between imaging indicators, clinical variables, and neuropsychological scores in all patients. Results T2DM‐MCI‐higher IR group had the smallest volumes of bilateral hippocampal tail, right subiculum‐body, right GC‐ML‐DG‐body, and right CA4‐body. IR in right hippocampal tail, right subiculum‐body, and right GC‐ML‐DG‐body exerted main effect. Furthermore, elevated functional connectivity was found between right subiculum‐body and bilateral dorsolateral prefrontal cortex and right anterior cingulate–medial prefrontal cortex. Hippocampal subfield volume positively correlates with total cholesterol and triglycerides and negatively correlates with fasting insulin. Conclusion The present study found that T2DM‐MCI patients have structural and functional alterations in hippocampal subfields, and IR is a negative factor influencing the alteration of hippocampal subfields volume. These findings support the importance of IR in T2DM‐MCI patients and might be potential neuroimaging biomarkers of cerebral impairment in T2DM‐MCI patients.

PurposeThe efficacy of tislelizumab plus chemotherapy in improving progression-free survival (PFS) and overall survival (OS) in unresectable gastric or gastroesophageal junction cancer (GC/GEJC) has recently been emphasized. This study compared the cost-effectiveness of tislelizumab plus chemotherapy versus placebo plus chemotherapy for the United States (US) and Chinese populations.MethodsUsing data from the RATIONALE-305 phase 3 trial, a Markov model was developed to analyze quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net health benefits (INHBs), and incremental net monetary benefits (INMBs). The health state utilities and direct medical costs were obtained from the relevant literature and local cost databases. The model uncertainty was evaluated using sensitivity analyses.FindingsIn the base-case analysis, the addition of tislelizumab to chemotherapy yielded an ICER of $37,768.48 per QALY in China, slightly below the willingness-to-pay (WTP) threshold of $38,042.49 per QALY, showing marginal cost-effectiveness with an INHB of 0.05 QALYs and an INMB of $1,852.49. Subgroup analyses revealed ICERs of $23,853.52 for patients with a PD-L1 TAP score ≥ 5% (TAP ≥ 5%). In the US, the ICER was $502,786.22 per QALY in the intent-to-treat (ITT) and $321,395.28 per QALY in the TAP ≥ 5% subgroup, exceeding the US WTP threshold of $150,000.00.ImplicationsIn China, tislelizumab plus chemotherapy is a cost-effective first-line therapy for unresectable GC/GEJC in both ITT and TAP ≥ 5% subgroups. In the US, tislelizumab plus chemotherapy is not cost-effective.

ObjectiveTo analyze the risk factors for pneumothorax after particle implantation in the treatment of advanced lung cancer and to construct and validate a nomogram prediction model.MethodsA retrospective analysis was conducted on 148 patients who underwent 125I particle implantation for advanced lung cancer at the *** from December 2022 to December 2023. Potential risk factors were identified using univariate logistic regression analysis, followed by a multivariate logistic regression analysis to evaluate the predictive factors for pneumothorax. Interaction effects between variables were studied and incorporated into the model construction. ROC curves and nomograms were generated for visualization. Calibration analysis was performed, and the corresponding net benefit was calculated to adjust the predictive model.ResultsAmong the 148 patients, 58 (39.19%) experienced pneumothorax, with a mean age of 62.5 (55.25, 70) years. Multivariate analysis showed that the angle between the puncture needle and the pleura < 50° (P = 0.002, OR: 3.908, CI: 1.621–9.422), preoperative CT suggesting emphysema (P = 0.002, OR: 3.798, CI: 1.600–9.016), atelectasis (P = 0.009, OR: 3.156, CI: 1.331–7.481), and lesion located in the left lung fissure (P = 0.008, OR: 4.675, CI: 14.683) were independent risk factors for pneumothorax after particle implantation in the treatment of advanced lung cancer. Preoperative CT suggesting lesions in the left lung fissure or suggesting emphysema had a significant impact in the nomogram, with probabilities of pneumothorax occurrence at 40% and 38%, respectively. The predictive AUC for the above four risk factors for pneumothorax after particle implantation in the treatment of lung adenocarcinoma was 0.837 (95% CI: 0.767–0.908). When the Youden index was 0.59, the sensitivity was 85.56%, specificity was 74.13%, accuracy was 81.01%, positive predictive value was 83.69%, and negative predictive value was 76.78%.ConclusionThe angle between the puncture needle and the pleura < 50°, preoperative CT suggesting emphysema, atelectasis, and lesion located in the left lung fissure are independent risk factors for pneumothorax after particle implantation in the treatment of advanced lung cancer. Preoperative planning of the puncture path should avoid lung bullae, interlobar fissures, areas of severe emphysema, and atelectasis.

Hepatocellular Carcinoma (HCC) is a serious primary solid tumor that is prevalent worldwide. Due to its high mortality rate, it is crucial to explore both early diagnosis and advanced treatment for HCC. In recent years, multi-omics approaches have emerged as promising tools to identify biomarkers and investigate molecular mechanisms of biological processes and diseases. In this study, we performed proteomics, phosphoproteomics, metabolomics, and lipidomics to reveal the molecular features of early- and advanced-stage HCC. The data obtained from these omics were analyzed separately and then integrated to provide a comprehensive understanding of the disease. The multi-omics results unveiled intricate biological pathways and interaction networks underlying the initiation and progression of HCC. Moreover, we proposed specific potential biomarker panels for both early- and advanced-stage HCC by overlapping our data with CPTAC database for HCC diagnosis, and deduced novel insights and mechanisms related to HCC origination and development, such as glucose depletion during tumor progression, ROCK1 deactivation and GSK3A activation.

Abstract Background Guanosine is a purine nucleoside that is widely used as a raw material for food additives and pharmaceutical products. Microbial fermentation is the main production method of guanosine. However, the guanosine-producing strains possess multiple metabolic pathway interactions and complex regulatory mechanisms. The lack of strains with efficiently producing-guanosine greatly limited industrial application. Results We attempted to efficiently produce guanosine in Escherichia coli using systematic metabolic engineering. First, we overexpressed the purine synthesis pathway from Bacillus subtilis and the prs gene, and deleted three genes involved in guanosine catabolism to increase guanosine accumulation. Subsequently, we attenuated purA expression and eliminated feedback and transcription dual inhibition. Then, we modified the metabolic flux of the glycolysis and Entner-Doudoroff (ED) pathways and performed redox cofactors rebalancing. Finally, transporter engineering and enhancing the guanosine synthesis pathway further increased the guanosine titre to 134.9 mg/L. After 72 h of the fed-batch fermentation in shake-flask, the guanosine titre achieved 289.8 mg/L. Conclusions Our results reveal that the guanosine synthesis pathway was successfully optimized by combinatorial metabolic engineering, which could be applicable to the efficient synthesis of other nucleoside products.

Abstract Background Triple Negative Breast Cancer (TNBC) is a particular type of breast cancer with the highest mortality rate. Essential oils are concerned more and more as potential anti-cancer drugs. Methods TNBC cells were treated with different concentrations of navel orange peel essential oil (NOPEO), and then a variety of experiments were performed to investigate the changes in the growth and progression of TNBC cells. MTT assay was performed to detect the proliferation of TNBC cells. The changes of cell cycle and apoptosis were analyzed by FACS. In order to explored the migration of TNBC cells, scratch wound assay was carried out. Western blotting and qPCR were used to examine the expression of proteins and mRNA of related genes. Furthermore, RNA-seq was used to analyze the altered genes and explored the possible signal pathway. Results NOPEO demonstrated dose- and time-dependent suppression of TNBC cell growth. TNBC cells showed an increased percentage of G2/M-phase cells and the protein levels of CyclinB1 and CyclinD1 were decreased after NOPEO treatment. The apoptotic cells were increased in the NOPEO treated TNBC cells. The migration mobility was significantly inhibited by NOPEO. In total, 1376 genes were found to be up-regulated and 1335 genes were down-regulated after NOPEO treatment. According to KEGG and GO pathways, the differentially expressed genes were related to MAPK, Jak/stat and FoxQ signaling pathways. Conclusion This investigation explored the bio-activity and molecular mechanisms of NOPEO against TNBC cells. These results indicated that NOPEO could suppress TNBC growth and migration perhaps via the MAPK and Jak/stat signaling pathways, which may provide theoretical reference for anticancer drug development. NOPEO may be a potential natural product for the chemotherapeutic of TNBC.

Abstract Background Intrauterine adhesion (IUA) is one of the most severe causes of infertility in women of childbearing age with injured endometrium secondary to uterine performance. Stem cell therapy is effective in treating damaged endometrium. The current reports mainly focus on the therapeutic effects of stem cells through paracrine or transdifferentiation, respectively. This study investigates whether paracrine or transdifferentiation occurs preferentially in treating IUA. Methods Human amniotic mesenchymal stem cells (hAMSCs) and transformed human endometrial stromal cells (THESCs) induced by transforming growth factor beta (TGF-β1) were co-cultured in vitro. The mRNA and protein expression levels of Fibronectin (FN), Collagen I, Cytokeratin19 (CK19), E-cadherin (E-cad) and Vimentin were detected by Quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and Immunohistochemical staining (IHC). The Sprague-Dawley (SD) rats were used to establish the IUA model. hAMSCs, hAMSCs-conditional medium (hAMSCs-CM), and GFP-labeled hAMSCs were injected into intrauterine, respectively. The fibrotic area of the endometrium was evaluated by Masson staining. The number of endometrium glands was detected by hematoxylin and eosin (H&E). GFP-labeled hAMSCs were traced by immunofluorescence (IF). hAMSCs, combined with PPCNg (hAMSCs/PPCNg), were injected into the vagina, which was compared with intrauterine injection. Results qPCR and WB revealed that FN and Collagen I levels in IUA-THESCs decreased significantly after co-culturing with hAMSCs. Moreover, CK19, E-cad, and Vimentin expressions in hAMSCs showed no significant difference after co-culture for 2 days. 6 days after co-culture, CK19, E-cad and Vimentin expressions in hAMSCs were significantly changed. Histological assays showed increased endometrial glands and a remarkable decrease in the fibrotic area in the hAMSCs and hAMSCs-CM groups. However, these changes were not statistically different between the two groups. In vivo, fluorescence imaging revealed that GFP-hAMSCs were localized in the endometrial stroma and gradually underwent apoptosis. The effect of hAMSCs by vaginal injection was comparable to that by intrauterine injection assessed by H&E staining, MASSON staining and IHC. Conclusions Our data demonstrated that hAMSCs promoted endometrial repair via paracrine, preferentially than transdifferentiation.

Abstract Background Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood. Methods The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats. Results The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application. Conclusions Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.

To address the issue of non-standard grain sizes and difficult control of uniformity in the manufacturing of large, complex-shaped nuclear power pipelines. In this paper, double wedge-shaped samples of X2 CrNiMo 18.12 (CN) austenitic stainless steel were hot deformed at 1000 °C, 1100 °C, and 1180 °C to obtain deformation samples with a gradient strain, and the deformation sample at 1180 °C was subjected to solid solution treatment at 1060 °C × 4 h (water quenching; the measured cooling rate of water cooling was approximately 4400 °C/min). Large-area electron backscattered diffraction mapping technology was used to characterize the 80 mm × 5 mm full-area range of samples. The initiation sequence of various dynamic recrystallization mechanisms and the grain evolution under continuous effective strain conditions at a hot deformation temperature of 1000–1180 °C were investigated. The influence of the hot deformation process parameters on the grains after solid solution treatment was examined, the process interval for the generation of severe mixed grains was determined. The results show that the recrystallization behavior of X2 CrNiMo 18.12 (CN) austenitic stainless steel is mainly determined by a combination of recrystallization mechanisms dominated by discontinuous dynamic recrystallization, supplemented by continuous dynamic recrystallization, twinning-induced dynamic recrystallization, and geometrical dynamic recrystallization during the hot deformation process at 1000–1180 °C. The effective strain intervals of the solid solution sample that produces severely mixed grains are in the range of 0.11–0.22 mm/mm, with the probability of producing severely mixed grains with an effective strain in the range of 0.13–0.14 mm/mm reaching 74%.

Abstract Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.

Abstract To explore the impact of the Mediterranean diet on cardiovascular risk factors, glycemic control and weight loss in patients with type 2 diabetes(T2D) by a meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Cochrance Library, EMBASE and four Chinese databases to identify RCTs that compared the Mediterranean diet with control diets in patients with T2D up to December 2021. The Risk of Bias of the included studies was assessed using the version 2 of the Cochrane risk-of-bias tools for randomized trials (ROB 2). Seven RCTs with 1371 patients met the eligibility criteria and entered into the meta-analysis. Compared to control diets, the beneficial effects of Mediterranean diet were not statistically significant in high-density lipoprotein (MD = 2.33; 95% CI: -0.27 to 4.92), low-density lipoprotein (MD = -2.34; 95% CI -5.67 to 0.99) and total cholesterol (MD = 2.60; 95% CI: -0.95 to 6.15). But Mediterranean diet led to reduce the level of diastolic blood pressure (MD = -1.20; 95% CI: -2.21 to -0.19) and systolic blood pressure (MD = -4.17; 95% CI: -7.12 to -1.22). Meanwhile, Mediterranean diet showed beneficial effects in glycemic control (HbA1[%]: MD = -0.39, 95% CI: -0.58 to -0.20; fasting plasma glucose: MD = -15.12, 95% CI: -24.69 to -5.55) and weight loss (BMI: MD = -0.71, 95% CI: -1.30 to -0.78; WC: MD = -1.69; 95% CI: -3.35 to -0.02) compared to the control diets. The meta-analysis presented evidence supporting the beneficial effects of the Mediterranean diet on blood pressure, glycemic control, and weight loss. However, the impact of the Mediterranean diet on the lipid profile was not found to be significant, warranting further verification. This Meta-analysis was registered on the INPLASY website (Registration number: INPLASY 202160096).

Purpose: To explore the parameters that may influence the effectiveness of femtosecond laser-assisted capsulotomy in white cataract surgery and its cutoff points. Design: A retrospective case series. Methods: This retrospective case series study enrolled patients with white cataract who had undergone surgery at Changsha Aier Eye Hospital from July 2018 to January 2020. All patients underwent femtosecond laser-assisted capsulotomy using a contact femtosecond laser device (LenSx, Alcon Laboratories, USA). The sex, age, corrected distance visual acuity (CDVA), intraocular pressure (IOP), axial length (AL), lens thickness (LT), anterior chamber depth (ACD) and mean keratometry (Km) were recorded. All eyes were divided into successful capsulotomy group and unsuccessful capsulotomy group according to the capsulotomy integrity. Both groups were compared and two-sample t-test was used in order to find the optimal cutoff points of the parameters. Results: 60 eyes of 59 patients were included in the study. A successful capsulotomy was achieved in 36 eyes (60 %), while unsuccessful capsulotomy occurred in 24 eyes (40 %). Although no significant differences were observed in sex (P = 0.704), AL (P = 0.598) and Km (P = 0.873) between both groups, LT (P

Large Cell Neuroendocrine Carcinoma (LCNEC) of the cervix is an extremely rare but highly aggressive type of cervical cancer and it requires multimodal therapy to improve their quality of life. At present, there are no established, standardized treatment protocols for managing large cell neuroendocrine carcinoma of the cervix. In this report, we present a case of a patient with cervical LCNEC, Who was a 39-year-old woman who presented with irregular vaginal bleeding accompanied by lower abdominal distension for over a month. Examination revealed a cauliflower-like cervical mass approximately 4cm in diameter, with the normal cervical architecture distorted and partially fused to the vaginal wall. Following further investigations, the stage assigned was IVB, and who was started on neoadjuvant chemotherapy with the TC (paclitaxel + carboplatin) regimen but during neoadjuvant chemotherapy, The patient developed a vaginal urinary leakage. Then, The patient underwent a comprehensive treatment regimen that included pelvic exenteration, urinary system reconstruction, pelvic floor reconstruction, and chemotherapy. Given the patient’s positive immunohistochemistry for EGFR, the treatment was combined with the anti-angiogenic drug, bevacizumab. The patient achieved complete remission following the comprehensive treatment. Through this case to explore individualized treatment for cervical LCNEC.

Abstract Diplopoda is one of the most diverse and important groups of soil arthropods, but little research has been done on their phylogenetic relationship and evolution. Here, we sequenced and annotated the complete mitochondrial genomes of Spirobolus grahami. The total mitogenome of S. grahami was typical circular, double-stranded molecules, with 14,875 bp in length, including 13 protein-coding genes, 22 tRNAs, two rRNAs, and one control region. Base composition analysis suggested that the mitochondrial sequences were biased toward A and T, with A + T content of 58.68%. The mitogenomes of S. grahami exhibited negative AT and positive GC skews. Most of the 13 PCGs had ATN as the start codon, except COX1 start with CGA, and most PCGs ended with the T stop codon. The dN/dS values for most PCGs were lower than 1, suggesting that purifying selection was likely the main driver of mitochondrial PCG evolution. Phylogenetic analyses based on 13 PCGs using BI and ML methods support the classification of genus Spirobolus and Tropostreptus. Glomeridesmus spelaeus is distantly related to the other Diplopoda species.

Abstract Urbanization has altered land surface properties driving changes in micro-climates. Urban form influences people’s activities, environmental exposures, and health. Developing detailed and unified longitudinal measures of urban form is essential to quantify these relationships. Local Climate Zones [LCZ] are a culturally-neutral urban form classification scheme. To date, longitudinal LCZ maps at large scales (i.e., national, continental, or global) are not available. We developed an approach to map LCZs for the continental US from 1986 to 2020 at 100 m spatial resolution. We developed lightweight contextual random forest models using a hybrid model development pipeline that leveraged crowdsourced and expert labeling and cloud-enabled modeling – an approach that could be generalized to other countries and continents. Our model achieved good performance: 0.76 overall accuracy (0.55–0.96 class-wise F1 scores). To our knowledge, this is the first high-resolution, longitudinal LCZ map for the continental US. Our work may be useful for a variety of fields including earth system science, urban planning, and public health.

AbstractThe complete mitogenome of the Slaty-backed Forktail (Enicurus schistaceus) was first sequenced using next-generation sequencing. It was 17,112 bp long, with a base composition of 14.17% G, 31.77% C, 30.73% A, and 23.33% T and an AT content of 54.06%. Similar to other mitochondrial genomes within the Muscicapidae family, E. schistaceus exhibited a relatively consistent mitogenome arrangement; it consisted of 22 tRNA genes, two rRNA genes, 13 protein-coding genes, and one control region. Notably, ND6 and eight tRNA genes were encoded on the light strand. Phylogenetic analysis of the 12 Muscicapidae mitogenomes substantiated the monophyly of all genera, including E. schistaceus. Furthermore, the analysis demonstrated a close relationship between Enicurus and Myophonus.

Autolysis in the sea cucumber Apostichopus japonicus is typically triggered by degradation caused by microorganisms within their bodies. However, information on this topic remains limited. Recently, we isolated and purified a bacterial strain from hydrolyzed instant sea cucumber samples. To investigate its potential role in the autolysis process, this study employed whole-genome sequencing and metabolomics to explore its genetic and metabolic characteristics. The identified strain was classified as Lysinibacillus xylanilyticus and designated with the number XL-2024. Its genome size is 5,075,210 bp with a GC content of 37.33%, encoding 5275 genes. Functional database comparisons revealed that the protein-coding genes were distributed among glucose metabolism hydrolase, metal hydrolase, lysozyme, cell wall hydrolase, and CAZymes. Compared to 20 closely related strains, L. xylanilyticus XL-2024 shared 1502 core homologous genes and had 707 specific genes. These specific genes were mainly involved in the carbohydrate metabolism pathway and exhibited glycosyl bond hydrolase activity. Metabolomic analysis showed that L. xlanilyticus XL-2024 produced several metabolites related to polysaccharide degradation, including peptidase, glucanase, and pectinase. Additionally, the presence of antibacterial metabolites such as propionic acid and ginkgo acid among its metabolites may enhance the stability of the sea cucumber hydrolysate. In summary, L. xylanilyticus XL-2024 may play a pivotal role in the autolysis of A. japonicus. The results of this study provide a strong foundation for understanding how to prevent autolysis in A. japonicus and for better utilizing L. xylanilyticus XL-2024.

N-methyl-n’-nitroso-n’-nitroso guanidine (MNNG) can induce esophageal squamous cell carcinoma (ESCC), and microRNAs are associated with the development of ESCC and may serve as potential tumor prognostic markers. Thus, the aim of this study was to evaluate the potential function of miR-101-3p in MNNG-induced ESCC. An investigation of risk factors in patients with ESCC was carried out and the concentration of nine nitrosamines in urine samples was detected by the SPE-GC-MS technique. Then, we performed cancer tissue gene sequencing analysis, and RT-qPCR verified the expression level of miR-101-3p. Subsequently, the relationship between miR-101-3p potential target genes and the ESCC patients’ prognosis was predicted. Finally, we investigated the function of miR-101-3p in MNNG-induced ESCC pathogenesis and the regulatory mechanism of the signaling pathway by in vivo and in vitro experiments. The results revealed that high dietary nitrosamine levels are high-risk factors for ESCC. MiR-101-3p is down-regulated in ESCC tissues and cells, and its potential target genes are enriched in cell migration and cancer-related pathways. MiR-101-3p target genes include AXIN1, CK1, and GSK3, which are involved in the regulation of the Wnt signaling pathway. MiR-101-3p overexpression promotes apoptosis and inhibits the proliferation and migration of Eca109 cells. The Wnt pathway is activated after subchronic exposure to MNNG, and the Wnt pathway is inhibited by the overexpression of miR-101-3p in Eca109 cells. Down-regulated miR-101-3p may exert tumor suppressive effects by regulating the Wnt pathway and may be a useful biomarker for predicting ESCC progression.

This study explores the complexity of generic graduate attributes, including soft skills, qualities, competencies, and capabilities in order to pinpoint how graduate attributes are cultivated in practice during the university experience. Few studies have examined the active and formative role of universities in cultivating generic graduate attributes. Even less have examined which skills and related subskills are developed according to graduates themselves, much less the extent to which those acquired specific skills mindsets and subskills are attributable to "micro-level" pedagogical practices, "meso-level" university experiences or "macro-level," institution-level frameworks, vision, or mission statements. Additionally, there is a paucity of research on the attributes of graduates from transnational higher education institutions and specifically from Sino-foreign cooperative universities. This study thus aims to address these gaps and is also timely as it coincides with the twentieth anniversary of the University of Nottingham Ningbo China, established in 2004, which is the first Sino-foreign higher education institution. This study adopts an overarching exploratory research methodology mobilizing both quantitative survey data collection and qualitative in-depth, semi-structured interviews. This research is innovative because it is a bottom-up retrospective mapping to localize exactly where, within the entire university experience, graduates attribute the acquisition of their skills/graduateness, including across both curricular and extracurricular experiences.

This research explores the perceptions of undergraduates at a Sino-foreign cooperative university in terms of extracurricular activities (ECAs) and co-curricular activities (CCAs) and their impact on social skills development. Few studies relate engagement in ECAs and CCAs with social skills development, and much less in the context of transnational and/or Sino-foreign higher education. This case study adopts an overarching exploratory research paradigm mobilizing quantitative and qualitative data collection in a concurrent mixed-methods approach. This study proposes an original conceptual framework for curricular, co-curricular and extracurricular activities in the context of a Sino-foreign higher education, such as the University of Nottingham Ningbo China. Suggestions for students to develop social skills through participation in ECAs and CCAs and suggestions for university staff to improve the offer and quality of ECAs and CCAs are investigated. Results of this study provide insights of relevance for both students and staff in the context of Sino-foreign higher education.