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Background: Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables. Methods: This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001–2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools. Results: Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival. Conclusions: We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of metformin (MET) monotherapy and pioglitazone plus MET (PIOMET) therapy on gonadal and metabolic profiles in normal-weight women with polycystic ovary syndrome (PCOS). Methods: Sixty normal-weight women with PCOS were recruited between January and September 2022 at the Shengjing Hospital of China Medical University. They were randomly assigned to the MET or PIOMET groups for 12 weeks of MET monotherapy or PIOMET therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and the oral glucose insulin-releasing test (OGIRT) were performed at baseline and after the 12-week treatment. Results: Thirty-six participants completed the trial. MET and PIOMET therapies improved menstrual cycles after the 4- and 12-week treatments; however, there was no statistical difference between the two groups. PIOMET therapy improved luteinizing hormone (LH), luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, and free androgen index (FAI) levels after the 4-week treatment, whereas MET monotherapy only improved total testosterone (TT) levels compared to baseline (P < 0.05). Both MET and PIOMET therapies improved TT and anti-Mullerian hormone (AMH) levels after the 12-week treatment (P < 0.05). In addition, only PIOMET therapy significantly improved sex hormone-binding globulin (SHBG), FAI, and androstenedione (AND) levels than the baseline (P < 0.05). PIOMET therapy improved SHBG and AMH levels more effectively than MET monotherapy (P < 0.05). Furthermore, PIOMET treatment was more effective in improving blood glucose levels at 120 and 180 min of OGIRT compared to MET monotherapy (P < 0.05). Conclusions: In normal-weight women with PCOS, PIOMET treatment may have more benefits in improving SHBG, AMH, and postprandial glucose levels than MET monotherapy, and did not affect weight. However, the study findings need to be confirmed in PCOS study populations with larger sample sizes. [ABSTRACT FROM AUTHOR]

Fish live in an aquatic environment rich in various microorganisms and pathogens. Fish mucosal-associated lymphoid tissue (MALT) plays a very important role in immune defence. This study was conducted to characterize the immune response mediated by CcIgZ3 in common carp (Cyprinus carpio.) and investigate the proliferating CcIgZ3+ B lymphocytes in gill. We determined the expression of CcIgZ3 in many different tissues of common carp following stimulation by intraperitoneal injection of TNP-LPS (2,4,6-Trinitrophenyl hapten conjugated to lipopolysaccharide) or TNP-KLH (2,4,6-Trinitrophenyl hapten conjugated to Keyhole Limpet Hemocyanin). Compared with TNP-KLH, TNP-LPS can induce greater CcIgZ3 expression in the head kidney, gill and hindgut, especially in the gill. The results indicate that the gill is one of the main sites involved in the immune response mediated by CcIgZ3. To examine the distribution of CcIgZ3+ B lymphocytes, immunohistochemistry (IHC) experiments were performed using a polyclonal antibody against CcIgZ3. The results indicated that CcIgZ3 was detected in the head kidney, hindgut and gill. To further examine whether CcIgZ3+ B lymphocytes proliferate in the gills, proliferating CcIgZ3+ B cells were analysed by immunofluorescence staining using an anti-CcIgZ3 polyclonal antibody and an anti-PCNA monoclonal antibody. CcIgZ3 and PCNA (Proliferating Cell Nuclear Antigen) double-labelled cells in the gills were located within the epithelial cells of the gill filaments of common carp stimulated with TNP-LPS at 3 dps and 7 dps, and relatively more proliferating CcIgZ3+ B cells appeared in the gills of common carp at 7 dps. These data imply that CcIgZ3+ B cells in the gills might be produced by local proliferation following TNP-LPS stimulation. In summary, compared with those in TNP-KLH, CcIgZ3 preferentially affects the gills of common carp following challenge with TNP-LPS. CcIgZ3+ B cells proliferate in the gills to quickly produce the CcIgZ3 antibody. In addition, CcIgZ3+ B cells can be activated to induce a strong immune response very early locally in the gill and produce the antibody CcIgZ3, which helps exert an immune-protective effect. These results suggest that an effective vaccine can be designed to promote production of the mucosal antibody CcIgZ3. [ABSTRACT FROM AUTHOR]

Objective: The present study is aimed to develop and validate a quality of life scale for systemic lupus erythematosus (SLE) patients with Chinese cultural background, QLICD-SLE (V2.0). Methods: The QLICD-SLE (V2.0) was developed using a systematic approach that involved focus groups, nominal discussions, and pilot testing. A total of 428 SLE patients participated in the scale's assessment. Validity was examined through qualitative analysis, item domain correlation, multidimensional scaling, and factor analysis. Reliability was assessed using Pearson's correlation and Cronbach's alpha coefficients. To evaluate responsiveness, paired T-tests were conducted to compare pre- and post-treatment measurements with the standardised response mean (SRM) being calculated. Results: Correlation and factor analyses demonstrated strong construct validity. When using SF-36 as criteria, the correlation between various domains of QLICD-SLE and SF-36 ranged from 0.55 to 0.70. Test–retest correlation coefficients exceeded 0.71, and Cronbach's alpha coefficients for both measurements in each domain were greater than or equal to 0.75. T-test results showed that both the overall score and most facet scores within each domain showed statistically significant changes after treatment (P < 0.05), indicating reasonable responsiveness. Conclusion: The QLICD-SLE (V2.0) appears to be a valid and reliable instrument for assessing the quality of life in patients with SLE. [ABSTRACT FROM AUTHOR]

Background: Despite the popularity of modern medicine, medicinal plants remain a cornerstone of treatment for numerous diseases, particularly among ethnic groups and tribal communities around the globe. Ethnomedicine offers advantages such as ease of use, convenience, and economic benefits. Medicinal plant knowledge within Bulang ethnic community of southwest China is a valuable complement to Chinese ethnomedicine systems. Accumulated medical knowledge is due to the extensive length of occupation by Bulang People, considered the earliest inhabitants of Xishuangbanna; this has resulted in the development of various traditional treatment methods with local characteristics and unique curative effects. Therefore, there is exceeding value in exploring the medical knowledge of Bulang. Methods: A total of 175 local informants participated in the interviews and distribution of questionnaires in 10 Bulang villages in Menghai County, Xishuangbanna Prefecture, Yunnan Province, China. We documented the community of Bulang's use of medicinal herbs, and we used both the informant consensus factor (ICF) and use value (UV) methodologies to analyze the data. Furthermore, we conducted a comparative study to explore the potential of Bulang traditional medicine by comparing it to traditional Dai medicine. Results: The study recorded 60 medicinal plant species belonging to 41 families and 59 genera, including 22 species of herb, 22 species of shrub, nine species of trees, and seven species of liana. Araceae, Compositae, Lamiaceae and Leguminosae were found to have the highest number of species. The affordability and cultural heritage of Bulang medicine make it advantageous, Investigated Informants report that increased usage of Western medicine (88%), less availability of herbal medicine (95.43%), and the reduction in medicinal plant resources (80.57%) pose significant threats to Bulang medicine. All Bulang medicinal plants are naturally grown, with only 22 per cent being cultivated. Camellia sinensis (0.94) and Zingiber officinale (0.89) showed the highest UV values, while the function of Phyllanthus emblica L. and Houttuynia cordata Thunb. were also noted. The ICF revealed digestive system related diseases were the most commonly treated, with conditions of the motor system using the highest number of plant species. Finally, a comparison with traditional Dai medicine determined that 22 plants (36.67%) of the 60 surveyed had higher medicinal value in Bulang medicine. Conclusion: Bulang communities primarily source medicinal plants from the wild. Should environmental damage lead to the extinction of these medicinal plants, it could result in a shift toward modern Western medicine as a preferred medical treatment. Bulang ethnomedicine is a vital supplement to China's traditional medicine, particularly aspects of ethnic medicine relevant to daily life. Future research should emphasize inter-ethnic medical studies to reveal the untapped potential of medicinal plants. [ABSTRACT FROM AUTHOR]

The immune-related microenvironment of thymic carcinoid has rarely been reported. We analyzed the expression of PD-L1 and VISTA, and the distribution of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the thymic carcinoid by immunohistochemical staining, and showed the correlation between these markers and clinical survival, indicating the potential therapeutic prospects. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this bibliometric analysis was twofold: to identify the 100 most cited research articles on thymoma and to highlight future research opportunities in light of past and current research efforts. Methods: The Web of Science database was queried to identify the 100 most cited articles on thymoma. Imformations relevant to scientific research were extracted and analyzed: first author, journal, impact factor, type of article, year of publication, country, organization and keywords. Results: The publication year of the top 100 most cited articles ranged from 1981 to 2018, and the number of citations ranged from 97 to 1182. Most of the included articles are original (75/100) and are mainly retrospective studies (52/75). The United States has the most published articles and citations, and the Annals of Thoracic Surgery is the most sourced journal (n = 16). Through VOSviewer analysis, high-density keywords mainly come from thymic carcinoma/invasive thymoma management, immune-related diseases, and laboratory research. Conclusions: To our knowledge, this is the first bibliometric study on thymoma. We found most of the top 100 most cited articles are original and retrospective research. The United States has the published and cited works. Presently, the hot keywords for thymoma research has gradually tilted towards immune-related diseases and laboratory research. [ABSTRACT FROM AUTHOR]

Background: Growth-promoting antibiotics have been banned by law in the livestock and poultry breeding industry in many countries. Various alternatives to antibiotics have been investigated for using in livestock. Epimedium (EM) is an herb rich in flavonoids that has many beneficial effects on animals. Therefore, this study was planned to explore the potential of EM as a new alternative antibiotic product in animal feed. Methods: A total of 720 1-day-old male broilers (Arbor Acres Plus) were randomly divided into six groups and fed basal diet (normal control; NC), basal diet supplemented with antibiotic (75 mg/kg chlortetracycline; CTC), and basal diet supplemented with 100, 200, 400 or 800 mg/kg EM extract for 6 weeks (EM100, EM200, EM400 and EM800 groups). The growth performance at weeks 3 and 6 was measured. Serum, intestinal tissue and feces were collected to assay for antioxidant indexes, intestinal permeability, lactic acid and short-chain fatty acids (SCFAs) profiles, microbial composition, and expression of intestinal barrier genes. Results: The average daily feed intake in CTC group at 1–21 d was significantly higher than that in the NC group, and had no statistical difference with EM groups. Compared with NC group, average daily gain in CTC and EM200 groups increased significantly at 1–21 and 1–42 d. Compared with NC group, EM200 and EM400 groups had significantly decreased levels of lipopolysaccharide and D-lactic acid in serum throughout the study. The concentrations of lactic acid, acetic acid, propionic acid, butyric acid and SCFAs in feces of birds fed 200 mg/kg EM diet were significantly higher than those fed chlortetracycline. The dietary supplementation of chlortetracycline and 200 mg/kg EM significantly increased ileal expression of SOD1, Claudin-1 and ZO-1 genes. Dietary supplemented with 200 mg/kg EM increased the relative abundances of g_NK4A214_group and Lactobacillus in the jejunal, while the relative abundances of Microbacterium, Kitasatospora, Bacteroides in the jejunal and Gallibacterium in the ileum decreased. Conclusion: Supplementation with 200 mg/kg EM extract improved the composition of intestinal microbiota by regulating the core bacterial genus Lactobacillus, and increased the concentration of beneficial metabolites lactic acid and SCFAs in the flora, thereby improving the antioxidant capacity and intestinal permeability, enhancing the function of tight junction proteins. These beneficial effects improved the growth performance of broilers. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overabundance of androgens; it affects 6–20% of women of reproductive age. PCOS involves various pathophysiological factors, and affected women usually have significant insulin resistance (IR), which is a major cause of PCOS. IR and compensatory hyperinsulinaemia have differing pathogeneses in various tissues, and IR varies among different PCOS phenotypes. Genetic and epigenetic changes, hyperandrogenaemia, and obesity aggravate IR. Insulin sensitization drugs are a new treatment modality for PCOS. We searched PubMed, Google Scholar, Elsevier, and UpToDate databases in this review, and focused on the pathogenesis of IR in women with PCOS and the pathophysiology of IR in various tissues. In addition, the review provides a comprehensive overview of the current progress in the efficacy of insulin sensitization therapy in the management of PCOS, providing the latest evidence for the clinical treatment of women with PCOS and IR. [ABSTRACT FROM AUTHOR]

Background: Thymic neuroendocrine tumors comprise a heterogeneous group of rare diseases. This study aimed to investigate the real-world clinicopathological features and treatment outcomes of thymic neuroendocrine tumors.Results: A total of 104 patients diagnosed with thymic neuroendocrine tumors in a single institution from 1983 to 2021 were eligible. Fourteen (13.46%) and 28 (26.92%) patients diagnosed with thymic neuroendocrine tumors suffered from multiple endocrine neoplasia and ectopic adrenocorticotropic hormone syndrome, respectively. Ninety-seven (93.27%) patients underwent surgical resection, including 79 (81.44%) with radical resection. Except for 5 patients lost during follow-up, the 1-, 3- and 5-year overall survival rates were 91.8%, 70.2% and 54.6%, respectively. The median overall survival was 61.57 months. Multivariate analysis revealed that years at diagnosis (HR 0.559, 95% CI 0.364-0.857, p = 0.008), radical resection (HR 2.860, 95% CI 1.392-5.878, p = 0.004), pathological grade (HR 1.963, 95% CI 1.058-3.644, p = 0.033) and Masaoka-Koga stage (HR 2.250, 95% CI 1.548-3.272, p = 0.000) exerted significant differences in overall survival among 99 patients. In the surgery group, multivariate Cox regression analysis exhibited significant overall survival differences in years at diagnosis (HR 0.563, 95% CI 0.367-0.866, p = 0.009), neoadjuvant therapy (HR 0.248, 95% CI 0.071-0.872, p = 0.030), radical resection (HR 3.674, 95% CI 1.685-8.008, p = 0.001), pathological grade (HR 2.082, 95% CI 1.098-3.947, p = 0.025) and Masaoka-Koga stage (HR 2.445, 95% CI 1.607-3.719, p = 0.000).Conclusions: Radical resection and Masaoka-Koga stage were independent prognostic factors for the survival of patients with thymic neuroendocrine tumors. Systemic therapy and integrated management of patients with advanced-stage disease require high-level clinical evidence. [ABSTRACT FROM AUTHOR]

Background: Transcranial magnetic stimulation (TMS) has attracted plenty of attention as it has been proved to be effective in facilitating motor recovery in patients with stroke. The aim of this study was to systematically review the effects of repetitive TMS (rTMS) and theta burst stimulation (TBS) protocols in modulating cortical excitability after stroke.Methods: A literature search was carried out using PubMed, Medline, EMBASE, CINAHL, and PEDro, to identify studies that investigated the effects of four rTMS protocols-low and high frequency rTMS, intermittent and continuous TBS, on TMS measures of cortical excitability in stroke. A random-effects model was used for all meta-analyses.Results: Sixty-one studies were included in the current review. Low frequency rTMS was effective in decreasing individuals' resting motor threshold and increasing the motor-evoked potential of the non-stimulated M1 (affected M1), while opposite effects occurred in the stimulated M1 (unaffected M1). High frequency rTMS enhanced the cortical excitability of the affected M1 alone. Intermittent TBS also showed superior effects in rebalancing bilateral excitability through increasing and decreasing excitability within the affected and unaffected M1, respectively. Due to the limited number of studies found, the effects of continuous TBS remained inconclusive. Motor impairment was significantly correlated with various forms of TMS measures.Conclusions: Except for continuous TBS, it is evident that these protocols are effective in modulating cortical excitability in stroke. Current evidence does support the effects of inhibitory stimulation in enhancing the cortical excitability of the affected M1. [ABSTRACT FROM AUTHOR]

Background: Silent information regulator 6 (SIRT6) is a mammalian homolog of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin family. Prior evidences suggested that the anti-inflammatory function of SIRT6 after spinal cord and brain injury, and it plays a crucial role in macrophages polarization of adipose tissue and skin. However, the role of SIRT6 in macrophages involved peripheral nerve injury is still unknown. Given the prominent role of macrophages in peripheral nerve recovery, we aim to investigate the role of SIRT6 in the regulation of phenotypes shift and functions in macrophages after peripheral nerve injury. Results: In the present study, we first identified a significant increase of SIRT6 expression during nerve degeneration and macrophages phagocytosis. Next, we found nerve recovery was delayed after SIRT6 silencing by injected shRNA lentivirus into the crushed sciatic nerve, which exhibited a reduced expression of myelin-related proteins (e.g., MAG and MBP), severer myoatrophy of target muscles, and inferior nerve conduction compared to the shRNA control injected mice. In vitro, we found that SIRT6 inhibition by being treated with a selective inhibitor OSS_128167 or lentivirus transfection impairs migration and phagocytosis capacity of bone marrow-derived macrophages (BMDM). In addition, SIRT6 expression was discovered to be reduced after M1 polarization, but SIRT6 was enhanced after M2 polarization in the monocyte-macrophage cell line RAW264.7 and BMDM. Moreover, SIRT6 inhibition increased M1 macrophage polarization with a concomitant decrease in M2 polarization both in RAW264.7 and BMDM via activating NF-κB and TNF-α expression, and SIRT6 activation by UBCS039 treatment could shift the macrophages from M1 to M2 phenotype. Conclusion: Our findings indicate that SIRT6 inhibition impairs peripheral nerve repair through suppressing the migration, phagocytosis, and M2 polarization of macrophages. Therefore, SIRT6 may become a favorable therapeutic target for peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Background: Loop-mediated isothermal amplification (LAMP) has been widely used to diagnose various infectious diseases. Malaria is a globally distributed infectious disease attributed to parasites in the genus Plasmodium. It is known that persons infected with Plasmodium vivax and P. ovale are prone to clinical relapse of symptomatic blood-stage infections. LAMP has not previously been specifically evaluated for its diagnostic performance in detecting P. ovale in an epidemiological study, and no commercial LAMP or rapid diagnostic test (RDT) kits are available for specifically diagnosing infections with P. ovale. Methods: An assay was designed to target a portion of mitochondrial DNA (mtDNA) among Plasmodium spp., the five human Plasmodium species and two other assays were designed to target the nuclear 18S ribosomal DNA gene (18S rDNA) of either P. vivax or P. ovale for differentiating the two species. The sensitivity of the assays was compared to that of nested PCR using defined concentrations of plasmids containing the target sequences and using limiting dilutions prepared from clinical isolates derived from Chinese workers who had become infected in Africa or near the Chinese border with Myanmar. Results: The results showed that 102 copies of the mitochondrial target or 102 and 103 copies of 18S rDNA could be detected from Plasmodium spp., P. vivax and P. ovale, respectively. In 279 clinical samples, the malaria Pan mtDNA LAMP test performed well when compared with a nested PCR assay (95% confidence interval [CI] sensitivity 98.48–100%; specificity 90.75–100%). When diagnosing clinical cases of infection with P. vivax, the 18S rDNA assay demonstrated an even great sensitivity (95.85–100%) and specificity (98.1–100%). The same was true for clinical infections with P. ovale (sensitivity 90.76–99.96%; specificity 98.34–100%). Using plasmid-positive controls, the limits of detection of Malaria Pan, 18S rDNA P. vivax and 18S rDNA P. ovale LAMP were 100-, 100- and tenfold lower than those of PCR, respectively. Conclusion: The novel LAMP assays can greatly aid the rapid, reliable and highly sensitive diagnosis of infections of Plasmodium spp. transmitted among people, including P. vivax and P. ovale, cases of which are most prone to clinical relapse. [ABSTRACT FROM AUTHOR]

A correction to the article "Ethnobotanical study on medicinal plants used by Bulang people in Yunnan, China" that was published in a 2023 issue of the journal is presented.

Background: Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear. Methods: We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target. Results: We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo. Conclusions: Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is one of the predominant malignancies globally. Percutaneous thermal ablation (PTA) has gained widespread use among NSCLC patients, with the potential to elicit immune responses but limited therapeutic efficacies for advanced-stage disease. T-helper type 9 (Th9) cells are a subset of CD4+ effector T cells with robust and persistent anti-tumor effects. This study proposes to develop PTA-Th9 cell integrated therapy as a potential strategy for NSCLC treatment. Methods: The therapeutic efficacies were measured in mice models with subcutaneously transplanted, recurrence, or lung metastatic tumors. The tumor microenvironments (TMEs) were evaluated by flow cytometry. The cytokine levels were assessed by ELISA. The signaling molecules were determined by quantitative PCR and Western blotting. The translational potential was tested in the humanized NSCLC patient-derived xenograft (PDX) model. Results: We find that PTA combined with adoptive Th9 cell transfer therapy substantially suppresses tumor growth, recurrence, and lung metastasis, ultimately extending the survival of mice with NSCLC grafts, outperforming both PTA and Th9 cell transfer monotherapy. Analysis of TMEs indicates that combinatorial therapy significantly augments tumor-infiltrating Th9 cells, boosts anti-tumor effects of CD8+ T cells, and remodels tumor immunosuppressive microenvironments. Moreover, combinatorial therapy significantly strengthens the regional and circulation immune response of CD8+ T cells in mice with tumor lung metastasis and induces peripheral CD8+ T effector memory cells in mice with tumor recurrence. Mechanically, PTA reinforces the anti-tumor ability of Th9 cells primarily through upregulating interleukin (IL)-1β and subsequently activating the downstream STAT1/IRF1 pathway, which could be effectively blocked by intercepting IL-1β signaling. Finally, the enhanced therapeutic effect of combinatorial therapy is validated in humanized NSCLC PDX models. Conclusions: Collectively, this study demonstrates that combinatorial therapy displays robust and durable anti-tumor efficacy and excellent translational potential, offering excellent prospects for translation and emerging as a promising approach for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Background: Prenatal diagnosis of Berry syndrome, a rare combination of cardiac anomalies including aortopulmonary window (APW), aortic origin of the right pulmonary artery (RPA), interrupted aortic arch (IAA), hypoplastic aortic arch, or coarctation of the aorta (COA), poses a significant challenge. Due to the rarity of the disease, and the limited case reports available to features the complex malformation of Berry syndrome postpartum, this article introduces an innovative approach to visually showcase this unusual disease. The proposed method provides a comprehensive display of the structural deformities, offering valuable insights for clinical practitioners seeking to comprehend this condition. Case presentation: In this report, we present a case where fetal echocardiography aided in diagnosing Berry syndrome, which was later confirmed through postpartum cardiovascular casting. Our experience highlights the importance of using the three-vessel view to diagnose APW and aortic origin of the right pulmonary artery. Additionally, obtaining true cross-sectional and sagittal views by continuously scanning from the three-vessel-trachea view to the long-axis view of the aortic arch is necessary to image IAA or coarctation of the aortic arch. Conclusions: Early and accurate prenatal diagnosis of Berry syndrome is feasible and our cardiovascular cast can perfectly display the microvascular morphology of the fetal heart, which may have great application prospects for postpartum diagnosis and teaching of complex cardiac abnormalities. [ABSTRACT FROM AUTHOR]

Methyltransferase-like 3 (METTL3) is the key subunit of methyltransferase complex responsible for catalyzing N6-methyladenosine (m6A) modification on mRNA, which is the most prevalent post-transcriptional modification in eukaryotes. In this study, we utilized online databases to analyze the association between METTL3 expression and various aspects of tumorigenesis, including gene methylation, immunity, and prognosis. Our investigation revealed that METTL3 serves as a prognostic marker and therapeutic target for liver hepatocellular carcinoma (LIHC). Through experimental studies, we observed frequent upregulation of METTL3 in LIHC tumor tissue and cells. Subsequent inhibition of METTL3 using a novel small molecule inhibitor, STM2457, significantly impeded tumor growth in LIHC cell lines, spheroids, and xenograft tumor model. Further, transcriptome and m6A sequencing of xenograft bodies unveiled that inhibition of METTL3-m6A altered genes enriched in SMAD and MAPK signaling pathways that are critical for tumorigenesis. These findings suggest that targeting METTL3 represents a promising therapeutic strategy for LIHC. [ABSTRACT FROM AUTHOR]

Nitrate is a primary nitrogen source for plant growth, and previous studies have indicated a correlation between nitrogen and browning. Nitrate transporters (NRTs) are crucial in nitrate allocation. Here, we utilized a genome-wide approach to identify and analyze the expression pattern of 74 potential GbNRTs under nitrate treatments during calluses browning in Ginkgo, including 68 NITRATE TRANSPORTER 1 (NRT1)/PEPTIDE TRANSPORTER (PTR) (NPF), 4 NRT2 and 2 NRT3. Conserved domains, motifs, phylogeny, and cis-acting elements (CREs) were analyzed to demonstrate the evolutionary conservation and functional diversity of GbNRTs. Our analysis showed that the NPF family was divided into eight branches, with the GbNPF2 and GbNPF6 subfamilies split into three groups. Each GbNRT contained 108–214 CREs of 19–36 types, especially with binding sites of auxin and transcription factors v-myb avian myeloblastosis viral oncogene homolog (MYB) and basic helix-loop-helix (bHLH). The E1X1X2E2R motif had significant variations in GbNPFs, indicating changes in the potential dynamic proton transporting ability. The expression profiles of GbNRTs indicated that they may function in regulating nitrate uptake and modulating the signaling of auxin and polyphenols biosynthesis, thereby affecting browning in Ginkgo callus induction. These findings provide a better understanding of the role of NRTs during NO3− uptake and utilization in vitro culture, which is crucial to prevent browning and develop an efficient regeneration and suspension production system in Ginkgo. [ABSTRACT FROM AUTHOR]

Background: Based on previous studies which failed to analyze important confounding variables, the association between preoperative anemia and outcomes of patients who underwent colorectal cancer (CRC) surgery has not been clearly demonstrated. This study aimed to investigate the relationship between preoperative anemia and short-term outcomes in patients with CRC. Methods: Data from a retrospective collective database of patients who underwent CRC surgery at our hospital between September 1, 2019 and September 30, 2021 were retrieved and analyzed, and the short-term postoperative outcomes of anemic (hemoglobin < 120 g dL− 1 for female, hemoglobin < 130 g dL− 1 for male) and non-anemic patients were analyzed, using a 1:1 propensity score matching (PSM) analysis. Results: After excluding some cases, the remaining 1894 patients had complete data available for analysis. The incidence of preoperative anemia was 39.8% (754/1894). Before PSM, preoperative anemia patients had a higher risk of major morbidity than non-anemia patients (27.2% vs. 23.1%, odds ratio [OR] 1.245, 95% confidence interval [CI] 1.008–1.538, P = 0.042). After PSM was performed in the cohort, 609 patients remained in the anemic and non-anemic groups. The incidence of major morbidity (25.8% vs. 24.0%, OR 1.102, 95% CI 0.849–1.429, P = 0.446) between anemic and non-anemic patients was comparable. No significant difference was found between the anemic and non-anemic groups in postoperative length of stay (8.0 [6.0–12.0] vs. 8.0 [7.0–11.0], P = 0.311). The sensitivity analysis results were in accordance with the primary outcome. Furthermore, we did not ascertain any discernible correlation between the extent of anemia and significant major morbidity. Conclusions: Compared with preoperative non-anemia, anemia status does not seem to be associated with major morbidity in patients with CRC surgery. It is noteworthy that, anemia is insufficient as a solitary risk factor and may be a better marker of poor health resulting from multiple factors. Trial registration: Registration Authority: Chinese Clinical Trial Registry; Registration number and date: ChiCTR2100049696, 08/08/2021; Principal investigator: Ting Yan; Link to trial registry: http://www.chictr.org.cn/showproj.aspx?proj=131698;. [ABSTRACT FROM AUTHOR]

Background: Gegen Qinlian decoction (GQD) is a classic prescription for treating ulcerative colitis (UC) in traditional Chinese medicine. However, the therapeutic mechanism has not been fully clarified. Purpose: In the present study, we aimed to evaluate the role of ferroptosis-mediated IEC death in UC treated mice with GQD by using DSS-induced a colitis mouse model and RSL3-induced ferroptosis in intestinal organoids. Methods: The effects of GQD on DSS-treated colitis were examined via daily body weight, DAI, colon length, HE staining, PAS staining, ZO-1 and Occludin immunohistochemical staining. Ferroptosis was determined by analysis of iron load, MDA, GSH, mitochondrial morphology, and expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Results: In vivo, GQD administration reduced body weight loss and DAI scores, increased colon length, and improved intestinal histological characteristics and epithelial barrier dysfunction. GQD administration obviously improved the levels of ferroptosis markers (iron load, MDA, GSH, and mitochondrial morphology) and the expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Consistent with in vivo results, GQD administration partially reversed the levels of mtROS, Fe2+ and MDA in intestinal organoids induced by RSL3, and notably improved morphological destruction, histological damage and epithelial barrier dysfunction in organoids. Conclusions: In this study, we demonstrated that ferroptosis was triggered in DSS-induced experimental colitis and that GQD adiministration could protect against colonic damage and intestinal epithelial barrier dysfunction by inhibiting ferroptosis. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid cancer, but 20% of cases are indeterminate (i.e., cannot be accurately diagnosed) based on preoperative cytology, which might lead to surgical removal of a normal thyroid gland. To address this concern, we performed an in-depth analysis of the serum proteomes of 26 PTC patients and 23 healthy controls using antibody microarrays and data-independent acquisition mass spectrometry (DIA-MS). We identified a total of 1091 serum proteins spanning 10–12 orders of magnitude. 166 differentially expressed proteins were identified that participate in complement activation, coagulation cascades, and platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicated that the expression of proteins such as lactate dehydrogenase A and olfactory receptor family 52 subfamily B member 4, which participate in fibrin clot formation and extracellular matrix-receptor interaction pathways, were changed. Further analysis of the proteomes of PTC and neighboring tissues revealed integrin-mediated pathways with possible crosstalk between the tissue and circulating compartments. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers for PTC identification and validated in an independent cohort. In differentiating between patients with benign nodules or PTC, FN1 produced the best ELISA result (sensitivity = 96.89%, specificity = 91.67%). Overall, our results present proteomic landscapes of PTC before and after surgery as well as the crosstalk between tissue and the circulatory system, which is valuable to understand PTC pathology and improve PTC diagnostics in the future. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to verify the correlation between medium and low radiation doses of the pelvic-bone marrow and the incidence of lymphocytic toxicity during concurrent chemoradiotherapy for cervical cancer. Materials and methods: This research included 117 cervical cancer patients, who received concurrent chemoradiotherapy. Radiotherapy included external-beam radiation therapy and brachytherapy. The dosimetry parameters include the Volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and the mean dose (D mean) of the bone marrow. Lymphocytic toxicity was calculated from lowest lymphocytic count after two cycles of concurrent chemotherapy. Results: During concurrent chemoradiotherapy, the incidence of lymphocytic toxicity is 94.88%. The incidence of grade 3–4 toxicity is 68.38%. Multivariate analysis findings show that the dosimetry parameters V5, V10, V20, and V30 are significantly correlated with lymphocytic toxicity. The patients are divided into small-volume subgroups and large-volume subgroups based on the cutoff values. The relative risk of both grade 1–4 and grade 3–4 lymphocytic toxicity is significantly lower in the small-volume subgroups than in the large-volume subgroups (P < 0.05). Kaplan–Meier analysis shows that the incidence of both grade 1–4 and grade 3–4 lymphocytic toxicity of the small-volume subgroups is significantly lower than that of the large-volume subgroups (P < 0.05). Conclusion: There is a significant correlation between a medium and low dose of pelvic-bone-marrow radiation and incidence of lymphocytic toxicity. Reducing the volume of medium and low radiation doses could effectively reduce incidence of lymphocytic toxicity. [ABSTRACT FROM AUTHOR]

Background: Fecal microbial transplantation has emerged in recent years as a method of treating disease by rebuilding the intestinal flora. However, few bibliometric analyses have systematically studied this area of research. We aimed to use bibliometric analysis to visualize trends and topical research in fecal microbial transplantation to help provide insight into future trends in clinical and basic research.Materials and Methods: Articles and reviews related to fecal microbial transplantation were collected from the Web of Science Core Collection. Significant information associated with this field was visually analyzed by using Biblioshiny and CtieSpace software.Results: A total of 3144 articles and overviews were included. The number of publications related to fecal microbial transplantation significantly increased yearly. These publications mainly came from 100 countries, led by the US and China, and 521 institutions. The most prolific and influential author is KHORUTS A. The main disciplines and application fields of fecal microbial transplantation included molecular /biology/immunology and medicine/clinical medicine, and the research foundation of fecal microbial transplantation was molecular /biology/genetics and health/nursing/medicine. An alluvial flow visualization showed several landmark articles. New developments were identified in terms of reference and keyword citation bursts. Data analysis showed that different FMT preparation and delivery methods gradually appeared as research hotspots. The main research keywords in the last 3 years were chain fatty acids, Akkermansia muciniphila, and insulin sensitivity, other keywords were current and developing research fields.Conclusion: Research on fecal microbial transplantation is flourishing and many new applications of fecal microbial transplantation are emerging. Microbial metabolites such as short-chain fatty acids and the microbiota-gut-brain axis have become the focus of current research and are future research trends. [ABSTRACT FROM AUTHOR]

Background: Non-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation but an absence of esophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPI step-down therapy for NERD patients who did not respond to PPIs alone.Method: This multicentered, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPI step-down group (n = 87) and the TCM granules placebo combined with PPI step-down group (n = 87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status, and quality of life at each visit. The primary outcome measurements include visual analog scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD-HRQL, and TCM syndromes scales.Discussion: Previous research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients' physical and psychological burdens, and achieve good social benefits.Trial Registration: Clinicaltrials.gov NCT04340297. Registered on April 9, 2020. [ABSTRACT FROM AUTHOR]

Background: Plenty of macrophages are recruited to the injured nerve to play key roles in the immunoreaction and engulf the debris of degenerated axons and myelin during Wallerian degeneration, thus creating a conducive microenvironment for nerve regeneration. Recently, drugs targeting the RhoA pathway have been widely used to promote peripheral axonal regeneration. However, the role of RhoA in macrophage during Wallerian degeneration and nerve regeneration after peripheral nerve injury is still unknown. Herein, we come up with the hypothesis that RhoA might influence Wallerian degeneration and nerve regeneration by affecting the migration and phagocytosis of macrophages after peripheral nerve injury.Methods: Immunohistochemistry, Western blotting, H&E staining, and electrophysiology were performed to access the Wallerian degeneration and axonal regeneration after sciatic nerve transection and crush injury in the LyzCre+/-; RhoAflox/flox (cKO) mice or Lyz2Cre+/- (Cre) mice, regardless of sex. Macrophages' migration and phagocytosis were detected in the injured nerves and the cultured macrophages. Moreover, the expression and potential roles of ROCK and MLCK were also evaluated in the cultured macrophages.Results: 1. RhoA was specifically knocked out in macrophages of the cKO mice; 2. The segmentation of axons and myelin, the axonal regeneration, and nerve conduction in the injured nerve were significantly impeded while the myoatrophy was more severe in the cKO mice compared with those in Cre mice; 3. RhoA knockout attenuated the migration and phagocytosis of macrophages in vivo and in vitro; 4. ROCK and MLCK were downregulated in the cKO macrophages while inhibition of ROCK and MLCK could weaken the migration and phagocytosis of macrophages.Conclusions: Our findings suggest that RhoA depletion in macrophages exerts a detrimental effect on Wallerian degeneration and nerve regeneration, which is most likely due to the impaired migration and phagocytosis of macrophages resulted from disrupted RhoA/ROCK/MLCK pathway. Since previous research has proved RhoA inhibition in neurons was favoring for axonal regeneration, the present study reminds us of that the cellular specificity of RhoA-targeted drugs is needed to be considered in the future application for treating peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Reference 1 Hu C, Wang T, Zhuang X, Sun Q, Wang X, Lin H, Feng M, Zhang J, Cao Q, Jiang Y. Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry. Cheng Hu, Tao Wang and Xiaoyu Zhuang contributed equally to this work Correction to: J Transl Med (2021)19:152 https://doi.org/10.1186/s12967-021-02820-7 Following publication of the original article [[1]], the authors identified an error in the affiliation for Jiaqi Zhang. [Extracted from the article]