Case report: A case of giant breast skin warts caused by HPV infection.

GCA, also known as Buschke-Lowenstein tumor, is a rare sexually transmitted disease associated with HPV types 6 and 111. These warts are considered histologically benign, but there is a risk of localized invasion and development of malignancy. This malignant transformation occurs most often in the perianal and vulvar areas, and involvement of other sites is relatively rare2. In this case, we report a rare case of a giant wart originating from breast skin infected with HPV and progressing to cutaneous squamous cell carcinoma.

Sources and Specified Health Risks of 12 PM2.5-Bound Metals in a Typical Air-Polluted City in Northern China during the 13th Five-Year Plan.

The continuous monitoring of PM2.5 (including 12 metal elements) was conducted in Jinan, a city with poor air quality in China, during the 13th Five-Year Plan (2016-2020). Positive matrix factorization (PMF) was used to identify emission sources of PM2.5-bound metals, and the health risks of the metals and their emission sources were assessed. During the study period, the concentration of most metals showed a decreasing trend (except Al and Be), and a significant seasonal difference was found: winter > fall > spring > summer. The PMF analysis showed that there were four main sources of PM2.5-bound metals, and their contributions to the total metals (TMs) were dust emissions (54.3%), coal combustion and industrial emissions (22.3%), vehicle emissions (19.3%), and domestic emissions (4.1%). The results of the health risk assessment indicated that the carcinogenic risk of metals (Cr and As) exceeded the acceptable level (1 × 10-6), which was of concern. Under the influence of emission reduction measures, the contribution of emission sources to health risks changes dynamically, and the emission sources that contribute more to health risks were coal combustion and industrial emissions, as well as vehicle emissions. In addition, our findings suggest that a series of emission reduction measures effectively reduced the health risk from emission sources of PM2.5-bound metals.

Combination of MRI-based prediction and CRISPR/Cas12a-based detection for IDH genotyping in glioma.

Early identification of IDH mutation status is of great significance in clinical therapeutic decision-making in the treatment of glioma. We demonstrate a technological solution to improve the accuracy and reliability of IDH mutation detection by combining MRI-based prediction and a CRISPR-based automatic integrated gene detection system (AIGS). A model was constructed to predict the IDH mutation status using whole slices in MRI scans with a Transformer neural network, and the predictive model achieved accuracies of 0.93, 0.87, and 0.84 using the internal and two external test sets, respectively. Additionally, CRISPR/Cas12a-based AIGS was constructed, and AIGS achieved 100% diagnostic accuracy in terms of IDH detection using both frozen tissue and FFPE samples in one hour. Moreover, the feature attribution of our predictive model was assessed using GradCAM, and the highest correlations with tumor cell percentages in enhancing and IDH-wildtype gliomas were found to have GradCAM importance (0.65 and 0.5, respectively). This MRI-based predictive model could, therefore, guide biopsy for tumor-enriched, which would ensure the veracity and stability of the rapid detection results. The combination of our predictive model and AIGS improved the early determination of IDH mutation status in glioma patients. This combined system of MRI-based prediction and CRISPR/Cas12a-based detection can be used to guide biopsy, resection, and radiation for glioma patients to improve patient outcomes.

Foritinib in advanced ROS1-rearranged non-small-cell lung cancer in China: a multicentre, open-label, single-arm, phase 2 study.

BACKGROUND: Currently approved targeted treatment for ROS1-rearranged non-small-cell lung cancer (NSCLC) has either inadequate intracranial activity or CNS-related toxicities. We evaluated the efficacy and safety of foritinib, a novel ALK and ROS1 inhibitor, in patients with advanced ROS1-rearranged NSCLC. METHODS: This two-part (phase 2a and 2b), multicentre, single-arm, open-label, phase 2 study was done in 29 centres in China. Eligible participants were adults (aged ≥18 years) with histologically or cytologically confirmed ROS1-rearranged, locally advanced or metastatic stage IIIB-IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 2 or less. Patients who had previously received no or one ROS1 inhibitor were enrolled into phase 2a, and patients who were naive to ROS1 inhibitor therapy were enrolled into phase 2b cohort 1. Participants in phase 2a received 80, 120, 160, or 210 mg foritinib succinate (foritinib) orally once daily over 21-day cycles; patients in phase 2b received the recommended phase 2 dose of 160 mg. The primary endpoint was objective response rate, assessed by the independent review committee in the full analysis set (ie, all participants who received at least one dose of study treatment). The safety analysis set included all participants who received at least one dose of study treatment and had available safety assessments. This study is ongoing and is registered with ClinicalTrials.gov, NCT04237805. FINDINGS: Between March 26, 2020, and Dec 29, 2022, 104 patients were enrolled and treated. Six patients who had previously received more than one ROS1 inhibitor were enrolled in phase 2a before a protocol amendment stating that patients in this phase should have received no more than one ROS1 inhibitor; these patients were included in the safety analysis but excluded from the efficacy analysis of the ROS1-inhibitor-pretreated cohort. Therefore, the efficacy analysis set (n=98) included 42 patients from phase 2a (17 who were ROS1 inhibitor naive and 25 who had previously received ROS1 inhibitor) and 56 patients from phase 2b cohort 1. In phase 2a, the objective response rate was 94% (95% CI 71-100; 16 of 17 patients) in patients who were ROS1 inhibitor naive and 40% (21-61; ten of 25) in patients who had previously received ROS1 inhibitor. In phase 2b cohort 1, the objective response rate was 88% (95% CI 76-95; 49 of 56 patients). In a prespecified exploratory analysis in 41 patients with CNS metastases at baseline, the objective response rate was 100% (95% CI 48-100; five of five patients) in patients in phase 2a who were ROS1 inhibitor naive, 40% (16-68; six of 15) in patients in phase 2a who had previously received ROS1 inhibitor, and 90% (70-99; 19 of 21) in patients in phase 2b cohort 1. Grade 3-4 treatment-related adverse events occurred in 33 (32%) of 104 patients; the most common were hyperglycaemia (12 [12%] patients) and electrocardiogram prolonged QT interval (six [6%]). Serious treatment-related adverse events occurred in 11 (11%) patients, with hyperglycaemia (six [6%]) being most common. No treatment-related adverse events led to death. INTERPRETATION: Foritinib showed systemic and intracranial antitumour activity and good tolerability in ROS1-inhibitor-naive patients with ROS1-rearranged NSCLC. Foritinib represents a promising treatment for these patients, especially in those with CNS metastases. FUNDING: Fosun Pharma, Wanbang Biopharmaceuticals, and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer.

Effects of cadmium on the intestinal health of the snail Bradybaena ravida Benson.

The heavy metal cadmium (Cd) is a toxic and bioaccumulative metal that can be enriched in the tissues and organs of living organisms through the digestive tract. However, more research is needed to determine whether food-sourced Cd affects the homeostasis of host gut microflora. In this study, the snail Bradybaena ravida (Benson) was used as a model organism fed with mulberry leaves spiked with different concentrations of Cd (0, 0.052, 0.71, and 1.94 mg kg-1). By combining 16S rRNA high-throughput sequencing with biochemical characterization, it was found that there were increases in the overall microbial diversity and abundances of pathogenic bacteria such as Corynebacterium, Enterococcus, Aeromonas, and Rickettsia in the gut of B. ravida after exposure to Cd. However, the abundances of potential Cd-resistant microbes in the host's gut, including Sphingobacterium, Lactococcus, and Chryseobacterium, decreased with increasing Cd concentrations in the mulberry leaves. In addition, there was a significant reduction in activities of energy, nutrient metabolism, and antioxidant enzymes for gut microbiota of snails treated with high concentrations of Cd compared to those with low ones. These findings highlight the interaction of snail gut microbiota with Cd exposure, indicating the potential role of terrestrial animal gut microbiota in environmental monitoring through rapid recognition and response to environmental pollution.

Transcriptional factor MdESE3 controls fruit acidity by activating genes regulating malic acid content in apple.

Acidity is a key factor controlling fruit flavor and quality. In a previous study, combined transcriptome and methylation analyses identified a P3A-type ATPase from apple (Malus domestica), MdMa11, which regulates vacuolar pH when expressed in Nicotiana benthamiana leaves. In this study, the role of MdMa11 in controlling fruit acidity was verified in apple calli, fruits, and plantlets. In addition, we isolated an APETALA2 domain-containing transcription factor, designated MdESE3, based on yeast one-hybrid (Y1H) screening using the MdMa11 promoter as bait. A subcellular localization assay indicated that MdESE3 localized to the nucleus. Analyses of transgenic apple calli, fruits, and plantlets, as well as tomatoes, demonstrated that MdESE3 enhances fruit acidity and organic acid accumulation. Meanwhile, chromatin immunoprecipitation quantitative PCR, luciferase (LUC) transactivation assays, and GUS reporter assays indicated that MdESE3 could bind to the ethylene-responsive element (ERE; 5'-TTTAAAAT-3') upstream of the MdMa11 transcription start site, thereby activating its expression. Furthermore, MdtDT, MdDTC2, and MdMDH12 expression increased in apple fruits and plantlets overexpressing MdESE3 and decreased in apple fruits and plantlets where MdESE3 was silenced. The ERE was found in MdtDT and MdMDH12 promoters, but not in the MdDTC2 promoter. The Y1H, LUC transactivation assays, and GUS reporter assays indicated that MdESE3 could bind to the MdtDT and MdMDH12 promoters and activate their expression. Our findings provide valuable functional validation of MdESE3 and its role in the transcriptional regulation of MdMa11, MdtDT, and MdMDH12 and malic acid accumulation in apple.

Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

OXPHOS-targeted nanoparticles for boosting photodynamic therapy against hypoxia tumor.

Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to ineffective reactive oxygen species (ROS) productivity for tumor eradication. In this study, an oxidative phosphorylation (OXPHOS) targeting nanoplatform was fabricated to alleviate hypoxia and enhance the performance of PDT by encapsulating IR780 and OXPHOS inhibitor atovaquone (ATO) in triphenylphosphine (TPP) modified poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) (mPEG-PLGA) nanocarriers (TNPs/IA). ATO by interrupting the electron transfer in OXPHOS could suppress mitochondrial respiration of tumor cells, economising on oxygen for the generation of ROS. Benefiting from the mitochondrial targeting function of TPP, ATO was directly delivered to its site of action to obtain highlighted effect at a lower dosage. Furthermore, positioning the photosensitizer IR780 to mitochondria, a more vulnerable organelle to ROS, was a promising method to attenuate the spatiotemporal limitation of ROS caused by its short half-life and narrow diffusion radius. As a result, TNPs/IA exhibited accurate subcellular localization, lead to the collapse of ATP production by damaging mitochondrion and elicited significant antitumor efficacy via oxygen-augmented PDT in the HeLa subcutaneous xenograft model. Overall, TNPs/IA was a potential strategy in photodynamic eradication of tumors.

Validation of the 9th edition of the TNM staging system for non-small cell lung cancer with lobectomy in stage IA-IIIA.

OBJECTIVES: The 9th edition of tumour-node-metastasis (TNM) staging for lung cancer was announced by Prof Hisao Asamura at the 2023 World Conference on Lung Cancer in Singapore. The purpose of this study was to externally validate and compare the latest staging of lung cancer. METHODS: We collected 19 193 patients with stage IA-IIIA non-small cell lung cancer (NSCLC) who underwent lobectomy from the Surveillance, Epidemiology and End Results database. Survival analysis by TNM stages was compared using the Kaplan-Meier method and further analysed using univariable and multivariable Cox regression analyses. Receiver operating characteristic curves were used to assess model accuracy, Akaike information criterion, Bayesian information criterion and consistency index were used to compare the prognostic, predictive ability between the current 8th and 9th edition TNM classification. RESULTS: The 9th edition of the TNM staging system can better distinguish between IB and IIA patients on the survival curve (P < 0.0001). In both univariable and multivariable regression analysis, the 9th edition of the TNM staging system can differentiate any 2 adjacent staging patients more evenly than the 8th edition. The 9th and the 8th edition TNM staging have similar predictive power and accuracy for the overall survival of patients with NSCLC [TNM 9th vs 8th, area under the curve: 62.4 vs 62.3; Akaike information criterion: 166 182.1 vs 166 131.6; Bayesian information criterion: 166 324.3 vs 166 273.8 and consistency index: 0.650 (0.003) vs 0.651(0.003)]. CONCLUSIONS: Our external validation demonstrates that the 9th edition of TNM staging for NSCLC is reasonable and valid. The 9th edition of TNM staging for NSCLC has near-identical prognostic accuracy to the 8th edition.

Dual cross-linked COL1/HAp bionic gradient scaffolds containing human amniotic mesenchymal stem cells promote rotator cuff tendon-bone interface healing.

The tendon-bone interface heals through scar tissue, while the lack of a natural interface gradient structure and collagen fibre alignment leads to the occurrence of retearing. Therefore, the promotion of tendon healing has become the focus of regenerative medicine. The purpose of this study was to develop a gradient COL1/ hydroxyapatite (HAp) biomaterial loaded with human amniotic mesenchymal stem cells (hAMSCs). The performance of common cross-linking agents, Genipin, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), and dual cross-linked materials were compared to select the best cross-linking mechanism to optimize the biological and mechanical properties of the scaffold. The optimal COL1/HAp-loaded with hAMSCs were implanted into the tendon-bone rotator cuff interfaces in rats and the effect on the tendon-bone healing was assessed by micro-CT, histological analysis, and biomechanical properties. The results showed that Genipin and EDC/NHS dual cross-linked COL1/HAp had good biological activity and mechanical properties and promoted the proliferation and differentiation of hAMSCs. Animal experiments showed that the group using a scaffold loaded with hAMSCs had excellent continuity and orientation of collagen fibers, increased fibrocartilage and bone formation, and significantly higher biomechanical functions than the control group at the interface at 12 weeks post operation. This study demonstrated that dual cross-linked gradient COL1/HAp-loaded hAMSCs could promote interface healing, thereby providing a feasible strategy for tendon-bone interface regeneration.

Is there a prognostic difference among stage I lung adenocarcinoma patients with different BRAF-mutation status?

BACKGROUND: The data of the prognostic role of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early-stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. METHODS: We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan-Meier method and compared by log-rank test. Cox proportional hazard models, propensity-score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence-free survival (RFS). RESULTS: The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E-mutant patients were detected to have concurrent EGFR mutations, one for 19-del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild-type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). CONCLUSIONS: In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.

Two transcription factors, AcREM14 and AcC3H1, enhance the resistance of kiwifruit Actinidiachinensis var. chinensis to Pseudomonas syringae pv. actinidiae.

Kiwifruit bacterial canker is a global disease caused by Pseudomonas syringae pv. actinidiae (Psa), which poses a major threat to kiwifruit production worldwide. Despite the economic importance of Actinidia chinensis var. chinensis, only a few resistant varieties have been identified to date. In this study, we screened 44 kiwifruit F1 hybrid lines derived from a cross between two A. chinensis var. chinensis lines and identified two offspring with distinct resistance to Psa: resistant offspring RH12 and susceptible offspring SH14. To identify traits associated with resistance, we performed a comparative transcriptomic analysis of these two lines. We identified several highly differentially expressed genes (DEGs) associated with flavonoid synthesis, pathogen interactions, and hormone signaling pathways, which play essential roles in disease resistance. Additionally, using weighted gene co-expression network analysis, we identified six core transcription factors. Moreover, qRT-PCR results demonstrated the high expression of AcC3H1 and AcREM14 in Psa-induced highly resistant hybrid lines. Ultimately, Overexpression of AcC3H1 and AcREM14 in kiwifruit enhanced disease resistance, and this was associated with upregulation of enzymatic activity and gene expression in the salicylic acid (SA) signaling pathway. Our study elucidates a molecular mechanism underlying disease resistance in kiwifruit and contributes to the advancement of research on kiwifruit breeding.

Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial.

INTRODUCTION: Treatment options for treatment-naive patients with advanced NSCLC harboring EGFR exon 20 insertion (ex20ins) mutations are limited. This study evaluated the safety, tolerability, and pharmacokinetics of YK-029A, a third-generation EGFR tyrosine kinase inhibitor, and the preliminary efficacy of YK-029A in treatment-naive patients with EGFR ex20ins mutation. METHODS: This multicenter, dose-escalation, and dose-expansion phase 1 clinical trial enrolled patients with NSCLC harboring EGFR mutations. During the dose-escalation phase, YK-029A was orally administered using the traditional 3+3 principle at 50, 100, 150, 200, and 250 mg/d. In the dose-expansion phase, treatment-naive patients with EGFR ex20ins mutations were enrolled and administered YK-029A 200 mg/d. The primary end point was safety and tolerability. RESULTS: The safety analysis included 108 patients. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common treatment-emergent adverse events were anemia (50.9%), diarrhea (49.1%), and rash (34.3%). There was minimal drug accumulation after multiple doses. A total of 28 treatment-naive patients with EGFR ex20ins mutations were enrolled in the dose-expansion and 26 were included in the efficacy analysis. According to the independent review committee evaluation, the objective response rate was 73.1% (95% confidence interval: 52.21%-88.43%), and the disease control rate was 92.3% (95% confidence interval: 74.87%-99.05%). CONCLUSIONS: YK-029A was found to have manageable safety and be tolerable in patients with NSCLC harboring EGFR mutations and have promising antitumor activity in untreated patients with EGFR ex20ins mutations.

Abdominal lymph node metastasis in non-surgical esophageal squamous cell carcinoma: prognostic significance and a novel staging strategy.

Purpose: This study aimed to evaluate the feasibility of a combination of abdominal lymph node (LN) metastasis and the number of LNs in esophageal squamous cell carcinoma (ESCC) patients to optimize its clinical nodal staging. Methods: A retrospective study, including a total of 707 ESCC patients treated with definitive radiotherapy, was conducted at two participating institutes. Different combinations of LN variables, including abdominal LN metastasis (R1: no-abdominal LN metastasis; R2: abdominal LN metastasis), were further analyzed to propose a potential revised nodal (rN) staging. Results: The multivariate analyses showed that the number of metastatic LN and abdominal LN metastasis were independent prognostic factors for the overall survival (OS). The results showed no significant differences in the OS between the N2 patients with abdominal LN metastasis and N3 patients. The OS of the stage III patients with abdominal LN metastasis was not significantly different from those with stage IVa. The N3R1 and N1-2R2 had similar hazard ratios (HRs). The N1R1 subset was defined as rN1, the N2R1 subset was defined as rN2, and the N3R1-2 and N1-2R2 subsets were defined as rN3. The HRs of OS of the rN2 and rN3 groups increased subsequently. The rN stage could identify the differences in the OS times of each subgroup based on the 8th AJCC cN staging or the 11th JES N staging. Conclusions: The rN staging, including the number of metastatic LNs and abdominal LN metastasis, might serve as a potential prognostic predictor for non-surgical patients with ESCC.

Bibliometric and visualized analysis of arthroscopic treatment of acromioclavicular joint injury.

BACKGROUND: Since arthroscopy was discovered to treat acromioclavicular joint injury, people have had great interest and attention to this beautiful and minimally invasive operation, and related research has been increasing worldwide. At present, there is no bibliometric and visualized analysis in this field. The purpose of this study is to explore the research hotspots and trends of arthroscopic treatment of acromioclavicular joint injury through bibliometric and visualized analysis and look forward to the future development direction of clinical practice. METHODS: The publications on arthroscopic treatment of acromioclavicular joint injury diseases from its establishment to April 2023 were obtained from the Web of Science (WOS) Core Collection database. CiteSpace, VOSviewer, Scimago graphica and Origin were used for bibliometric and visualized analysis. RESULTS: This study included a total of 330 publications. The number of publications tends to increase every year. The USA has the most significant number of publications and citations. Imhoff AB is the most relevant scholar with the largest number of publications in this field, and the scholar with the highest citation and average citations is Mazzocca AD. Tech Univ Munich, Rush University and Charite are the three institutions with the greatest contribution. Tech Univ Munich, Rush University and Charite are the three institutions with the greatest contribution. In addition, "Arthroscopy-the Journal of Arthroscopic and Related Surgery" and "American Journal of Sports Medicine" are the institutions with the most significant number of publications and average citations, respectively. The most common keywords are "acromioclavicular joint dislocation," "arthroscopic resection," "arthroscopic reconstruction" and "coracoclavicular ligament." CONCLUSION: The number of publications shows a steady upward trend as a whole. However, there is still a lack of cooperation among countries, institutions and scholars around the world, so various countries, institutions and scholars need to strengthen academic exchanges and expand the field of cooperation, so as to promote further research and development in related fields. However, minimally invasive methods such as arthroscopy are still the hotspots and frontiers in the treatment of acromioclavicular joint injury in the future.

The clinical-histologic and prognostic characteristics in patients with a second primary non-small-cell lung cancer after a lobectomy.

OBJECTIVES: The goal of this study was to investigate whether an operation can offer survival benefits for patients with a second primary non-small-cell lung cancer (NSCLC) after a lobectomy for a first primary NSCLC and to analyse the characteristics affecting the survival of those patients. METHODS: We performed survival analyses of patients with a second primary NSCLC based on the Surveillance, Epidemiology and End Results program and used propensity score matching to reduce the potential bias and analyse the data. In addition, the primary observational end point was overall survival (OS), and the secondary observational end point was histologic migration. RESULTS: The data from 944 patients were used to perform the main analysis. A total of 36.2% of patients experienced a shift in tumour histologic type between 2 diagnoses of primary NSCLC, and this shift significantly affected OS (P = 0.0065). The median survival time in patients with surgical resection and those without an operation was 52.0 months versus 33.0 months, respectively. Patients with surgical resection at the secondary diagnosis had better survival than those without surgery (5-year OS rate: 48.0% vs 34.0%, P < 0.001). In addition, compared with a pneumonectomy and a sublobar resection, a lobectomy was the optimal surgical procedure for patients diagnosed with a second primary NSCLC after adjusting for other confounders (adjusted hazard ratio: 0.68, P < 0.01). However, in the subgroup analysis, lobar and sublobar resections could provide similar survival benefits for patients with tumour size ≤20 mm (P = 0.5). CONCLUSIONS: The operation, especially a lobectomy, can prolong OS in patients with a second primary NSCLC. Besides, sublobar resection can be performed in selected patients with tumour size ≤20 mm. Moreover, histologic migration may impact the survival of those patients with a secondary primary NSCLC.

Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors.

OBJECTIVES: Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I-IIA ADC. METHODS: We included 1585 patients with pathologically diagnosed stage I-IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS: Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717-0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P < 0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS: We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I-IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I-IIA ADC patients.

Regulation of gut bacteria in silkworm (Bombyx mori) after exposure to endogenous cadmium-polluted mulberry leaves.

Soil cadmium (Cd) pollution presents a severe pollution burden to flora and fauna due to its non-degradability and transferability. The Cd in the soil is stressing the silkworm (Bombyx mori) out through a soil-mulberry-silkworm system. The gut microbiota of B.mori are reported to shape host health. However, earlier research had not reported the effect of endogenous Cd-polluted mulberry leaves on the gut microbiota of B.mori. In the current research, we compared the phyllosphere bacteria of endogenous Cd-polluted mulberry leaves at different concentrations. The investigation of the gut bacteria of B.mori fed with the mulberry leaves was done to evaluate the impact of endogenous Cd- polluted mulberry leaves on the gut bacteria of the silkworm. The results revealed a dramatic change in the gut bacteria of B.mori whereas, the changes in the phyllosphere bacteria of mulberry leaves in response to an increased Cd concentration were insignificant. It also increased the α-diversity and altered the gut bacterial community structure of B. mori. A significant change in the abundance of dominant phyla of gut bacteria of B.mori was recorded. At the genus level, the abundance of Enterococcus, Brachybacterium and Brevibacterium group related to disease resistance, and the abundance of Sphingomonas, Glutamicibacter and Thermus related to metal detoxification was significantly increased after Cd exposure. Meanwhile, there was a significant decrease in the abundance of the pathogenic bacteria Serratia and Enterobacter. The results demonstrated that endogenous Cd-polluted mulberry leaves caused perturbations in the gut bacterial composition of B.mori, which may driven by Cd content rather than phyllosphere bacteria. A significant variation in the specific bacterial community indicated the adaptation of B. mori gut for its role in heavy metal detoxification and immune function regulation. The results of this study help to understand the bacterial community associated with endogenous Cd-polluted resistance in the gut of B.mori, which proves to be a novel addition in describing its response in activating the detoxification mechanism and promoting its growth and development. This research work will help to explore the other mechanisms and microbiota associated with the adaptations to mitigate the Cd pollution problems.

Interaction of AcMADS68 with transcription factors regulates anthocyanin biosynthesis in red-fleshed kiwifruit.

In red-fleshed kiwifruit, anthocyanin pigmentation is a crucial commercial trait. The MYB-bHLH-WD40 (MBW) complex and other transcription factors regulate its accumulation. Herein, a new SEP gene, AcMADS68, was identified as a regulatory candidate for anthocyanin biosynthesis in the kiwifruit by transcriptome data and bioinformatic analyses. AcMADS68 alone could not induce the accumulation of anthocyanin both in Actinidia arguta fruit and tobacco leaves. However, in combination with AcMYBF110, AcMYB123, and AcbHLH1, AcMADS68 co-overexpression increased anthocyanin biosynthesis, whereas its silencing reduced anthocyanin accumulation. The results of the dual-luciferase reporter, firefly luciferase complementation, yeast two-hybrid and co-immunoprecipitation assays showed that AcMADS68 could interact with both AcMYBF110 and AcMYB123 but not with AcbHLH1, thereby co-regulating anthocyanin biosynthesis by promoting the activation of the target genes, including AcANS, AcF3GT1, and AcGST1. Moreover, AcMADS68 also could activate the promoter of AcbHLH1 surported by dual-luciferase reporter and yeast one-hybrid assays, thereby further amplifying the regulation signals from the MBW complex, thus resulting in enhanced anthocyanin accumulation in the kiwifruit. These findings may facilitate better elucidation of various regulatory mechanisms underlying anthocyanin accumulation and contribute to the quality enhancement of red-fleshed kiwifruit.

Identification of THSD7B and PRMT9 mutations as risk factors for familial lung adenocarcinoma: A case report.

RATIONALE: Lung tumors arise from the unrestrained malignant growth of pulmonary epithelial cells. Lung cancer cases include both small and non-small cell lung cancers, with lung adenocarcinoma (LUAD) accounting for roughly half of all non-small cell lung cancer cases. Research focused on familial cancers suggests that approximately 8% of lung cancer cases are linked to genetic susceptibility or heritability. The precise genetic factors that underlie the onset of lung cancer, however, remain to be firmly established. PATIENT CONCERNS: A 43-year-old presented with nodules in the lower left lung lobe. Following initial antibiotic treatment in a local hospital, these nodules remained present and the patient subsequently underwent the resection of the left lower lobe of the lung. The patient also had 4 family members with a history of LUAD. DIAGNOSIS: Immunohistochemical staining results including cytokeratin 7 (+), TTF-1 (+), new aspartic proteinase A (+), CK5/6 (-), P63 (-), and Ki-67 (5%+) were consistent with a diagnosis of LUAD. INTERVENTION: Whole exome sequencing analyses of 5 patients and 6 healthy family members were performed to explore potential mutations associated with familial LUAD. OUTCOMES: Whole exome sequencing was conducted, confirming that the proband and their 4 other family members with LUAD harbored heterozygous THSD7B (c.A4000G:p.S1334G) mutations and homozygous PRMT9 (c.G40T:p.G14C) mutations, as further confirmed via Sanger sequencing. These mutations were predicted to be deleterious using the SIFT, PolyPhen2, and MutationTaster algorithms. Protein structure analyses indicated that the mutation of the serine at amino acid position 1334 in THSD7B to a glycine would reduce the minimum free energy from 8.08 kcal/mol to 68.57 kcal/mol. The identified mutation in the PRMT9 mutation was not present in the predicted protein structure. I-Mutant2.0 predictions indicated that both of these mutations (THSD7B:p.S1334G and PRMT9: p.G14C) were predicted to reduce protein stability. LESSONS: Heterozygous THSD7B (c.A4000G:p.S1334G) and the homozygous PRMT9 (c.G40T:p.G14C) mutations were found to be linked to LUAD incidence in the analyzed family. Early analyses of these genetic loci and timely genetic counseling may provide benefits and aid in the early diagnosis of familial LUAD.