Clinical outcomes of three haploidentical transplantation protocols for hematologic malignancies based on data from the Chinese Bone Marrow Transplantation Registry Group.

This study aimed to demonstrate the clinical outcomes of granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG), posttransplantation cyclophosphamide (PTCy) and PTCy combined with lowdose ATG (PTCy with ATGlow)-based haploidentical transplantation protocols in patients with haematologic malignancies. The comparisons were conducted via propensity score matching (PSM) analysis to balance the basic characteristics among different groups and were based on the transplantation data reported to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG) from January 2020 to December 2022. For each patient in the PTCy or PTCy with ATGlow group, patients (at a 1:2 ratio) from the GCSF/ ATG group were selected. In total, the PTCy group (n=122) was matched with G-CSF/ATG Group 1 (n=230), and the PTCy+ATGlow group (n=123) was matched with G-CSF/ATG Group 2 (n=226). Compared with those in the PTCy group, the incidences of 28-day neutrophil engraftment (P=0.005), 100- day platelet engraftment (P=0.002), median time to neutrophil engraftment (P.

Application of a single-cell-RNA-based biological-inspired graph neural network in diagnosis of primary liver tumors.

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Tumor budding in pre-neoadjuvant biopsy and post-neoadjuvant resection specimens is associated with poor prognosis in intrahepatic cholangiocarcinoma-a cohort study of 147 cases by modified ITBCC criteria.

Tumor budding (TB) has been associated with poor survival in a variety of cancers including intrahepatic cholangiocarcinoma (iCCA). As tumor histomorphological features are significantly altered after neoadjuvant therapy (NAT), our study aims to assess the prognostic significance of TB in iCCA patients before and after NAT, by the modified International Tumor Budding Consensus Conference (ITBCC) criteria. 147 NAT-treated iCCA cases were included in this study. In biopsy specimens obtained before NAT, the TB-positive subgroup had lower overall survival (OS) in univariate analysis (P = 0.010). In resection specimens obtained after NAT, the TB-positive subgroup had reduced OS (P = 0.002) and recurrence-free survival (RFS) (P = 0.013) in univariate analysis. In multivariate analysis including TNM stage, lymphovascular invasion and perineural invasion, TB-positive in post-NAT resection was also found as an independent prognostic factor for both OS and RFS (OS, HR, 3.005; 95% CI, 1.333-6.775, P = 0.008; RFS, HR, 1.748; 95% CI, 1.085-2.816, P = 0.022). In conclusion, assessing the presence of TB by modified ITBCC criteria provides robust prognostic information in the NAT setting of iCCA patients and can be considered to be included in routine pathological reporting.

Low penicillin susceptibility in Streptococcus mitis/oralis from bloodstream infections in pediatric populations.

Streptococcus mitis/oralis can cause invasive diseases, including bloodstream infections. However, existing research primarily focuses on specific populations, and limited studies have been conducted on the prevalence of bloodstream infection caused by S. mitis/oralis across the entire pediatric population. Therefore, clinical data of S. mitis/oralis isolated from blood samples at Children's Hospital, Zhejiang University School of Medicine, during the period 2019-2023 were collected retrospectively to provide a comprehensive understanding of the clinical characteristics and drug resistance patterns associated with bloodstream infections caused by S. mitis/oralis in pediatric populations. There were 57 (43.5%) instances of contamination across various departments, indicating a relatively dispersed pattern. Bloodstream infections caused by S. mitis/oralis are notably prevalent among pediatric patients with hematological diseases and tumors. The susceptibility rates of the 74 S. mitis/oralis isolates to different antibiotics were as follows: penicillin (23%), ceftriaxone (74.3%), levofloxacin (86.5%), chloramphenicol (89.2%), erythromycin (27%), clindamycin (67.6%), linezolid (100%), and vancomycin (100%). Notably, 21.6% of the isolates exhibited multi-drug resistance (MDR). The predominant mode of MDR in S. mitis/oralis infections was identified as resistance to ß-lactams, erythromycin, and clindamycin. The observed low susceptibility rate to penicillin, coupled with the emergence of MDR strains, underscores the imperative for continuous monitoring of the evolving antimicrobial resistance in S. mitis/oralis. IMPORTANCE: Existing research primarily focuses on specific populations, such as those with hematopathy or tumors, who experience Streptococcus mitis/oralis bacteremia. Limited studies have been conducted on the prevalence of bloodstream infections caused by S. mitis/oralis across the entire pediatric population. It was found that the contamination rate of S. mitis/oralis isolated from blood cultures was notably high in our study. Therefore, this study evaluated the clinical characteristics and drug resistance patterns of bloodstream infections caused by S. mitis/oralis across the entire pediatric populations, explicitly excluding cases of blood culture contamination. The observed low susceptibility rate to penicillin, coupled with the emergence of multi-drug-resistant strains, underscores the imperative for continuous monitoring of the evolving antimicrobial resistance in S. mitis/oralis.

Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment. METHODS: Keywords such as "prostate cancer", "tumor microenvironment", "immune cells", "vascular system", "stromal cells", and "microbiota" were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment. RESULTS: The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment. CONCLUSIONS: A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation.

Impact of Duration of Adjuvant Therapy on Patients with Initially Unresectable Hepatocellular Carcinoma After Conversion Surgery: A Propensity Score Matching Study.

Background: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery. Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts. Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229-1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119-1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092-0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079-0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373-4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147-372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent. Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.

The Effect of Stereoelectroencephalography on the Long-Term Outcomes of Different Side Anterior Temporal Lobectomy: A Single-Center Retrospective Study.

PURPOSE: Anterior temporal lobectomy (ATL) is the most common surgical treatment for temporal lobe epilepsy (TLE), and Stereoelectroencephalography (SEEG) plays a critical role in precisely localizing the epileptogenic zone (EZ). This study aimed to explore the effect of SEEG on the long-term outcomes of different side ATL. METHODS: From March 2012 to February 2020, a retrospective analysis was conducted on 231 TLE patients who underwent standard ATL surgery. According to the surgical sides and the utilization of SEEG during preoperative evaluation, the patients were categorized into 4 groups, with a follow-up period exceeding 2 years. RESULTS: Among the 231 TLE patients, the probability of being seizure-free 2 years after the surgery was 80.52%, which decreased to 65.65% after 5 years. There was no significant difference in outcomes between SEEG and non-SEEG patients. For overall and non-SEEG patients, there was no significant difference in short-term outcomes between different surgical sides. However, the long-term outcomes of right ATL patients were significantly better than left. Interestingly, for patients who underwent SEEG, there was no significant difference in both short-term and long-term outcomes between different surgical sides. CONCLUSIONS: Some TLE patients encounter challenges in localizing the EZ through noninvasive evaluation, necessitating the use of SEEG for precise localization. Furthermore, their seizure outcomes after surgery can be the same with the patients who have a clear EZ in noninvasive evaluation. And SEEG patients can achieve a more stable long-term prognosis than non-SEEG patients.

[Free vastus lateralis flap combined with skin grafting for repairing small- and medium-sized lacunar defects in non-weight-bearing area of diabetic foot].

Objective: To explore the feasibility and effectiveness of free vastus lateralis flap combined with skin grafting for repairing small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot. Methods: Between January 2022 and October 2023, 8 patients (8 feet) with small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot were admitted. There were 6 males and 2 females, with an average age of 64.3 years (range, 58-76 years). The duration of the diabetic foot ulcer ranged from 2 to 7 weeks (mean, 4.3 weeks). The wound was located between the metatarsal bones in 4 cases, on the medial side of the foot in 2 cases, on the lateral side of the foot in 1 case, and on the dorsal and lateral sides of the foot in 1 case. The length of wound was 4.0-12.0 cm, the width was 3.0-5.0 cm, and the depth was 1.2-2.0 cm. The free vastus lateralis flaps were designed to repair the wounds, and skin grafting covered the vastus lateralis flaps. The length of the vastus lateralis flap was 5.0-14.0 cm, the width was 3.5-6.0 cm, and the thickness was 1.0-1.5 cm. The donor sites of the muscle flaps were directly sutured. Results: The time for vastus lateralis flaps harvested ranged from 30 to 80 minutes (mean, 55.0 minutes), and the total operation time ranged from 125 to 170 minutes (mean, 147.5 minutes). All muscle flaps and skin grafts survived successfully, and the wounds and the incisions at the donor sites healed by first intention. All patients were followed up 6-24 months, with an average of 12.8 months. The appearances of 3 patients who did not follow the doctor's instructions for pressure treatment of the muscle flaps were a little bloated, and the rest had a good appearance. The texture of the muscle flaps was soft. There were linear scars at the donor sites. There was no recurrence of ulcers during follow-up. All patients could walk independently without limitation of daily activities at last follow-up. Conclusion: The application of free vastus lateralis flap combined with skin grafting to repair small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot has the advantages of simple operation and time-saving as well as small damage to the donor site, with good repair effect, especially for the elderly patients who are not suitable for prolonged anesthesia.

Facilitating integrative and personalized oncology omics analysis with UCSCXenaShiny.

The continuous generation of multi-omics and phenotype data is propelling advancements in precision oncology. UCSCXenaShiny was developed as an interactive tool for exploring thousands of cancer datasets available on UCSC Xena. However, its capacity for comprehensive and personalized pan-cancer data analysis is being challenged by the growing demands. Here, we introduce UCSCXenaShiny v2, a milestone update through a variety of improvements. Firstly, by integrating multidimensional data and implementing adaptable sample settings, we create a suite of robust TPC (TCGA, PCAWG, CCLE) analysis pipelines. These pipelines empower users to conduct in-depth analyses of correlation, comparison, and survival in three modes: Individual, Pan-cancer and Batch screen. Additionally, the tool includes download interfaces that enable users to access diverse data and outcomes, several features also facilitate the joint analysis of drug sensitivity and multi-omics of cancer cell lines. UCSCXenaShiny v2 is an open-source R package and a web application, freely accessible at https://github.com/openbiox/UCSCXenaShiny .

Total organic carbon content estimation for mixed shale using Xgboost method and implication for shale oil exploration.

In this study, the Xgboost method is employed for TOC estimation in mixed carbonate and siliciclastic shale from the Hashan area, Junggar Basin. The results show that this approach is effective for TOC estimation in this area although the model performance is not very excellent with a correlation coefficient of 0.54 between measured TOC and predicted TOC values, likely due to a small samples dataset. Therefore, the PCA method is applied to debase dimension of well log data from five dimensional to two-dimensional data, which enhances the correlation coefficient between the predicted and measured TOC from 0.54 to 0.68. Based on the model, the isopleth maps of TOC distributions in Fengcheng Formation were redrawn showing two shale oil exploration targets, which likely correspond to two depositional centers of this strata. All the same, the model in this work provides reliable data for shale oil evaluation in the study area and a good example under similar geological setting.

Vedolizumab for second-line treatment of steroid-refractory gastrointestinal late acute graft-versus-host disease.

Background: Late acute graft-versus-host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with little data regarding treatment and outcomes. There is no standard treatment for gastrointestinal (GI) late aGVHD, especially for steroid-refractory (SR) GI late aGVHD. Vedolizumab, a monoclonal antibody inhibiting the migration of both naive and activated lymphocytes into the GI endothelium, has been verified to be effective for SR GI aGVHD. Methods: We retrospectively analyzed the clinical efficacy and safety of vedolizumab as the second line for SR GI late aGVHD in seven patients after allo-HSCT. Results: Four patients received two doses of vedolizumab infusion, while three patients received only one dose of vedolizumab infusion. The complete response and partial response rates were 57.1% (4/7) and 42.9% (3/7), respectively. No patient progressed to chronic GVHD during the period of follow-up. There was no severe adverse event related to vedolizumab. Conclusion: Our data suggest that vedolizumab is expected to ameliorate SR GI late aGVHD. Further data on the treatment timing, efficacy, and safety of vedolizumab are warranted in prospective clinical trials.

Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti-PD-1 therapy in hepatocellular carcinoma.

BACKGROUND: The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine- and arginine-rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. METHODS: To identify the key genes associated with immunotherapy resistance, we conducted single-nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co-culture systems, flow cytometry, various tumor-bearing mouse models, and patient-derived organotypic tumor spheroids. RESULTS: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8+ T cell activity. Mechanistically, SRSF10 interacted with the 3'-untranslated region of MYB, enhancing MYB RNA stability, and subsequently upregulating key glycolysis-related enzymes including glucose transporter 1 (GLUT1), hexokinase 1 (HK1), lactate dehydrogenase A (LDHA), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro-tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8+ T cells and the proportion of interferon-γ+CD8+ T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) in both murine and human preclinical models. CONCLUSIONS: The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti-PD-1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti-PD-1 tolerance in HCC.

Characterization of serum proteomic and inflammatory profiling at early stage of iron deficiency in weaned piglets.

The objective of this study was to examine the early serum proteomic and inflammatory profiles of weaned piglets subjected to iron deficiency. Twelve healthy piglets (Duroc × Landrace × Large Yorkshire, body weight: 4.96 ± 0.05 kg) were weaned at 21 days of age. Subsequently, these animals were randomly allocated to one of two groups, with six replicates in each group (maintaining a male-to-female ratio of 1:1), the control group (administered 100 mg/kg Fe as FeSO4·H2O) and L-Fe group (no additional Fe supplementation). The results showed that 42 days after initiating, compared with control group, routine blood analysis revealed a reduction in serum iron content, red blood cell (RBC) count, hemoglobin (HGB) content, hematocrit (HCT), and mean corpuscular volume (MCV) (P < 0.05). Subsequent sample analysis indicated a noteworthy decrease in iron deposition in the liver, spleen, and kidneys of piglets fed the L-Fe diet compared with control group (P < 0.05). However, final body weight, average daily gain (ADG), average daily feed intake (ADFI), feed conversion ratio, and tissue coefficients were similar between the two groups (P > 0.05). During the early stages of iron deficiency, piglets exhibited increased villus height (VH) and the ratio of VH to crypt depth (CD) in the duodenum (P < 0.05) and increased expression levels of iron transporters, including duodenal cytochrome (Cybrd), divalent metal transport 1 (DMT1), and ferritin light chain (FTL) (P < 0.05). Subsequently, isobaric tags for relative and absolute quantitation (iTRAQ) were used to identify serum proteins. Gene Ontology (GO) analysis of the differentially abundant proteins (DAP) revealed that 24 of the 30 DAP were involved in platelet function, immune response, cellular metabolism, transcription, and protein synthesis. Notably, prothrombin, asporin (ASPN), and Rac family small GTPase 3 (RAC3) expression was induced, whereas glycoprotein Ib platelet subunit alpha (GPIbA) expression was decreased. This was accompanied by a substantial reduction in serum complement 3 (C3) and complement 4 (C4) contents (P < 0.05), with elevated the contents of interleukin-1ß (IL-1ß), interleukin-4 (IL-4), interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and tumor necrosis factor-α (TNF-α) (P < 0.05). Our findings underscore the essential role of dietary iron supplementation in maintaining iron homeostasis and modulating inflammatory responses in piglets.

The effect of tempering temperature on microstructure and corrosion resistance of M390 powder metallurgical martensitic stainless steel.

The corrosion resistance of M390 powder metallurgical martensitic stainless steel with different tempering temperatures was investigated by potentiodynamic polarization measurements, salt spray tests, and microstructural analyses utilizing scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The tempering temperature had no significant effect on the size and volume fraction of carbides. The corrosion resistance of M390 steel gradually deteriorated with increasing tempering temperature, and a loss passivation (LOP) effect was observed when tempered at 450 °C, 500 °C, and 550 °C. Transmission electron microscopy (TEM) analysis showed that the width of the Cr-depleted zones around the undissolved M7C3 carbides increased with increasing tempering temperature, while the Cr content in these zones decreased, which was the main reason for the deterioration of corrosion resistance. This study offers valuable insights into optimizing the tempering process to improve the corrosion resistance of M390 steel for practical applications.

Effect of family history of cancer on postoperative survival in patients with non-small cell lung cancer.

Background: Family history of cancer (FHC) has been reported to increase mortality of non-small cell lung cancer, mainly comprised of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). However, the impact of FHC on long-term survival remains controversial. This study aims to identify the impact of FHC on postoperative survival in LUAD and LUSC. Methods: Patients underwent lung resection for LUAD or LUSC in West China Hospital from 2009 to 2021 were enrolled. The 5-year overall survival (OS), lung cancer-specific survival (LCSS) and progression-free survival (PFS) were compared between the patients with and without FHC. Multivariable Cox regression was also performed. Results: A total of 6,253 patients were enrolled, including 5,685 LUAD and 568 LUSC. Altogether 18.9% (1,077/5,685) patients had FHC in LUAD, and 12.7% (72/568) patients had FHC in LUSC. In LUAD, the patients with FHC showed comparable survival compared with the patients without FHC regarding 5-year OS (87.9% vs. 86.5%, P=0.49), 5-year PFS (84.8% vs. 80.9%, P=0.06), and 5-year LCSS (89.2% vs. 88.0%, P=0.96). In LUSC, the patients with FHC had poorer survival compared with the patients without FHC according to 5-year OS (40.9% vs. 68.2%, P=0.007), 5-year PFS (42.3% vs. 66.2%, P=0.003), and 5-year LCSS (45.8% vs. 72.7%, P=0.003). Multivariate analyses indicated that FHC was an independent prognostic factor of OS, PFS, and LCSS in the patients with LUSC. Conclusions: FHC was associated with a poor survival after lung resection in LUSC not LUAD patients. More attention should be paid in postoperative monitoring and treatment in LUSC patients with FHC.

A nomogram predicting the risk of extrathoracic metastasis at initial diagnosis of T≤3cmN0 lung cancer.

Background: The risk and risk factors of extrathoracic metastasis at initial diagnosis in T≤3cmN0 lung cancer patients are not fully understood. We aimed to develop a model to predict the risk of extrathoracic metastasis in those patients. Methods: Clinicopathological data of patients were collected from Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable analyses using logistic regression were conducted to identify risk factors. A predictive model and corresponding nomogram were developed based on the risk factors. The model was assessed using the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow test, and decision curve. Results: A total of 20,057 T≤3cmN0 patients were enrolled, of whom 251 (1.25%) were diagnosed with extrathoracic metastasis at the initial diagnosis. Aged ≤50 [odds ratio (OR): 2.05, 95% confidence interval (CI): 1.19-3.53, P=0.01] and aged ≥81 [1.65 (1.05-2.58), P=0.03], Hispanic [1.81 (1.20-2.71), P=0.004], location of bronchus [3.18 (1.08-9.35), P=0.04], larger tumor size, pleural invasion, and a history of colorectal cancer [2.01 (1.01-4.00), P=0.046] were independent risk factors. In the training cohort and validation cohort, the AUCs of the developed model were 0.727, 0.728 respectively, and the results of Hosmer-Lemeshow test were P=0.47, P=0.61 respectively. The decision curve showed good clinical meaning of the model. Conclusions: Extrathoracic metastasis at initial diagnosis in T≤3cmN0 lung cancer patients was not rare. The model based on the risk factors showed good performance in predicting the risk of extrathoracic metastasis.

Analysis of D-dimer levels for the detection of deep venous thrombosis for patients with spinal metastasis undergoing decompression with fixation.

BACKGROUND: Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. METHODS: We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. RESULTS: Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. CONCLUSIONS: Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. TRIAL REGISTRATION: Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.

The long-term outcomes in drug-resistant epilepsy patients who underwent subtotal hemispherotomy: A single-center retrospective cohort study.

OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68 %) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63 %) patients; seven (37 %) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.

Masks As a New Hotspot for Antibiotic Resistance Gene Spread: Reveal the Contribution of Atmospheric Pollutants and Potential Risks.

The consumption of disposable surgical masks (DSMs) considerably increased during the coronavirus pandemic in 2019. Herein, we explored the spread of antibiotic resistance genes (ARGs) and the potential risks of antibiotic resistant bacteria (ARB) on DSMs. At environmentally relevant concentrations, the conjugate transfer frequency (CTF) of ARGs increased by 1.34-2.37 folds by 20 µg/m3 of atmospheric water-soluble inorganic ions (WSIIs), and it increased by 2.62-2.86 folds by 80 ng/m3 of polycyclic aromatic hydrocarbons (PAHs). Total suspended particulates (TSP) further promoted the CTF in combination with WSIIs or PAHs. Under WSII and PAH exposure, gene expression levels related to oxidative stress, cell membrane, and the adenosine triphosphate (ATP) were upregulated. WSIIs predominantly induced cellular contact, while PAHs triggered ATP formation and membrane damage. Molecular dynamics simulations showed that WSIIs and PAHs reduced membrane lipid fluidity and increased membrane permeability through interactions with the phosphatidylcholine bilayer. DSM filtering performance decreased, and the CTF of ARGs increased with the wearing time. The gut simulator test showed that ARB disrupted the human gut microbial community and increased total ARG abundance but did not change the ARG abundance carried by ARB themselves. A mathematical model showed that long-term WSII and PAH exposure accelerated ARG dissemination in DSMs.

Smoking timing, genetic susceptibility, and the risk of incident atrial fibrillation: a large prospective cohort study.

AIMS: Although smoking is a well-known risk factor for atrial fibrillation (AF), the association of smoking timing with AF risk remains unclear. This study aimed to prospectively investigate the association of smoking timing with risk of incident AF, and test the modification effect of genetic susceptibility. METHODS AND RESULTS: A total of 305,627 participants with detailed information for time from waking to first cigarette were enrolled from UK Biobank database. Cox proportional hazard model was employed to assess the relationship between smoking timing and AF risk. Weighted genetic risk score for AF was calculated. Over a median 12.2-year follow-up, 13,410 AF cases were documented. Compared to non-smokers, time from waking to the first cigarette showed gradient inverse associations with risk of incident AF (P-trend <0.001). The adjusted hazard ratio related to smoking timing was 1.13 (95% CI: 0.96-1.34) for >120 minutes, 1.20 (95% CI: 1.01-1.42) for 61-120 minutes, 1.34 (95% CI: 1.19-1.51) for 30-60 minutes, 1.43 (95% CI: 1.26-1.63) for 5-15 minutes, and 1.49 (95% CI: 1.24-1.63) for <5 minutes, respectively. Additionally, we found that the increased risk of AF related to shorter time from waking to the first cigarette was strengthened by the genetic susceptibility to AF. CONCLUSIONS: Our findings suggest gradient inverse association between time from waking to the first cigarette and risk of incident AF, and the association is strengthened by the genetic susceptibility to AF.

Our study aimed to analyze the relationship between the time from waking to the first cigarette and incidence of AF, and the modification role of genetic susceptibility.Shorter time from waking to the first cigarette was related to elevated risk of incident atrial fibrillation.Genetic susceptibility to atrial fibrillation strengthened the gradient inverse association of time from waking to the first cigarette with incidence of AF.