Advances in combined neuroendocrine carcinoma of lung cancer.

Lung cancer incidence and mortality rates are increasing worldwide, posing a significant public health challenge and an immense burden to affected families. Lung cancer encompasses distinct subtypes, namely, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). In clinical investigations, researchers have observed that neuroendocrine tumors can be classified into four types: typical carcinoid, atypical carcinoid, small-cell carcinoma, and large-cell neuroendocrine carcinoma based on their unique features. However, there exist combined forms of neuroendocrine cancer. This study focuses specifically on combined pulmonary carcinomas with a neuroendocrine component. In this comprehensive review article, the authors provide an overview of combined lung cancers and present two pathological images to visually depict these distinctive subtypes.

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-related connective tissue disease with a complex and unknown pathophysiological mechanism with genes association. Several articles have reported a high prevalence of thyroid disease in SSc patients, while one study suggested a potential contribution of appendicitis to the development of SSc. To investigate this causal association, we conducted Mendelian randomization (MR) analysis using instrumental variables (IVs) to assess exposure and outcome. In the MR study involving two cohorts, all analyses were conducted using the TwoSampleMR package in R (version 4.3.0). Single nucleotide polymorphisms (SNPs) meeting a statistically significant threshold of 5E-08 were included in the analysis. Multiple complementary approaches including MR-IVW, MR-Egger, weighted median, simple mode, and weighted mode were employed to estimated the relationship between the exposure and outcome. Leave-one-out analysis and scatter plots were utilized for further investigation. Based on the locus-wide significance level, all of the MR analysis consequences manifested no causal association between the risk of appendicitis with SSc (IVW OR 0.319, 95% CI 0.063-14.055, P = 0.966). Negative causal effects of autoimmune thyroiditis (AT) on SSc (IVW OR 0.131, 95% CI 0.816-1.362, P = 0.686), Graves' disease (GD) on SSc (IVW OR 0.097, 95% CI 0.837-1.222, P = 0.908), and hypothyroidism on SSc (IVW OR 1.136, 95% CI 0.977-1.321, P = 0.096) were derived. The reverse MR revealed no significant causal effect of SSc on thyroid disease. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. The consequences indicated no significant association between AT, GD, and hypothyroidism with SSc. Similarly, there was no observed relationship with appendicitis.

CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4.

BACKGROUND: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. METHODS: Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. RESULTS: CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. CONCLUSION: Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.

Nanoparticles Mediated circROBO1 Silencing to Inhibit Hepatocellular Carcinoma Progression by Modulating miR-130a-5p/CCNT2 Axis.

Background: Circular RNAs (circRNAs) are becoming vital biomarkers and therapeutic targets for malignant tumors due to their high stability and specificity in tissues. However, biological functions of circRNAs in hepatocellular carcinoma (HCC) are still not well studied. Methods: Gene Expression Omnibus (GEO) database and qRT-PCR were used to evaluate expression of circROBO1 (hsa_circ_0066568) in HCC tissues and cell lines. CCK-8, colony formation, EdU staining, flow cytometry for cell cycle analysis, and xenograft model assays were performed to detect the circROBO1 function in vitro and in vivo. RNA pull-down, RNA immunoprecipitation (RIP), and Luciferase reporter assays were used to investigate the relationship among circROBO1, miR-130a-5p, and CCNT2. More importantly, we developed nanoparticles made from poly lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) chains as the delivery system of si-circROBO1 and then applied them to HCC in vitro and in mice. Results: circROBO1 was obviously upregulated in HCC tissues and cell lines, and elevated circROBO1 was closely correlated with worse prognosis for HCC patients. Functionally, knocking down circROBO1 significantly suppressed HCC cells growth in vitro and in mice. Mechanistically, circROBO1 acted as a competing endogenous RNA to downregulate miR-130a-5p, leading to CCNT2 expression upregulation. Furthermore, miR-130a-5p mimic or CCNT2 knockdown reversed the role of circROBO1 overexpression on HCC cells, which demonstrated that circROBO1 promoted HCC development via miR-130a-5p/CCNT2 axis. In addition, we developed nanoparticles loaded with si-circROBO1, named as PLGA-PEG (si-circROBO1) NPs, which significantly prevented the proliferation of HCC cells, and did not exhibit apparent toxicity to major organs in vivo. Conclusion: Our findings firstly demonstrate that circROBO1 overexpression promotes HCC progression by regulating miR-130a-5p/CCNT2 axis, which may serve as an effective nanotherapeutic target for HCC treatment.

Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma.

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development，and functioned as a regulator of ferroptosis. Clinically, the downregulation of RBMS1 occurred in HCC tissues, and low RBMS1 expression was associated with worse HCC patients survival. Mechanistically, RBMS1 overexpression inhibited HCC cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. Collectively, our findings established circIDE/miR-19b-3p/RBMS1 axis as a regulator of ferroptosis, which could be a promising therapeutic target and prognostic factor.

Time-trends in liver cancer incidence and mortality rates in the U.S. from 1975 to 2017: a study based on the Surveillance, Epidemiology, and End Results database.

Background: A previous study has examined the overall cancer statistics. However, more detailed statistics regarding liver cancer have not been provided. We evaluated the incidence and mortality trends of liver and intrahepatic bile duct cancer in the United States from 1975 to 2017 based on the data in the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Age, gender, race, metastasis, tumor site, and tumor grade of patients were extracted from the SEER database. Codes C22.0 and C22.1 of the International Classification of Disease for Oncology were applied to identify patients with hepatocellular carcinoma (HCC) and/or intrahepatic cholangiocarcinoma (ICC). Age-specified incidence, age-standardized incidence and mortality, 5-year relative survival, race-specific accumulative incidence and mortality, and geographic-specific accumulative mortality were calculated in different groups. Changes in trends of liver cancer incidence and mortality were assessed using Joinpoint regression. Results: The overall incidence increased significantly from 2.641/100,000 person-years in 1975 to 8.657/100,000 person-years in 2017 [average annual percent change (AAPC) =3.42, 95% confidence interval (CI): 3.28-3.62, P<0.001]. The steepest incidence rate increase was observed in the 60-69-year-old age group (AAPC =4.40, 95% CI: 4.10-4.70, P<0.001). Males exhibited a more rapid increase in cancer incidence, from 3.928/100,000 to 13.128/100,000 person-years (AAPC =3.41, 95% CI: 3.21-3.61, P<0.001), than females [from 1.642/100,000 to 4.783/100,000 person-years (AAPC =3.03, 95% CI: 2.91-3.21, P=0.001)]. The overall mortality rate increased from 2.808/100,000 person-years in 1975 to 6.648/100,000 person-years in 2017 (AAPC =2.41, 95% CI: 2.29-2.51, P<0.001). The highest mortality rate was observed in Hawaii (6.996/100,000 person-years). Conclusions: The incidence and mortality rates of HCC and ICC increased from 1975 to 2017, especially in males, non-Hispanic Blacks and older individuals. Comprehensive policy and control measures should be implemented to reduce the burden of disease, particularly through health monitoring and intervention for high-risk groups.

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR-625-5p axis.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

Effects of N-butanol extract of Amygdalus mongolica on rats with bleomycin‐induced pulmonary fibrosis based on metabolomics

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor β (TGF-β) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-β1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-β1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

Incidence and risk factors for surgical site infection following volar locking plating (VLP) of unstable distal radius fracture (DRF).

PURPOSE: Volar locking plating (VLP) is the mainstay of treatment for distal radius fracture (DRF) but may be compromised by postoperative surgical site infection (SSI). This study aimed to identify the incidence and the risk factors for SSI following VLP of DRF. METHODS: This retrospective study identified consecutive patients who underwent VLP for closed unstable DRFs in our institution between January 2015 and June 2021. Postoperative SSI was identified by inquiring the medical records, the follow-up records or the readmission medical records for treatment of SSI. The potential factors for SSI were extracted from the medical records. Univariate and multivariate logistic regression analyses were performed to identify the independent factors. RESULTS: There were 930 patients included, and 34 had an SSI, representing an incidence of 3.7% (95% CI 2.4-4.9%). Patients with an SSI had threefold extended hospitalization stay (44.1 ± 38.2 versus 14.4 ± 12.5 days) as did those without. In univariate analysis, 18 variables were tested to be statistically different between SSI and non-SSI group. In multivariate analysis, 6 factors were identified as independently associated with SSI, including sex (male vs. female, OR 3.5, p = 0.014), ASA (III and IV vs. I, OR 3.2, p = 0.031), smoking (yes vs. no, OR 2.4, p = 0.015), bone grafting (OR 4.0, p = 0.007), surgeon volume (low vs. high, OR 2.7, p 0.011) and operation at night-time (vs. day-time, OR 7.8, p < 0.001). CONCLUSION: The postoperative SSI of VLP of DRF was not uncommon, and the factors identified in this study, especially those modifiable, would help identify individual SSI risk, target clinical surveillance and inform patient counseling.

Enhancing the selective synthesis of butyrate in microbial electrosynthesis system by gas diffusion membrane composite biocathode.

The reduction of carbon dioxide (CO2) to high value-added multi-carbon compounds at the cathode is an emerging application of microbial electrosynthesis system (MES). In this study, a composite cathode consisting of hollow fiber membrane (HFM) and the carbon felt is designed to enhance the CO2 mass transfer of the cathode. The result shows that the main products are acetate and butyrate without other substances. The electrochemical performance of the electrode is significantly improved after biofilm becomes matures. The composite cathode significantly reduces the "threshold" for the synthesis of butyrate. Moreover, CO2 is dissolved and protons are consumed by synthesizing volatile fatty acids (VFAs) to maintain a stable pH inside the composite electrode. The synthesis mechanism of butyrate is that CO2 is converted sequentially into acetate and butyrate. The microenvironment of the composite electrode enriches Firmicute. This composite electrode provides a novel strategy for regulating the microenvironment.

Bone marrow mesenchymal stem cell-derived extracellular vesicles facilitate endometrial injury repair by carrying the E3 ubiquitin ligase WWP1.

Bone marrow mesenchymal stem cells-derived extracellular vesicles (BMSC-EVs) relieve endometrial injury. This study aimed to elucidate the BMSC-EV mechanism in alleviating endometrial injury. Endometrial injury model in vivo was induced using 95% ethanol, and endometrial epithelial cells (EECs) treated with mifepristone were applied as an endometrial injury model in vitro. After BMSCs and BMSC-EVs were isolated and identified, the BMSC-EV function was evaluated by hematoxylin-eosin and Masson staining, immunohistochemistry, quantitative real-time PCR, Cell Counting Kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and Transwell and tubule formation assays. The BMSC-EV mechanism was assessed using Western blot, ubiquitination, and cycloheximide-chase assays. After isolation and identification, BMSC-EVs were effective in endometrial injury repair in vivo and facilitated EEC proliferation and repressed cell apoptosis in vitro; the EEC supernatants accelerated human umbilical vein endothelial cell proliferation, migration, and invasion and facilitated angiogenesis after endometrial injury in vitro. For the BMSC-EV mechanism, E3 ubiquitin ligase WWP1 in BMSC-EVs mediated the ubiquitination of peroxisome proliferator-activated receptor gamma (PPARγ), thus relieving the PPARγ inhibition on vascular endothelial growth factor expression. Furthermore, the WWP1 in BMSC-EVs alleviated endometrial injury in vitro and in vivo. BMSC-EVs facilitated endometrial injury repair by carrying WWP1.

Bone marrow mesenchymal stem cells inhibit hepatic fibrosis via the AABR07028795.2/rno-miR-667-5p axis.

BACKGROUND: The mechanism of bone marrow mesenchymal stem cells (BMSCs) in treating hepatic fibrosis remains unclear. METHODS: TGF-ß1-induced hepatic stellate cell (HSC)-T6 and CCl4-induced hepatic fibrosis rats were treated with BMSCs. HSC-T6 cell activity was determined using the cell counting kit-8 assay, and the histology change was evaluated using hematoxylin and eosin and Masson staining. The expression of fibrosis markers was determined using real-time quantitative PCR, Western blotting, and immunocytochemistry. RNA sequencing (RNA-seq) was used to screen the lncRNAs involved in the effect of BMSCs in fibrosis, and the function of fibrosis-associated lncRNA in fibrosis histology change and fibrosis marker expression was investigated. The potential miRNA target of lncRNA was predicted using R software. The interaction between lncRNA and miRNA was verified using luciferase report system and RNA immunoprecipitation (RIP) in 293T and HSC-T6 cells. RESULTS: BMSC attenuated TGF-ß1-induced HSC-T6 activation and suppressed the expression of fibrosis-associated gene (MMP2, Collagen I, and αSMA) expression at the transcription and translation levels. BMSC treatment also improves hepatic fibrosis in rats with CCl4-induced fibrosis by decreasing the expression of fibrosis-associated genes and suppressing collagen deposition in the liver. RNA-seq revealed that AABR07028795.2 (lnc-BIHAA1) was downregulated in the TGF-ß1-induced HSC-T6 after treatment with BMSCs as compared with those in TGF-ß1-induced HSC-T6, and subsequently, functional analysis showed that lnc-BIHAA1 plays a beneficial role in suppressing hepatic fibrosis. Luciferase activity assay and RIP revealed that lnc-BIHAA1 interacted with the miRNA, rno-miR-667-5p, functioning as a fibrosis phenotype suppressor in TGF-ß1-induced HSC-T6. Moreover, overexpression of rno-miR-667-5p significantly reverses the effect of lnc-BIHAA1 on HSC-T6. CONCLUSIONS: BMSC treatment suppresses hepatic fibrosis by downregulating the lnc-BIHAA1/rno-miR-667-5p signaling pathway in HSCs. Our results provide a scientific basis for establishing BMSCs as a biological treatment method for liver fibrosis.

Treatment of distal radius fractures using a cemented K-wire frame.

BACKGROUND: This retrospective study included an alternative treatment for types A2, A3, and B1 distal radius fractures using percutaneous fixation with a cemented K-wire frame. METHODS: From January 2017 to January 2020, 78 patients with distal radius fractures were treated with percutaneous internal fixation using a cemented K-wire frame. There were 47 male patients and 31 female patients. The fractures were classified into types A2 (n = 10), A3 (n = 46), and B1 (n = 22). X-rays were taken immediately after surgery and after the bone had healed. Wrist function was assessed using the Mayo Wrist Score (90-100, excellent; 80-90, good; 60-80, satisfactory; < 60, poor). Patient satisfaction was assessed using the 10-cm visual analog scale. RESULTS: Neither fixation failure nor K-wire migration was found (P > 0.05). Osteomyelitis was not observed in this series. All patients achieved bone healing after a mean of 4.5 weeks (range, 4 to 8 weeks). Follow-up lasted a mean of 27 months (range, 24 to 33 months). The mean score of wrist function was 97 (range, 91 to 100). Among them, 66 results were excellent and 12 results were good. The mean patient satisfaction was 10 cm (range, 8 to 10 cm). CONCLUSIONS: Percutaneous fixation with cemented K-wire frame is a safe and preferred choice for the treatment of types A2, A3, and B1 distal radius fractures. The frame provides support to prevent wire migration. The fixation technique is a minimally invasive procedure that is easy to perform. LEVEL OF EVIDENCE: Therapeutic study, Level IVa.

Comparison of the diagnostic efficacy of 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT in patients with pancreatic cancer.

PURPOSE: We sought to assess the performance of 68 Ga-FAPI-04 PET/MR for the diagnosis of primary tumours as well as metastatic lesions in patients with pancreatic cancer and to compare the results with those of 18F-FDG PET/CT. METHODS: Prospectively, we evaluated 33 patients suspected to have pancreatic adenocarcinoma, of whom thirty-two were confirmed by histopathology, and one had autoimmune pancreatitis confirmed by needle biopsy and glucocorticoid treatment. Within 1 week, each patient underwent both 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT. Comparisons of the detection abilities for primary tumours, lymph nodes, and metastases were conducted for the two imaging approaches. The original maximum standard uptake values (SUVmax) and normalised SUVmax (SUVmax/SUVbkgd) of paired lesions on 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT were measured and compared. RESULTS: Thirty pancreatic cancer patients and three pancreatitis patients were enrolled. 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT exhibited equivalent (100%) detection rates for primary tumours. The original/normalised SUVmax of primary tumours on 68 Ga-FAPI-04 PET was markedly higher than that on 18F-FDG (p < 0.05). Sixteen pancreatic cancer patients had pancreatic parenchymal uptake, whereas 18F-FDG PET images showed parenchymal uptake in only four patients (53.33% vs. 13.33%, p < 0.001). 68 Ga-FAPI-04 PET detected more positive lymph nodes than 18F-FDG PET (42 vs. 30, p < 0.001), while 18F-FDG PET was able to detect more liver metastases than 68 Ga-FAPI-04 (181 vs. 104, p < 0.001). In addition, multisequence MR imaging helped explain ten pancreatic cancers that could not be definitively revealed due to 68 Ga-FAPI-04 inflammatory uptake and identified more liver metastases than 18F-FDG (256 vs. 181, p < 0.001). CONCLUSION: 68 Ga-FAPI-04 PET might be better than 18F-FDG PET in the detection of suspicious lymph node metastases. MR multiple sequence imaging of 68 Ga-FAPI-04 PET/MR was helpful for explaining pancreatic lesions in patients with obstructive inflammation and detecting tiny liver metastases.

A multi-analyte cell-free DNA-based blood test for early detection of hepatocellular carcinoma.

The limited performance of guideline-recommended abdominal ultrasound and serum alpha-fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers for more accurate detection of early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate the performance of the HelioLiver Test, a multi-analyte blood test combining cell-free DNA methylation patterns, clinical variables, and protein tumor markers. A blinded, multicenter validation study was performed with 247 subjects, including 122 subjects with HCC and 125 control subjects with chronic liver disease. The performance of the HelioLiver Test was compared with AFP and the GALAD score as established HCC surveillance blood tests. The performance of the HelioLiver Test (area under the receiver operating characteristic curve [AUROC] = 0.944) was superior to both AFP (AUROC = 0.851; p < 0.0001) and GALAD (AUROC = 0.899; p < 0.0001). Using a prespecified diagnostic algorithm, the HelioLiver Test showed sensitivities of 85% (95% confidence interval [CI], 78%-90%) for HCC of any stage and 76% (95% CI, 60%-87%) for early stage (American Joint Committee on Cancer [AJCC] I and II) HCC. In contrast, AFP (≥20 ng/mL) alone and the GALAD score (≥-0.63) showed lower sensitivities of 62% (95% CI, 54%-70%) and 75% (95% CI, 67%-82%) for HCC overall, and 57% (95% CI, 40%-71%) and 65% (95% CI, 49%-79%) for early stage (AJCC I and II) HCC, respectively. The specificities of the HelioLiver Test (91%; 95% CI, 85%-95%), AFP (97%; 95% CI, 92%-99%), and the GALAD score (94%; 95% CI, 88%-97%) were similar for control subjects. The HelioLiver Test showed superior performance for HCC detection compared to with both AFP and the GALAD score and warrants further evaluation in HCC surveillance settings.

Incidence and risk factors for decreased range of motion of the knee joint after surgery for closed tibial plateau fracture in adults.

PURPOSE: The aim of this study was to quantify the incidence of and identify independent risk factors for decreased range of motion (ROM) of the knee joint after surgery for closed tibial plateau fractures in adults. METHODS: This retrospective study was performed at the trauma centre in our hospital from January 2018 to December 2019. Data from adult patients with tibial plateau fractures treated by surgery were extracted from the electronic medical records. A total of 220 tibial plateau fracture patients were enrolled. We extracted the patients' demographic characteristics, fracture characteristics, and surgery-related variables. Univariate and multivariate logistic regression models were used to investigate the potential independent risk factors. RESULTS: Fifty-seven patients developed decreased ROM of the knee joint at the 1-year follow-up in this study. The overall incidence was 25.9%. The independent predictors of decreased ROM after surgery, as identified in the multivariate analysis, were orthopedic polytrauma (odds ratio = 3.23; 95% CI = 1.68-6.20; p = 0.000), fracture type (Schatzker V-VI) (odds ratio = 2.52; 95% CI = 1.16-5.47; p = 0.019), and an open reduction and internal fixation approach (odds ratio = 2.10; 95% CI = 1.07-4.12; p = 0.031). CONCLUSIONS: The study confirmed that patients with orthopaedic polytrauma, more complex fractures and those treated with open reduction and internal fixation (ORIF) surgery were more likely to suffer decreased ROM of the knee joint 1 year after surgery.

A metabolomic approach to elucidate the inhibitory effects of baicalin in pulmonary fibrosis.

CONTEXT: Baicalin, a major flavonoid extracted from Scutellaria baicalensis Georgi (Lamiaceae), has been shown to exert therapeutic effects on pulmonary fibrosis (PF). OBJECTIVE: To use serum metabolomics combined with biochemical and histopathological analyses to clarify anti-PF mechanisms of baicalin on metabolic pathways and the levels of potential biomarkers. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were randomly divided into the control, PF model, prednisolone acetate-treated (4.2 mg/kg/day) and baicalin-treated (25 and 100 mg/kg/day) groups. A rat model of PF was established using a tracheal injection of bleomycin, and the respective drugs were administered intragastrically for 4 weeks. Histomorphology of lung tissue was examined after H&E and Masson's trichrome staining. Biochemical indicators including SOD, MDA and HYP were measured. Serum-metabonomic analysis based on UPLC-Q-TOF/MS was used to clarify the changes in potential biomarkers among different groups of PF rats. RESULTS: Both doses of baicalin effectively alleviated bleomycin-induced pathological changes, and increased the levels of SOD (from 69.48 to 99.50 and 112.30, respectively), reduced the levels of MDA (from 10.91 to 5.0 and 7.53, respectively) and HYP (from 0.63 to 0.41 and 0.49, respectively). Forty-eight potential biomarkers associated with PF were identified. Meanwhile, the metabolic profiles and fluctuating metabolite levels were normalized or partially reversed after baicalin treatment. Furthermore, baicalin was found to improve PF potentially by the regulation of four key biomarkers involving taurine and hypotaurine metabolism, glutathione metabolism, and glycerophospholipid metabolism. CONCLUSIONS: These findings revealed the anti-fibrotic mechanisms of baicalin and it may be considered as an effective therapy for PF.

Incidence of and risk factors for new-onset deep venous thrombosis after intertrochanteric fracture surgery.

This study aimed to investigate the incidence of and risk factors for postoperative new-onset deep venous thrombosis (PNO-DVT) following intertrochanteric fracture surgery. Information on 1672 patients who underwent intertrochanteric fracture surgery at our hospital between January 2016 and December 2019 was extracted from a prospective hip fracture database. Demographic information, surgical data, and preoperative laboratory indices were analysed. Receiver operating characteristic curve analysis, univariate analyses and binary logistic regression analyses were performed. The incidences of postoperative deep venous thrombosis (DVT) and PNO-DVT in inpatients after intertrochanteric fracture surgery were 11.5% (202 of 1751 patients) and 7.4% (123 of 1672 patients), respectively. PNO-DVT accounted for 60.9% of postoperative DVT. Additionally, there were 20 cases of central thrombosis (16.3%), 82 cases of peripheral thrombosis (66.7%), and 21 cases of mixed thrombosis (17.1%). In addition, 82.1% of PNO-DVTs were diagnosed within 8 days after surgery. The multivariate analysis revealed that age > 70 years, duration of surgery (> 197 min), type of anaesthesia (general), and comorbidities (≥ 3) were independent risk factors for the development of PNO-DVT after intertrochanteric fracture surgery. This study demonstrated a high incidence of PNO-DVT in inpatients after intertrochanteric fracture surgery. Therefore, postoperative examination for DVT should be routinely conducted for patients.

Prevalence of Preoperative Lower Extremity Deep Vein Thrombosis in Bilateral Calcaneal Fractures.

There are no studies on epidemiologic characteristics of deep vein thrombosis (DVT), when specified at in patients with bilateral calcaneal fractures. This study aimed to address the preoperative DVT in bilateral calcaneal fractures. Between October 2014 and December 2018, adult patients presenting with bilateral calcaneal fractures and having preoperative Duplex ultrasound (DUS) of bilateral lower extremities for detection of DVT were included. Their medical data were collected, with regards to demographics, comorbidities, injury-related data and biomarkers. Baseline characteristics between patients with and without DVT were compared using bivariate tests. The further multivariate logistics regression analysis was conducted to identify independent factors associated with DVT. In total, 258 patients with bilateral calcaneal fractures were included, with 21 (8.1%) having preoperative DVT, diagnosed at 7.7 ± 4.2 days after injury. The prevalence rate of proximal DVT was 1.9% and of distal DVT was 6.2%. Thirty five thrombi were found, with 6 (17.1%) in proximal veins and 29 (82.9%) in distal veins. Nine patients had DVTs in multiple veins, and 2 patients had bilateral DVTs. The multivariate analyses showed history of allergy (odds ratio [OR] = 2.17), concurrent other fractures (OR = 4.53), prolonged time since injury (for each day, OR = 1.16), elevated plasma D-dimer level (≥1.73 vs <1.73 mg/L, OR = 3.74) and reduced albumin level (<34.2 g/L vs ≥34.2 g/L, OR = 2.92) were independent factors associated with DVT. Multiple factors were identified to be associated with DVT and greater consideration should be given to the use of pharmacologic prophylaxis in patients involving these factors, to reduce DVT occurrence.