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Hong-Xia Yu,1,* Guo-Shuai Lin,1,* Ji-Fan Zhang,2 Cong-Cong Wang,1 Xiang-Jun Long,1 Mao-Mao Zhao1 1Department of Infection, Yuhuangding Hospital, Yantai, People’s Republic of China; 2Department of Critical Care Medicine, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Mao Zhao, Department of Infection, Yuhuangding Hospital, No. 20 of Yuhuangding East Road, Zhifu District, Yantai, People’s Republic of China, Tel +86 13863872227, Fax +86 6240341, Email zhaomm295@126.comObjective: This study was designed to analyze the clinical characteristics, etiological characteristics, drug resistance, and empirical use of antibiotics for community-acquired pyogenic liver abscess (PLA) to provide a basis for rational and effective empirical treatment of PLA in the local area.Methods: The clinical data, etiological characteristics, drug resistance, and empirical anti-infective therapy schemes of 606 patients with PLA were collected and analyzed retrospectively.Results: The included patients were mainly males, with a male-to-female ratio of 1.3:1. The average age of the patients was 60.3 ± 14.1 years. The underlying diseases were diabetes and biliary tract disease, accounting for 38.7% and 22.3%, respectively. The main clinical manifestations were fever (92.9%), abdominal pain (44.7%), and nausea (33.3%). Imaging findings: the proportion of patients with a single lesion was 74.7%, and 67% of the patients had involvement in the right lobe of the liver. The main pathogen was Klebsiella pneumoniae accounted for 74.9% in blood culture and 84.1% in pus culture, mainly extended-spectrum β-lactamase. In 272 strains negative for extended-spectrum β-lactamase (ESBLs), 100% were resistant to ampicillin and less than 50% were sensitive to nitrofurantoin. Only 36 ESBL-positive strains had higher than 80% sensitivity to carbapenems, β-lactamase inhibitor compound, and amikacin. Patients treated with different treatment methods showed significantly different average length of hospital stay (14 [9– 21] vs 13 [8– 18]). Empirical anti-infective therapy: Beta-lactamase complex, carbapenems, cephalosporins, and quinolones were used in 280 (37.6%), 180 (29.7%), 180 (29.7%), and 147 (24.3%) patients, respectively.Conclusion: Patients with community-acquired PLA in this area are mainly males, and the underlying diseases are mainly diabetes and hepatobiliary system disease. The main clinical manifestation is fever, so patients with fever of unknown cause should pay attention to possible liver abscesses. Based on drug sensitivity tests, the empirical use of antibiotics is somewhat unreasonable.Keywords: liver abscess, Klebsiella pneumoniae, epidemiological, community

Guo-Shuai Lin,* Mao-Mao Zhao,* Xiao-Qing Li, Hong-Xia Yu Department of Infectious Disease, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, People’s Republic of China*The authors contributed equally to this workCorrespondence: Hong-Xia Yu, Department of Infectious Disease, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, People’s Republic of China, Tel +86 15053573266, Email yuhongxiag6d@163.comBackground: Infective endocarditis (IE) can be caused by a variety of pathogens. Endocarditis due to the Coxiella burnetii (C. burnetii) infection is common in patients with negative blood culture results and usually occurs in patients with previous valvular heart disease, impaired immune function, and during pregnancy. The diagnosis is difficult based on the conventional diagnostic method, and serious adverse outcomes may occur in the case of delayed diagnosis.Case Report: In the present study, a case of a 43-year-old male patient with previous valvular heart disease was reported. The patient was admitted with a diagnosis of IE, but the etiology was unclear. Accurate diagnosis and treatment were achieved by combining metagenomic next-generation sequencing (mNGS) with Q fever serological antibody assay.Conclusion: Metagenomic next-generation sequencing has been increasingly applied in clinical practice in recent years to detect the DNA or RNA in samples, and this could play a decisive role in the etiological diagnosis of some infectious diseases.Keywords: Q fever, endocarditis, diagnosis, metagenomic next-generation sequencing

Ming-Ming Zhao, Lin-Yang Ge, Liang-Feng Yang, Hai-Xia Zheng, Gang Chen, Li-Zheng Wu, Shao-Ming Shi, Nan Wang, Yan-Ping Hang Department of Respiratory and Critical Care Medicine, People’s Hospital of Gaochun, Nanjing 211300, People’s Republic of ChinaCorrespondence: Yan-Ping HangDepartment of Respiratory and Critical Care Medicine, People’s Hospital of Gaochun, No. 53, Maoshan Road, Nanjing 211300, People’s Republic of ChinaTel +86 25-57311232Email hangyanping4444@163.comBackground: Long non-coding RNA (lncRNA) is a key part of non-coding RNA, and more and more evidence has revealed that it plays a vital role in tumors. NEAT1 is a lncRNA discovered in the early stage. However, it is still unclear whether NEAT1 and miR-204 play a regulatory role in lung cancer (LC). This research aimed to determine the biological function of NEAT1/miR-204 in non-small cell lung cancer (NSCLC).Materials and Methods: In order to research the function of NEAT1 in NSCLC, RT-PCR, Western blot, luciferase assay and RNA immunoprecipitation assay were used to determine the relationship between NEAT1, miR-204 and NUAK1. CCK8 test, cell migration and invasion test were used to explore the influence of NEAT1 on proliferation and metastasis of LC cells. Tumor allotransplantation was used to detect the influence of NEAT1 on the growth of LC.Results: The results revealed that NEAT1 was obviously enhanced in LC cell lines. Further functional analysis showed that low expression of NEAT1 obviously suppressed the growth, migration and invasion of NSCLC and facilitated cell apoptosis. Determination of luciferase reporter gene revealed that miR-204 was the direct target of NEAT1 in LC. In addition, NUAK1 was called the direct target of miR-204, and miR-204/NUAK1 had saved the role of NEAT1 in NSCLC cells. Tumor allotransplantation experiments showed that knocking down NEAT1 could inhibit the growth of LC.Conclusion: In summary, our results showed that the down-regulation of NEAT1 in NSCLC inhibited its growth, migration and invasion through the miR-204/NUAK1 axis.Keywords: NEAT1, miR-204, NUAK1, non-small cell lung cancer

Introduction and objectives The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study. Methods Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis. Results The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group ( P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant ( P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls ( P = 0.013). Although not statistically significant ( P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 + and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.

This study aimed to explore advances in biomarkers related to anti-angiogenic therapy in patients with non-small cell lung cancer (NSCLC), thereby enhancing treatment selection, advancing personalized and precision medicine to improve treatment outcomes and patient survival rates. This article reviews key discoveries in predictive biomarkers for anti-angiogenic therapy in NSCLC in recent years, such as (1) liquid biopsy predictive biomarkers: studies have identified activated circulating endothelial cells (aCECs) via liquid biopsy as potential predictive biomarkers for the efficacy of anti-angiogenic therapy; (2) imaging biomarkers: advanced imaging technologies, such as dynamic contrast-enhanced integrated magnetic resonance positron emission tomography (MR-PET), are used to assess tumor angiogenesis in patients with NSCLC and evaluate the clinical efficacy of anti-angiogenic drugs; (3) genetic predictive biomarkers: research has explored polymorphisms of Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) and vascular endothelial growth factor-A (VEGF-A), as well as how plasma levels of VEGF-A can predict the outcomes and prognosis of patients with non-squamous NSCLC undergoing chemotherapy combined with bevacizumab. Despite progress in identifying biomarkers related to anti-angiogenic therapy, several challenges remain, including limitations in clinical trials, heterogeneity in NSCLC, and technical hurdles. Future research will require extensive clinical validation and in-depth mechanistic studies to fully exploit the potential of these biomarkers for personalized treatment.

We reported 5 patients with unilateral or bilateral tubal discontinuity between the ampulla and fimbria, occasionally detected through laparoscopy combined with hysteroscopy at the Reproductive Hospital Affiliated with Shandong University from 2017 to 2023. Three cases were observed to have this malformation on the left fallopian tube, 1 case on the right side, and 1 case bilaterally. None of these cases were combined with urological malformations. After surgery, there was 1 instance of postoperative delivery, 1 ongoing pregnancy, and 3 not yet conceived. The congenital ampulla and fimbria interruption of the fallopian tube may be independent of other significant deformities of reproductive or renal tracts. However, it can lead to hydrosalpinx and primary or secondary infertility. Surgical management options, such as salpingostomy, salpingectomy, and tubal ligation, have shown the potential to improve pregnancy outcomes.

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan–Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% ( P = .042), and the 3-year DFS rates were 70.4% and 47.4% ( P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS ( P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS ( P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients ( P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.

Objective: To compare the risk of death, tumor recurrence, metastasis, and disease progression in early-stage non-small cell lung cancer (NSCLC) patients treated with thoracoscopic surgery and stereotactic body radiotherapy (SBRT). Methods: Patients who underwent radical surgery and SBRT for NSCLC between April 2010 and November 2021 were retrospectively analyzed. Continuous and categorical variables were compared using the Mann–Whitney U and Chi-square test, respectively. Kaplan–Meier curves were used to evaluate the survival outcomes of each patient group. Cox proportional hazard regression analyses were performed to estimate the risk of death, tumor recurrence, metastasis, and disease progression. Results: A total of 167 patients were enrolled, of whom 75 and 92 underwent SBRT and surgery, respectively. The median follow-up was 45 months (range, 4-105 months). SBRT patients were observed to be significantly older (median, 76.0 vs 67.0 years; P

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) – related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy ( P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [ HR ] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 ( HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Facing the increasingly severe aging situation, China has started to implement the “integrated medical services and elderly care (IMSEC)” policy, which covers a variety of IMSEC models. However, there is currently little research on middle-aged and elderly people’s choice preference for these IMSEC models and their associated factors. Through the face-to-face questionnaire method, the choice preference of middle-aged and elderly people aged 45 years and over in Zhejiang Province, China, to the IMSEC model is explored. Through the multinomial logistic regression model, the influencing factors of choice preference are analyzed. A total of 1034 people are included in 2022. Their choice preference for the 4 major types of IMSEC models are Home IMSEC model (48.07%), Community IMSEC model (23.79%), Institutional IMSEC model (21.76%), and Internet Plus IMSEC model (6.38%). “C1. Home elderly care and contracted with a family doctor” is the most chosen subtype, accounting for 34.53%. The rural elderly are more likely to choose “Home IMSEC model” (OR(95%CI) = 2.977(1.343-6.601)). Elderly people with relatively large life care needs are more likely to choose “Institutional IMSEC model” (OR(95%CI) = 1.114(1.042-1.190)). Moreover, age, education, and self-reported health status are also influencing factors of choice preference. The government should focus on promoting the development of the “Home IMSEC model” and increase the promotion of “Internet Plus IMSEC model.” In addition, the life care service capacity and spiritual comfort capacity of IMSEC institutions, as well as the medical service capacity of the community, need to be enhanced.

Objective As monotherapy such as topotecan has reached a plateau of effectiveness, new second-line treatments based on experience have been used in clinical application. This study compared the efficacy and safety of different second-line treatments for advanced small-cell lung cancer (SCLC). Methods A total of 380 patients with advanced SCLC were screened selectively in the retrospective study. Adverse events and patient responses were assessed using Common Terminology Criteria for Adverse Events v5.0 and Response Evaluation Criteria for Solid Tumors v1.1. The progression-free survival (PFS) was estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test. Results In the platinum-resistant group, disease control rate (DCR) and median PFS (mPFS) were prolonged in the combination group versus single-agent group (DCR: 49.24% vs 24.39%, P = .004; mPFS: 3.73 vs 1.90 months, P

Objective: It is not well determined whether liver metastasis is a prognostic factor for survival of metastatic non-small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitors (ICIs). We compared the efficacy of ICIs in patients with NSCLC with or without liver metastases, aiming to evaluate the impact of liver metastasis on survival of NSCLC. Methods: We systematically searched Pubmed, Embase, and the Cochrane library databases for randomized controlled trials (RCTs) on the efficacy of ICIs in the treatment of NSCLC patients with or without liver metastases. The duration of this search was from January 1, 2000 to June 1, 2022. The reviewers screened the literature, extracted data and conducted quality assessment, and used RevMan 5.4 software and Stata 14 to perform analyses. Results: A total of 17 RCTs were included, published from 2019 to 2022. For NSCLC patients with liver metastases, the risk of disease progression decreased by 36% (HR = 0.64; 95% CI: 0.55-0.75; P

Introduction Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor response to chemotherapy and an extremely poor prognosis. Recent studies have revealed that phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) can inhibit the growth of various cancers. Therefore, the current study was conducted to investigate the antitumor effects of LHPP in PDAC and to explore its mechanism using proteomics analysis. Methods and Results Immunohistochemical analysis of clinical samples demonstrated that LHPP expression levels were lower in tumor tissues compared to adjacent nontumor tissues. Moreover, multivariate COX regression analysis showed that LHPP expression level was an independent prognostic factor for the patients with PDAC. Patients with high LHPP expression had a better prognosis. The lentiviral vectors for normal control (NC), LHPP knockdown (KD), and LHPP overexpression (OE) were infected with BxPC-3 and PANC-1 cell lines. Cell counting kit-8 assay, Transwell assay, and flow cytometry analyses showed that LHPP overexpression significantly inhibited the cell viability, migration, and proliferation of BxPC-3 and PANC-1 cells. Moreover, xenograft tumor model demonstrated that LHPP overexpression inhibited xenograft tumor growth in vivo. Subsequently, proteins with significantly altered expression in BxPC-3 cells after lentivirus infection were detected using proteomics analyses. Interestingly, compared to the NC group, the expression of Syndecan 1 (SDC1) was significantly upregulated in the KD group, while that of S100P was significantly downregulated in the OE group. Conclusion LHPP might emerge as an important target for delaying the advancement of PDAC, thereby providing a novel therapeutic approach for the treatment of PDAC.

Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

Epidermal growth factor receptor (EGFR) mutations are common driver genes in nonsmall-cell lung cancer and have different sensitivities to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). EGFR is divided into classic mutations and rare mutations. Classic mutations are well known, but the understanding of rare mutations is not sufficient. In this article, we summarize the clinical research and treatment progress of rare mutations for different EGFR-TKIs and provide a basis for clinical treatment decisions.

Background ARID3B (AT-rich interaction domain 3B) has been demonstrated to be associated with the progression and patient prognosis of several human tumors. We conducted the present study to investigate the biological behavior and clinical relevance of ARID3B in gastric cancer (GC). Methods Detection of the expression level in GC tissues and cell lines were performed by Western blot and immunohistochemistry. We also retrospectively analyzed the correlation of ARID3B with clinicopathological characteristics and patient prognosis in gastric cancer. The biological functions of ARID3B in GC cells were further explored by transwell migration assays, wound healing assays and cell proliferation assay. Results The present study suggested that the expression of ARID3B was significantly lower in GC tissues than in adjacent normal tissues. IHC staining in tissues of 406 GC patients from training and validation sets verified that ARID3B over-expression correlated with clinicopathological features, such as degree of differentiation and clinical stage. Meanwhile, ARID3B was proved to be an independent prognostic factor for GC prognosis. Furthermore, over-expression of ARID3B suppressed proliferation in GC cells according CCK8 assay. We found that over-expression of ARID3B inhibited GC cell migration by transwell assay and wound healing assay. Furthermore, EMT markers were detected in ARID3B over-expression GC cells, which showed that ARID3B may inhibit metastasis of GC cells. Conclusion Our results firstly revealed that the expression level of ARID3B was closely correlated with clinicopathological features and may serve as an independent prognostic factor for GC patients. More importantly, ARID3B could suppress GC progression, including cell proliferation, migration and metastasis.

Background: Axillary lymph node (ALN) metastatic load is very important in the diagnosis and treatment of breast cancer (BC). We aimed to construct a model for predicting ALN metastatic load using deep learning radiomics (DLR) techniques based on the preoperative ultrasound and clinicopathologic information of patients with stage T 1-2 BC. Methods: Retrospective analysis was performed on 176 patients with pathologically confirmed BC in our hospital from February 2018 to April 2020. ALN metastases were divided into a low-load group (< 3 lymph node metastases) and a high-load group (≥ 3 lymph node metastases) according to pathological results. Pyradiomics and pre-trained ResNet50 were used to extract radiomics and deep learning features, respectively. Independent sample T-test, random forest recursive elimination, and Lasso were used to screen the features to construct the deep learning radiomics signature (DLRS). Based on single/multivariate logistic regression analysis results, a DLR nomogram (DLRN) model was constructed by combining valuable clinical features and DLRS. Results: The DLRS was composed of 3 radiomics features and 14 deep learning features and combined with the maximum diameter of lesions to construct the DLRN. The AUCs of the training and test sets were 0.900 (95% CI: 0.853-0.931) and 0.821 (95% CI: 0.769-0.868), respectively. The calibration curve and Hosmer–Lemeshow test confirmed that the DLRN model has a good consistency. The decision curve also confirmed its good clinical practicality. Conclusion: Ultrasound-based DLRN has an excellent performance in predicting ALN load in patients with BC.

Abstract. Background:. There are still controversies about the optimal anesthesia protocol for patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). The aim of this study was to explore the effect of supraglottic airway device (SAD) versus endotracheal intubation (EI) general anesthesia on clinical and angiographic outcomes in patients with AIS undergoing MT. Methods:. One hundred sixteen patients with large-vessel occlusion stroke were randomized to receive either SAD or EI general anesthesia. The primary outcome was the rate of occurrence of >20% fall in mean arterial pressure (MAP). Secondary outcomes included hemodynamics, successful recanalization, time metrics, satisfaction score of neurointerventionalist, number of passes performed, the conversion rate from SAD to EI, the National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT Score before and 24 hours after surgery, length of stay in the stroke unit and hospital, complications and functional independence at discharge, and 90 days after stroke. Results:. Both the lowest systolic blood pressure and lowest diastolic blood pressure were significantly lower in the EI group (P = .001). The consumption of vasoactive agents, the occurrence of >20% reduction in MAP and time spent with >20% fall in MAP were significantly higher in the EI group (P

Objective To establish a predictive model for poor prognosis after incomplete revascularization (ICR) in patients with multivessel coronary artery disease (MVD). Methods Clinical data of 757 patients with MVD and ICR after percutaneous coronary intervention (PCI) in the Affiliated Hospital of Chengde Medical University from January 2020 to August 2021 were retrospectively collected. The least absolute shrinkage and selection operator regression method was used to screen variables, and multivariate logistic regression was used to establish a predictive model. An independent cohort was used to validate the model. The C-statistic was used to verify and evaluate the discriminative ability of the model; the calibration curve was drawn, and the decision curve analysis (DCA) was performed to evaluate the calibration degree, the clinical net benefit, and the practicability of the model. Results The predictive factors included female, age, unconjugated bilirubin, uric acid, low-density lipoprotein, hyperglycemia, total occlusion, and severe tortuosity lesion on coronary angiography. The C-statistic of the training and validation sets were 0.628 and 0.745, respectively. The statistical value of the Hosmer–Lemeshow test for the calibration curve of the training and validation sets were 5.27(P = 0.873) and 6.27 (P = 0.792), respectively. DCA showed that the model was clinically applicable when the predicted probability value of major adverse cardiovascular events(MACEs) ranged from 0.07 to 0.68. Conclusions We established a predictive model for poor prognosis after ICR in patients with MVD. The predictive and calibration ability and the clinical net benefit of the predictive model were good, indicating that it can be used as an effective tool for the early prediction of poor prognosis after ICR in patients with MVD.

Background: Naples Prognostic Score (NPS) is a novel score based on inflammatory-nutritional indicators. We aimed to analyze the prognostic value of the Naples Prognostic Score in non-small cell lung cancer (NSCLC) patients following surgery. Methods: A total of 319 NSCLCpatients following surgery were analyzed in the retrospective cohort study. We analyzed the predictive value of Naples Prognostic Score for overall survival and recurrence-free survival in postoperative non-small cell lung cancer patients by using Kaplan-Meier survival curves and multivariate Cox regression analysis. At the same time, the time-dependent ROC and the area under curves were also created to compare the accuracy of different scoring systems. Results: According to NPS, we divided all patients into 3 groups，120 patients were divided into group 0, 161 patients were divided into group 1, and 38 patients were divided into group 2. The median survival time for all patients is 32 months, and the median survival times for different groups were 35 months, 31 months, and 28 months, respectively. The overall survival and recurrence-free survival survival curves of different groups were significantly different (both P < .05), and patients in the higher NPS groups had a disappointing prognosis. NPS may be an independent prognostic factor for overall survival and recurrence-free survival, according to the results of multivariate analysis (both P

Background and aims Novel pro- and anti-inflammatory adipocytokines affect inflammation, energy metabolism, and insulin signaling. However, their role in acute coronary syndrome (ACS) development is unclear. We evaluated the diagnostic and risk predictive value of such adipocytokines for ACS. Methods We enrolled 168 consecutive inpatients with suspected ACS and detected serum PLIN1, PLIN2, PLIN5, CTRP6, CTRP7, CTRP11, WISP1, FAM19A5, TNF-α, and adiponectin levels. Multivariate logistic regression analysis and Spearman's test were used to assess risk factors for ACS and correlations between serum adipocytokines and continuous variables, respectively. Results Serum levels of the adipocytokines differed between ACS and Non-ACS groups ( p

ABSTRACT: Introduction: Female sexual dysfunction (FSD) seriously affects the quality of life of women. However, most women do not have access to effective treatment. Aim: This study aimed to determine the feasibility and effectiveness of the use of acupuncture in FSD treatment based on existing clear acupuncture protocol and experience-supported face-to-face therapy. Methods: A retrospective analysis was performed on 24 patients with FSD who received acupuncture from October 2018 to February 2022. The Chinese version of the female sexual function index , subjective sensation, sexual desire, sexual arousal, vaginal lubrication, orgasm, sexual satisfaction, and dyspareunia scores were compared before and after the treatment in all 24 patients. Main Outcome Measure: A specific female sexual function index questionnaire was used to assess changes in female sexual function before and after the acupuncture treatment. Results: In this study, the overall treatment improvement rate of FSD was 100%. The Chinese version of the female sexual function index total score, sexual desire score, sexual arousal score, vaginal lubrication score, orgasm score, sexual satisfaction score, and dyspareunia score during intercourse were significantly different before and after the treatment (P < .05). Consequently, participants reported high levels of satisfaction with acupuncture. This study indicates that acupuncture could be a new and effective technique for treating FSD. The main advantages of this study are its design and efficacy in treating FSD. To the best of our knowledge, this is the first study to evaluate the efficacy of acupuncture in the treatment of FSD using the female sexual function index scale from 6 dimensions. The second advantage is that the method used (ie, the nonpharmacological method) is simple, readily available, highly safe with few side effects, and relatively inexpensive with high patient satisfaction. However, limitations include small sample size and lack of further detailed grouping, pre and post control study of patients, blank control group, and pre and post control study of sex hormones. Conclusion: Acupuncture can effectively treat FSD from all dimensions with high safety, good satisfaction, and definite curative effect, and thus, it is worthy of promotion and application.Zhang JT, Ma L, Gong X, et al. Clinical Study on the Use of Acupuncture for the Treatment of Female Sexual Dysfunction: A Pilot Study. Sex Med 2022;XX:XXXXXX.

Objectives: Research on the role of mast cells (MCs) in cervical tumor immunity is more limited. Therefore, our study aimed to evaluate the prognostic value of MCs and their correlation with the immune microenvironment of cervical carcinoma (CC). Methods: The Cancer Genome Atlas (TCGA) data was utilized to obtain the degree of immune infiltration of MCs in CC. Meanwhile, this study retrospectively collected patient clinical characteristic data and tissue specimens to further verify the relevant conclusions. Mast cell density (MCD) was measured by the CIBERSORT algorithm in TCGA data and immunohistochemical staining of tryptase in CC tissues. Finally, differentially expressed genes (DEGs) of TCGA data were performed using “limma” packages and key gene modules were identified using the MCODE application in Cytoscape. Results: The results showed MCs were diffusely distributed in CC tissues. Moreover, we found that low tumor-infiltrating MCD was beneficial for overall survival (OS) in the TCGA cohort. Consistent conclusions were also obtained in a clinical cohort. In addition, a total of 305 DEGs were analyzed between the high tumor-infiltrating MCD and low tumor-infiltrating MCD group. Seven key modules, a total of 34 genes, were screened through the MCODE plug-in, which was mainly related to inflammatory response and immune response and closely correlated with cytokines including CSF2, CCL20, IL1A, IL1B, and CXCL8. Conclusion: In short, high tumor-infiltration MCs in CC tissue was associated with worse OS in patients. Furthermore, MCs were closely related to cytokines in the tumor microenvironment, suggesting that they collectively played a role in the immune response of the tumor. Therefore, MCD may be a potential prognostic indicator and immunotherapy target of CC.

Abstract. Rationale:. For locally advanced non-small cell lung cancer (NSCLC), the neoadjuvant therapy strategy of preoperative nivolumab combined with chemotherapy has great potential, especially for locally advanced NSCLC which are initially unresectable. They may be cured after neoadjuvant immunotherapy, and this may become a new direction of treatment. We hope that this representative medical record and literature review can provide some assistance for clinicians using immune checkpoint inhibitors to treat lung cancer. Patient concerns:. A 50-year-old male patient was admitted to Zhongshan Hospital of Traditional Chinese Medicine on April 27, 2020 due to “coughing for more than one month.”. The patient had nothing of note in either his medical history or that of his family, and no history of smoking. Diagnosis:. The diagnosis was cT4N2M0IIIB stage right lower lung NSCLC with right hilar and mediastinal lymph node metastasis. The stage was inoperable stage IIIB NSCLC, but the patient had a strong willingness for doing surgery. Interventions:. The patient received 3 rounds of the neoadjuvant nivolumab therapy combined with TP (paclitaxel plus cisplatin) regimen, on 5-14-21, 06-07-21 and 07-07-21. Outcomes:. The tumor's area shrunk. Then the patient underwent thoracoscopic radical resection of the cancer in the right upper lung and postoperative pathology achieved pathological complete response (pCR) Lessons:. In this case, combined with the wishes of the patient and the latest research results, we confirmed pCR by radical surgery after 3 rounds of the neoadjuvant nivolumab therapy combined with chemotherapy. This may be a modality to cure more lung cancer patients in the future.

Abstract. Hepatitis B virus infection is a major global public health concern. This study explored the epidemic characteristics and tendency of hepatitis B in 31 provinces of mainland China, constructed a SARIMA model for prediction, and provided corresponding preventive measures. Monthly hepatitis B case data from mainland China from 2013 to 2020 were obtained from the website of the National Health Commission of the People's Republic of China. Monthly data from 2013 to 2020 were used to build the SARIMA model and data from 2021 were used to test the model. Between 2013 and 2020, 9,177,313 hepatitis B cases were reported in mainland China. SARIMA(1,0,0)(0,1,1)12 was the optimal model and its residual was white noise. It was used to predict the number of hepatitis B cases from January to December 2021, and the predicted values for 2021 were within the 95% confidence interval. This study suggests that the SARIMA model simulated well based on epidemiological trends of hepatitis B in mainland China. The SARIMA model is a feasible tool for monitoring hepatitis B virus infections in mainland China.

Abstract. Background:. Little is known about the renoprotective effects of statins on the regulation of urinary oxidative stress markers and proteinuria in patients with diabetic nephropathy. Therefore, we conducted this protocol of systematic review and meta-analysis to evaluate the role of statins in patients with early diabetic nephropathy. Methods:. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines to conduct this study. The electronic databases EMBASE, PUBMED, CINAHL, and Web of Science will be searched from the earliest available time to July 2022. The population is defined as participants with early diabetic nephropathy. The Intervention groups are given any one of the statins, such as simvastatin or rosuvastatin. The control groups are treated with angiotensin-converting enzyme inhibitor or placebo alone. The primary outcome is estimated glomerular filtration rate; secondary outcome is serological indicators including triglyceride, cholesterol, C-reactive protein, and complications. The Jadad scale will be used to assess the methodological quality of each study included in this meta-analysis. Result & Conclusion:. We hypothesized that statins would have a positive renoprotective effect in such patients. OSF registration number:. 10.17605/OSF.IO/ESMWR.

Abstract. Background:. For the rectal cancer

Secondary failure of platelet recovery (SFPR) is a life-threatening complication that may affect up to 20% of patients after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, to evaluate the efficacy of recombinant human thrombopoietin (rhTPO), we retrospectively analyzed 29 patients who received continuous rhTPO for the treatment of SFPR. Overall response and complete response were observed in 24 (82.8%) patients and 10 (34.5%) patients, at a median time of 21.5 days (range, 3-41 days) and 39.5 days (range, 7-53 days) after initiation of rhTPO treatment, respectively. Among the responders, the probability of keeping overall response and complete response at 1 year after response was 77.3% and 80.0%, respectively. In multivariate analysis, higher CD34 + cells (≥3 × 10 6 /kg) infused during HSCT (HR: 7.22, 95% CI: 1.53-34.04, P = 0.01) and decreased ferritin after rhTPO treatment (HR: 6.16, 95% CI: 1.18-32.15, P = 0.03) were indicated to associate with complete response to rhTPO. Importantly, rhTPO was well tolerated in all patients without side effects urging withdrawal and clinical intervention. The results of this study suggest that rhTPO may be a safe and effective treatment for SFPR.

Chronic constrictive pericarditis (CCP) is one of the common causes of cardiogenic cirrhosis; it is rare for a patient to have both CCP and recurrent black stool, so we consider that CCP causes cardiogenic cirrhosis. Cardiogenic cirrhosis caused portal hypertension which then resulted in gastrointestinal bleeding. Herein, we report a case of a 40-year-old Chinese woman suffering from CCP who had upper gastrointestinal bleed and had to undergo emergency surgery. Two years after the emergency surgery, multiple reexaminations showed significantly improved cardiac functions, hemoglobin, and WBC levels and gastrointestinal functions.

Purpose: The objective of this retrospective study is to evaluate the efficacy and safety of hypofractionated simultaneous integrated boost radiotherapy for early breast cancer patients undergoing breast-conserving surgery. Methods: A total of 185 women with early breast cancer undergoing breast-conserving surgery were retrospectively divided into hypofractionated simultaneous integrated boost group and conventional fractionation group. Hypofractionated simultaneous integrated boost included 104 patients and the dose of whole-breast radiation reached 42.56 Gy in 16 fractions and simultaneously tumor bed boost to 48 Gy in 16 fractions, which course of radiotherapy was 22 days. The 81 patients of the conventional fractionation group received whole breast radiation to 50 Gy in 25 fractions and followed by tumor bed boost to 10 Gy in 5 fractions, which course of radiotherapy was 40 days. Clinical information including patients’ characteristics, skin toxicity, myelosuppression, radiation pneumonia, and cosmetic effects was recorded to analyze the influence of age, chemotherapy, position, and breast volume on the results of radiotherapy. Results: Hypofractionated simultaneous integrated boost group had no case of recurrence after a median follow-up of 25.6 months (9-47 months)) as compared with 2 after a median follow-up of 33.4 months (25-45 months) in the conventional fractionation group. The 2 groups had similar results in skin toxicity, cosmetic outcomes, and radiation pneumonia. In terms of myelosuppression, grade 1, grade 2, and grade 3 of myelosuppression in the hypofractionated simultaneous integrated boost group accounted for 16.7%, 12.3%, and 3.5% as compared with 30.0%, 21.1%, and 12.3% of the conventional fractionation group, respectively ( P = .000). Conclusions: HF-SIB RT is a considerable option in patients after breast-conserving surgery with a lower degree of myelosuppression and shorter treatment time.

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) serve important roles in the development of OSCC. The purpose of this study was to investigate the biological function and underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) in OSCC. RT-qPCR was performed to analyze the HOXA-AS2 expressions in human immortalized oral epithelial cell (HIOEC) line, human OSCC cell lines, and plasma. The expression of HOXA-AS2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in Tca-8113 cells were knocked down or overexpressed by transfection with shRNA-HOXA-AS2 or pcDNA-EZH2, respectively. The interaction between HOXA-AS2 and EZH2 was validated by RNA immunoprecipitation assay. In addition, cell proliferation was assessed by CCK-8 and EdU assays. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion were detected using wound healing and Transwell assays, respectively. Apoptosis was detected by TUNEL staining. The protein expression levels of cell cycle and apoptosis-related proteins were measured by western blot analysis. Compared with HIOEC cells, HOXA-AS2 expression in OSCC cells was upregulated. HOXA-AS2 knockdown significantly inhibited Tca-8113 cell proliferation, blocked the cell cycle by arresting cells in the G0/G1 phase, promoted apoptosis, and suppressed migration and invasion. In addition, HOXA-AS2 was predicted to directly target EZH2 and positively regulate EZH2 expression. EZH2 overexpression could reverse the inhibitory effect of HOXA-AS2 knockdown on the proliferation, migration, and invasion of Tca-8113 cells. In summary, the findings suggested that HOXA-AS2 may inhibit cell proliferation, invasion, and migration, induce cell cycle arrest in the G0/G1 phase, and increase cell apoptosis by targeting EZH2. The research indicated that HOXA-AS2/EZH2 axis may play a key role in the development of OSCC.

Background: Anti-programmed cell death protein-1 immunotherapy has been approved as a new treatment option for advanced hepatocellular carcinoma (HCC) based on the promising results of several studies. Methods: This retrospective study included 71 patients with advanced HCC treated with anti-programmed cell death protein-1 immunotherapy between June 1, 2017 and September 30, 2020 at the First Affiliated Hospital of Anhui Medical University. Responses to pulmonary metastases were evaluated. Results: The median follow-up duration was 7.73 months (95% confidence interval (CI), 4.48-10.98). Of 71 patients, the overall response rate (ORR) and disease control rate (DCR) were 32% (23/71) and 73% (52/71), respectively. The median progression-free survival (PFS) and overall survival (OS) were 4.90 (95% CI, 2.71-7.09) and 20.23 (95% CI, 6.87-33.59) months, respectively. Forty-two patients had HCC pulmonary metastases, whereas 29 did not have pulmonary metastasis. No significant differences were observed in the ORR (38% [16/42] vs. 24% [7/29], P = 0.22) and DCR (74% [31/42] vs. 72% [21/29], P = 0.90) between groups. In patients with pulmonary metastases, the median disease control duration of pulmonary lesions was significantly longer than extrapulmonary lesions (Not Reached vs. 12.37 months, P = 0.048). Pulmonary metastases were not associated with an increased incidence of adverse events (67% vs. 62%, P = 0.69). Conclusions: Anti-programmed cell death protein-1 immunotherapy showed promising efficacy and safety in patients with advanced HCC, with good responses observed in pulmonary metastases. The mechanism underlying the differences in responses between pulmonary and extrapulmonary metastases requires further investigation.

In recent years, a rising number of studies have confirmed that microRNA (miRNA) plays a prominent role in the early diagnosis and prognostic value assessment of cardiovascular diseases. The current study was conducted to examine the expression of miR-675-3p in atherosclerosis (AS) patients and to evaluate its clinical diagnosis and prognostic value. 110 AS patients and 70 healthy controls were included in the study. Serum miR-675-3p levels were detected by quantitative real-time PCR (qRT-PCR). The clinical diagnostic significance of serum miR-675-3p in AS patients were investigated by the receiver operating characteristic (ROC) curve. The correlation between miRNA and carotid intima-media thickness (CIMT) was analyzed by the Spearman correlation coefficient. The prognostic significance of serum miR-675-3p was evaluated by the Kaplan-Meier method and Cox regression analysis. The patient’s serum miR-675-3p was significantly increased than the healthy individuals ( P < 0.05). An increase of carotid intima-media thickness (CIMT) was positively correlated with the promotion of serum miR-675-3p levels. The area under the ROC curve (AUC) was 0.918, with high sensitivity and specificity. miR-675-3p is a key independent predictor of cardiovascular adverse events in AS patients (HR = 5.375, 95%CI = 1.590-18.170, P = 0.007), and patients with elevated miR-675-3p were more likely to have cardiovascular adverse events (log-rank P = 0.030). Increased miR-675-3p can be used as a potential marker for the diagnosis of AS, and was associated with the poor prognosis of AS.

Background: Some evidence supports that the significance of inflammation is linked to a variety of tumors, including thyroid carcinoma. This work measured the preoperative serum inflammatory factors in thyroid tumors to explore their diagnostic values. Material and Methods: Altogether 487 thyroid tumor patients were recruited, their neutrophil (NE), white blood cell (WBC), monocyte (MO), lymphocyte (LY), platelet (PLT) counts, together with monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), interleukin (IL)-1β, IL-2, IL-27, and tumor necrosis factor-α (TNF-α) levels were compared with controls. Afterward, the receiver operating characteristics (ROC) curve was plotted to further evaluate the values of these inflammatory markers in diagnosis. In addition, multivariable regression analysis was conducted to analyze all these inflammatory factors. Results: Serum PLR, NLR, CRP, and IL-27 levels in thyroid adenoma (TA) and differentiated thyroid carcinoma (DTC) patients were higher than those in controls. Only the areas under the curve (AUC) for CRP and IL-27 were significant in the context of DTC. Besides, the AUC for IL-27 was significant between papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) groups, while that for NLR+PLR was also significant between PTC and healthy control groups. According to multivariable logistic regression analysis, IL-27 and CRP were associated with DTC. Conclusions: Inflammation plays an important role in TA and DTC progression. Preoperative IL-27 and CRP levels help to differentially diagnose DTC. Moreover, IL-27 assists in distinguishing FTC from PTC, and NLR+PLR is important for the differential diagnosis of PTC.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Investigating the underlying molecular mechanism is essential for the treatment and prognosis of HCC. Emerging evidence suggests that microRNAs (miRNAs) play pivotal roles in cancer progression. Down-regulation of miR-936 has been found in several cancers, which serves as a tumor suppressor to inhibit the development of cancers. However, the clinical significance and functional roles of miR-936 in HCC have not been determined. To explore this, the expression of miR-936 in HCC tissues and cells was detected by RT-qPCR. Cell Counting Kit-8 (CCK-8) assay, cell migration and cell cycle analysis were performed to evaluate the effects of miR-936 on the growth of HCC cells. The targets of miR-936 were predicted using the miRDB database and confirmed by luciferase reporter experiments. The protein expression of targets was determined by western blot. The results showed that miR-936 was significantly decreased in HCC tissues and cell lines. Low expression of miR-936 was associated with the advance progression and poor survival of HCC patients (P = 0.0036). Functional study revealed that overexpression of miR-936 inhibited the proliferation, migration (decreased to ∼0.26 fold) and induced cell cycle arrested in G 1 phase (from 35.3% to 44.7%) of HCC cells. Additionally, miR-936 targeted the 3′-untranslated region (UTR) of jagged-1 (JAG1) and reduced the expression of JAG1 (decreased to ∼0.35 fold). JAG1 was found to be up-regulated in HCC tissues and was inversely correlated with the expression of miR-936 (Pearson r = −0.4633; P = 0.0007). The anti-cancer effects of miR-936 on the proliferation of HCC cells were partially reversed by the rescue of JAG1. Therefore, these results suggested that miR-936 might be a potential target for HCC treatment.

Background: As a common pathological type of lung cancer, lung adenocarcinoma (LUAD) is mainly treated by surgery, chemotherapy, targeted therapy and radiotherapy. Although a relatively mature treatment system has been established, there are few studies on the microenvironment of LUAD. Material and Methods: The immune and stromal scores of patients from the LUAD cohort in the TCGA database were obtained by using ESTIMATE. The relationship of immune and stromal scores with the clinicopathological characteristics and overall survival of LUAD patients was assessed by R. GO, KEGG and Cox regression analyses were employed to analyze intersecting genes and to identify reliable prognostic markers. The identified genes were also analyzed in the GEPIA database to assess their correlations with survival, and these relationships were verified with the Kaplan-Meier Plotter database. Results: The immune score was related to the survival time and tumor topography of LUAD patients. There was a significant correlation between stromal score and tumor metastasis. Through multivariate analysis, stage (HR = 1.640, 95% CI = 1.019-2.642, P = 0.042) and risk score (HR = 1.036, 95% CI = 1.026-1.046, P < 0.001). The genes (ARHGAP15, BTLA, CASS4, CLECL1, FAM129C, STAP1, TESPA1, and S100P) showed credible prognostic value in LUAD patients in TCGA through GEPIA database online analysis and verification in the Kaplan-Meier plotter database. Conclusions: In the microenvironment of lung adenocarcinoma, the differentially expressed genes screened by immune score and stromal score have certain value in evaluating the survival/prognosis of patients, as well as the invasion and progression of tumors.

To evaluate variations in coagulation, fibrinolysis and endothelial marker expression in cirrhotic patients and to explore their clinical value and predictive performance in cirrhotic patients with or without portal vein thrombosis (PVT), we performed a case-control study with 175 cirrhotic patients and 50 healthy individuals. 99 patients had PVT and another 76 patients did not. All participants were evaluated for plasma levels of conventional hemostatic markers. Thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (t-PAIC), von Willebrand factor antigen (vWF: Ag) and coagulation factor Ⅷ (FⅧ: c) were also assessed and the ratio of TAT/t-PAIC was calculated. We analyzed differences in these biomarkers among the three groups and constructed receiver operating characteristic (ROC) curves. Patients with PVT exhibited significantly higher TAT and TAT/t-PAIC than cirrhotic patients without PVT (both P < 0.001). Areas under the curve (AUC) of ROC analyses for TAT and TAT/t-PAIC were 0.68 and 0.66, the cut-off levels were 1.55 ng/ml and 0.46, with sensitivities and specificities of 78.79% and 51.32% regarding TAT, 39.8% and 90.79% regarding TAT/t-PAIC. Levels of FⅧ: c and vWF: Ag in patients with PVT were significantly lower than those without PVT (p = 0.026 and p = 0.027, respectively). The AUC ROC , cut-off level, sensitivity and specificity of FⅧ: c were 0.64, 111.1%, 66.67% and 60%, respectively. For vWF: Ag they were 0.61, 429%, 89.66% and 38.71%, respectively. Cirrhotic patients have disorders of coagulation, fibrinolysis and the endothelial system. TAT, TAT/t-PAIC, FⅧ: c and vWF: Ag can be used as potential biomarkers for predicting PVT in cirrhotic patients.

Osteosarcoma (OS) is a cancerous tumor in a bone. We aimed to identify the critical genes involved in OS progression, and then try to elucidate the molecular mechanisms of this disease. The microarray data of GSE32395 was used for the present study. We analyzed differentially expressed genes (DEGs) in OS cells compared with control group by Student’s t-test. The significant enriched gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways were analyzed for upregulated genes and downregulated genes, respectively. In addition, a protein-protein interaction (PPI) network was constructed. GO and KEGG enrichment analyses were conducted for genes in the PPI network. In total, 183 DEGs, including 100 upregulated DEGs and 83 downregulated DEGs were screened. The upregulated DEGs were significantly enriched in 2 KEGG pathways, such as “Glycosaminoglycan biosynthesis-chondroitin sulfate” and the downregulated DEGs were significantly enriched in 12 pathways, including “cell adhesion molecules,” “pentose phosphate pathway” and “allograft rejection.” GO enrichment analysis indicated that the upregulated DEGs were significantly involved in biological process, such as “multicellular organismal metabolic process” and “limb morphogenesis,” while the downregulated DEGs were significantly enriched in biological process, such as “Positive regulation of pathway-restricted SMAD protein phosphorylation.” The PPI network included 84 interactions and 51 nodes. The “glycosaminoglycan biosynthesis-chondroitin sulfate pathway,” “microtubule motor activityfunction,” and “regulation of mitosis process” were significantly enriched by genes in PPI network. In particular, CENPE, PRC1, TTK, and PLK4 had higher degrees in the PPI network. The interactions between TTK and PLK4 as well as CENPE and PRC1 may involve in the OS development. These 4 genes might be possible biomarkers for the treatment and diagnosis of OS.

Purposes: Minichromosome maintenance (MCM) proteins play an important role in replication and cell cycle progression. Even so, their expression and prognostic roles in cancer remain controversial. Methods: To address this issue, the study investigated the roles of MCMs in the prognosis of GC by using ONCOMINE, GEPIA2, UALCAN, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, and DAVID databases. Results: Over expressions of mRNA and cell lines were found in all members of the MCM family, and MCMs were found to be significantly associated with pathological tumor grades in GC patients. Besides, higher mRNA expressions of MCM1/5/7 were found to be significantly associated with shorter overall survival (OS) and progression-free survival (FP) in GC patients, while higher mRNA expression of MCM4/6/9 were connected with favorable OS and FP. Moreover, a high mutation rate of MCMs (68%) was also observed in GC patients. Conclusions: The results indicated that MCM1/5/7 were potential targets of precision therapy for patients with GC. And MCM4/6/9 were new biomarkers for the prognosis of GC. The results of the study will contribute to supplement the existing knowledge, and help to explore therapeutic targets and enhance the accuracy of prognosis for patients with GC.

Background: In the present study, we aimed to find an effective target for the treatment of tongue cancer using gene chip screening and signal pathway research. Methods: We used microarray screening and gene expression profile analyses to find important differentially expressed genes in tongue cancer. We constructed a protein-protein interaction network, and used enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes to screen for important genes. We then silenced the genes of interest in SCC154 cells to study the relationship with the Phosphatidylinositol 3-kinase/Akt signal pathway. Western blot analyses, the 3-(4,5Dimethylthiazol-yl)-2,5Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) test, and immunofluorescence assays were used to compare the expression levels of Phosphatidylinositol 3-kinase/Akt signal pathway-related proteins, cell viability, and cell proliferation ability in normal SCC154 cells, Si-RNA SCC154 cells, and gene-silenced SCC154 cells. The scratch test, Transwell test, and western blotting were used to determine migration, invasion, and carcinogenesis. Results: Using GSE9844, GSE13601, and GSE31056 gene chips, we identified 93 upregulated genes and 76 downregulated genes in tongue cancer. Using the protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we further identified 47 differentially expressed genes. Using Kaplan-Meier plotter online tools, we also identified 3 genes (SPP1, Recombinant Human Secreted Phosphoprotein 1; PLAU, plasminogen activator urinary; and APP, amyloid precursor protein). Compared with normal SCC154 cells and Si-RNA control SCC154 cells, the expressions of Phosphatidylinositol 3-kinase/Akt pathway proteins in si-SPP1 SCC154 cells were significantly decreased (*P < 0.05), and the protein activities and proliferation abilities were also significantly decreased (*P < 0.05), while the migration ability, invasion ability, and cancer forming ability were significantly increased (*P < 0.05). Conclusion: Inhibition of the SPP1 gene may have a therapeutic effect on tongue cancer, and could be an effective target for the treatment of this disorder.

The aberrant expression of microRNA is an important regulator in the tumorigenesis of non-small cell lung cancer. In this study, we found that miR-499a-5p was notably downregulated in non-small cell lung cancer tissues and cell lines. Decreased miR-499a-5p expression was associated with larger tumor size and higher TNM stage. Non-small cell lung cancer patients with low expression of miR-499a-5p exhibited a worse overall survival rate compared with those patients with high expression of miR-499a-5p. Ectopic expression of miR-499a-5p significantly suppressed non-small cell lung cancer cell proliferation and colony formation, and hampered cell cycle at G0/G1 phase in vitro . Conversely, knockdown of miR-499a-5p promoted non-small cell lung cancer cell proliferation and colony formation, and induced cell cycle at S phase. Furthermore, in vivo experiments revealed that overexpression of miR-499a-5p inhibited the tumor formation in a nude mouse xenograft model. Mechanistic studies showed that fibroblast growth factor 9 was a direct target gene of miR-499a-5p. miR-499a-5p directly bound to fibroblast growth factor 9 mRNA 3’-UTR, therefore led to the reduction in fibroblast growth factor 9 protein expression. Finally, rescue experiments confirmed that silencing of fibroblast growth factor 9 partially reversed the phenotypes of miR-499a-5p knockdown on non-small cell lung cancer cell proliferation. In conclusion, our study demonstrates that downregulation of miR-499a-5p predicts a worse prognosis of patients with non-small cell lung cancer and restrains the tumorigenesis by targeting fibroblast growth factor 9. These findings may provide valuable clues for the future development of therapeutic strategies against this cancer.

Objectives. Triphala is a herbal medicine that has been widely used for treating a variety of ailments. This study aims to systematically analyze the antitumor effects of Triphala on gynecological cancers. Methods. The antineoplastic activities of Triphala on gynecological cancers were analyzed using network pharmacology-based strategies. Afterward, the human ovarian cancer cell line SK-OV-3, cervical cancer cell line HeLa, and endometrial cancer cell line HEC-1-B were selected for experimetal valification. Results. Network pharmacology analysis suggested that Triphala could comprehensively intervene in proliferation and apoptosis through diverse signaling pathways, mainly including MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53. The Cell Counting Kit 8 (CCK-8) assay illustrated that Triphala was able to inhibit cell proliferation with half inhibition concentration (IC 50 ) values of 98.28 ± 13.71, 95.56 ± 8.94, and 101.23 ± 7.76 µg/mL against SK-OV-3, HeLa, and HEC-1-B cells, respectively. The ELISA experiment demonstrated that Triphala was capable of promoting programmed cell death, with dosage correlations. The antiproliferative and proapoptotic activities were confirmed by flow cytometric analysis using Ki67 antibody and Annexin V/propidium iodide (PI) dual staining. Western blotting revealed a decrease in expression levels of phospho-Akt, phospho-p44/42, and phospho-NF-κB p56 in cells administered Triphala, which indicated that the possible mechanism could involve downregulation of MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53 signaling pathways, as was predicted. Conclusion . Triphala holds great promise for treating gynecological cancers. Although the favorable pharmacological properties have been preliminarily investigated in this study, further studies are still needed to uncover the sophisticated mechanism of Triphala in cancer therapy.