The characteristics and prognosis of different disease patterns of multiple primary lung cancers categorized according to the 8th edition lung cancer staging system.

INTRODUCTION: The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. METHOD: We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. RESULTS: In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P < 0.05). Sex was an independent prognostic factor for sMPLC (5-year survival, female vs. male, 88.0% vs. 69.5%, P < 0.05), and in multiple tumors, the highest tumor stage was an independent prognostic factor for all categories of MPLC. CONCLUSIONS: The different disease patterns of MPLC have significantly different characteristics and prognoses. Clinicians should place treatment emphasis on the tumor with the highest stage as it is the main contributor to the prognosis of all categories of MPLC patients.

Gypenoside induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway and enhances T-cell antitumor immunity by inhibiting PD-L1 in gastric cancer.

Introduction: Gypenoside is a natural extract of Gynostemma pentaphyllum (Thunb.) Makino, a plant in the Cucurbitaceae family. It has been reported to have antitumor effects on the proliferation, migration and apoptosis of various types of cancer cells. However, the use of gypenoside in the treatment of gastric cancer has not been studied. In the present study, we explored the therapeutic effect of gypenoside on gastric cancer and the potential molecular mechanism. Methods and Results: Our results showed that gypenoside induced apoptosis in HGC-27 and SGC-7901 cells in a time-dependent and dose-dependent manner. Network pharmacology analyses predicted that gypenoside exerts its therapeutic effects through the PI3K/AKT/mTOR signaling pathway. Furthermore, molecular docking and western blot experiments confirmed that gypenoside induced the apoptosis of gastric cancer cells through the PI3K/AKT/mTOR signaling pathway. In addition, network pharmacological analysis revealed that the common targets of gypenoside in gastric cancer were enriched in the immune effector process, PD-L1 expression, the PD-1 checkpoint pathway, and the Jak-STAT signaling pathway. Furthermore, molecular docking and western blot assays demonstrated that gypenoside could bind to STAT3 and reduce its phosphorylation. Thus, the transcription of PD-L1 was inhibited in gastric cancer cells. Moreover, coculture experiments of gastric cancer cells with gypenoside and primary mouse CD8+ T cells showed that gastric cancer cells treated with gypenoside could enhance the antitumor ability of T cells. Animal experiments confirmed the antitumor effect of gypenoside, and the expression of PD-L1 was significantly downregulated in the gypenoside-treated group. Conclusion: Gypenoside induced the apoptosis of gastric cancer cells by inhibiting the PI3K/AKT/mTOR pathway and simultaneously inhibited the expression of PD-L1 in gastric cancer cells, thus enhancing the antitumor immunity of T cells. This study provides a theoretical basis for applying gypenoside as a new therapeutic agent to enhance the efficacy of immunotherapy in gastric cancer.

Hemorheology and Inflammatory Marker Changes in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis with Mechanical Thrombectomy.

Objective: To investigate hemorheology and inflammatory marker changes after treatment for acute ischemic stroke (AIS) using intravenous thrombolysis (IVT) with mechanical thrombectomy (MT). Methods: We retrospectively reviewed clinical records of patients with AIS (n=83) treated in The First Affiliated Hospital of Bengbu Medical College between January 2021 and December 2022 (n=83). The control group consisted of 38 patients who underwent IVT alone and the observation group consisted of 45 patients who underwent IVT with MT. We compared differences in mean variables related to hemorheology, inflammatory markers, and total efficacy between the two groups. Results: We found that hemorheology values (plasma viscosity [PV], whole blood viscosity [WBV], fibrinogen [FIB], and hematocrit [HCT]), and the levels of inflammatory markers (tumor necrosis factor ɑ [TNF-ɑ] and interleukin-6 [IL-6]) were higher in the control group than in the observation group after treatment (P<0.05). In addition, the total efficacy of the observation group (93.3%) was higher than that in the control group (76.3%; P=0.016). Conclusions: The clinical efficacy of combined IVT and MT in the treatment of AIS is superior to IVT alone, improving levels of hemorheology and inflammatory markers in patients with AIS.

Study on the association between pregnancy-associated plasma protein-A and acute cerebral infarction.

Objective: We aimed to study the correlation between pregnancy-associated plasma protein-A (PAPP-A) and acute cerebral infarction (ACI). Methods: Patients who had the symptoms of paralysis, aphasia, or sudden neurological impairment from June 2020 to October 2021 were chosen. There were 159 patients diagnosed with ACI as the experimental group and 102 patients without ACI as the control group. We collected clinical data and observed whether they have a certain impact on plasma PAPP-A levels. The ACI group was divided into two groups: mild neurological deficit group (NIHSS score < 3) and moderate and severe neurological deficit group (NIHSS score > 3). The ACI group was divided into the atherosclerotic-type group and the arteriolar occlusion-type group according to the TOAST classification. The ACI group was divided into a good prognosis group (mRS ≤ 2 points) and a poor prognosis group (mRS > 2 points) using the Modified Rankin Scale (mRS) for 90 days of follow-up. Plasma PAPP-A levels were compared between those groups. Results: (1) The plasma PAPP-A level in patients with ACI (1.840 ± 0.281) was significantly higher than that in the control group (1.690 ± 0.260). Smoking history, leukocyte count, cystatin C, homocysteine, and plasma PAPP-A levels were independently correlated with ACI. (2) The level of PAPP-A in patients with moderate and severe neurological impairment was lower than that in patients with mild neurological impairment. (3) The level of PAPP-A in patients in the arteriolar occlusion-type group was higher than that in patients in the atherosclerosis-type group. (4) The PAPP-A levels in the group with elevated low-density lipoprotein are higher than those in the group with normal low-density lipoprotein. (5) Plasma PAPP-A level was not correlated with infarction location, infarction volume, or prognosis at the 90-day follow-up. Conclusion: (1) The level of plasma PAPP-A could be the independent risk factor of ACI. It is positively correlated with triglyceride and cholesterol content. (2) PAPP-A level is positively correlated with low-density lipoprotein. (3) PAPP-A levels between different disease severities have a significant difference. (4) The level of plasma PAPP-A in the arteriolar occlusion-type group was higher than that in the atherosclerotic-type group.

LncRNA HOXA11-AS modulates the miR-148b-3p/MLPH axis to promote prostate cancer cell proliferation.

Prostate cancer refers to the epithelial malignant tumor of the prostate. It has a high incidence and mortality rate, seriously endangering the lives of men. In recent years, lncRNAs have become a hot topic for lots of scholars for their regulation functions on assorted cancers. Several lncRNAs have been proven they can take part in the regulation of prostate cancer development. Nevertheless, how HOXA11-AS (homeobox A11 antisense RNA)functioned in prostate cancer is not explained. In our research, the expression of HOXA11-AS in prostate cancer cells was evaluated through qRT-PCR. Colony formation experiments, EdU experiments, Tanswelland TUNEL experiments, as well as caspase-3 detection, were designed to test cell proliferation, migration, invasion and apoptosis. RIP, pull down and luciferase reporter experiments examined the correlations of HOXA11-AS, miR-148b-3p and MLPH. We discovered a high level of HOXA11-AS in prostate cancer cells.HOXA11-AS silence could restrain the mentioned cell malignant behavior. Mechanically, HOXA11-AS could sponge miR-148b-3p to target MLPH. MLPH was positively associated with HOXA11-AS and overexpressed it accelerated the progression of prostate cancer. Taken together, HOXA11-AS elevated MLPH expression by sponging miR-148b-3p and accelerated prostate cancer cell proliferation.

Guillain-Barre syndrome after myocardial infarction: a case report and literature review.

BACKGROUND: Guillain-Barre syndrome after myocardial infarction occurs infrequently, and its occurrence following percutaneous coronary intervention is extremely rare. Due to the high mortality rate of myocardial infarction and the disability of Guillain-Barre syndrome, early identification of Guillain-Barre syndrome after myocardial infarction and early intervention can decrease the mortality rate, lead to early recovery, and provide a better outcome. CASE PRESENTATION: Herein, we reported a rare case of Guillain-Barre syndrome after myocardial infarction treated with percutaneous coronary intervention. The patient was a 75-year-old woman from China who was admitted to hospital due to sudden loss of consciousness. Electrocardiography showed acute myocardial infarction in the right ventricle and inferior and posterior walls. The patient underwent emergency percutaneous intervention of the posterior collateral artery of the right coronary artery. Soon after, her condition worsened resulting in limb weakness and numbness. Unfortunately, she continued to develop respiratory failure, and treated with intravenous immunoglobulin and ventilator-assisted breathing. A physical examination showed hypotonia of all four limbs, complete quadriplegia, bulbar palsy, dysarthria, and tendon areflexia. Serum immunoglobulin (Ig) G anti-ganglioside antibody analysis was positive with anti-GT1a antibodies (+ +), anti-GM1 antibodies ( +), anti-GM2 antibodies ( +), and anti-GM4 antibodies ( +), and he was diagnosed with Guillain-Barre syndrome after myocardial infarction. She was discharged due to poor response to treatment. The patient died two days after being discharged. CONCLUSIONS: Myocardial infarction and/or percutaneous coronary intervention may activate immune-mediated response and cause severe complications. Clinician should be alert to Guillain-Barre syndrome after myocardial infarction and/or percutaneous coronary intervention.

PLGA Nanoparticles Containing VCAM-1 Inhibitor Succinobucol and Chemotherapeutic Doxorubicin as Therapy against Primary Tumors and Their Lung Metastases.

The treatment of malignant tumors is usually accompanied by poor prognosis due to metastasis of tumor cells. Hence, it is crucial to enhance anti-metastasis efficacy when anti-tumor treatments are conducted. It has been reported that the vascular cell adhesion molecule-1 (VCAM-1) is highly expressed on the surface of tumor cells and plays an essential role in the metastasis of tumor cells. Thus, reducing VCAM-1 expression offers hope for inhibiting the metastasis of tumor cells. Evidence has shown that succinobucol (Suc) can selectively and efficiently inhibit VCAM-1 expression. Inspired by these, we designed dual drug-loaded PLGA nanoparticles (Co-NPs) to co-deliver VCAM-1 inhibitor Suc and the chemotherapeutic doxorubicin (Dox) which could both effectively suppress primary melanoma and its lung metastases. Co-NPs were composed of PLGA encapsulated Suc and Dox as hydrophobic cores and DSPE-mPEG2000 as surface modification materials. With an appropriate particle size (122.4 nm) and a negatively charged surface (-6.77 mV) we could achieve prolonged blood circulation. The in vitro experiments showed that Co-NPs had potent cytotoxicity against B16F10 cells and could significantly inhibit VCAM-1 expression and migration of B16F10 cells. Additionally, the in vivo experiments showed that Co-NPs could efficiently suppress not only primary melanoma but also its lung metastases. In conclusion, PLGA nanoparticles containing VCAM-1 inhibitor Suc and chemotherapeutic Dox as therapy against primary tumors and their lung metastases provides a promising drug delivery strategy for the treatment of metastatic malignant tumors.

Mechanism of vascular endothelial cell-derived exosomes modified with vascular endothelial growth factor in steroid-induced femoral head necrosis.

Steroid-induced avascular necrosis of the femoral head (SANFH) is an intractable orthopedic disease. This study investigated the regulatory effect and molecular mechanism of vascular endothelial cell (VEC)-derived exosomes (Exos) modified with vascular endothelial growth factor (VEGF) in osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in SANFH. VECs were culturedin vitroand transfected with adenovirus Adv-VEGF plasmids. Exos were extracted and identified.In vitro/vivoSANFH models were established and treated with VEGF-modified VEC-Exos (VEGF-VEC-Exos). The internalization of Exos by BMSCs, proliferation and osteogenic and adipogenic differentiation of BMSCs were determined by the uptake test, cell counting kit-8 (CCK-8) assay, alizarin red staining, and oil red O staining. Meanwhile, the mRNA level of VEGF, the appearance of the femoral head, and histological analysis were assessed by reverse transcription quantitative polymerase chain reaction and hematoxylin-eosin staining. Moreover, the protein levels of VEGF, osteogenic markers, adipogenic markers, and mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinases (ERK) pathway-related indicators were examined by Western blotting, along with evaluation of the VEGF levels in femur tissues by immunohistochemistry. Glucocorticoid (GC) induced adipogenic differentiation of BMSCs and inhibited osteogenic differentiation. VEGF-VEC-Exos accelerated the osteogenic differentiation of GC-induced BMSCs and inhibited adipogenic differentiation. VEGF-VEC-Exos activated the MAPK/ERK pathway in GC-induced BMSCs. VEGF-VEC-Exos promoted osteoblast differentiation and suppressed adipogenic differentiation of BMSCs by activating the MAPK/ERK pathway. VEGF-VEC-Exos accelerated bone formation and restrained adipogenesis in SANFH rats. VEGF-VEC-Exos carried VEGF into BMSCs and motivated the MAPK/ERK pathway, thereby promoting osteoblast differentiation of BMSCs in SANFH, inhibiting adipogenic differentiation, and alleviating SANFH.

Recent Advances of Circular RNAs as Biomarkers for Osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in young adult, which is prone to early metastasis and poor prognosis. The current treatment methods need to be improved. Circular RNA is a covalently blocked circular, non-coding RNA that plays an essential role in the occurrence, development, clinical diagnosis, and treatment of various diseases. Recently, an increasing number of circRNAs have been identified in osteosarcoma. Understanding its role in osteosarcoma is conducive to the early detection, diagnosis, and treatment of osteosarcoma. In this paper, we reviewed the mechanism of action of circular RNA in the occurrence and development of osteosarcoma and its clinical application in recent years.

Long-term Incidence Rates of Esophageal Squamous Cell Carcinoma in Chinese Patients With Low-grade Intraepithelial Neoplasia and Association of Surveillance Endoscopy With Incidence.

Importance: Surveillance endoscopy is recommended for patients with low-grade intraepithelial neoplasia (LGIN); high-quality evidence about the use of surveillance endoscopy and esophageal squamous cell carcinoma (ESCC) incidence in patients with LGIN is important but limited. Objective: To estimate long-term ESCC incidence rates in patients with LGIN and the association between surveillance endoscopy and ESCC incidence. Design, Setting, and Participants: This community-based, multicenter, prospective cohort study in 9 regions in rural China included patients with LGIN diagnosed by endoscopic screening between July 1, 2007, and December 31, 2016; all participants were followed up until December 31, 2021. Main Outcomes and Measures: The primary outcome was ESCC incidence. The ESCC standardized incidence ratio (SIR) was estimated using sex- and age-specific incidence in the general population of rural China in 2010 and hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Results: A total of 3258 patients with LGIN were included; 1772 (54.39%) were men, with a mean (SD) age of 58.21 (6.97) years. Among them, 1378 patients (42.30%) underwent at least 1 surveillance endoscopy (surveillance group) and 1880 (57.70%) did not undergo any surveillance endoscopy (nonsurveillance group). During the follow-up period (median, 7.96 years; IQR, 6.08-10.54 years), 170 ESCC cases were diagnosed, with a cumulative incidence of 6.28 per 1000 person-years. A higher incidence of ESCC (incidence rate, 7.07 per 1000 person-years) was observed in the nonsurveillance group than in the surveillance group (incidence rate, 5.14 per 1000 person-years). Patients with LGIN in the surveillance group had a lower SIR (SIR, 4.07; 95% CI, 1.13-10.34) than those in the nonsurveillance group (SIR, 5.65; 95% CI, 2.00-12.58); however, patients with LGIN in both groups had a higher risk of ESCC than the general population. Patients in the surveillance group had a 31% decreased risk of ESCC incidence (HR, 0.69; 95% CI, 0.50-0.95) compared with those in the nonsurveillance group, after adjusting for baseline risk factors. Conclusions and Relevance: In this prospective cohort study, patients with LGIN had a higher risk of developing ESCC than the general population, and endoscopic surveillance was associated with a decrease in ESCC incidence in these patients.

Colorectal cancer burden, trends and risk factors in China: A review and comparison with the United States.

Objective: China and the United States (the U.S.) have the heaviest colorectal cancer (CRC) burden with considerable variations in temporal trends. This study aims to analyze the temporal patterns of CRC burden and its risk factors in China and the U.S. across the past three decades. Methods: Data were extracted from the Global Burden of Disease (GBD) Study in 2019, including cases, deaths, disability-adjusted life-years (DALYs), age-standardized rate (ASR), and summary exposure value (SEV) of CRC in China and the U.S. between 1990 and 2019. Annual average percentage changes (AAPCs) of CRC burden were calculated using the Joinpoint regression model. The mortality in CRC attributable to potential risk factors was characterized by countries, gender, and age groups. Results: In 2019, there were 607,900 and 227,241 CRC cases, and 261,777 and 84,026 CRC deaths in China and the U.S., respectively. The age-standardized incidence rate (ASIR) was 30.55 per 100,000 in China and 41.86 per 100,000 in the U.S., and the age-standardized mortality rate (ASMR) was 13.86 per 100,000 in China and 14.77 per 100,000 in the U.S. CRC incidence, mortality, and DALY rate in the U.S. showed downward trends in the past three decades (AAPC=-0.47, -1.06, and -0.88, respectively), while upward trends were observed in China (AAPC=3.11, 1.05, and 0.91, respectively). Among the cause of CRC, the leading risk factor contributing to CRC death was low milk in China and smoking in the U.S., respectively. Conclusions: From 1990 to 2019, the burden of CRC in China increased dramatically, particularly for males and middle-aged and elderly people. The management of the major risk factors associated with the high burden of CRC should be enhanced.

Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1.

Background: Exosomes have been identified to mediate the transmission of RNAs among different cells in tumor microenvironment, thus affecting the progression of different diseases. However, exosomal messenger RNAs (mRNAs) have been rarely explored. RNF157 mRNA has been found to be up-regulated in PCa patients' exosomes, but the role of exosomal RNF157 mRNA in PCa development remains unclear. Methods: Online databases were utilized for predicting gene expression and binding correlation between different factors. RT-qPCR and western blot assays were respectively done to analyze RNA and protein expressions. Flow cytometry analysis was implemented to analyze M2 polarization. Results: RNF157 expression was high in PCa tissues and cells. M2 polarization of macrophages was enhanced after co-culture with PCa cells or with exosomes released by PCa cells. Upon RNF157 knockdown in PCa cells, the extracted exosomes could not lead to the facilitated M2 polarization. Mechanistically, RNF157 could bind to HDAC1 and contribute to HDAC1 ubiquitination, which led to HDAC1 degradation and resulting in promoting M2 polarization of macrophages. Animal experiments validated that exosomal RNF157 accelerated PCa tumor growth through facilitating macrophage M2 polarization. Conclusion: Exosome-mediated RNF157 mRNA from PCa cells results in M2 macrophage polarization via destabilizing HDAC1, consequently promoting PCa tumor progression.

Cognition-enhancing effect of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in the 5 × FAD transgenic mouse model of Alzheimer's pathology.

BACKGROUND: Intracerebral translocator protein 18 kDa (TSPO) mediates the transport of cholesterol from cytoplasm to mitochondria and activation of microglia. The change of TSPO and the dysfunction of microglia are closely related to the pathogenesis of Alzheimer's disease (AD). AIMS: This study aimed to investigate the effects of microglial TSPO and its selective ligand YL-IPA08 on the cognitive function of transgenic mice in 5 × familial Alzheimer's disease (FAD) mouse model of AD. METHODS: The TSPO knockout 5 × FAD transgenic mice were bred, and tested by Morris water maze. The effects of YL-IPA08 on cognitive abilities and expression of Aß in 5 × FAD mice were also explored into. RESULTS: The latency of escape by TSPO knockout 5 × FAD mice was significantly prolonged compared with the 5 × FAD group, indicating that the cognitive impairment of mice aggravated. With the attenuated phagocytic ability of microglia, the deposition of Aß in prefrontal cortex of TSPO knockout 5 × FAD mice increased, and the expression of proinflammatory factors (IL-1ß, TNF-α, IL-6) were upregulated. In addition, YL-IPA08 significantly reduced the latency of escape by 5 × FAD mice, increased the number of times of crossing over the platform by mice, and inhibited the deposition of Aß in the prefrontal cortex of 5 × FAD mice without affecting the cleavage of APP. CONCLUSION: Our findings suggested that TSPO knockout in 5 × FAD mice inhibited microglial phagocytosis, promoted Aß deposition and neuroinflammation, and aggravated cognitive dysfunction in AD mice. YL-IPA08 had a significant cognition-enhancing effect in 5 × FAD transgenic mice, which might provide a new basis for potential drug candidates in AD treatment.

The Effect of Intraoperative Fentanyl Consumption on Prognosis of Colorectal Liver Metastasis treated by Simultaneous Resection: A Propensity Score Matching Analysis.

Background: No previous studies have reported the effect of intraoperative opioid consumption in colorectal liver metastasis (CRLM). Methods: Medical records of patients who received simultaneous resection of CRLM were retrospectively reviewed. Patients with epidural anesthesia, intraoperative morphine, or intraoperative oxycodone were excluded. Patients were separated into high- and low-dose groups by median intraoperative equianalgesic fentanyl dose. Short-term outcomes, progression-free surcical (PFS) and overall survival (OS) were compared between groups before and after 1:1 propensity score matching (PSM). Univariable and multivariable Cox regression analysis were performed to identify independent predictors of survival. Results: The final study population included 343 patients. Patients were separated into the low dose group (n=172) and the high dose group (n=171) by median intraoperative equianalgesic fentanyl dose (8.33 µg/kg). After PSM, 55 patients in the low dose group were matched to 55 patients in the high dose group and the baseline characteristics of the two groups were balanced. The two groups had no statistically significance difference in severity and categories of postoperative complications before and after PSM. Before PSM, the two groups had similar PFS (median 10.2 vs. 12.4 months, P=0.54) and OS (median 59.0 vs. 58.3 months, P=0.76). Univariate and multivariate Cox regression analyses revealed no statistically significant association between intraoperative equianalgesic fentanyl and PFS (multivariate HR=0.852, 95% CI 0.655-1.11, P=0.235) and OS (multivariate HR=1, 95% CI 0.68-1.49, P = 0.981). After PSM, the two groups also had similar PFS (median 9.2 vs. 10.7 months, P=0.98) and OS (median 51.0 vs. 46.0 months, P=0.39). Univariate and multivariate Cox regression analyses revealed no statistically significant association between intraoperative equianalgesic fentanyl and PFS (multivariate HR=1.05, 95% CI 0.632-1.73, P=0.861) and OS (multivariate HR=1.74, 95% CI 0.892-3.38, P = 0.105). Conclusion: Intraoperative opioids consumption was not correlated with outcomes of CRLM patients treated with simultaneous resection.

Analysis of the Role of Comprehensive Treatment Model in the Treatment of Prostate Cancer.

The incidence of prostate cancer is gradually increasing. There are many methods for clinical treatment of prostate cancer, such as surgical treatment and endocrine treatment. In the case of advanced prostate cancer, we must not only extend patients' survival times but also enhance their quality of life. Endocrine medications are the most effective therapy for advanced prostate cancer. This research will investigate the therapeutic impact of a complete treatment model in prostate cancer in order to discover a trustworthy clinical treatment model. This research discovered that, as compared to endocrine treatment, radical resection of prostate cancer may diminish and reach lower serum PSA levels in a short amount of time, as well as sustain low PSA levels and delay progression to castration resistance. Moreover, the comprehensive treatment mode can effectively reduce the possibility of complications. The research results show that the comprehensive treatment model can play an important role in the treatment of prostate cancer.

ßKlotho Inhibits Cell Proliferation by Downregulating ELK4 and Predicts Favorable Prognosis in Prostate Cancer.

OBJECTIVE: Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on ßKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa. METHODS: Western blotting was used to determine the expression of ßKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of ßKlotho and ELK4 in the proliferation of PCa cells. The expression of ßKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson's χ2 test and Fisher's exact test were performed to investigate the associations among ßKlotho, ELK4 and various clinical factors. Kaplan-Meier curves and Cox regression model were established to reveal the correlation among ßKlotho, ELK4 expression and the prognosis of patients. RESULTS: ßKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. ßKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher ßKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, ßKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa. CONCLUSION: ßKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both ßKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.

Risk factors for the severity of Guillain-Barré syndrome and predictors of short-term prognosis of severe Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a neurological disorder characterized by paralysis. Identifying the severity, appropriate therapeutic method, and prognosis of GBS at an early stage is highly important. This study aimed to investigate the modifiable risk factors for the severity of GBS and consequent need for mechanical ventilation (MV) and to identify clinical predictive factors for poor short-term outcomes of severe GBS. 155 GBS patients who were admitted to the Affiliated Yantai Yuhuangding Hospital of Qingdao University during 2014-2020 were enrolled. Demographic, clinical, therapeutic and evolutionary data were collected and were then analyzed using univariate and multivariate regression analyses. Our analytic data demonstrated that the significant clinical predictors of severe GBS were recent history of surgery, older age, cranial nerve impairment, and elevated levels of liver enzymes (p < 0.05). Furthermore, autonomic dysfunction, lower Medical Research Council (MRC) score at nadir, and elevated levels of liver enzymes were significantly associated with MV for severe GBS (p < 0.05), and lower MRC score at nadir and autonomic dysfunction remained significant predictors of MV in severe GBS (p < 0.05). Lastly, recent history of surgery, lower MRC score at admission and at nadir, requirement for MV, and pneumonia during hospitalization were significantly associated with the short-term outcome of severe GBS and that lower MRC score at admission and need for MV were confirmed to be predictors of poor short-term prognosis (p < 0.05). Of note, this study suggested that recent history of surgery is a predictor of severity in GBS patients and is associated with the poor short-term prognosis of severe GBS.

A new model based on gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts prognostic outcome after curative resection of solitary hepatocellular carcinoma.

BACKGROUND: This study intends to explore the potential clinical value of gamma-glutamyl transpeptidase to platelet ratio (GPR) and the new multi-factor scoring model for recurrence and prognosis prediction in solitary HCC patients who received radical resection. METHODS: This study retrospectively analyzed 295 HCC patients after curative resection. According to the Receiver Operating Characteristic (ROC) curve, the optimal cut-off value of GPR for predicting prognosis of HCC after resection was determined. The Kaplan Meier method and Cox regression analysis were performed to assess the important potential factors in the prognosis of HCC and determine the independent risk factors. Assign a value to each independent risk factor and establish a new scoring model. Then, using GPR and the new scoring model to evaluate overall survival (OS) and postoperative recurrence probability. RESULTS: When GPR's cut-off value was selected as 0.30, its predictive efficiency for postoperative prognosis was more favorable than those of other cut-off values (0.76, 0.84 and 0.94). GPR, tumor size, microvascular invasion and neutrophil to lymphocyte ratio (NLR) were identified as independent prognostic predictors. Using these variables, a novel prognostic scoring model was devised and established to identify different levels of risk: high, intermediate and low risk groups. We found that patients with high GPR level and of high risk group would have a poorer OS and a higher recurrence rate after radical resection. CONCLUSIONS: GPR may serve as a promising predictor for postoperative prognosis and recurrence probability of HCC, and the new prognostic scoring model may be available for postoperative management among HCC patients.

miRNAs as potential markers for breast cancer and regulators of tumorigenesis and progression (Review).

Breast cancer (BC) is one of the most common malignancies affecting women. BC is a heterogeneous disease that involves multiple oncogenic pathways and/or genetic alterations. MicroRNAs (miRNAs or miRs) are a type of small endogenous single­stranded RNA that pairs with the 3'untranslated region of target mRNAs to negatively regulate the gene expression of specific mRNA targets. miRNAs are thus involved in various cellular processes, including proliferation, differentiation, apoptosis, migration, metabolism and the stress response. Over the past decade, a number of studies have demonstrated that the expression levels of miRNAs are dysregulated in a number of types of cancer, including BC. In the present review, recent research on miRNAs involved in the occurrence and development of BC, as well as the current findings on miRNAs as potential biomarkers for BC are summarized. In addition, the association between miRNA dysregulation and BC development, and the current status of BC treatment and prognosis are discussed. Finally, several signaling pathways involved in the development of BC and the potential roles of miRNAs in these pathways are reviewed. The present review aims to provide insight into the roles of miRNAs in BC.

Establishment of Novel DNA Methylation-Based Prostate Cancer Subtypes and a Risk-Predicting Eight-Gene Signature.

Prostate cancer (PCa) is the most common malignant tumor affecting males worldwide. The substantial heterogeneity in PCa presents a major challenge with respect to molecular analyses, patient stratification, and treatment. Least absolute shrinkage and selection operator was used to select eight risk-CpG sites. Using an unsupervised clustering analysis, called consensus clustering, we found that patients with PCa could be divided into two subtypes (Methylation_H and Methylation_L) based on the DNA methylation status at these CpG sites. Differences in the epigenome, genome, transcriptome, disease status, immune cell composition, and function between the identified subtypes were explored using The Cancer Genome Atlas database. This analysis clearly revealed the risk characteristics of the Methylation_H subtype. Using a weighted correlation network analysis to select risk-related genes and least absolute shrinkage and selection operator, we constructed a prediction signature for prognosis based on the subtype classification. We further validated its effectiveness using four public datasets. The two novel PCa subtypes and risk predictive signature developed in this study may be effective indicators of prognosis.