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Yue-Chen Zhao,1,2 Xin Li,3 Chao-Qun Wang,4 Yan Jiao,5 Yan-Nan Shen,2 Tie-Jun Wang,1,2,* Chao-He Zhang6,* 1Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, Jilin, People’s Republic of China; 3Department of Radiology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Gynaecology, Aviation General Hospital, Beijing, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, People’s Republic of China; 6Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tie-Jun Wang, Department of Radiation Oncology, The Second Hospital of Jilin University, NO. 218 Ziqiang Street, Changchun, 130041, People’s Republic of China, Email tjwang@jlu.edu.cn Chao-He Zhang, Department of Hematology and Oncology, The Second Hospital of Jilin University, NO. 218 Ziqiang Street, Changchun, 130041, People’s Republic of China, Email zhangchaohe@jlu.edu.cnPurpose: Abraxane (nanoparticle albumin-bound paclitaxel) is a chemotherapeutic employed commonly for the management of various cancers including breast cancer, non-small cell lung cancer, and pancreatic adenocarcinoma. Although it has clinically beneficial properties, Abraxane is accompanied by multiple adverse events (AEs) that require close observation. This study aims to evaluate the AE profile of Abraxane using recently available data from January 2004 through December 2023 in the FDA Adverse Event Reporting System (FAERS).Patients and Methods: The data for Abraxane-related AEs were obtained from the FAERS database. The dataset consisted of patient demographic characteristics as well as information on the types and outcomes of AEs reported. Reporting odds ratios (ROR) as well as proportional reporting ratio (PRR), considering the used definition of anti-cancer agent and AEs, were calculated to investigate any association with Abraxane.Results: A total of 10,310 reports associated with Abraxane AEs were identified. Blood and lymphatic system disorders were the most frequent (ROR 6.44), followed by hepatobiliary (ROR 3.16), infections (ROR 1.45), and gastrointestinal disorders (ROR 1.42). Serious outcomes included hospitalization in 36.35% and death in 29.76% of cases. The top adverse reactions matched known profiles, including peripheral sensory neuropathy (ROR: 49.48). The analysis also found new adverse reactions, such as scleroderma-like reactions (ROR: 95.4) and vascular pseudoaneurysm ruptures (ROR: 87.71).Conclusion: Our results re-emphasize the importance of a robust Post Marketing Surveillance system and suggest this FAERS database based analysis provides an updated, independent information on Abraxane related AEs to enrich its safety profile. A process of continuous vigilance and additional investigations on specific areas that may have some undesired events are imperative to increase our knowledge on how Abraxane should be handled in terms of its safety.Keywords: Abraxane, FAERS database, adverse events, signal detection, pharmacovigilance

Hao Wu, Yan Na Shen, Zhongxiao Wu, Feng Mao, You Gang Ren, Li Zhang Department of Dermatology, Ningbo No 6 Hospital, Ningbo, 315040, People’s Republic of ChinaCorrespondence: Li Zhang, Email lishay1022@hotmail.comAbstract: Although the use of biologics has led to great improvement in psoriasis patients, the treatment of psoriasis during pregnancy still faces many challenges. We herein report on a 29-year-old pregnant woman treated with ustekinumab for generalized pustular psoriasis. Upon becoming pregnant, the woman underwent continued treatment with ustekinumab in the first trimester. We also considered the need for neonatal vaccination. The patient discontinued ustekinumab therapy in the second trimester, and during the period of drug discontinuation we noted a slight rash recurrence. The patient was treated with ultraviolet B phototherapy and topical corticosteroids, and the rash was localized to the abdomen. However, in the 27th week of pregnancy, the patient was infected with COVID-19, which made the condition worse. The rash erupted rapidly and spread throughout her body, and she experienced a high fever with her blood count showing augmented numbers of white blood cells. The patients self-administered 0.3 g of acetaminophen three times per day, and after four days her core body temperature was 38.0°C; the rash, however, did not diminish. We diagnosed an outbreak of generalized pustular psoriasis and treated the patient with ustekinumab. The rash resolved quickly, and a healthy newborn was delivered by caesarean section at 39 weeks.Keywords: Ustekinumab, interleukin-12/-23, generalized pustular psoriasis, pregnancy, COVID-19

Objective: To evaluate the association between early net ultrafiltration (NUF) rate and risk of death in patients with cardiac surgery-associated acute kidney injury (CSA-AKI) requiring continuous renal replacement therapy (CRRT). Methods: Adult patients who received CRRT for more than 24 hours due to CSA-AKI in the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2021 were prospectively included. The NUF rate during the first 48 hours of CRRT was taken as a classified variable (low rate:<1.70 ml·kg -1 ·h -1 ; moderate rate: 1.70-2.47 ml·kg -1 ·h -1 ; high rate:>2.47 ml·kg -1 ·h -1 ). The association between 90-day mortality and NUF rates was analyzed by Cox regression and mediation analyses. Results: A total of 262 patients were enrolled (171 males and 91 females), with the median ( Q 1 , Q 3 ) age of 64 (54, 71) years and median ( Q 1 , Q 3 ) NUF rate of 2.03 (1.58, 2.62) ml·kg -1 ·h -1 . The 90-day mortality was 60.3% (158/262). Compared with the moderate NUF rate, patients with the low NUF rate (adjusted HR =1.52, 95% CI : 1.01-2.27, P =0.043) and high NUF rate (adjusted HR =1.54, 95% CI : 1.02-2.33, P =0.039) had a significantly higher risk of 90-day death. In mediation analysis, compared with the moderate NUF rate, the putative effect of the high NUF rate on 90-day mortality was direct [adjusted average direct effects (ADE)=1.12, 95% CI : 1.04-1.21, P =0.004] and not mediated by effects of the NUF rate on fluid balance [adjusted average causal mediation effects (ACME)=1.00, 95% CI :0.98-1.01, P =0.502]. The putative effect of the low NUF rate on mortality was not direct (adjusted ADE=0.93, 95% CI :0.81-1.05, P =0.274), but was mediated by its effect on fluid balance (adjusted ACME=0.93, 95% CI :0.87-0.98, P =0.018). Conclusion: Compared with NUF rates between 1.70-2.47 ml·kg -1 ·h -1 within the first 48 hour of CRRT, NUF rates>2.47 and<1.70 ml·kg -1 ·h -1 were associated with higher mortality in CSA-AKI patients receiving CRRT.

Objective: To evaluate the association between fluid balance within 48 hours after initiating continuous renal replacement therapy (CRRT) and 90-day mortality of patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Methods: Adult patients who received CRRT for CSA-AKI for more than 24 hours between January 2016 and December 2021 in the First Affiliated Hospital of Nanjing Medical University were prospectively included. Exposures were fluid input, fluid output, fluid balance and percentage of fluid overload change (defined as weight-standardized fluid input/output difference) within 48 hours after CRRT initiation. The primary outcome was 90-day mortality. The relationship between the exposures and 90-day mortality was determined by restricted cubic spline and segmented Cox regression. Results: The study enrolled 262 patients, and 90-day mortality was 60.3% (158/262). There were 171 males and 91 females, with a median age of 64 (54, 71) years. The dead patients ( n =158) had more fluid input [6.43 (5.62, 7.34) L vs 6.07 (5.09, 6.90) L, P= 0.013], greater fluid balance [-0.01 (-1.36, 1.34) L vs -0.65 (-1.71, 0.42) L, P =0.005] and higher percentage of fluid overload change [-0.01% (-2.17%, 2.01%) vs -0.85% (-2.49%, 0.52%), P= 0.013] within 48 hours after CRRT initiation than the survived patients ( n =104). The cumulative fluid balance and fluid overload changes have a "J" curve relationship with 90-day mortality. Higher positive fluid balance (adjusted HR per 1 L increase above 0.5 L=1.33, 95% CI : 1.17-1.50) and greater proportion of fluid overload changes (adjusted HR per 1% increase above 0.7%=1.20, 90% CI : 1.11-1.30) were associated with an increased risk of death. Cumulative fluid input was linearly related to the 90-day mortality. Higher input (adjusted HR per 1 L increase=1.13, 95% CI : 1.03-1.24) was associated with an increased risk of death. The cumulative fluid output showed a U-shaped relationship with risk of death. Both lower output (adjusted HR per 1 L increase below 6.7 L=0.73, 95% CI : 0.58-0.90) and higher output (adjusted HR per 1 L increase above 6.7 L=1.24, 95% CI : 1.01-1.53) were associated with increased risk of death. Conclusion: In patients with CSA-AKI, excessive fluid input, insufficient or excessive output and a positive fluid balance or percentage of fluid overload change within the first 48 hours after CRRT initiation are associated with increased risk of 90-day mortality.

Background: Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development., Methods: RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed., Results: SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis., Conclusion: SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment., (© 2024. The Author(s).)

Compared with conventional treatments, oncolytic virotherapy has the advantages of enhanced cytotoxicity, improved targeting, and minimal side effects. However, its efficacy is not as good as expected for the single drug treatment. The purpose of synergistic effect is one of the development directions of existing oncolytic virus therapy. In this paper, through a systematic review of the current preclinical and clinical trials progress of oncolytic virus combination therapy, the combined treatment strategies of oncolytic virus and immune checkpoint inhibitors, chemotherapy, targeted therapy,and cell therapy are reviewed to provide reference for further clinical application.

The activation of innate antiviral immunity is a promising approach for combatting viral infections. In this study, we screened Chinese herbs that activated human immunity and identified coptisine as a potent inhibitor of the influenza virus with an EC 50 of 10.7 μM in MDCK cells. The time of an addition assay revealed that pre-treatment with coptisine was more effective at reducing viral replication than co-treatment or post-treatment. Our bulk RNA-sequencing data showed that coptisine upregulated the p21 signaling pathway in MDCK cells, which was responsible for its antiviral effects. Specifically, coptisine increased the expression of p21 and FOXO1 in a dose-dependent manner while leaving the MELK expression unchanged. Docking analysis revealed that coptisine likely inhibited MELK activity directly by forming hydrogen bonds with ASP-150 and GLU-87 in the catalytic pocket. These findings suggest that coptisine may be a promising antiviral agent that regulates the p21 signaling pathway to inhibit viral replication.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma , prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2., Competing Interests: None of the authors have any conflict of interest to declare.

Although targeted therapies and immunotherapies have been effective against several malignancies, the respective monotherapies are limited by low and/or short-term responses. Specific inhibitors of oncogenic signaling pathways and tumor-associated angiogenesis can activate the anti-tumor immune responses by increasing tumor antigen presentation or intratumor T cell infiltration. Additional insights into the effects and mechanisms of targeted therapies on the induction of anti-tumor immunity will facilitate development of rational and effective combination strategies that synergize rapid tumor regression and durable response. In this review, we have summarized the recent combinations of targeted therapies and immunotherapies, along with the associated clinical challenges., Competing Interests: Conflict-of-interest statement: The authors declare no potential conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The mechanism of enhanced radiosensitivity induced by mitochondrial uncoupling protein UCP2 was investigated in HeLa cells to provide a theoretical basis as a novel target for cervical cancer treatment., Methods: HeLa cells were irradiated with 4 Gy X-radiation at 1.0 Gy/min. The expression of UCP2 mRNA and protein was assayed by real-time quantitative polymerase chain reaction and western blotting. UCP2 siRNA and negative control siRNA fragments were constructed and transfected into HeLa cells 24 h after irradiation. The effect of UCP2 silencing and irradiation on HeLa cells was determined by colony formation, CCK-8 cell viability, γ H2AX immunofluorescence assay of DNA damage, Annexin V-FITC/PI apoptosis assay, and propidium iodide cell cycle assay. The effects on mitochondrial structure and function were investigated with fluorescent probes including dichlorodihydrofluorescein diacetate (DCFH-DA) assay of reactive oxygen species (ROS), rhodamine 123, and MitoTracker Green assay of mitochondrial structure and function., Results: Irradiation upregulated UCP2 expression, and UCP2 knockdown decreased the survival of irradiated HeLa cells. UCP2 silencing sensitized HeLa cells to irradiation-induced DNA damage and led to increased apoptosis, cell cycle arrest in G2/M, and increased mitochondrial ROS. Increased radiosensitivity was associated with an activation of P53, decreased Bcl-2, Bcl-xl, cyclin B, CDC2, Ku70, and Rad51 expression, and increased Apaf-1, cytochrome c, caspase-3, and caspase-9 expression., Conclusions: UCP2 inhibition augmented the radiosensitivity of cervical cancer cells, and it may be a potential target of radiotherapy of advanced cervical cancer., Competing Interests: The authors confirm that there are no conflicts of interest., (Copyright © 2020 Cui Hua Liu et al.)

Purpose: The International Study Group on Pancreatic Fistula's definition of postoperative pancreatic fistula (POPF) has recently been updated. This study aimed to identify risk factors for POPF in patients having pancreaticoduodenectomy (PD) and to generate a nomogram to predict POPF., Methods: Data on 298 patients who underwent PD from March 2012 to October 2017 was retrospectively reviewed and POPF statuses were redefined. A nomogram was constructed using data from 220 patients and validated using the remaining 78 patients. Independent risk factors for POPF were identified using univariate and multivariate analyses. A predictive nomogram was established based on the independent risk factors and was compared with existing models., Results: Texture of the pancreas, size of the main pancreatic duct, portal vein invasion, and definitive pathology were the identified risk factors. The nomogram had a C-index of 0.793 and was internally validated. The nomogram performed better (C-index of 0.816) than the other most cited models (C-indexes of 0.728 and 0.735) in the validation cohort. In addition, the nomogram can assign patients into low- (less than 10%), intermediate- (10% to 30%), and high-risk (equal or higher than 30%) groups to facilitate personalized management., Conclusion: The nomogram accurately predicted POPF in patients having PD., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2020, the Korean Surgical Society.)

In the last two decades, with the wide use of azoles, antifungal resistance among Candida parapsilosis has considered a matter of concern worldwide. The aim of this study is to evaluate the antifungal potentials of tetrandrine (TET) alone and in combination with fluconazole (FLC)/voriconazole (VRC) against C. parapsilosis. Susceptibility tests were performed by microdilution method, checkerboard assay, time-kill test, spot assay. Subsequently, rhodamine 6G efflux test and the expressions of transporter related genes, namely CDR1 and MDR1 for C. parapsilosis were analyzed by qRT-PCR. The susceptibility test showed that TET presented strong synergism with FLC and VRC with fractional inhibitory concentration index (FICI) in a range of 0.094-0.562. The susceptibility results were also confirmed by spot assay and time-kill studies. With TET treatment, a vast quantity of rhodamine 6G could not be pumped out from the cells as considerably intracellular red fluorescence was accumulated. Meanwhile, the expressions of efflux-associated genes presented varying degrees of inhibition. These results indicated that TET was a decent antifungal synergist to promote the antifungal efficacy of FLC/VRC, and the underlying antifungal mechanism might be associated with the inhibition of efflux pump and the elevation of intracellular drug content.

To generate a nomogram to predict posthepatectomy liver failure (PHLF), we attempted to elucidate salient risk factors in patients with hepatocellular carcinoma (HCC).We performed a retrospective review of 665 patients with HCC who received hepatectomy in 2 academic institutions in China. Independent risk factors for PHLF were identified from putative demographic, intrinsic, biochemical, surgery-related, and volumetric data. A predictive nomogram was formulated based on relevant risk factors, and we compared this with existing models.We identified clinical signs of portal hypertension (P = .023), serum total bilirubin (P = .001), serum creatinine (P = .039), and intraoperative hemorrhage (P = .015) as being important risk factors in predicting PHLF. The nomogram had a C-index of 0.906 for the externally validated data. The nomogram displayed better predictive value than 2 of the other most cited models (C-indices of 0.641 and 0.616, respectively) in the current cohort. Additionally, we were able to patients into low- (<10%), intermediate- (10-30%), and high-risk (≥30%) groups based on the nomogram. This allows us to facilitate person-specific management.Here, we constructed a simple nomogram for prediction of PHLF in patients with HCC weighted by independent risk factors. Further prospective studies are required to confirm the predictive ability of our nomogram.

Background: Surgical site infections (SSI) remain a major cause of morbidity after hepatectomy for hepatocellular carcinoma (HCC)., Aim: To identify the risk factors associated with SSI, and develop a nomogram to predict SSI among patients undergoing hepatectomy., Methods: We retrospectively reviewed the data of patients diagnosed with HCC undergoing hepatectomy at two academic institutions in China, and evaluated the occurrence of SSI. Independent risk factors for SSI were identified using univariate and multivariate analyses. Based on these independent risk factors, a nomogram was established using the data of patients in the first institution, and was validated using data from an external independent cohort from the second institution., Results: The nomogram was established using data from 309 patients, whereas the validation cohort used data from 331 patients. The operation duration, serum albumin level, repeat hepatectomy, and ASA score were identified as independent risk factors. The concordance index (C-index) of the nomogram for SSI prediction in the training cohort was 0.86; this nomogram also performed well in the external validation cohort, with a C-index of 0.84. Accordingly, we stratified patients into three groups, with a distinct risk range based on the nomogram prediction, to guide clinical practice., Conclusion: Our novel nomogram offers good preoperative prediction for SSIs in patients undergoing hepatectomy., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.

In order to improve the therapeutic effect of non-small cell lung cancer (NSCLC), it is critical to combine radiation and gene therapy. Our study found that the activation of microRNA-9 (miR-9) conferred ionizing radiation (IR) sensitivity in cancer cells. Furthermore, increased microRNA-9 promoter methylation level was observed after IR. Our study combined the IR and microRNA-9 overexpression treatment which leads to a significant enhancement in the therapeutic efficiency in lung cancer both in vitro and in vivo. Therefore, it is plausible that microRNA-9 can be used as a novel therapeutic strategy of NSCLC. MTT assay was performed to detect the effect of microRNA-9 on the survival and growth of NSCLC cells. Flow cytometry results showed that microRNA-9 enhanced the apoptosis of NSCLC cells. Wound healing assay found that microRNA-9 can inhibit the migration of NSCLC cells and enhance the effect of radiation on the migration of NSCLC cells. In addition, bisulfate sequencing PCR was performed to analyze the methylation status of the microRNA-9 promoter. In order to determine the effect of microRNA-9 and its promoter methylation status on proliferation and radio-sensitivity in vivo, a subcutaneous tumor formation assay in nude mice was performed. Results have shown that microRNA-9 overexpression increased the radiosensitivity of A549 cells by inhibiting cell activity and migration, and by increasing apoptosis. In addition, the promoter methylation status of the microRNA-9 gene increased in response to ionizing radiation. Our study demonstrated that microRNA-9 enhanced radiosensitivity in NSCLC and this effect is highly regulated by its promoter methylation status. These results will help to clarify regulatory mechanisms of radiation resistance thus stimulate new methods for improving radiotherapy for NSCLC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Situs inversus (SI) is a rare congenital anomaly characterized by the transposition of thoracic and abdominal viscera. Laparoscopic pancreaticoduodenectomy (LPD) is increasingly used in patients with periampullar and pancreatic carcinomas. For patients with SI, LPD can be more complicated because of reversed anatomy and possible other associated anomalies that have not been expected before surgery., Case Presentation: A female patient with SI totalis presented with inappetence, vomiting, and weight loss for 2 months. Imaging modalities and angiography revealed a mass in the periampullary region without obvious vascular abnormalities. The mass was successfully resected via LPD based on an elaborate preoperative plan. The surgical pathology report demonstrated adenocarcinoma of the duodenal papilla. The patient has been followed up for 4 months and no tumor recurrence or long-term complications were observed., Conclusion: LPD is technically difficult but feasible in patients with SI.

Objective: To investigate the regulatory mechanism of MEN1 gene in radiation-induced lung fibrosis in mice and provide a new theoretical basis for the clinical treatment of radiation pulmonary fibrosis., Methods: First, 80 C57BL/6 mice aged 8 weeks and weighing 18-22 g were selected, half of them were male and the other half were female. The mice were divided into control group and irradiation group (40 mice in each group) according to the method of the random number table. A radiation-induced lung fibrosis mouse model was established in which a single X-ray irradiation of 20 Gy was applied to the right lung in the irradiation group; H&E and Masson staining were used to verify whether the model was successful at 4, 8, 16 and 24 weeks after irradiation. The expression of MEN1, smooth muscle actin (α-SMA), Collagen-1 and transforming growth factor (TGF-β) in lung tissue were detected by Western blot and qPCR. Secondly, in the mouse embryonic fibroblast cell line (MEF) and mouse lung epithelial cell line (MLE-12), we constructed cell models of MEN1 knockout and interference separately with the irradiation of 10 Gy X-rays. The expression of α-SMA, Collagen-1, and TGF-β/Smads signaling pathway molecules was detected by qPCR. Finally, using the immunoprecipitation (IP) method, we can detect the interaction between Smad2 and the protein menin encoded by the MEN1 gene., Results: The results of the radiation pulmonary fibrosis model in mice showed that compared with the control group, the alveolar septum widens, the alveolar integrity decreases, the lung tissue slightly thickens, and a small amount of collagen deposits appear after 4-8 weeks in the model group. At twenty-fourth weeks, a large number of cells in the interstitial space of the lung tissue and a localized focal fibrosis area were observed. Further study found that radiation induced fibrogenic inflammatory cytokines TGF-β up-regulation, down-regulation of MEN1 gene expression, and then enhanced the expression of α-SMA and promotes the transformation of fibroblasts to myofibroblasts; At the same time, the expression of Collagen-1 was enhanced, which suggested that the extracellular matrix was overconcentrated and eventually promoted the formation of pulmonary fibrosis. In vitro, we found that knockout and interference of MEN1 gene can significantly enhance radiation-induced fibrosis, and up-regulate the expression of downstream molecules Smad2 and Smad3 of TGF-β signaling pathway, and down-regulate the expression of Smad7. Furthermore, it played an important role in regulating the process of radionuclide fibrosis., Conclusion: MEN1 plays a key role in the formation of pulmonary fibrosis by regulating the secretion of TGF-β and the activation of TGF-β/Smads signaling pathway., (Copyright © 2018. Published by Elsevier B.V.)

Background: Pancreatic adenocarcinoma is often diagnosed at an advanced stage when adjacent vascular invasion is present. Accurate evaluation of presence of vascular invasion can help guide therapy. The aim of this study was to construct a nomogram for preoperative prediction of peripancreatic vein invasion in patients with pancreatic head cancer., Study Design: Data of patients with carcinoma head of pancreas and suspected peripancreatic invasion (n = 247) who underwent pancreatic resection with venous reconstruction between January 2012 and January 2017 at four academic institutions were retrospectively analyzed. Univariate and multivariate analyses were used to identify independent risk factors for vein invasion from among demographic, biological, conditional host-related, and anatomical data. A predictive nomogram was constructed based on the identified independent risk factors., Results: The nomogram was constructed using data from 181 patients while the validation cohort consisted of 66 patients. Length of tumor contact (P = 0.031), circumferential vein involvement (P = 0.048), and venous contour abnormalities (P = 0.001) were independent predictors of venous invasion. The C-index of the model in predicting venous invasion was 0.963 for the external validation cohort. Patients could be assigned into low- (< 50%), intermediate- (50-90%), and high-risk (> 90%) groups based on the nomogram to facilitate personalized management., Conclusions: Vein invasion by pancreatic head cancer is mainly associated with anatomical factors. The nomogram for prediction of vein invasion was found to be practicable.

Post-hepatectomy liver failure (PHLF) is not only a leading cause of mortality but also a leading cause of life-threatening complications in patients undergoing liver resection. The ability to accurately detect the emergence of PHLF represents a crucially important step. Currently, PHLF can be predicted by a comprehensive evaluation of biological, clinical, and anatomical parameters. With the development of new technologies, imaging methods including elastography, diffusion-weighted magnetic resonance imaging, and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI play a more significant role in the pre-operative prediction and assessment of PHLF. In this review, we summarize the mainstream studies, with the aim of evaluating the role of imaging and improving the clinical value of existing scoring systems for predicting PHLF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a preoperative prognostic nomogram for patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peripancreatic venous invasion., Methods: Data on all consecutive patients were retrospectively collected from 2012 to 2016 at four academic institutions. The demographic and radiological parameters were analyzed using univariate and multivariate Cox regression analyses. The final nomogram was established using the concordance Harrell's C-indices and calibration curves from data obtained in three institutions and validated in the cohort of patients coming from the fourth institution., Results: The nomogram was constructed using data from 178 patients while the validation cohort consisted of 61 patients. Age, length of tumor contact, peripancreatic venous abnormalities and lymph node staging were independent factors of overall survival. The nomogram showed good probabilities of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.824 for the validation cohort., Conclusions: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Transmembrane protein 165 (TMEM165), a Golgi protein, functions in ion homeostasis and vesicular trafficking in the Golgi apparatus. While mutations in TMEM165 are known to cause human 'congenital disorders of glycosylation', a recessive autosomal metabolic disease, the potential association of this protein with human cancer development has not been explored to date. In the present study, we revealed that TMEM165 is overexpressed in HCC and its depletion weakens the invasive activity of cancer cells through suppression of matrix metalloproteinase‑2 (MMP‑2) expression. Levels of TMEM165 mRNA and protein were clearly increased in HCC patient tissues and cell cultures. Quantitative real‑time RT‑PCR analysis of fresh HCC tissues (n=88) revealed association of TMEM165 overexpression with more frequent macroscopic vascular invasion, microscopic serosal invasion and higher α‑fetoprotein levels. Notably, depletion of TMEM165 led to a marked decrease in the invasive activity of two different HCC cell types, Huh7 and SNU475, accompanied by downregulation of MMP‑2. Our collective findings clearly indicated that TMEM165 contributed to the progression of HCC by promoting invasive activity, supporting its utility as a novel biomarker and therapeutic target for cancer.

Gastric cancer is characterized by resistance to ionizing radiation. The development of resistance to radiotherapy in gastric cancer patients is one of the obstacles to effective radiotherapy. MicroRNAs are small well-conserved non-coding RNA species that regulate post-transcriptional activation. Our study aimed to investigate the role of miR-196b in radiation-induced gastric cancer. In the present study, we found that miR-196b expression was significantly reduced following radiation. The ectopic miR-196b expression sensitized SNU-638 gastric cancer cells and increased γ-H2AX foci upon radiation treatment. Bioinformatics analysis suggested that the DNA repair protein RAD23B was a putative target gene of miR-196b. Overexpression of miR-196b suppressed RAD23B expression in SNU-638 cells. Reporter assays further showed that miR-196b inhibited RAD23B 3'-UTR luciferase activity. Knockdown of RAD23B by small interfering RNA transfection closely mimicked the outcomes of miR-196b transfection, leading to impaired DNA damage repair in gastric cancer cells. Our results show that miR-196b improved radiosensitivity of SNU-638 cells by targeting RAD23B. Our data indicate that miR-196b is a potential target to enhance the effect of radiation treatment on gastric cancer cells. These findings will provide evidence for a new therapeutic target in radiotherapy., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The aim of this study was to conduct a meta-analysis comparing associating liver partition and portal vein ligation (ALPPS) with conventional 2-stage hepatectomy (TSH) in terms of clinical outcomes and to determine the feasibility and safety of ALPPS., Methods: A comprehensive search strategy was adopted to search the PubMed, Embase, Cochrane Library, and China Biology Medicine disc databases for studies comparing ALPPS and TSH. The search was broadened by looking up the reference lists of the retrieved articles. A meta-analysis was performed using the statistical software RevMan (v 5.3; Cochrane Collaboration)., Results: A total of 7 studies involving 561 patients (ALPPS group, 136 patients; TSH group, 425 patients) were included in the present study, all of which were observational studies. Compared with TSH, ALPPS was associated with high completion rates of both stages [odds ratio (OR): 10.68, 95% confidence interval (95% CI): 3.26-34.97, P < .0001]. No significant differences were found in other outcomes such as complications of the first (OR: 4.04, 95% CI: 0.81-20.27, P = .09) and second surgical stage (OR: 1.59, 95% CI: 0.71-3.57, P = .26), liver failure (OR: 0.76, 95% CI: 0.29-1.98, P = .58) and the 90-day mortality rate (OR: 2.20, 95% CI: 1.00-4.84, P = .05)., Conclusion: ALPPS is associated with lower noncompletion rate and had similar perioperative outcomes relative to TSH. However, only retrospective observational studies were included in this meta-analysis, which may have limited the strength of the evidence. High-quality, large-scale studies are required to further evaluate the outcomes of ALPPS.

Protein arginine methyltransferase 5 (PRMT5) is a protein that catalyzes transfer of methyl groups to the arginine residues of proteins and is involved in diverse cellular and biological responses. While the participation of PRMT5 in cancer progression has been increasingly documented, its association with the invasive phenotype currently remains poorly understood. In the present study, we revealed that PRMT5 is overexpressed in human hepatocellular carcinoma (HCC) and in colon cancer and its depletion leads to the suppression of cell invasive activity via the reduction of the expression of MMP-2. Real-time quantitative RT-PCR analysis of 120 HCC patient tissues revealed the overexpression of PRMT5 in HCC and the association of PRMT5 with aggressive clinicopathological parameters, such as poorer differentiation (P=0.004), more frequent hepatic vein invasion (P=0.019), larger tumor size (P=0.011) and higher α-fetoprotein levels (P=0.020). Similarly to the data obtained with HCC, overexpression of PRMT5 was also displayed in colon cancer tissues, compared to matched non-tumor regions. Consistent with the significant association of the overexpression of PRMT5 with hepatic vein invasion in patient specimens, PRMT5 depletion via siRNA transfection led to a marked reduction in the invasion rate in both HCC and colon cancer cells. Reduced invasion associated with PRMT5 depletion was accompanied by a decrease in the expression of MMP-2. Collectively, our results indicated that PRMT5 overexpression in HCC and colon cancer cells contributed to their acquisition of aggressive characteristics, such as invasiveness, thus presenting a promising therapeutic target for the treatment of these diseases.

We report a case of primary cutaneous mucormycosis caused by Mucor irregularis. A 66-year-old man was presented to our hospital with a history of gradually enlarging plaque on the right leg for about a year. The identification of pathogen based on the fungus morphology and DNA sequencing revealed M. irregularis as the responsible fungus for skin lesion. The lesion was removed incidentally by a surgery procedure, and no recrudescence was seen during a follow-up of 24-month observation.

Background: The metastasis of colorectal cancer frequently tends to liver, which is one of the three leading causes of cancer-related deaths worldwide. Growing evidence showed that aspirin could effectively inhibit liver metastasis of colorectal cancer. However, the potential mechanism has not been fully understood., Methods: Mouse splenic vein metastasis assay was used to examine the metastatic ability of colon cancer cells in vivo. And wound healing and transwell assay were applied to detect the metastasis potential of C26 and HCT116 colon cancer cell lines in vitro. RT-PCR and western blotting were used to explore Toll-like receptor 4 (TLR4) expression in colon cancer cell lines. The functions of TLR4 in the migration of the colon cancer cell line were analyzed by infecting cells with lentivirus containing TLR4 siRNA., Results: We demonstrated that lipopolysaccharides (LPS) could enhance the metastasis potential of C26 and HCT116 colon cancer cell lines. However, aspirin effectively decreased the metastasis capacity of colon cancer cells in vitro and in vivo. We found that the enhancement of LPS on the migration of colon cancer cells by inducing epithelial-mesenchymal transition (EMT) phenotype demonstrated a TLR4-dependent manner. Aspirin treatment lead to the downregulation of TLR4 on C26 cells which resulted in the decrease of C26 cells migration and EMT phenotype that induced by LPS. Additionally, the inhibitory effect from aspirin on the expression of TLR4 on C26 cells leads to the downregulation of NF-κB., Conclusion: The results of our study indicate that LPS origin from intestinal flora may promote the metastasis of colon cancer to liver and aspirin may inhibit the metastasis of colon cancer by inhibiting the expression of TLR4.

Study Design: A retrospective study., Objectives: The objectives of the study were to investigate the predictors for hyponatraemia in patients with cervical spinal cord injuries (CSCIs) and to define the relationship between magnetic resonance imaging (MRI) scans and hyponatraemia., Setting: The study was carried out at The First Affiliated Hospital of Anhui Medical University., Methods: A total of 292 patients with CSCIs were retrospectively reviewed to determine the predictors of hyponatraemia. Fourteen variables were extracted from the medical records: age, sex, blood pressure (BP), tracheostomy, serum potassium, serum chloride, serum bicarbonate, serum albumin, intravenous fluid intake and urine volume for 24 h, haematocrit, haemoglobin, neurological assessment and four MRI signal patterns. Univariate and multivariate analyses were used to determine the effect of each variable on hyponatraemia., Results: Eighty-two of the 270 patients (30%) developed hyponatraemia. Univariate analyses indicated that the following variables were significant predictors of hyponatraemia: tracheostomy; the initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) A assessment; and haemorrhage changes on T2-weighted MRI scans, and low BP. Multivariate regression analyses revealed two variables were significant predictors of hyponatraemia: haemorrhage changes on T2-weighted MRI scans and low BP., Conclusions: Haemorrhage changes on MRI scans were closely associated with the onset of hyponatremia and could provide objective data for forecasting hyponatraemia in CSCI patients. Low BP was also a reasonable predictor of hyponatremia.

Objective: To investigate the effect of oridonin on the human acute lymphocytic leukemia cell line Jurkat and its mechanism., Methods: Jurkat cells were cultured in vitro and treated with various concentrations (0, 1.25, 2.5, 5, and 10 μmol/L) of oridonin for different lengths of time (24, 48, and 72 hours). The proliferation of Jurkat cells was analyzed by MTT assay. The changes in nuclear morphology were evaluated by fluorescence microscopy at 12 hours after treatment with various concentrations of oridonin. The expression levels of Brg1, P53, and C-myc were determined by semi-quantitative Western blot in Jurkat cells treated with various concentrations of oridonin for 24 hours or 5 μmol/L oridonin for various lengths of time (0, 2, 6, 12, and 24 hours). The expression levels of P53 and C-myc and proliferation of Jurkat cells were evaluated after Brg1 expression was knocked down by Brg1-specific siRNA., Results: Compared with the control group, the proliferation of oridonin-treated Jurkat cells was significantly inhibited in a concentration- and time-dependent manner (P<0.05). According to the florescence microscopic analysis, oridonin treatment led to nuclear pyknosis in Jurkat cells. Compared with the control group, Jurkat cells treated with 5 μmol/L oridonin had reduced expression of Brg1 and C-myc but elevated expression of P53. Brg1 knock-down led to a significant reduction in proliferation of Jurkat cells (P<0.05), up-regulated expression of P53, and down-regulated expression of C-myc., Conclusions: Oridonin can inhibit the proliferation of Jurkat cells, probably via the Brg1 signaling pathway.

FOLFIRINOX chemotherapy has shown remarkable responses in patients with metastatic pancreatic cancer (MPC), and has significantly improved prognosis. However, FOLFIRINOX is currently not frequently applied in China because of its high incidence of adverse events, and there is no recognized optimization for this therapy in Chinese population. Modification of FOLFIRINOX may be better for its acceptance in China. In this study, we evaluated the efficacy and safety of modified-FOLFIRINOX in patients with MPC. A total of 62 MPC patients were treated with modified-FOLFIRINOX (no Fluorouracil bolus, 85% Oxaliplatin and 75% Irinotecan) between April 2014 and April 2017 in our institute. 40 of them were evaluated, with a response rate of 32.5% (13/40). The frequent grade 3/4 adverse events are neutropenia (29%) and alanine aminotransferase elevation (14.5%). No treatment-related death was observed. The median overall survival and median progression-free survival are 10.3 months and 7.0 months, respectively. In conclusion, modified-FOLFIRINOX had significantly improved tolerance with similar efficacy to FOLFIRINOX. These findings may provide evidence for the use of FOLFIRINOX in Chinese patients with MPC., (Copyright © 2017. Published by Elsevier B.V.)

Background: Although coal miners are susceptible to dyslipidaemia owing to their highly risky and stressful working environment as well as unhealthy lifestyle, very few studies have focused on this issue thus far. Therefore, this study investigated the current epidemiological characteristics of dyslipidaemia among Chinese coal miners., Methods: Demographic, anthropometric, and biochemical data were gathered from 4341 coal miners in China. Dyslipidaemia was diagnosed based on the serum lipid levels. Univariate and multivariate logistic regression analyses were used to assess the related risk factors for dyslipidaemia., Results: The average concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 5.01 ± 0.93 mmol/L, 1.90 ± 1.72 mmol/L, 1.21 ± 0.35 mmol/L, and 3.15 ± 0.80 mmol/L, respectively. Additionally, 38.08% of participants had a high TC level, 25.84% had a low HDL-C level, 35.08% had a high LDL-C level, and 40.46% had a high TG level. The overall prevalence of dyslipidaemia was 68.28% (95% CI: 66.90-69.66%). Factors associated with dyslipidaemia were age, sex, marital status, monthly family income, type of work, length of service, smoking status, smoking index, drinking status, alcohol consumption per day, elevated fasting glucose, hypertension, obesity and abdominal obesity., Conclusions: Our study's results indicated a very high prevalence of dyslipidaemia among Chinese coal miners and identified various risk factors for dyslipidaemia.

Several prediction models for fatty liver disease (FLD) are available with limited externally validation and less comprehensive evaluation. The aim was to perform external validation and direct comparison of 4 prediction models (the Fatty Liver Index, the Hepatic Steatosis Index, the ZJU index, and the Framingham Steatosis Index) for FLD both in the overall population and the obese subpopulation.This cross-sectional study included 4247 subjects aged 20 to 65 years recruited from the north of Shanxi Province in China. Anthropometric and biochemical features were collected using standard protocols. FLD was diagnosed by liver ultrasonography. We assessed all models in terms of discrimination, calibration, and decision curve analysis.The original models performed well in terms of discrimination for the overall population, with the area under the receiver operating characteristic curves (AUCs) around 0.85, while AUCs for obese individuals were around 0.68. Nevertheless, the predicted risks did not match well with the observed risks both in the overall population and the obese subpopulation. The FLI 2006 was 1 of the 2 best models in terms of discrimination (AUCs were 0.87 and 0.72 for the overall population and the obese subgroup, respectively) and had the best performance in terms of calibration, and attained the highest net benefit.The FLI 2006 is overall the best tool to identify high risk individuals and has great clinical utility. Nonetheless, it does not perform well enough to quantify the actual risk of FLD, which need to be (re)calibrated for clinical use.

Pancreatic cancer is mainly diagnosed at an advanced stage when adjacent vessel invasion is present; however, radical resection is potentially curative for selected patients with adjacent vessel invasion. Therefore, accurately judging the resectability of patients with adjacent vessel invasion represents a crucially important step in diagnosis and treatment. Currently, decisions regarding resectability are based on imaging studies, commonly contrast computed tomography (CT). Several radiological classifications have been published for vascular infiltration in pancreatic cancer. However, radiologists always formulate these CT grading systems according to their own experience, resulting in different judgment methods and parameters. And it is controversial in evaluating performance and clinical application. Besides, the conventional CT grading systems mainly focus on the evaluation of vessel invasion so as to less on the outcome of patient evaluation. In this review, we summarize the mainstream CT grading systems for vascular invasion in pancreatic cancer, with the aim of improving the clinical value of CT grading systems for predicting resectability and survival.

Krüppel-like factor 8 (KLF8) is highly expressed in hepatocellular carcinoma (HCC) and contributes to tumor initiation and progression by promoting HCC cell proliferation and invasion. However, the role of KLF8 in liver cancer stem cells (LCSCs) is not known. In the current study, we investigated the role of KLF8 in LCSCs to determine if KLF8 is a novel marker of these cells. We found that KLF8 was highly expressed in primary HCC tumors, distant migrated tissues, and LCSCs. Patients with high KLF8 expression had a poor prognosis. KLF8 promoted stem cell-like features through activation of the Wnt/β-catenin signaling pathway. Cell apoptosis was significantly increased in HCC cells with knockdown of KLF8 compared with the control cells when treated with the same doses of sorafenib or cisplatin. Taken together, our study shows that KLF8 plays a potent oncogenic role in HCC tumorigenesis by maintaining stem cell-like features through activation of the Wnt/β-catenin signaling pathway and promoting chemoresistance. Thus, targeting KLF8 may provide an effective therapeutic approach to suppress tumorigenicity of HCC. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background & Aims: Whether perioperative blood transfusions (PBTs) negatively impact oncologic outcomes after curative resection for HCC remains controversial. We aimed to identify the independent predictive factors of PBT for curative resection of hepatocellular carcinoma (HCC), and to investigate the impact of PBT on long-term recurrence and survivals after resection., Methods: Of 1103 patients who underwent curative liver resection for HCC between 1999 and 2010, 285 (25.8%) patients received PBT. Univariable and multivariable regression analyses were used to identify independent predictive factors of PBT. Propensity scores and Cox regression analyses were used to compare the overall survival (OS) and recurrence-free survival (RFS) between patients who did and did not receive PBT., Results: Multivariable regression analysis revealed that performance status, preoperative hemoglobin, cirrhosis, portal hypertension, tumor rupture, tumor size, macroscopic vascular invasion, and intraoperative blood loss were independent predictive factors of PBT for HCC resection. Propensity score matching analysis created 234 pairs of patients. Before propensity matching, PBT was significantly associated with increased risks of OS (HR: 2.455, 95% CI: 2.077-2.901, p<0.001) and RFS (HR: 2.018, 95% CI: 1.718-2.370, p<0.001) in the entire cohort. After propensity matching, PBT was not significantly associated with increased risks of OS (HR: 1.229, 95% CI: 0.988-1.527, p=0.063) and RFS (HR: 1.188, 95% CI: 0.960-1.469, p=0.113). After adjustment for other prognostic variables in the propensity matched cohort, PBT was still found not to be associated with OS and RFS after HCC resection., Conclusions: The present study identified that PBT did not influence RFS and OS after curative resection of HCC., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the overall qualities of published surgical meta-analysis and predictive factors for high qualities., Study Design and Setting: All meta-analyses pertinent to surgical procedures published in year 2013 were selected from PubMed and EMBASE. The characteristics of the included meta-analyses were collected, and their reporting and methodologic qualities were assessed by the PRISMA (27 items) and AMSTAR (11 items) checklists, respectively. Independent predictive factors associated with these two qualities were evaluated by univariate and multivariate analyses., Results: Hundred ninety-seven meta-analyses representing 10 surgical subspecialties were included. The mean PRISMA and AMSTAR adherences (by items) were 22.2 ± 2.4 and 7.8 ± 1.2, respectively, and a positive linear correlation was found between them with an R(2) of 0.793. Those meta-analyses conducted by the first authors having meta-analysis publication previously had significantly higher reporting and methodologic qualities than those who did not (P = 0.002 and P = 0.001). Meanwhile, there were also significant differences in these two qualities between studies published in Q1-ranked and (Q2 + Q3)-ranked journals as rated by the SCImago indicator (P < 0.001 and P < 0.001). On multivariate analyses, region of origin (non-Asia vs. Asia), publishing experience of first authors (ever vs. never), rank of publishing journals (Q1 vs. Q2 + Q3), and preregistration (presence vs. absence) were independently associated with superior reporting and methodologic qualities., Conclusions: The reporting and methodologic qualities of current surgical meta-analyses remained suboptimal, and first authors' experience and ranking of publishing journals were independently associated with both qualities. Preregistration might be an effective measure to improve the quality of meta-analyses, which deserves more attention from future study conductors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Intrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary malignancy arising from the epithelial cells of the intrahepatic bile ducts. The increased incidence of ICC worldwide may reflect both a true increase and the earlier detection of the disease. Despite the advances in modern surgical care, the curative chance for ICC remained suboptimal: tumor-free margins are hard to achieve due to tumor locations, and technical challenges and recurrence, either local or distant, may hamper the resectability in a large number of patients. Lymph node involvement and vascular invasions are considered negative predictive factors for survival of ICC patients. This review discusses the epidemiology, risk factors and surgical management of ICCs, and mainly focuses on outcomes and factors associated with surgical treatment., Competing Interests: Financial & competing interests disclosure This study was supported by National Natural Science Foundation of China (No. 81472284, 81372262 and 81172020); Program for Excellent Young Scholars of SMMU; Charitable Project on Cancer Research of Shanghai and State Key Project on Infectious Diseases of China (No. 2012ZX10002–016). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

BACKGROUND Primary Sjögren's syndrome (pSS) is one of the most common chronic systemic autoimmune diseases, and thrombocytopenia is one of the hematological manifestations of pSS. When platelet and endothelial cells are activated, P-selectin is expressed on the cell surface. This study aimed to investigate the role of P-selectin autoantibodies in the pathogenesis of thrombocytopenia in pSS. MATERIAL AND METHODS P-selectin autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 38 pSS patients without thrombocytopenia and 32 pSS patients with thrombocytopenia, 32 idiopathic thrombocytopenic purpura (ITP) patients, and 35 healthy controls. RESULTS The plasma P-selectin autoantibodies (A490) in ITP patients and pSS patients with/without thrombocytopenia were significantly higher than those in healthy controls, but there were no significant differences between ITP patients and pSS patients with thrombocytopenia. The positive rate of P-selectin autoantibodies in pSS patients with thrombocytopenia was significantly higher than that in ITP patients. The platelet count was lower in P-selectin autoantibodies-positive patients, while among pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients than in P-selectin autoantibodies-negative patients. In ITP patients and pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients. CONCLUSIONS Elevated plasma P-selectin autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS patients.

Majocchi's granuloma (MG) is a rare deep skin dermatophyte infection that can occur either in immunocompetent or in immunocompromised individuals. Oral itraconazole or terbinafine is considered to be the first choice of treatment. We report an immunocompetent man with deep nodular form of MG, the form which is generally found in immunosuppressed individuals. Previous treatment with either oral itraconazole or terbinafine yielded no apparent improvement. After a series of examination, the man was diagnosed as having Trichophyton rubrum-induced MG mixed with bacterial infection as evidenced by growth of Klebsiella pneumoniae in tissue bacterial culture. The patient was treated with a combination of cefoselis and levofloxacin for bacterial clearance followed by voriconazole treatment. After approximately 4 months of voriconazole treatment, the lesions completely resolved. Alternative medicine (voriconazole) can be considered in case of refractory infections during MG treatment.

Aortic valve calcification (AVC) is a pathological process correlated with multiple disease causes and actively regulated by cardiac valve cells. In this study, porcine aortic valve myofibroblasts cultured in vitro were treated with 50 μg z L(-1) of pathological factor tumor necrosis factor α (TNF-α). Tanshinone II A (TSN) with the concentration of 50 mg x L(-1) and TNF-α were combined in incubating cells for 72 h (3 d) and 120 h (5 d). The Western blotting and Real-time PCR were adopted to detect the changes in smooth muscle α actin (α-SMA), bone morphogenetic protein 2 ( BMP2), alkaline phosphatase (ALP) in cells, and expressions of key effect proteins GSK-3β and β-catenin on Wnt/β-catenin signal pathway. According to the findings, TNF-α can significantly increase the expression of myofibroblasts α-SMA and add the transformation activity to them, with nearly no expression of BMP2, ALP and mRNA in the control group and the TSN group but significant increase in their expressions in the TNF-α group (P < 0.01), which showed osteoblast-like phenotype. Moreover, TNF-α down-regulated the expression of up-streaming regulator GSK-3β and mRNA expression (P < 0. 01) , notably increased the expression of key effect protein β-catenin, but with no significant difference in mRNA with the control group and the TSN group. The result demonstrated that TSN showed a certain inhibitory effect on TNF-α's pathological impact (P < 0.05) in a time-dependent manner. Inflammatory factor TNF-α may promote the transformation of aortic valvular myofibroblasts to osteoblast-like phenotype by activating Wnt/β-catenin signal pathway in aortic valvular myofibroblasts, so as to cause AVC. Tanshinone II A can have a preventive effect in AVC by activating GSK-3β proteins and regulating signal transduction of Wnt/β-catenin signal pathway.

We assessed the capability of paclitaxel, one of the taxanes, to induce death in two prostate cancer lines, LNCaP and PC3. Paclitaxel drove an apoptotic pathway in LNCaP, but not in PC3 cells, in response to G2/M arrest. An examination of the levels of anti-apoptotic proteins revealed that Bcl-xl was much higher in PC3 cells than in LNCaP cells and Bcl2 could be detected only in PC3 cells, not in LNCaP cells. Knocking down Bcl-xl enhanced paclitaxel-induced apoptosis in LNCaP cells, while we were unable to knock down Bcl-xl efficiently in PC3 cells. Significantly, a comparison of ABT-263, a specific inhibitor of Bcl2 and Bcl-xl, with ABT-199, a Bcl2 selective inhibitor, disclosed that only ABT-263, not ABT-199, could induce apoptosis in LNCaP and PC3 cells. The results indicate that Bcl-xl has a protective role against paclitaxel-induced apoptosis in LNCaP and PC3 cells, and its overexpression causes the paclitaxel resistance seen in PC3 cells. Interestingly, combined paclitaxel with ABT-263 to treat LNCaP and PC3 cells demonstrated synergistic apoptosis activation, indicating that ABT-263 could enhance paclitaxel-induced apoptosis in LNCaP cells and overcome Bcl-xl overexpression to trigger paclitaxel-induced apoptosis in PC3 cells. We also observed that the activation of apoptosis in LNCaP cells was more efficient than in PC3 cells in response to paclitaxel plus ABT-263 or to ABT-263 alone, suggesting that the apoptosis pathway in PC3 cells might have further differences from that in LNCaP cells even after Bcl-xl overexpression is accounted for.

DNA lesion-induced centrosomal abnormalities during the replication phase are relatively unknown. Here, we report that RNAi-mediated depletion of RRM1 induces cell-cycle arrest at the replication phase, along with severe DNA damage and centrosomal amplification. Interestingly, CHK1 depletion synergistically increased RRM1-depletion-induced centrosomal amplification. In response to hydroxyurea, CHK1 was delocalized from the centrosome by RRM1 depletion. Moreover, CDK1, which functions in centrosome separation and is inhibited by CHK1, was found to be essential for RRMI1-depletion-induced centrosomal amplification. Thus, we herein demonstrate that RRM1 preserves chromosomal stability via the CHK1- and CDK1-dependent stabilization of the centrosomal integrity at the replication stage., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A study of 7,388 consecutive patients after hepatic resection between 2011 and 2012 identified hepatolithiasis, cirrhosis, and intraoperative blood transfusion as the only independent risk factors of both incisional and organ/space surgical site infection (SSI). Patients with these conditions should be cared for with caution to lower SSI rates.

Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: SHOX2 (short stature homeobox 2) is a crucial transcriptional regulator in several genetic disorders and has been demonstrated to be an excellent biomarker in the diagnosis and evaluation of lung cancer. However, its expression pattern and prognostic value for hepatocellular carcinoma (HCC) are still unknown., Methods: Expression of SHOX2 gene and protein in HCC tissues and cell lines were evaluated by RT-qPCR and western blot. Impact of RNAi-mediated SHOX2 silence on the proliferation and invasion ability of Huh7 cell line in vitro was determined by CCK-8 assay and matrigel invasion assay, respectively., Results: Elevated expression of SHOX2 gene was significantly associated with higher incidence of tumor recurrence (n = 60, p = 0.001), absence of tumor capsule (p = 0.015), presence of tumor thrombi (p < 0.0001), and advanced TNM stage (p < 0.0001) of HCC. SHOX2 protein expression was more abundant in HCC cell lines compared with hepatic cell line (p = 0.001), which was associated with tumor recurrence (n = 40, p = 0.046). RNAi-mediated silence of SHOX2 expression significantly inhibited the proliferation (p < 0.001) and invasion (p = 0.006) of Huh7 cell line in vitro., Conclusions: Elevated SHOX2 expression was associated with HCC recurrence, probably by enhancing proliferation and invasion capability of cancer cells.

β-Transducin repeat-containing protein (β-TrCP), an E3 ligase, promotes the degradation of substrate proteins in response to various stimuli. Even though several β-TrCP substrates have been identified to date, limited information of its upstream regulators is available. Here, we showed that SIRT1 suppresses β-TrCP protein synthesis via post-translational degradation. SIRT1 depletion led to a significant increase in the β-TrCP accumulation without affecting the mRNA level. Consistently, β-TrCP protein accumulation induced by resveratrol was further enhanced upon SIRT1 depletion. Rescue of SIRT1 reversed the effect of resveratrol, leading to reduced β-TrCP protein levels. Proteasomal inhibition led to recovery of β-TrCP in cells with SIRT1 overexpression. Notably, the recovered β-TrCP colocalized mostly with SIRT1. Thus, SIRT1 acts as a negative regulator of β-TrCP synthesis via promoting protein degradation., (Copyright © 2013 Elsevier Inc. All rights reserved.)