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Aims Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. Method and results MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and type 2 innate lymphoid cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. Conclusion IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Translational perspective Accumulating evidence suggests that modulation of innate and adaptive immune responses is a promising therapeutic strategy for myocardial infarction. In this study, we demonstrate that IL-5 exerts cardioprotective effects on infarcted myocardium by promoting eosinophil accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Hence, regulation of cardiac IL-5 level or eosinophil count may become a therapeutic approach for post-myocardial infarction cardiac repair in humans.

Ferroptosis is a newly identified cell death mechanism and potential biomarker for hepatocellular carcinoma (HCC) therapy; however, its clinical relevance and underlying mechanism remain unclear. In this study, transcriptome and methylome data from 374 HCC cases were investigated for 41 ferroptosis‐related genes to identify ferroptosis activity‐associated subtypes. These subtypes were further investigated for associations with clinical and pathological variables, gene mutation landscapes, deregulated pathways and tumour microenvironmental immunity. A gene expression signature and predictive model were developed and validated using an additional 232 HCC cases from another independent cohort. Two distinct ferroptosis phenotypes (Ferroptosis‐H and Ferroptosis‐L) were identified according to ferroptosis gene expression and methylation in the patients with HCC. Patients with the Ferroptosis‐H had worse overall and disease‐specific survival, and the molecular subtypes were significantly associated with different clinical characteristics, mRNA expression patterns, tumour mutation profiles and microenvironmental immune status. Furthermore, a 15‐gene ferroptosis‐related prognostic model (FPM) for HCC was developed and validated which demonstrated accurate risk stratification ability. A nomogram included the FPM risk score, ECOG PS and hepatitis B status was developed for eventual clinical translation. Our results suggest that HCC subtypes defined by ferroptosis gene expression and methylation may be used to stratify patients for clinical decision‐making.

Background Liver cancer is a major public health concern, but the mechanistic actions of bio-markers contributing to liver cancer remain to be determined. In this study, we aimed to investigate the regulatory cascade of microRNA-424-5p (miR-424-5p), X-inactive-specific transcript (XIST), and O-GlcNAc transferase (OGT) in liver cancer. Methods Differentially expressed miRNAs and target genes related to liver cancer were predicted by bioinformatic analyses, and their expression was determined in liver tissues of patients with liver cancer and liver cancer cells. The RNA immunoprecipitation (RIP), RNA pull-down, and dual luciferase reporter assay were used to examine the binding affinity among XIST and miR-424-5p and OGT. Then, gain- and loss- of function assays were conducted to evaluate the effects of the XIST/miR-424-5p/OGT axis on malignant phenotypes. A nude mouse model of liver cancer was further established for in vivo substantiation. Results XIST and OGT were up-regulated in liver cancer tissues and cells, responsible for poor prognosis in patients with liver cancer, while miR-424-5p was down-regulated. XIST competitively bound to miR-424-5p to increase OGT expression. XIST silencing inhibited malignant phenotypes of liver cancer cells, while miR-424-5p downregulation negated its effect.. miR-424-5p suppressed RAF1 glycosylation by negatively regulating OGT expression and promoted its ubiquitination/degradation. Further, XIST knockdown inhibited tumor growth and metastasis in nude mice, while ectopic OGT reversed its effect. Conclusion These results reveal a novel mechanism by which the interaction of XIST/miR-424-5p/OGT participates in the malignancy and metastasis of liver cancer.

Increased glycolysis has been reported as a major metabolic hallmark in many cancers, and is closely related to malignant behavior of tumors. However, the potential mechanism of glycolysis in hepatocellular carcinoma (HCC) and its prognostic value are not well understood. To address this, we investigated glycolysis-related gene expression data of patients with HCC from TCGA and ICGC. Patients were categorized into three different glycolysis-associated subgroups: Glycolysis-M, Glycolysis-H, and Glycolysis-L. We found that Glycolysis-H combined with Glycolysis-M (Glycolysis-H+M) subgroup was associated with poor overall survival and distinct cancer stem cell characteristics and immune infiltrate patterns. Additionally, multiomics-based analyses were conducted to evaluate genomic patterns of glycolysis subgroups, including their gene mutations, copy number variations, and RNA-sequencing data. Finally, a glycolysis-associated multiomics prognostic model (GMPM) consisting of 19 glycolysis-associated genes was developed. The capability of GMPM in categorizing patients with HCC into high- and low-risk groups was validated with independent HCC datasets. Finally, GMPM was confirmed as an independent risk factor for the prognosis of patients with HCC. We believe that our findings provide new insights into the mechanism of glycolysis and highlight the potential clinical value of GMPM in predicting the prognosis of patients with HCC.

Altered expression of circEPHB4, miR‐637 or SOX10 was independently associated with overall survival of glioma patients. By sponging miR‐637, circEPHB4 up‐regulated SOX10 and its target Nestin to promote stemness and self‐proliferation of glioma cells, stimulating the malignant progression of gliomas. Consistently, silencing circEPHB4 or overexpressing miR‐637 inhibited xenograft growth of glioma cells in vivo and has therapeutic prospects., Gliomas are the most common type of primary brain tumors. CircRNA ephrin type‐B receptor 4 (circEPHB4) is a circular RNA derived from the receptor tyrosine kinase EPHB4. However, the clinical significance and the specific roles of circEPHB4 in gliomas and glioma cancer stem cells (CSC) have not been studied. Here, we found that circEPHB4 (hsa_circ_0081519) and SOX10 were up‐regulated and microRNA (miR)‐637 was down‐regulated in glioma tissues and cell lines. Consistently, circEPHB4 was positively correlated with SOX10 but negatively correlated with miR‐637. The altered expressions of these molecules were independently associated with overall survival of patients. CircEPHB4 up‐regulated SOX10 and Nestin by directly sponging miR‐637, thereby stimulating stemness, proliferation and glycolysis of glioma cells. Functionally, silencing circEPHB4 or increasing miR‐637 levels in glioma cells was sufficient to inhibit xenograft growth in vivo. In conclusion, the circEPHB4/miR‐637/SOX10/Nestin axis plays a central role in controlling stem properties, self‐renewal and glycolysis of glioma cells and predicts the overall survival of glioma patients. Targeting this axis might provide a therapeutic strategy for malignant gliomas.

The aim of this study was to compare the diagnostic values of red blood cell distribution width-coefficient of variation (RDW-CV) and red blood cell distribution width-standard deviation (RDW-SD) in mid-pregnancy women with iron deficiency anemia (IDA). To obtain the results, 115 mid-pregnancy women with IDA, defined as the IDA group, and 142 healthy mid-pregnancy women, selected as the control group, were enrolled in this study. Hematological parameters and ferritin concentrations in the serum were analyzed. The efficiency of RDW-CV and RDW-SD to distinguish IDA from mid-pregnancy women was evaluated using receiver operating characteristic (ROC) curves. The RDW-SD value in the IDA group was significantly higher than that in the control group (p < 0.05), while the RDW-CV value did not differ between them (p = 0.84). Significantly negative correlations were found between RDW-CV (r = −0.297, p = 0.001), RDW-SD (r = −0.404, p = 0.000), and serum ferritin in the IDA group but not in the control group. For the diagnosis of IDA, RDW-CV and RDW-SD produced areas under the ROC curves of 0.58 and 0.84. To conclude, our results suggest that RDW-SD, but not RDW-CV, can be used as a diagnostic index of IDA for mid-pregnancy women.

Distal metaphyseal tibial fractures (3-5 cm from the joint with zones of comminution or3 cm from the joint) are challenging to fix and are associated with many complications. The study objective was to evaluate the functional outcomes and complications after treating distal metaphyseal tibial fractures using anatomical anterolateral tibia locking plates or anterolateral-medial plates. This retrospective study included 57 patients with distal metaphyseal tibial fractures. Thirty patients were treated by open reduction internal fixation with anterolateral plates; 27 patients were treated with anterolateral-medial plates. Patients were followed at regular intervals. The time to fracture union and complications were recorded. We evaluated the stage of fracture healing using the Radiographic Union Score for Tibial fractures. The patients treated with anterolateral plates had significantly higher rates of loss of reduction and malunion than those treated with anterolateral-medial plates (p = .02 and p = .002, respectively). There were no significant differences in the radiographic union scores (p = .22), non-union (p = .17), incision necrosis (p = .91), or infection (p = .94) between the 2 groups. The functional outcomes were assessed using the American Orthopedic Foot and Ankle Society hindfoot-ankle score at the 12-month follow-up. The mean hindfoot-ankle scores were 90.9 ± 5.0 (range 79 to 100, median 90) and 92.3 ± 5.1 (range 82 to 100, median 92) for the anterolateral plates and anterolateral-medial plates, respectively (p = .29). For distal metaphyseal tibial fractures, anterolateral-medial plates may be worthwhile for reducing loss of reduction and malunion.

BACKGROUND Total pancreatectomy (TP) is usually considered a therapeutic option for pancreatic cancer in which Whipple surgery and distal pancreatectomy are undesirable, but brittle diabetes and poor quality of life (QoL) remain major concerns. A subset of patients who underwent TP even died due to severe hypoglycemia. For pancreatic cancer involving the pancreatic head and proximal body but without invasion to the pancreatic tail, we performed partial pancreatic tail preserving subtotal pancreatectomy (PPTP-SP) in selected patients, in order to improve postoperative glycemic control and QoL without compromising oncological outcomes. AIM To evaluate the efficacy of PPTP-SP for patients with pancreatic cancer. METHODS We retrospectively reviewed 56 patients with pancreatic ductal adenocarcinoma who underwent PPTP-SP (n = 18) or TP (n = 38) at our institution from May 2014 to January 2019. Clinical outcomes were compared between the two groups, with an emphasis on oncological outcomes, postoperative glycemic control, and QoL. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 and EORTC PAN26). All patients were followed until May 2019 or until death. RESULTS A total of 56 consecutive patients were enrolled in this study. Perioperative outcomes, recurrence-free survival, and overall survival were comparable between the two groups. No patients in the PPTP-SP group developed cancer recurrence in the pancreatic tail stump or splenic hilum, or a clinical pancreatic fistula. Patients who underwent PPTP-SP had significantly better glycemic control, based on their higher rate of insulin-independence (P = 0.014), lower hemoglobin A1c (HbA1c) level (P = 0.046), lower daily insulin dosage (P < 0.001), and less frequent hypoglycemic episodes (P < 0.001). Global health was similar in the two groups, but patients who underwent PPTP-SP had better functional status (P = 0.036), milder symptoms (P = 0.013), less severe diet restriction (P = 0.011), and higher confidence regarding future life (P = 0.035). CONCLUSION For pancreatic cancer involving the pancreatic head and proximal body, PPTP-SP achieves perioperative and oncological outcomes comparable to TP in selected patients while significantly improving long-term glycemic control and QoL.

Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.

Background and Objectives: In the recent years, EUS is one of the routine procedures in the diagnosis of pancreatic diseases. EUS-guided needle-based confocal laser endomicroscopy (nCLE) is a novel minimally invasive imaging technique in diagnosis of pancreatic diseases. The pilot researches provided us some preliminary findings and conclusions with small samples, low rate of pathological correspondence. The aim of this current study was to evaluate the diagnostic efficacy of EUS-guided nCLE in solid pancreatic lesions (SPLs) and pancreatic cystic lesions (PCLs) based on large samples. The date was obtained on nCLE imaging findings and high rate of correlation with pathology. Material and Methods: Patients enrolled in the study were underwent EUS-nCLE to achieve the nCLE images and diagnosis. Comparing with the final diagnosis, including surgical histopathological results or cyto-/histopathology through FNA, the efficacy and accuracy of nCLE in diagnosis in solid and cystic pancreatic lesions were evaluated. In other cases, clinical diagnoses were achieved based on the combination with clinical history, image findings and fluid analysis and cytology, by 3 independent committee members strongly agreed with a concordant diagnosis. Results: Totally 172 patients were enrolled into the study. The overall rate of final diagnosis was about 65% while 50% in cystic lesion. The mean sensitivity, specificity, negative predictive value, positive predictive value and accuracy of the nCLE in diagnosis of PDAC is 90.3%, 89.5%, 93.3%, 85.0% and 90.0% respectively. The efficacy and accuracy of pancreatic cystic lesions were very satisfying and some additional nCLE signs were found, including “black aggregates of cells, forming as gland-like structure, surrounding by fibro and vessels” in neuroendocrine tumors (NETs); “black columnar protrusions near vascular area” in the pseudopapillary solid tumor (SPT); macrophage in tuberculosis (TB) and small aggregate of black regular cells maybe corresponds to ovarian-like stroma in mucinous cystadenoma (MCN). In the study, 20 (11.6%) patients suffered complications, including symptomatic (5.2%) and asymptomatic (6.4%). Conclusions: nCLE observation could improve characterization of indeterminate cysts, or confirm the EUS impression, when cytological confirmation is missing. The technique may deliver information to better guide our clinical decisions.

To assess and compare clinical outcomes and sagittal balance after unstable hangman fracture between C2-C3 anterior discectomy and fusion (ACDF) and posterior C2-C3 short-segment fixation and fusion.A total of 45 patients underwent ACDF (20 patients) and posterior C2-C3 short-segment fixation and fusion (25 patients) between March 2005 and June 2013. Visual analog scale, Neck Disability Index, Odom grading system, American Spinal Injury Association Impairment Scale (AIS), C2-C3 angle, displacement of C2-C3 (DThe follow-up duration was 20.0 months (range, 18.0-21.0 months) in the anterior group and 19.0 months (range, 18.0-20.0 months) in the posterior group. Satisfactory bony fusions were achieved in 2 groups. The VAS score and NDI score were significantly lower than their respective preoperative score in each group (P0.001), whereas there was no difference between 2 groups (P = 0.78; P = 0.85). A statistically significant decrease of O-C2 angle and cSVA between preoperative and postoperative data was found in each group (P0.001), and CL increased statistically (P0.001). For O-C2 angle, CL, and cSVA, the changes of parameters after the posterior approach were more significant than after the anterior approach (P0.05).Both anterior and posterior surgical techniques are effective for unstable hangman fracture and both can restore the sagittal balance of the cervical spine. Furthermore, the posterior approach has an advantage over the anterior approach in promoting recovery of cervical sagittal balance.

Objective: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention. Here, we try to assess the applicability of ctDNA in PC. Methods and materials: Next generation sequencing (NGS) was performed from blood samples of 223 PC patients and tissue sample of 564 PC patients. Genomic data from the TCGA database were also utilized. In addition, two cases received personalized treatment based on ctDNA sequencing results were reported. Results: Based on ctDNA sequencing, the genomic features of PC was revealed. Totally, 68.2% of patients detected at least one reportable genomic alteration (GA) from ctDNA. The frequently altered genes were KRAS (53.5%), followed by TP53 (52.8%), and CDKN2A (15.1%). Cell cycle control (8%) and DNA damage response (8%) pathways enriched the most mutated genes. Compared with mutations from tissue samples and a tissue-genomic database, similar frequencies of GAs were detected from ctDNA. The first two highest frequent mutation of genes were the same, but some of mutated genes were inclined to be observed in ctDNA, like AR. And two cases who received personalized therapy achieved better clinical benefit. Conclusion: Blood-source ctDNA sequencing could be regarded as a meaningful complement to tissue testing, and might guide clinically therapeutic regimen.

Background The survival rates of patients with metastatic osteosarcoma are poor, and the prognosis is closely related to the choice of treatment, especially surgery. This study aimed to evaluate the survival outcomes of patients with metastatic osteosarcoma undergoing regional dissections. Methods We collected data on patients with metastatic osteosarcoma between 2004 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS), while univariate and multivariate Cox regression analyses were used to evaluate outcomes. Propensity score matching (PSM) was used to minimize the effects of confounding factors. Results The SEER database had records of 2768 patients diagnosed with osteosarcoma, of whom 398 were included in our study. Of the included patients, 116 (29.15%) underwent regional dissections, while 282 (70.85%) underwent non-regional dissections. The univariate and multivariate Cox regression analyses, prior to PSM, showed that OS (hazard ratio (HR): 0.34, 95% confidence interval (CI): 0.26–0.44, P Conclusions Compared with non-regional dissection, regional dissection resulted in better survival in patients with metastatic osteosarcoma.

Rationale: The crosstalk between cardiac microvascular endothelial cells (CMECs) and cardiomyocytes (CMs) has emerged as a key component in the development of, and protection against, cardiac diseases. For example, activation of endothelial nitric oxide synthase (eNOS) in CMECs, by therapeutic strategies such as ischemic preconditioning, plays a critical role in the protection against myocardial ischemia/reperfusion (I/R) injury. However, much less is known about the signals produced by CMs that are able to regulate CMEC biology. Here we uncovered one such mechanism using Tongxinluo (TXL), a traditional Chinese medicine, that alleviates myocardial ischemia/reperfusion (I/R) injury by activating CMEC eNOS. The aim of our study is to identify the signals produced by CMs that can regulate CMEC biology during I/R. Methods: Ex vivo, in vivo, and in vitro settings of ischemia-reperfusion were used in our study, with the protective signaling pathways activated in CMECs identified using genetic inhibition (p70s6k1 siRNA, miR-145-5p mimics, etc.), chemical inhibitors (the eNOS inhibitor, L-NNA, and the small extracellular vesicles (sEVs) inhibitor, GW4869) and Western blot analyses. TritonX-100 at a dose of 0.125% was utilized to inactivate the eNOS activity in endothelium to investigate the role of CMEC-derived eNOS in TXL-induced cardioprotection. Results: We found that while CMEC-derived eNOS activity was required for the cardioprotection of TXL, activation of eNOS in CMECs by TXL did not occur directly. Instead, eNOS activation in CMECs required a crosstalk between CMs and CMECs through the uptake of CM-derived sEVs. We further demonstrate that TXL induced CM-sEVs contain increased levels of Long Intergenic Non-Protein Coding RNA, Regulator Of Reprogramming (Linc-ROR). Upon uptake into CMECs, linc-ROR downregulates its target miR-145-5p leading to activation of the eNOS pathway by facilitating the expression of p70s6k1 in these cells. The activation of CMEC-derived eNOS works to increase survival in both the CMECs and the CMs themselves. Conclusions: These data uncover a mechanism by which the crosstalk between CMs and CMECs leads to the increased survival of the heart after I/R injury and point to a new therapeutic target for the blunting of myocardial I/R injury.

Background For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection. Methods In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3–6 and 6–9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized. Results We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94–3.46]), alopecia (OR 3.09, 95% CI [2.53–3.76]), chest pain (OR 1.27, 95% CI [1.09–1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22–2.10]), shortness of breath (OR 1.41, 95% CI [1.22–1.64]), pneumonia (OR 1.66, 95% CI [1.28–2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22–1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65. Conclusions The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Background: As more than 200,000 neonates participate in newborn congenital hypothyroidism (CH) screening in Guangxi, China each year, the overall number of false positives has increased. The potential demographic impact on parental stress and knowledge of CH results has attracted many concerns. Methods: The parents of neonates with false-positive (FP) CH results were invited to participate in the FP group, and the parents of neonates with all negative results were invited to participate in the control group. After providing consent, the parents completed a questionnaire on demographic characteristics, knowledge of CH and the parental stress index (PSI) - short form (Chinese version). Results: As a result, there were 258 and 1040 parents participated in FP group and control group respectively. The parents in the FP group had better knowledge of CH and higher PSI scores than did the parents in the control group (both P < 0.001). The result of Logistic Regression showed that the major influence factors of knowledge of CH were FP experience and source of knowledge (both P P > 0.05). The parents in the FP group who were well-informed during the recall phone call had lower PSI scores than did the other parents (P = 0.001). The results suggested that FP screening results may affect parental stress and the parent-child relationships. Conclusion: FP results increased the stress on the parents, and increased their knowledge of CH passively. Targeted health education should be carried out to increase prospective parents’ knowledge of NBS and reduce parental stress when false-positive results are received.

Cholangiocarcinoma (CCA) is a malignant hepatic tumor with a poor prognosis, which needs early diagnosis urgently. The gut microbiota has been shown to play a crucial role in the progression of liver cancer. Here, we explored a gut microbiota model covering genera Burkholderia-Caballeronia-Paraburkholderia, Faecalibacterium, and Ruminococcus_1 (B-F-R) for CCA early diagnosis. A case-control study was conducted to enroll 53 CCA patients, 47 cholelithiasis patients, and 40 healthy controls. The feces samples and clinical information of participants were collected in the same period. The gut microbiota and its diversity of individuals were accessed with 16S rDNA sequencing, and the gut microbiota profile was evaluated according to microbiota diversity. Finally, four enriched genera in the CCA group (genera Bacteroides, Muribaculaceae_unclassified, Muribaculum, and Alistipes) and eight enriched genera in the cholelithiasis group (genera Bifidobacterium, Streptococcus, Agathobacter, Ruminococcus_gnavus_group, Faecalibacterium, Subdoligranulum, Collinsella, Escherichia-Shigella) constitute an overall different microbial community composition (P = 0.001). The B-F-R genera model with better diagnostic value than carbohydrate antigen 19-9 (CA19-9) was identified by random forest and Statistical Analysis of Metagenomic Profiles (STAMP) to distinguish CCA patients from healthy controls [area under the curve (AUC) = 0.973, 95% CI = 0.932–1.0]. Moreover, the correlative analysis found that genera Burkholderia-Caballeronia-Paraburkholderia were positively correlated with body mass index (BMI). The significantly different microbiomes between cholelithiasis and CCA were found via principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe), and Venn diagram and LEfSe were utilized to identify four genera by comparing microbial compositions among patients with malignant obstructive jaundice (MOJ-Y) or not (MOJ-N). In brief, our findings suggest that gut microbiota vary from benign and malignant hepatobiliary diseases to healthy people and provide evidence supporting gut microbiota to be a non-invasive biomarker for the early diagnosis of CCA.

Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides.

Made available in DSpace on 2022-04-29T08:35:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Division of Intramural Research, National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases National Institute of Allergy and Infectious Diseases National Center for Advancing Translational Sciences National Heart, Lung, and Blood Institute National Institute of Environmental Health Sciences U.S. National Library of Medicine National Institute of Neurological Disorders and Stroke Division of Cancer Prevention, National Cancer Institute Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease. Department of Biostatistics Epidemiology and Informatics University of Pennsylvania Perelman School of Medicine Department of Biomedical Informatics Harvard Medical School Department of Neurology University of Pittsburgh, Biomedical Science Tower 3, Suite 7014, 3501 5th Avenue Department of Pediatrics Wake Forest School of Medicine Department of Critical Care National University Health Systems Department of Preventive Medicine Northwestern University Department of Biomedical Informatics University of Pittsburgh Department of Surgery National University Health Systems Department of Internal Medicine University of Kansas Medical Center Data Analytics Center University of Pennsylvania Health System Department of Computational Medicine and Bioinformatics University of Michigan Department of Biomedical Informatics University of Kentucky Department of Legal Economic and Social Sciences University Magna Graecia of Catanzaro Health Catalyst INC. Department of Surgery ASST Pavia Lombardia Region Health System Clinical Research Unit of Botucatu Medical School São Paulo State University Pediatric Emergency Department Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris National Center for Infectious Diseases Tan Tock Seng Hospital Departments of Biomedical Informatics Pediatrics Cincinnati Children’s Hospital Medical Center University of Cincinnati Department of Pediatrics Medical University of South Carolina Department of Surgery St. Luke’s University Health Network Department of Medicine David Geffen School of Medicine at UCLA UOC Ricerca Innovazione e Brand Reputation ASST Papa Giovanni XXIII Department of Electrical Computer and Biomedical Engineering University of Pavia IT Department Innovation & Data APHP Greater Paris University Hospital I.T. Department ASST Pavia Health Informatics Hospital Universitario, 12 de Octubre Strategy and Transformation Department APHP Greater Paris University Hospital Faculty of Medicine and Medical Center University of Freiburg Digital Research Informatics and Virtual Environments (DRIVE), Great Ormond Street Hospital for Children Scientific Direction IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano North Carolina Translational and Clinical Sciences (NC TraCS) Institute University of North Carolina BIOMERIS (BIOMedical Research Informatics Solutions) Department of Biomedical Informatics HEGP APHP Greater Paris University Hospital Department of Medical and Surgical Sciences Data Analytics Research Center University Magna Graecia of Catanzaro Department of Anesthesia St. Luke’s University Health Network Université Paris-Saclay Inria CEA INRIA Sophia-Antipolis–ZENITH Team LIRMM Computational Health Informatics Program Boston Children’s Hospital Department of Internal Medicine University of Kentucky Unit of Internal Medicine and Endocrinology Istituti Clinici Scientifici Maugeri SpA SB IRCCS Department of Internal Medicine and Therapeutics University of Pavia Informatics Institute University of Alabama at Birmingham IAM Unit Bordeaux University Hospital/ERIAS-Inserm U1219 BPH Biomedical Informatics Center Medical University of South Carolina Clinical Research Informatics Boston Children’s Hospital Department of Biomedical and Health Informatics Children’s Hospital of Philadelphia SED/SIERRA Inria Centre de Paris Health Information Technology & Services University of Michigan Internal Medicine Department Botucatu Medical School São Paulo State University Heinrich-Lanz-Center for Digital Health University Medicine Mannheim Heidelberg University Department of Anesthesiology Critical Care and Pain Medicine Boston Children’s Hospital Department of Learning Health Sciences University of Michigan Medical School MSHI Medical University of South Carolina Department of Medicine Massachusetts General Hospital Division of Human Genetics Department of Pediatrics The Children’s Hospital of Philadelphia Center for Medical Information and Communication Technology University Hospital Renaissance Computing Institute/Department of Computer Science University of North Carolina Clinical Research Unit Saint Antoine Hospital APHP Greater Paris University Hospital Clevy.io Department of Biostatistics Harvard T.H. Chan School of Public Health VA Informatics and Computing Infrastructure VA Salt Lake City Health Care System MICHR Informatics University of Michigan Laboratory of Informatics and Systems Engineering for Clinical Research Istituti Clinici Scientifici Maugeri SpA SB IRCCS Harvard Catalyst Harvard Medical School Clinical Research Unit Paris Saclay APHP Greater Paris University Hospital Department of Anesthesiology and Critical Care Children’s Hospital of Philadelphia VA Informatics and Computing Infrastructure Tennessee Valley Healthcare System Veterans Affairs Medical Center École Normale Supérieure PSL Université Paris BIG-ARC The University of Texas Health Science Center at Houston School of Biomedical Informatics Pediatric Infectious Disease Department Hospital Universitario, 12 de Octubre Department of Infectious Diseases Great Ormond Street Hospital for Children Department of Neurology Massachusetts General Hospital Internal Medicine Department of Botucatu Medical School São Paulo State University Department of Pediatrics Boston Children’s Hospital Center for Biomedical Informatics Wake Forest School of Medicine Department of Medical Informatics University of Erlangen-Nürnberg Department of Veterans Affairs Office of Research and Development Biomedical Data Science Lab ITACA Institute Universitat Politècnica de València Nurse Department of FMB-Medicine School of Botucatu Management Engineering ASST Pavia Lombardia Region Health System Department of Anesthesiology University Hospital Erlangen FAU Erlangen-Nürnberg Critical Care Medicine Department of Medicine St. Luke’s University Health Network Department of Medicine National University Hospital Department of Information Management Chang Gung University Clinical & Translational Science Institute Medical College of Wisconsin Montréal Neurological Institute McGill University SequeL Inria Lille Respiratory Department ICS S Maugeri IRCCS Department of Health Management and Informatics University of Missouri Department of Oncology ASST Papa Giovanni XXIII Clinical Research Unit of Botucatu Medical School São Paulo State University Internal Medicine Department Botucatu Medical School São Paulo State University Internal Medicine Department of Botucatu Medical School São Paulo State University Division of Intramural Research, National Institute of Allergy and Infectious Diseases: AI11679 Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases: AI11679 National Institute of Allergy and Infectious Diseases: AI11679 National Center for Advancing Translational Sciences: CTSA Award #UL1TR001878 National Center for Advancing Translational Sciences: CTSA Award #UL1TR002366 National Heart, Lung, and Blood Institute: K23HL148394 National Institute of Environmental Health Sciences: P30ES017885 U.S. National Library of Medicine: R01LM012095 National Institute of Neurological Disorders and Stroke: R01NS098023 Division of Cancer Prevention, National Cancer Institute: U24CA210967 National Center for Advancing Translational Sciences: UL1TR001420 National Center for Advancing Translational Sciences: UL1TR001857

Background. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to a common disorder with unclear etiology and unsatisfactory treatment, which reduces the male’s quality of life. Objective. To examine the effects of genetic polymorphisms of IFNG, IFNGR1, and androgen receptor (AR) on CP/CPPS. Methods. The single nucleotide polymorphisms (SNPs) of IFNG, IFNGR1, and AR were genotyped with the improved multiplex ligation detection reaction. The GTEx, RegulomeDB, HaploReg, and 3DSNP databases were adopted to predict the regulatory functions of the genotyped SNPs. The correlation between SNPs and CP/CPPS was analyzed with the χ 2 test, logistic regression, and two genetic models (codominant and log-additive models). The nomogram was built to predict the risk of CP/CPPS occurrence. Results. On the whole, 130 CP/CPPS patients and 125 healthy controls were recruited in the study, and 18 SNPs of IFNG, IFNGR1, and AR were genotyped. The results of functional annotation indicated that the 18 genotyped SNPs might have regulatory effects in the whole blood. The rs144488434 was correlated with the elevated CP/CPPS risk (odds ratio (OR): 2.40, 95% confidence interval (CI): 1.12-5.13, χ 2 = 5.37 , and P = 0.021 ) by the χ 2 test. In the built genetic models, rs10457655 was correlated with the elevated National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores (codominant model: GA/GG: crude mean difference MD = 0.98 , 95% CI: -1.71-3.67 and AA/GG: crude MD = 9.10 , 95% CI: 0.58-17.62, P = 0.10 ). In subgroup analysis, rs2069718 was correlated with the elevated CP/CPPS risk (log-additive model: crude OR = 2.18 , 95% CI: 1.03-4.64, and P = 0.034 ) in patients ≥ 35 years. The nomogram integrating age, rs2069718, rs10457655, and rs144488434 showed good performance to predict the risk of CP/CPPS. Conclusions. Genetic polymorphisms of IFNG, IFNGR1, and AR might act as the genetic factors for CP/CPPS susceptibility, which deserved further explorations.

BACKGROUND: Perioperative glycemic status after pancreatic surgery has never been described. However, it’s essential for optimal perioperative glucose management and understanding the pathogenesis of new-onset diabetes mellitus (NODM) after pancreatectomy. Continuous glucose monitoring (CGM) system provides us a helpful tool for closely monitoring and studying perioperative glucose change. This study tried to describe and compare perioperative glucose level and glycemic variability between different types of pancreatic surgeries via CGM device. METHODS: This study was designed as a prospective observational study. Eighteen patients were enrolled and were grouped by different types of surgery received: control group (CTRL), pancreaticoduodenectomy (PD), distal pancreatectomy (DP), and total pancreatectomy (TP). CGM devices were implanted and initiated right after the surgery. Mean glucose value (MGV), coefficient of variation (CV), mean of daily difference (MODD), continuous overall net glycemic action (CONGA), and time above range (TAR)/time below range (TBR) was compared between groups to assess glucose level and glycemic variability. RESULTS: TP showed the highest MGV and CV among all groups (P

The present work aims to evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (Li-ESWT) on patients with prostatitis-like symptoms (PLS). Patients with PLS were recruited and received four-week Li-ESWT (once per week), which was conducted at a frequency of 3 Hz with a preferred energy flow density of 0.25 mJ/mm2 . The scores of the National Institute of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and Visual Analogue Scale (VAS) were recorded to assess the remission of disease in the 0, 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks. A decrease of the NIH-CPSI score ≥6 was regarded as the effectiveness standard of Li-ESWT. Among 91 enrolled patients, the scores of all validated questionnaires presented significant improvements in the 4th week (p < .05) compared with that in baseline, except for IIEF-5. The treatment effective rates in the 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks were 28.57%, 38.46%, 47.25%, 51.65%, 57.30%, 68.18% and 69.44%, respectively. No pronounced undesirable side effect has occurred. Li-ESWT is effective and safe in treating PLS. The efficacy can be maintained within three months.

In the past decades, global climate change has greatly changed the natural environment. Due to the lack of measurement data and technical means, there is no consensus on the structure and dynamic mechanism of the b-sea cycle. In this paper, based on ROMs model and grey estimation of parameters, a three-dimensional baroclinic model of thermodynamic coupling in b-ocean region under new background field is established by using high-quality data recently obtained. According to the simulation results and comparative experiments, the seasonal distribution characteristics of b-sea circulation and the water exchange form between b-sea and high seas are analyzed and explained. And many scientific problems of coastal circulation, such as education and mutation mechanism. However, good physical exercise is an important way to improve the physical quality of residents. As the basic requirement of residents’ physical exercise, the community sports environment affects and limits the residents’ physical exercise behavior. Environmental behavior studies show that the relationship between environment and behavior is not directly related to the individual’s response to environmental stimuli. The principle of “applicability” should be emphasized in the construction of sports environment in society. Therefore, the residents’ behavior evaluation of the school sports environment should become an important feedback information in the construction of community sports environment. The purpose of this paper is to analyze the correlation between residents’ sports environment evaluation and sports exercise behavior orientation, and to provide a theoretical basis for improving residents' sports exercise behavior and optimizing and perfecting the sports environment of the community.

To explore the expression profile and prognostic relevance of GLUT-1 in pancreatic cancer, a meta-analysis, bioinformatics analysis based on Gene Expression Omnibus (GEO), Oncomine dataset and The Cancer Genome Atlas (TCGA) database, and immunohistochemistry in tumor and normal tissue from 88 pancreatic ductal adenocarcinoma (PDAC) patients were performed. GLUT-1 was significantly overexpressed in pancreatic cancer but it could not be a significant biomarker for prognosis. TNM stage and pathological grade could be biomarker of poor prognosis of patients with pancreatic cancer.

Background Hyaluronan (HA), an extracellular matrix component, accumulates in most chronic inflammatory tissues. Here, we studied the impact of HA on the pathogenesis of chronic prostatitis. Materials and methods First, we sorted demographic characteristics and peripheral blood serum samples from patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to assess the relationship between the levels of HA in peripheral blood serum and the severity of inflammation in patients. Second, we induced an experimental autoimmune prostatitis (EAP) mouse model and treated the mice with 4-methylumbelliferone (4-MU) (200 mg/kg/day). After the mice were sacrificed, RNA from Th1 cells of the mouse spleens was extracted for RNA sequencing. We used weighted gene co-expression network analysis (WGCNA) to identify co-expressed gene modules and hub-gene related to the pathogenesis of EAP. The expression of critical genes associated with the identified pathway was confirmed by using western blot analysis. Results HA was significantly more highly expressed in CP/CPPS patients than in healthy volunteers and positively correlated with the severity of pain, urination symptoms, and quality of life. Besides, the protein expression of HA was significantly higher in prostate tissues derived from EAP models than in those derived from controls. 4-MU, an oral inhibitor of HA synthesis, relieved immunocyte infiltration to the prostate and significantly reduced the proportion of Th1 cells. Based on the WGCNA, we identified 18 co-expression modules and identified that the Grey60 and brown modules were positively associated with the EAP and negatively associated with the Control and 4-MU-treated groups. Pathway enrichment analyses and western blot assays proved that HA potentially activated the cell cycle pathway, increasing the proportion of Th1 cells promoting chronic prostatitis pathogenesis, while these processes were reversed by 4-MU treatment. Conclusions Our results suggest that HA is elevated in patients with CP/CPPS compared with healthy controls and that targeting HA through 4-MU suppresses the activity of the cell cycle-related pathway, potentially by decreasing the proportion of Th1 cells and relieving chronic prostatitis. Our findings might inspire the clinical treatment of chronic prostatitis.

This cohort study aims to describe international hospitalization trends and key epidemiological and clinical features of children and youth with COVID-19., Key Points Question What are international trends in hospitalizations for children and youth with SARS-CoV-2, and what are the epidemiological and clinical features of these patients? Findings This cohort study of 671 children and youth found discrete surges in hospitalizations with variable trends and timing across countries. Common complications included cardiac arrhythmias and viral pneumonia, and laboratory findings included elevations in markers of inflammation and abnormalities of coagulation; few children and youth were treated with medications directed specifically at SARS-CoV-2. Meaning These findings suggest large-scale informatics-based approaches used to incorporate electronic health record data across health care systems can provide an efficient source of information to monitor disease activity and define epidemiological and clinical features of pediatric patients hospitalized with SARS-CoV-2 infections., Importance Additional sources of pediatric epidemiological and clinical data are needed to efficiently study COVID-19 in children and youth and inform infection prevention and clinical treatment of pediatric patients. Objective To describe international hospitalization trends and key epidemiological and clinical features of children and youth with COVID-19. Design, Setting, and Participants This retrospective cohort study included pediatric patients hospitalized between February 2 and October 10, 2020. Patient-level electronic health record (EHR) data were collected across 27 hospitals in France, Germany, Spain, Singapore, the UK, and the US. Patients younger than 21 years who tested positive for COVID-19 and were hospitalized at an institution participating in the Consortium for Clinical Characterization of COVID-19 by EHR were included in the study. Main Outcomes and Measures Patient characteristics, clinical features, and medication use. Results There were 347 males (52%; 95% CI, 48.5-55.3) and 324 females (48%; 95% CI, 44.4-51.3) in this study’s cohort. There was a bimodal age distribution, with the greatest proportion of patients in the 0- to 2-year (199 patients [30%]) and 12- to 17-year (170 patients [25%]) age range. Trends in hospitalizations for 671 children and youth found discrete surges with variable timing across 6 countries. Data from this cohort mirrored national-level pediatric hospitalization trends for most countries with available data, with peaks in hospitalizations during the initial spring surge occurring within 23 days in the national-level and 4CE data. A total of 27 364 laboratory values for 16 laboratory tests were analyzed, with mean values indicating elevations in markers of inflammation (C-reactive protein, 83 mg/L; 95% CI, 53-112 mg/L; ferritin, 417 ng/mL; 95% CI, 228-607 ng/mL; and procalcitonin, 1.45 ng/mL; 95% CI, 0.13-2.77 ng/mL). Abnormalities in coagulation were also evident (D-dimer, 0.78 ug/mL; 95% CI, 0.35-1.21 ug/mL; and fibrinogen, 477 mg/dL; 95% CI, 385-569 mg/dL). Cardiac troponin, when checked (n = 59), was elevated (0.032 ng/mL; 95% CI, 0.000-0.080 ng/mL). Common complications included cardiac arrhythmias (15.0%; 95% CI, 8.1%-21.7%), viral pneumonia (13.3%; 95% CI, 6.5%-20.1%), and respiratory failure (10.5%; 95% CI, 5.8%-15.3%). Few children were treated with COVID-19–directed medications. Conclusions and Relevance This study of EHRs of children and youth hospitalized for COVID-19 in 6 countries demonstrated variability in hospitalization trends across countries and identified common complications and laboratory abnormalities in children and youth with COVID-19 infection. Large-scale informatics-based approaches to integrate and analyze data across health care systems complement methods of disease surveillance and advance understanding of epidemiological and clinical features associated with COVID-19 in children and youth.

To quantify the degree of available space for the cord and cord swelling in patients following traumatic cervical spinal cord injury (TCSCI), and to assess the relationship among the available space for the cord, cord swelling, and the severity of neurological impairment. This study included 91 patients. The following indexes were measured by two blinded observers: maximum cord available area (CAAmax) and maximum cord swelling area (CSAmax). The American Spinal Injury Association (ASIA) impairment scale (AIS) grades were used to evaluate the extent of neurological injury. Relationship among CAAmax, CSAmax, and initial AIS grades was assessed via univariate and multivariate analyses. Patients who were AIS grade A (complete injury) demonstrated significantly greater median CAAmax and CSAmax than AIS grade C or D (incomplete injury) (P 38%) and cord swelling (CSAmax > 29%) can be used to identify patients at risk for TCSCI and both imaging characteristics are associated with an increased likelihood of severe neurological deficits. Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Portal vein (PV) involvement is common in patients with pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, pancreatectomy combined with PV resection (PVR) is the only radical therapy for patients with PV involvement. However, there remains a debate on whether patients with PV involvement could benefit from PVR or not. The present study aimed to compare the survival outcomes between patients receiving pancreatoduodenectomy (PD) with PVR and those receiving PD alone. A total of 377 patients with PDAC were enrolled, 138 patients with PV involvement were placed in the PVR group, while the other 239 patients were in the non-PVR group. To reduce selection bias and estimate the causal effect, 123 pairs of propensity score matched (PSM) patients were selected and compared for the survival outcomes. Before PSM, the survival of patients in the PVR group was worse compared with those in the non-PVR group (mean survival, 25.1 vs. 29.3 months; P=0.038). After balancing the baseline characteristics using the PSM method, the significant survival difference between the two groups was insignificant (mean survival, 25.9 vs. 31.2 months; P=0.364). Tumor stage, body mass index, serum albumin, R1 resection, lymph node metastasis, carbohydrate antigen (CA)125 and CA19-9 were significant independent prognostic factors. The incidence of serious postoperative complications was similar between the two groups. PVR is safe and effective for patients with PDAC. Patients with PV involvement could achieve the similar survival outcome as patients without PV involvement, through radical resection combined with PVR, without increasing the risk of serious complications.

Our previous studies showed that the combination of atorvastatin (ATV) and single injection of ATV-pretreated mesenchymal stem cells (MSCs) (ATV-MSCs) at 1 week post-acute myocardial infarction (AMI) promoted MSC recruitment and survival. This study aimed to investigate whether the combinatorial therapy of intensive ATV with multiple injections of ATV-MSCs has greater efficacy at different stages to better define the optimal strategy for MSC therapy in AMI. In order to determine the optimal time window for MSC treatment, we first assessed stromal cell-derived factor-1 (SDF-1) dynamic expression and inflammation. Next, we compared MSC recruitment and differentiation, cardiac function, infarct size, and angiogenesis among animal groups with single, dual, and triple injections of ATV-MSCs at early (Early1, Early2, Early3), mid-term (Mid1, Mid2, Mid3), and late (Late1, Late2, Late3) stages. Compared with AMI control, intensive ATV significantly augmented SDF-1 expression 1.5∼2.6-fold in peri-infarcted region with inhibited inflammation. ATV-MSCs implantation with ATV administration further enhanced MSC recruitment rate by 3.9%∼24.0%, improved left ventricular ejection fraction (LVEF) by 2.0%∼16.2%, and reduced infarct size in all groups 6 weeks post-AMI with most prominent improvement in mid groups and still effective in late groups. Mechanistically, ATV-MSCs remarkably suppressed inflammation and apoptosis while increasing angiogenesis. Furthermore, triple injections of ATV-MSCs were much more effective than single administration during early and mid-term stages of AMI with the best effects in Mid3 group. We conclude that the optimal strategy is multiple injections of ATV-MSCs combined with intensive ATV administration at mid-term stage of AMI. The translational potential of this strategy is clinically promising. Stem Cells Translational Medicine 2019;8:1068–1083

Pancreatic cancer is one of the leading causes of cancer death worldwide. Adjuvant chemotherapy has been developed based on the experiences made with palliative chemotherapy, and advocated to improve long-term survival of patients with this disease. However, the optimal chemotherapeutic regimen remains controversial. Recently, Conroy et al demonstrated the impressive benefits of modified FOLFIRINOX over gemcitabine alone in the multicenter Partenariat de Recherche en Oncologie Digestive 24 (PRODIGE-24) trial. The remarkable results mark a new milestone in treating resectable pancreatic cancer and have now changed the standard of care for this patient population. In this commentary, we discuss an issue of difference of tumor grade between the PRODIGE-24 trial and previous phase III trials. We also discuss potential biomarkers predicting therapeutic response to modified FOLFIRINOX. Finally, we summarize several ongoing clinical trials of replacing part of the FOLFIRINOX regimen with Xeloda/S-1/nanoliposomal irinotecan for pancreatic cancer.

Phosphatidylcholine (PC), a main phospholipid component in egg yolk, provides nourishment and protection for the body. In this study, an attempt has been made to explore the neuroprotective effect of PC that extracted and purified from egg yolk and its corresponding molecular species profile. Egg-yolk PC was obtained by solvent extraction and silica column chromatography, and the purity reached 98%. The neuroprotective effect of egg-yolk PC was investigated via scopolamine-induced PC12 cell model. The results indicated that the pre-treatment of egg-yolk PC could inhibit scopolamine-induced neurotoxicity and oxidative stress in PC12 cells via down-regulation of acetylcholinesterase (AChE) activity, monoamine oxidase (MAO) activity, and the malonaldehyde (MDA) level. This neuroprotective effect might be attributed to plentiful unsaturated fatty acids in egg-yolk PC that was identified to possess 9 kinds of molecular species including 16:0/16:0-PC, 16:0/16:1Δ9-PC, 16:0/18:0-PC, 16:0/18:1Δ9-PC, 16:0/18:2Δ9,12-PC, 18:0/18:1Δ9-PC, 18:0/18:2Δ9,12-PC, 18:1/18:2Δ9,12-PC and 18:0/20:4Δ5,8,11,14-PC by MALDI TOF-MS combined with GC-MS.

The gold standard for diagnosing pulmonary Mycobacterium tuberculosis (TB) is the detection of tubercle bacillus in patient sputum samples. However, current methods either require long waiting times to culture the bacteria or have a risk of getting false-positive results due to cross-contamination. In this study, a method to detect tubercle bacillus based on the molecular typing technique is presented. This method can detect genetic units, variable number of tandem repeat (VNTR), which are the characteristic of tuberculosis (TB), and performs quality control using a mathematical model, ensuring the reliability of the results. Compared to other methods, the proposed method was able to process and diagnose a large volume of samples in a run time of six hours, with high sensitivity and specificity. Our method is also in the pipeline for implementation in clinical testing. Reliable and confirmed results are stored into a database, and these data are used to further refine the model. As the volume of data processed from reliable samples increases, the diagnostic power of the model improves. In addition to improving the quality control scheme, the collected data can be also used to support other TB research, such as that regarding the evolution of the tubercle bacillus.

Distal pancreatectomy (DP) remains associated with significant morbidity, but little data is available about the clinical significance of drain contamination. We explored the incidence, risk factors, and association with surgical outcomes of positive drainage culture (PDC) after DP. In addition, the predictive capacity of early PDC for postoperative pancreatic fistula (POPF) was evaluated. We retrospectively analyzed our prospectively collected database of patients who underwent DP between January 2005 and December 2015. Surveillance drainage cultures for microorganisms were conducted until drain removal or positive culture. The relationships between clinical variables and PDC were examined. Of 480 consecutive cases who underwent DP, 176 (36.7%) had PDC. One hundred twelve patients (23.3%) developed POPF according to the 2016 ISGPS definition, with the 90-day mortality rate of 0.2%. Staphylococcus spp. was the most frequent isolate. Thirty-eight (21.6%) patients had PDC within 3 days after surgery, and 129 (73.3%) within the first 7 days of operation. Body mass index (BMI) ≥ 25 kg/m2 and massive intraoperative blood loss were independent predictors for PDC. PDC had a negative impact on surgical outcomes, including POPF. Early PDC was identified as a newly independent risk factor for POPF. Compared with other microorganisms, those contaminated with Staphylococcus and Klebsiella had higher incidences of POPF. PDC occurs commonly after DP and plays a critical role in the development of surgical morbidities including POPF. Extreme caution is warranted in patients involving contamination with specific types of microorganisms.

Background The abnormal expression of leucine-rich-alpha-2-glycoprotein 1 (LRG-1) is reported to be associated with multiple malignancies, but its role in the progression of pancreatic ductal adenocarcinoma (PDAC) remains to be determined. Methods The expression of LRG-1 was assessed in PDAC tissues by RT-PCR, Western blot and immunohistochemistry. LRG-1-silenced or overexpressed cell lines were constructed using shRNA or LRG-1-overexpressing plasmids. EdU incorporation assay, Transwell invasion and wound-healing assays were performed to evaluate the proliferation, invasion and migration of PDAC cells. In addition, protein expression of the mitogen-activated protein kinase (MAPK) pathway was detected using Western blot. Finally, Co-immunoprecipitation assay was conducted in search of the potential interaction between LRG-1 and epidermal growth factor receptor (EGFR). Results The expression of LRG-1 in PDAC tissue was significantly higher than that in adjacent normal tissue, and high LRG-1 expression predicted poor survival and a late tumor stage. In addition, LRG-1 markedly promoted the viability, proliferation, migration and invasion of PDAC cells in vitro and facilitated tumor growth in vivo. More importantly, we revealed that these bioactivities of LRG-1 might result from its selective interaction with EGFR, which might further activate the p38/MAPK signaling pathways. Conclusion LRG-1 may prove to be a promising biomarker for predicting prognosis of PDAC patients. Inhibition of LRG-1 or its downstream pathway could be a potential therapeutic target for the treatment of PDAC.

Background: Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury remains unclear. Methods: The rat model of intestinal I/R was induced by occlusion (for 60 min) and reopening (for 60 min) of superior mesenteric artery. The rats were randomly divided into the following 5 groups: sham-operation(S), model (I/R),10 mg/kgIL-1Ra + I/R (C1),20 mg/kgIL-1Ra + I/R (C2), and30 mg/kgIL-1Ra + I/R (C3). Results: In this study it was the first time to confirm that IL-1Ra had a significant protection against the intestinal ischemia reperfusion injury. IL-1Ra not only effectively inhibited the expression of inflammatory factors (such as IL-1β, IL-6 and TNF-α) and the activation of neutrophil in intestinal tissues, but also decreased the death of intestinal cells and the damages of intestinal tissues. Interestingly, besides anti-inflammation effect, it was also found that IL-1Ra possessed a significant inhibitory effect on the oxidative stress caused by ischemia/reperfusion injury. Furthermore, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and the phosphorylation level of Nrf2 were greatly promoted by IL-1Ra. At the same time, IL-1Ra inhibited the mitogen-activated protein kinase (MAPKs) pathway. Conclusion: IL-1Ra had the protective effect against intestinal ischemia reperfusion injury, its mechanism included anti-inflammation and anti-oxidative stress in which the Nrf2/HO-1 pathway played an important role. The above-mentioned results may extend the clinical application of IL-1Ra in the treatment of intestinal ischemia reperfusion injury. Keywords: Interleukin 1 receptor antagonist (IL-1Ra), Intestinal ischemia reperfusion injury, Protective effect, Nrf2/HO-1, Clinical application

Background Total pancreatectomy may be necessary to achieve margin-negative resection for pancreatic cancer. However, despite the desirability of saving the spleen, the feasibility, safety, and oncological outcomes of spleen-preserving total pancreatectomy have not been studied in patients with malignancy involving the pancreatic neck or proximal body. The aim of this study was to report the efficacy of spleen-preserving total pancreatectomy using the Warshaw technique for patients with pancreatic malignancies. Methods A retrospective analysis of patients who underwent total pancreatectomy for malignant pancreatic diseases between December 2006 and January 2018 focused on comparing the clinical outcomes between conventional operations with splenectomy and spleen-preserving total pancreatectomy using the Warshaw technique. Results Thirty-eight patients among a total of 59 total pancreatectomies had the spleen preservation by the Warshaw operation. In this series, the pancreatic ductal adenocarcinomas resected with the Warshaw technique were of smaller tumor size but had greater rates of vascular invasion, resulting in the more frequent vascular resection. No patients had splenic complications requiring splenectomy, but two patients intended to have the Warshaw operation were converted to splenectomy because of splenic malperfusion. Asymptomatic perigastric varices were noted in 4 patients. Postoperative morbidity and mortality were comparable between the Warshaw and conventional operation groups. Recurrence-free and overall survival was similar in both groups. Conclusion In patients with pancreatic malignancy, total pancreatectomy with preservation of the spleen using the Warshaw technique achieves outcomes comparable with conventional total pancreatectomy with splenectomy in selected patients.

Purpose. Nonsurgical therapies, including biotherapy, chemotherapy, and liver-directed therapy, provided a limit survival benefit for PNET patients with hepatic metastases. With the development of liver resection technique, there was a controversy on whether to perform a liver resection for these patients. Methods. A computerized search was made of the Medline/PubMed, EMbase, Cochrane Library, and SinoMed (CBM) before March 2018. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonliver resection treatments based on the evaluation of morbidity, 30-day mortality, symptom relief rate, and 1-, 3-, and 5-year survival. Two investigators reviewed all included articles and extracted the data of them. The meta-analysis was performed via Review Manager 5.3 software. Results. A total of 13 cohort studies with 1524 patients were included in this meta-analysis. Compared with the nonliver resection group, liver resection group had a longer 1-, 3-, and 5-year survival time and a higher symptom relief with an acceptable mortality and morbidity. Conclusions. Liver resection is a safe treatment and could significantly prolong the long-term prognosis for highly selected patients with resectable liver metastases from PNET. Further randomized, controlled trials are needed.

Background: The CCDC family plays a significant role in the development and progression of malignant tumors. However, the relationship between CCDC family members and HCC progression is incompletely known. This study used bioinformatics analysis to investigate the expression as well as clinical prognostic value of CCDC family members in HCC and to predict the role of CCDCs family in the development and progression of HCC. Methods: This study utilized the data from two platforms databases to explore the diagnostic value and prognostic significance of CCDC family members by Cox proportional hazards regression analysis, Kaplan-Meier curve and log-rank test, ROC and nomogram diagnostic and prognostic analysis methods. GSEA and tumor microenvironment analysis were employed to investigate the underlying mechanisms and cell-cell interactions of CCDCs family in the development and progression of HCC. The relationship between mutational signatures and CCDCs family were evaluated in HCC patients with somatic mutation. Results: Five CCDC family members (CCDC34, CCDC137, CCDC77, CCDC93 and CCDC21) mRNA expression showed significantly higher in HCC tissues than in normal tissues and high expression levels of these genes predicted poor prognosis in HCC patients. The combined effect analysis of five CCDCs family prognostic markers suggests that the prognosis difference for CCDC family members combination was more significant than that for any individual CCDC family genes. We then developed a risk score model that could predict the prognosis of HCC, and nomogram gene expression was visualized with the probability of predicting the prognosis of HCC by clinical factors. GSEA revealed that, while five CCDCs family combined high expression was associated with increased cell cycle progression and low expression was associated with complement activation pathway. Mutation analysis showed that the combined high expression group had a higher TP53 mutation rate than the combined low expression group, and the high expression group showed higher TMB, which was associated with a better prognosis than high TMB. Conclusions: Our data suggest that the expression of CCDC34, CCDC137, CCDC77, CCDC93 and CCDC21 may be potential prognostic markers in HCC and in combination have a strong interaction and better predictive value for HCC prognosis.

Background and objective: Osteoporosis (OP) is a systemic disease of bone metabolism, characterized by decreasing bone mass, increasing bone microstructure damages and fracture risk. It affects the quality of life of nearly 200 million people worldwide and is a major burden on the public health systems. We want to identify hub genes and miRNAs by the miRNA-mRNA interaction network in osteoporosis disease so that further understand the pathogenesis of this disease.Materials and methods: The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were selected using data of OP patients downloaded from the GEO database (GSE93883, GSE74209 and GSE35959). Gene Ontology (GO) pathway analysis and transcription factor enrichment analysis were used for selecting DEMis, and the target mRNAs of DEMis were filtered by using FunRich. Cytoscape software was used to visualize the network between miRNAs and mRNAs and calculate the hub genes. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the mRNAs in the regulatory network.Results: A total of 17 DEMis and 655 DEMs were selected, from which we reconstructed the miRNA-mRNA network consisting of 6 miRNAs and 37 mRNAs. The top 10 nodes, hsa-let-7a-5p, hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-223-3p, hsa-miR-320c, SLC2A3(Solute Carrier Family 2 Member 3), LBX1(ladybird homeobox 1), HCN2(hyperpolarization-activated cyclic nucleotide-gated ion channel 2), DAB2IP(DAB2 Interacting Protein) and CIC(capicua transcriptional repressor), were identified as important regulators.Conclusions: The study uncovered several important hub genes and miRNAs involved in the pathogenesis of OP, among which, the hsa-let-7a-5p, hsa-miR-92a-3p and hsa-miR-92b-3p may play an important role in osteoporosis, which can help us provide potential therapeutic targets of OP.

Saponin is an active component of many phytomedicine, which has extensive pharmacology effects. Meanwhile, it is reported that cytotoxicity, especially hemolysis and hepatotoxicity, in pentacyclic triterpenoid saponin (PTS) hindered their further development and application. Surface activity, a unique physical property of saponins, is believed to be related to membrane toxicity. However, the correlation between the surface activity and cytotoxicity of saponins is still unexplained. In this paper, our aim was to explore the relationship between surface activity-cytotoxicity of pulchinenosides and the hepatotoxicity mechanism of PTS in vitro. The surface activity of different saponins was investigated by contact angle, surface free energy (SFE), and oil/water partition coefficient (log Papp). In the cytotoxicity study, the hemolysis and hepatotoxicity activity of different saponins was compared by HD50 of erythrocyte and MTT, flow cytometry and LDH assay in LO2 cells respectively. And in the hepatotoxicity mechanism study, western blot was used for observing the expression of proteins related to apoptosis and exploring the liver injury mechanism of PTS. The results suggested that the influences of surface activity on hepatocytes and erythrocytes were different, indicating that the correlation of surface activity-cytotoxicity could provide more information for development of PTS. And the result of hepatotoxicity mechanism study of saponins suggested that endogenous and exogenous apoptotic pathways could be the potential targets of PTS, which could not only provide basis for clinical monitoring and treatment of the toxicity in saponins, but also provide more reference for the clinical application of PTS and phytomedicine containing PTS.

Objective: To evaluate the prognostic influence of the presence of right ventricular myocardial infarction (RVMI) on patients with acute inferior myocardial infarction (MI) in the contemporary reperfusion era. Methods: A total of 9,308 patients with acute inferior MI were included from the prospective, nationwide, multicenter China Acute Myocardial Infarction Registry, including 1,745 (18.75%) patients with RVMI and 7,563 (81.25%) patients without RVMI. The primary outcome was all-cause mortality. The secondary outcome was major adverse cardiac and cerebrovascular event (MACCE) defined as a composite of all-cause mortality, recurrent MI, revascularization, stroke, and major bleeding. Results: There were no significant differences between acute inferior MI patients with or without RVMI in all-cause mortality and MACCE. Acute inferior MI patients with RVMI was associated with higher risks of in-hospital atrial-ventricular block (5.8% vs 3.1%; adjusted OR: 1.39; 95% CI: 1.06 to 1.84; P=0.0187) and two-year revascularization (10.3% vs 8.1%; adjusted HR: 1.21; 95% CI: 1.01 to 1.45; P=0.0418) relative to patients without RVMI. Primary percutaneous coronary intervention (PCI) and thrombolysis were all independent predictors to decrease both in-hospital and two-year all-cause mortality. For patients who received timely reperfusion, RVMI involvement did not increase all-cause mortality, whereas for those who did not undergo reperfusion treatment, RVMI involvement significantly increased all-cause mortality (20.3% vs 15.7%; HR: 1.34; 95% CI: 1.10 to 1.63). Conclusion: RVMI involvement did not increase all-cause mortality for acute inferior MI patients in contemporary reperfusion era, whereas the risk of all-cause mortality was increased for patients with no reperfusion treatment.

The prevalence and incidence of cancers has risen over the last decade. Available treatments have improved outcomes, yet mortality and morbidity remain high, creating an urgent demand for personalized and new therapy targets. Interferon induced transmembrane protein (IFITM3) is highly expressed in cancers and is a marker of poor prognosis. In this review, we discuss recent advances in IFITM3 biology, the regulatory pathways, and its function within cancer as part of immunity and maintaining stemness. Overexpression of IFITM3 is likely an indirect effect of ongoing inflammation, immune and cancer epithelial-to-mesenchymal (EMT) related pathways i.e., interferons, TGF-β, WNT/β-catenin, etc. However, IFITM3 also influences tumorigenic phenotypes, such as cell proliferation, migration and invasion. Furthermore, IFITM3 plays a key role in cancer growth and maintenance. Silencing of IFITM3 reduces these phenotypes. Therefore, targeting of IFITM3 will likely have implications for potential cancer therapies.

ObjectivePancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Pro-oncogenic secretome delivery and trafficking via exosomes are crucial for pre-metastatic microenvironment formation and metastasis. This study aimed to explore the underlying mechanisms of how PDAC-derived exosomes (Pex) modulate the liver microenvironment and promote metastasis.DesignC57BL/6 mice were ‘educated’ by tail vein Pex injection. The intrasplenic injection liver metastasis and PDAC orthotopic transplantation models were used to evaluate liver metastasis. Stable cell lines CD44v6 (CD44 variant isoform 6) or C1QBP (complement C1q binding protein) knockdown or overexpression was established using lentivirus transfection or gateway systems. A total of 142 patients with PDAC in Huashan Hospital were retrospectively enrolled. Prognosis and liver metastasis were predicted using Kaplan-Meier survival curves and logistic regression models.ResultsPex tail vein injection induced the deposition of liver fibrotic extracellular matrix, which promoted PDAC liver metastasis. Specifically, the exosomal CD44v6/C1QBP complex was delivered to the plasma membrane of hepatic satellite cells (HSCs), leading to phosphorylation of insulin-like growth factor 1 signalling molecules, which resulted in HSC activation and liver fibrosis. Expression of Pex CD44v6 and C1QBP in PDAC patients with liver metastasis was significantly higher than in PDAC patients without liver metastasis, and simultaneous high expression of exosomal CD44v6 and C1QBP correlated with a worse prognosis and a higher risk of postoperative PDAC liver metastasis.ConclusionThe Pex-derived CD44v6/C1QBP complex is essential for the formation of a fibrotic liver microenvironment and PDAC liver metastasis. Highly expressed exosomal CD44v6 and C1QBP are promising biomarkers for predicting prognosis and liver metastasis in patients with PDAC.

Congenital pseudarthrosis of the tibia (CPT) is a rare congenital malformation. It is characterized by a tibial anterior bowing deformity or specific types of non-union, which typically result from abnormal development of the tibia, leading to the formation of local pseudarthrosis. The treatment of CPT is very challenging. The advent of 3D printing and computer-assisted techniques in recent years has provided a new ancillary technique for treatment planning and implementation. This case report describes the successful surgical treatment of a 14-year-old male that presented with a shortened limb deformity. Ahead of elective surgery, 3D printing and computer-assisted techniques were used to provide a 1:1 model of his left tibia, fibula and ankle joint to precisely determine the surgical procedure. The first surgery did not result in complete calcification of the tibial extension area, so a second proximal tibia iliac bone graft and internal fixation surgery was undertaken. Following regular follow-up and rehabilitation, by the 18-month follow-up, the proximal tibial bone graft had healed and the patient had resumed walking with a normal gait. This case report describes in detail the successful use of unilateral external fixation using the Ilizarov technique, 3D printing and computer-assisted orthopaedic surgery in the planning of treatment for CPT.

Objective To study the differential diagnosis of MPLC and IM by detecting the different lesions of the same patient. To explore the differences in prognosis between MPLC and IM, and to explore the factors affecting the prognosis of multi-focal lung cancer. Methods Fifty patients with multi-focal lung cancer were screened, and the relevant clinical information was noted; the patients were diagnosed by ACCP standard. Mutations of the lesions were detected by ARMS-PCR, and the detected genes included EGFR, ALK, ROS1, MET, KRAS, RET, HER-2, BRAF, NRAS and PIK3CA. The results of genetic testing were compared with those of ACCP standard diagnosis. Results We analyzed a total of 101 tumors from 50 patients. Classification based on gene testing contradicted the clinicopathologic diagnosis in 10 (20%) of the comparisons, identifying independent primaries in 6 cases diagnosed as metastasis and metastases in 4 cases diagnosed as independent primaries. Another 7(14%) tumor pairings were assigned an “equivocal” result based on gene testing. The results of gene testing of the remaining 33(66%) tumor pairings were consistent with the clinicopathologic diagnosis. The mutant heat map indicated that IM patients have a higher rate of mutation consistency than MPLC patients. Conclusion Multi-gene detection of multi-focal lung cancer has a certain auxiliary effect on the differential diagnosis of MPLC and IM, which can complement the clinical standards, but also has some limitations.

Intrahepatic Cholangiocarcinoma (ICC) is the second most common primary liver cancer with dismal survival rates. This study aimed to explore the prognostic value of sarcopenia combine with hepatolithiasis in surgically treated ICC patients and develop a prognostic nomogram to help make clinical decisions.A prospective cohort study was conducted including patients who underwent hepatectomy for ICC between August 2012 and October 2019. The association between the sarcopenia combined with hepatolithiasis and survival, including overall survival (OS) and recurrence-free survival (RFS) was investigated using the Kaplan-Meier (K-M) method. Univariable and multivariable Cox regression analysis was performed to determine the independent prognostic factors and a nomogram establishment was undertaken based on the multivariable analysis.A total of 121 ICC patients were included in the study. K-M analysis revealed that ICC patients with sarcopenia and hepatolithiasis have worse OS and RFS than those without sarcopenias and/or hepatolithiasis (p 0.01). Multivariable analysis showed that age, serum CEA, hepatolithiasis, sarcopenia and diabetes were independent prognostic factors for OS(p 0.05). Finally, a nomogram with good performance in survival prediction was established (C-index was 0.721; the area under the curve of OS was 0.837). The stratified analysis based on the nomogram disclosed that the median OS was 11.9 months in high-risk patients and 51.2 months in low-risk patients (p 0.001).ICC patients with sarcopenia and hepatolithiasis have worse OS and RFS. The nomogram we developed is a practical tool that can provide a more individualized risk assessment for surgically treated ICC patients.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain. Extracorporeal shock wave therapy (ESWT) has been used to treat patients with CP/CPPS, but the parameters used by ESWT are not uniformly determined. Herein, this study aims to assess the effects of ESWT with different energy flux densities on pelvic pain in CP/CPPS rats and to explore the mechanisms. A rat model of CP/CPPS was induced by intraprostatic injection of 1% carrageenan. ESWT with different energy flux densities (0.09, 0.20, 0.30, 0.40 mJ/mm2) was applied in the pelvic region of CP/CPPS rats once a week for 4 weeks. The results showed that compared with the other energy flux densities (0.09, 0.30, and 0.40 mJ/mm2), ESWT with 0.20 mJ/mm2 exhibited a more powerful effect in alleviating pelvic pain and prostate damage. The therapeutic effect is associated with the reduction of the number of total and degranulated mast cells. Collectively, ESWT with 0.20 mJ/mm2 achieved the optimal therapeutic effect in alleviating pelvic pain in CP/CPPS rats.

Background: : Postoperative pancreatic fistula (POPF) is one of the most common complications and the leading cause of morbidity and mortality after pancreatic operation with pancreatojejunostomy (PJ). Many strategies have been used to prevent the incidence of POPF, among which drainage of pancreatic juice is effective. There are two types of drainage methods used in clinical practice; however, the method with a superior effect remains unknown. This study compared the effect of external and internal drainage without stent (in other words, no drainage, only PJ by duct-to-mucosa) on the incidence of clinically relevant POPF (CR-POPF) to provide evidence to select a better drainage scheme in clinical practice. Methods: Overall, 520 patients undergoing pancreatic operation, including PJ were included in this single-centre study and were divided into two groups according to drainage methods. We compared the incidence of CR-POPF between the two groups and performed stratified analysis according to the Fistula Risk Score (FRS) and pancreatic gland texture. Factors such as gender, age, Body Mass Index (BMI), operative procedure, and drainage methods were included in univariable and multivariable analyses. Results: The incidence rate of CR-POPF between two groups was significantly different (23.3% vs 13.6%, P

Ethnopharmacological relevance In traditional Chinese medicine, the fruit of Schisandra chinensis (Turcz.) Baill (SC) is used to treat various nervous system diseases, such as dysphoria, anxiety, insomnia and many dreams. It is worthy to be noted that wine processed Schisandra chinensis (WSC) has been applied in clinic for thousands of years. Aim of study This study aimed to investigate the possible mechanism and related metabolism of SC and WSC ameliorating anxiety behavior through modulating gut microbiota. Materials and methods The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for the quality control of chemical components in SC and WSC. Chronic unpredictable stress procedure (CUSP)-induced anxiety rats were administrated with SC and WSC via gavage for five weeks. An untargeted UPLC/LTQ-Orbitrap MS metabolomic analysis of plasma was conducted to understand the effects of long-term intake of WSC and SC extracts on anxious rats. 16S rRNA microbial sequencing technology was applied to investigate gut microbiota structure. Expression of GPR81, TNF-α, S1PR2 as well as molecules in cAMP pathway was assayed by immunohistochemistry staining, RT-qPCR, or Western blot, respectively. Results 12 compounds were identified using UPLC-QTOF-MS technology, all of which are lignans. Results demonstrate that the amounts of 6-O-Benzoylgomisin O, Schisandrin, Gomisin D, Schizandrin A, Gomisin T, Schizandrin B, Schisandrin C were higher in wine-processed samples than in raw samples. Furthermore, both SC and WSC significantly ameliorated anxiety- and depression-like behavior and lipid metabolism dysfunction and attenuated hippocampal neuritis in anxiety rats. After WSC treatment, the structure and composition of gut microbiota in anxiety rats changed significantly, and gut microbiota derivatives lactate level was significantly lower in the plasma and feces. WSC treatment help restore gut microbial ecosystem dysbiosis and reverse the changes in Lachnospiraceae, Lactobacillus, Alloprevotella, and Bacteroidales in anxiety rat. In addition, the expression of liver GPR81 was decreased, and the molecules in cAMP pathway were increased in SC and WSC-treated anxiety rat. Conclusion Raw and wine processed Schisandra chinensis treatment improved anxiety- and depression-like behavior through modulating gut microbiota derivatives in association with GPR81 receptor-mediated lipid metabolism pathway. And WSC has more exhibition than SC.

Malignant gliomas remain significant challenges in clinic and pose dismal prognosis on patients. In this study, we focused on growth arrest-specific 5 (GAS5), a tumor suppressive long non-coding RNA in glioma, explored its crosstalk with miR-424, and examined their biological functions in glioma. Expressions of GAS5 and miR-424 were measured using qRT-PCR. The regulation of GAS5 on miR-424 expression was examined in GAS5-overexpressing glioma cells by combining methylation-specific PCR, western blotting, and RNA immunoprecipitation. Functional significance of GAS5 and miR-424 on in vitro cell proliferation, apoptosis, migration, invasion, and in vivo tumor growth was examined using colony formation, flow cytometry, wound healing, transwell assay, and the xenograft model, respectively. The potential targeting of AKT3 by miR-424 was investigated using luciferase reporter assay. GAS5 and miR-424 were significantly down-regulated in glioma cells. GAS5 directly interacted with enhancer of zeste homolog 2 (EZH2), stimulated the formation of polycomb repressive complex 2 (PRC2), reduced the levels of DNA methyltransferases (Dnmts), alleviated promoter methylation of miR-424, and promoted miR-424 expression. Functionally, GAS5, by up-regulating miR-424, inhibited cell proliferation, migration, and invasion, while increased apoptosis of glioma cells in vitro, and suppressed xenograft growth in vivo. miR-424 directly inhibited AKT3 and altered the expressions of AKT3 targets, cyclinD1, c-Myc, Bax, and Bcl-2, which might contribute to its tumor suppressive activities. GAS5, by inhibiting methylation and boosting expression of miR-424, inhibits AKT3 signaling and suppresses multiple malignant phenotypes. Therefore, stimulating GAS5/miR-424 signaling may benefit the treatment of glioma.