[A cross-sectional survey on the types of antiviral treatment plans for patients with chronic hepatitis B].

Objective: To understand the current antiviral treatment status and various clinical types of treatment plans in Xiamen City so as to explore ways to improve and optimize the diagnosis and treatment standards for chronic hepatitis B. Methods: A cross-sectional survey method was used to study the antiviral treatment status and treatment plans for chronic hepatitis B patients who visited and were diagnosed in the Department of Infectious Diseases and Hepatology of all tertiary hospitals in Xiamen City at 0:00~23:59 on May 25, 2022. Results: A total of 665 cases were surveyed in this study, with an antiviral treatment rate of 81.2%(540/665). The antiviral treatment rate of patients who accorded with the current guidelines for antiviral treatment indications was 85.8%(507/591). The antiviral treatment rate for 362 outpatients was 72.9%(264/362). Among them, the antiviral treatment rates were 80.1%, 89.3%, and 25.0%(226/282, 25/28, 13/52), respectively, for patients diagnosed with chronic hepatitis B, hepatitis B cirrhosis, and hepatitis B surface antigen-carrying status. The treatment plan for all outpatient patients was mainly oral nucleos(t)ide analogues, accounting for 59.1%(214/362). The antiviral treatment rate for 303 inpatients was 91.1%(276/303). The various clinical types of antiviral therapy rates among all patients were 70%~95%. The antiviral treatment plan for inpatients was mainly based on pegylated interferon alpha treatment, accounting for 72.6%(220/303). Conclusion: Antiviral treatment for chronic hepatitis B in Xiamen City can still be strengthened to meet the current demand for expanding antiviral treatment indications. Antiviral treatment rates and various types of treatment plans differ between outpatients and inpatients; thus, further awareness and acceptance of the goal of improving antiviral therapy, especially in outpatients, and the possibility for a clinical cure based on pegylated interferon alpha treatment are needed to maximize the benefit to more patients.

Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach.

AIM: To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. RESULTS: Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. CONCLUSION: The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

Clinical effectiveness of fluorouracil and cisplatin intraperitoneal perfusion combined with intravenous chemotherapy for peritoneal metastasis in gastric cancer.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies worldwide, often accompanied by peritoneal metastasis. This work aimed to investigate the clinical efficacy of intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC. PATIENTS AND METHODS: A total of 286 patients with primary GC admitted to the hospital from March 2017 to December 2020 were recruited in the study. A 1:1 matched case-control study was conducted, with the normal control (NC) group and experimental (E) group being composed of patients who underwent the corresponding treatment for primary GC with surgery within 2 months and the same pathological tumor-node-metastasis (pTNM) stage. The NC group consisted of 143 patients receiving only intravenous chemotherapy, while the E group consisted of 143 patients receiving intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy. Baseline characteristics, clinical efficacy, complications, peritoneal recurrence and metastasis, disease-free survival (DFS), and overall survival (OS) of the patients, as well as their quality of life (QoL) after chemotherapy, were compared between groups. RESULTS: After six cycles of chemotherapy, DFS was observed in both groups (70% vs. 59%; 48% vs. 29.7%; p<0.05), so did OS (85.7% vs. 85.4%; 73.1% vs. 69.3%; p>0.05). The total effective rate of treatment in the E group (46.15%) was drastically superior to that in the NC group (27.97%), and the total recurrence and metastasis rate of the E group (23.08%) was markedly inferior to that of the NC group (83.9%) (p<0.05). The total incidence of adverse reactions in the E group (11.89%) was considerably inferior to that in the NC group (35.66%) (p<0.05). In addition, the E group had markedly superior scores for physical function (PF), emotional function (EF), role function (RF), social function (SF), and cognitive function (CF) than the NC group (p<0.05). CONCLUSIONS: Intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC had certain benefits for patients and is worth applying in clinical practice.

Machine Learning Differentiation of Autism Spectrum Sub-Classifications.

PURPOSE: Disorders on the autism spectrum have characteristics that can manifest as difficulties with communication, executive functioning, daily living, and more. These challenges can be mitigated with early identification. However, diagnostic criteria has changed from DSM-IV to DSM-5, which can make diagnosing a disorder on the autism spectrum complex. We evaluated machine learning to classify individuals as having one of three disorders of the autism spectrum under DSM-IV, or as non-spectrum. METHODS: We employed machine learning to analyze retrospective data from 38,560 individuals. Inputs encompassed clinical, demographic, and assessment data. RESULTS: The algorithm achieved AUROCs ranging from 0.863 to 0.980. The model correctly classified 80.5% individuals; 12.6% of individuals from this dataset were misclassified with another disorder on the autism spectrum. CONCLUSION: Machine learning can classify individuals as having a disorder on the autism spectrum or as non-spectrum using minimal data inputs.

[Application of methylene blue near-infrared fluorescence imaging for oral sentinel lymph node mapping in rats].

OBJECTIVE: To explore the concentration range and penetration depth of methylene blue near-infrared fluorescence imaging, and to clarify the role of methylene blue in oral lymphatic drainage and sentinel lymph node localization, so as to lay a foundation for the potential research and application of sentinel lymph node in oral cancer. METHODS: 10% (mass fraction) methylene blue injection was diluted into 29 different concentrations with 0.9% (mass fraction) normal saline, and the concentration range of methylene blue near-infrared fluorescence imaging was determined by near-infrared fluorescence imager. The maximum penetration depth of methylene blue near-infrared fluorescence was determined by covering pigskin with different thicknesses (1, 2, 3, 4 and 5 mm) in methylene blue solution. 0.2 mL methylene blue solution was injected into the submucosal 0.5 cm at the lateral margin of tongue on one side of the rats. The near-infrared fluorescence imager was used for continuously monitoring for 3 hours. The first near-infrared fluorescence hotspot was identified as sentinel lymph node and labeled by percutaneous observation. The rats were then sacrificed and dissected in the head and neck. Near-infrared fluorescence imaging was performed again to observe whether the fluorescent tissue was consistent with the labeled fluorescent hotspot in vitro, and the presence of lymphoid tissue was confirmed by pathological examination after resection. RESULTS: Except that no fluorescence signals were detected in the blank control groups, the fluorescence intensity of methylene blue increased first and then decreased with its solution concentration decreased. When the concentration of methylene blue was diluted to the picomole level, the fluorescence signal could still be detected. The maximum penetration depth of methylene blue fluorescence was 4 mm. Methylene blue near-infrared fluorescence could be localized in oral lymphatic drainage and sentinel lymph node. The fluorescence was sustained for more than 3 hours after methylene blue injection. Methylene blue solution concentrations of 3.34 mmol/L, 6.68 mmol/L, 13.37 mmol/L and 26.74 mmol/L were selected in the rats to map sentinel lymph node by near-infrared fluorescence. CONCLUSION: Methylene blue near-infrared fluorescence has a certain penetrating ability and can transcuta-neously map the sentinel lymph node and their associated lymphatic vessels in rats, which is expected to be further applied in the study of sentinel lymph node in oral cancer.

Workplace bullying and suicidal ideation and behaviour: a systematic review and meta-analysis.

OBJECTIVES: Suicidal ideation and behaviour are potential outcomes of workplace bullying. This review aimed to determine the extent of the association between workplace bullying and suicidal ideation and behaviour. STUDY DESIGN: The study incorporated a systematic review and meta-analysis. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed to conduct a comprehensive systematic review and meta-analysis. A combination of subject terms and free words was used to search nine electronic databases. Two reviewers independently screened articles and extracted information according to the inclusion criteria. A meta-analysis was performed with averaged weighted correlations across samples using the STATA software (version 16.0) from pooled estimates of the main results from all studies. RESULTS: In total, 25 articles of high or medium quality were included in the systematic review; 15 of these were included in the meta-analysis. The prevalence of suicidal ideation and behaviour was 18% and 4%, respectively. Individuals who experienced workplace bullying had 2.03-times and 2.67-times higher odds of reporting suicidal ideation and behaviour, respectively, after adjustment for confounding factors. Moderating and mediating factors may help reduce the risk of suicidal ideation and behaviour for individuals experiencing workplace bullying. CONCLUSION: This study indicated that exposure to workplace bullying significantly increased the risk of suicidal ideation and behaviour.

Retraction Note: Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal.

The article "Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal", by K. Zhao, J.-Y. Tan, Q.-D. Mao, K.-Y. Ren, B.-G. He, C.-P. Zhang, L.-Z. Wei published in Eur Rev Med Pharmacol Sci 2019; 23 (1): 312-320-DOI: 10.26355/eurrev_201901_16778-PMID: 30657572 has been retracted by the authors for the following reasons: We are still conducting research in the effect of long non-codingRNA TUG1 in interstitial cells of Cajal recently. It turned out that some of the current experimental results are inconsistent with the previous results. Some data cannot be repeated by further research. We need to further confirm the effect of long non-coding RNA TUG1 on alleviating TNF-α-induced inflammatory injury in interstitial cells of Cajal and for this reason, the authors all agreed to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16778.

[Postoperative complications and their influence on the prognosis factors in gastric cancer patients receiving neoadjuvant treatment].

Objective: To investigate postoperative complications of patients undergoing neoadjuvant therapy followed by radical gastrectomy, and to analyze their influence on the prognosis. Methods: A retrospective case-control study was used. Case inclusion criteria: (1) gastric adenocarcinoma confirmed by histopathology; (2) preoperative imaging examination showed no distant metastasis or peritoneal dissemination; (3) undergoing radical gastrectomy and D2 lymph node dissection after neoadjuvant therapy; (4) complete clinicopathological and follow-up data. According to the above criteria, clinical data of 490 gastric cancer patients who underwent radical gastrectomy in the Cancer Hospital of Chinese Academy of Medical Sciences, Peking Union Medical College from January 2008 to December 2018 were retrospectively collected, including 358 males and 132 females with mean age of (55.0±10.6) years. Neoadjuvant chemotherapy regimens included SOX (S-1+ oxaliplatin, n=151), XELOX (capecitabine+oxaliplatin, n=155), FLOT (docetaxel+oxaliplatin+fluorouracil, n=66), and DOS (docetaxel+ oxaliplatin+S-1, n=68). Preoperative concurrent chemoradiotherapy was performed in 100 patients. SOX regimen was used for 2-4 cycles as induction chemotherapy plus concurrent chemoradiotherapy (3D IMRT+S-1). Postoperative complications were defined as surgery-related complications, mainly including hemorrhage, anastomotic leakage, obstruction, anastomotic stenosis, pulmonary infection, abdominal infection, etc. Postoperative complications were graded according to Clavien-Dindo classification. Log-rank test and Cox regression model were used for univanriate multivariate prognostic analysis, respectively. Results: A total of 101 complications ocaured after operation in 87 (17.8%) patients, including 29 cases of major complications (Clavien-Dindo III to V), and 58 cases of minor complications (Clavien-Dindo I to II). Multivariate analysis showed that age > 65 years (HR=3.077, 95% CI: 1.827-5.184, P<0.001) and total gastrectomy (HR=1.735, 95% CI: 1.069-2.814, P=0.026) were independent risk factors for postoperative complications in patients with gastric cancer undergoing neoadjuvant therapy and radical gastrectomy (both P<0.05). The follow-up period was 0.7 to 131.8 months (median 21.5 months), and the 5-year overall survival rate was 47.4%. The 5-year overall survival rates of the complication group (87 cases) and the non-complication group (403 cases) were 33.2% and 50.9%, respectively (P=0.001). Multivariate analysis showed that age (HR=1.906, 95% CI: 1.248-2.913, P=0.003), ypTNM II to III stage (II stage: HR=5.853, 95% CI: 1.778-19.260, P=0.004; III stage: HR=10.800, 95% CI: 3.411-34.189, P<0.001), surgery time>3.5 h (HR=1.492, 95% CI: 1.095-2.033, P=0.011), total gastrectomy (HR=1.657, 95% CI: 1.216-2.257, P=0.001) and postoperative complications (HR=1.614, 95% CI: 1.125-2.315, P=0.009) were independent risk factors for prognosis, and postoperative adjuvant therapy (HR=0.578, 95% CI: 0.421-0.794, P=0.001) was an independent protective factor for prognosis. Conclusions: The occurrence of postoperative complications in gastric cancer patients undergoing neoadjuvant therapy is closely related to the age of the patients and the range of surgical resection. It is beneficial to improve the prognosis for these patients by paying more attention to the prevention of postoperative complications and the reinforcement of postoperative adjuvant therapy.

miR-92a-3p promotes the proliferation and invasion of gastric cancer cells by targeting KLF2.

MicroRNAs (miRNAs) have pivotal roles in the initiation and progression of gastric cancer (GC), and miR-92a-3p has been proved to act as an oncogene in multiple malignancies. However, the molecular mechanisms by which miR-92a-3p contributes to GC remain unclear. The differentially expressed miRNAs were screened by GEO dataset, and the association of miR-92a-3p expression with clinicopathological characteristics and prognosis in patients with GC was analyzed by TCGA dataset. The target genes of miR-92a-3p were identified by bioinformatic analysis, and their interaction was confirmed by luciferase reporter assay. MTT, EdU and Transwell assays were conducted to determine the role of miR-92a-3p in GC cells. As a result, it was found that the expression levels of miR-92a-3p were increased in GC tissues and were associated with tumor size, lymph node infiltration and distant metastasis, acting as an independent prognostic factor of poor survival in patients with GC. Restored expression of miR-92a-3p facilitated cell proliferation, DNA synthesis and cell invasion, but its inhibitor reversed these effects. KLF2 was further identified as a direct target of miR-92a-3p, indicating a negative correlation with miR-92a-3p expression and harboring a favorable prognosis in GC. In addition, KLF2 repressed cell proliferation and invasion and attenuated the tumor-promoting effects of miR-92a-3p in GC cells. Altogether, our findings demonstrated that miR-92a-3p promoted the proliferation and invasion of GC cells by targeting KLF2.

MiR-20a Promotes kidney injury in sepsis rats through autophagy.

The aim of this work was to study the effects of micro ribonucleic acid (miR)-20a on acute kidney injury (AKI) in sepsis rats and its key molecular mechanism. Sprague-Dawley rats were randomly divided into healthy rat group (H group, n=3), sham group (S group, n=3), sepsis rat group (D group, n=3), sepsis rat + negative control transfection group (N group, n=3) and sepsis rat + miR-20a inhibitor transfection group (M group, n=3). At 6 h, 12 h and 24 h, serum creatinine (Scr) and blood urea nitrogen (BUN) were detected, the changes in miR-20a expression in kidney tissues were determined via reverse transcription-polymerase chain reaction (RT-PCR), the expression of autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) was measured via Western blotting, and the inflammatory cell infiltration in kidney tissues was detected using hematoxylin-eosin (HE) staining. There was no obvious change in each index in S group compared with H group. D group, N group and M group had higher levels of Scr, BUN and LC3 in kidney tissues than S group. The levels of Scr, BUN and LC3 in kidney tissues were lower in M group than those in N group. MiR-20a may cause AKI in sepsis rats via activating autophagy.

[Feasibility of near-infrared fluorescence imaging in assisting with the determination of the resection range of radiation intestinal injury].

Objective: To investigate the feasibility of near-infrared fluorescence imaging (NIRFI) to assist in determining the resection range of radiation intestinal injury (RII). Methods: A descriptive cohort study was conducted. Clinical data of 10 RII patients who presented intestinal obstruction and received operation with more than 100 cm of small intestine had been resected atGeneral Department of Jinling Hospital from October 2014 to January 2015 were retrospectively analyzed. The Novadaq SPY Intra-operative Imaging System was used in capturing and viewing fluorescent images. Firstly, the dense adhesion was mobilized and the obstructive intestine was fully freed under laparoscopy, then entering into abdomen from the corresponding incision. The surgeon determined the resection range according to the color of the intestinal serous layer of the diseased intestinal wall, the thickness of the intestinal wall, and the degree of swelling of the mesentery. Afterwards, intra-operative NIRFI was performed by intravenous injection of 2 ml indocyanine green (ICG) and the imaging results of the diseased intestinal arteriovenous phase were observed and recorded. The evaluation criteria for the final resection range were mainly based on the changes in mesenteric arterial phase imaging. In RII lesions, mesenteric vessels in mesenteric artery phase were disordered, and the comb-like distribution of normal mesenteric vessels completely disappeared. Only the clouded appearance in the intestinal wall was observed. Imaging results of the diseased intestinal tissue during the development phase and mesenteric vein phase were not significantly different from normal intestinal tissue. Intraoperative and postoperative conditions under NIRFI-assisted positioning, including the resection range, anastomosis site, operation-related complications, hospitalization time and cost were recorded. Data of abdominal contrast-enhanced CT and gastrointestinal angiography during 5 years of follow-up were collected to evaluate whether there was anastomotic stenosis or insufficient resection of diseased bowel. Results: Based on the imaging of mesenteric arterial phase of NIRFI, the median resection length of the small intestine was 185 (120-260) cm. After NIRFI imaging, only local lesion of ileum was excised in 6 patients, and jejunum-ileum anastomosis was performed to preserve ileocecal flap. No serious complications such as anastomotic leakage and anastomotic hemorrhage, or chronic intestinal failure such as short bowel syndrome occurred. The median hospitalization time was 32 (22-51) days, and the median hospitalization cost was 142 000 (90 000-175 000) RMB. The hospitalization time and cost were mainly used for the enteral and parenteral nutrition support treatment during the perioperative period. All the patients had normal oral diet and/or oral enteral nutrient. After 5 years of follow-up, no recurrence was found. Abdominal contrast-enhanced CT and gastrointestinal angiography showed no thickening of the intestinal wall or stenosis of the lumen. Conclusion: Mesenteric arterial phase imagingof NIRFI can help surgeons to determine the site and range of resection of RII lesions.

Association of Padua prediction score with in-hospital prognosis in COVID-19 patients.

BACKGROUND: Nearly 20% novel coronavirus disease 2019 (COVID-19) patients have abnormal coagulation function. Padua prediction score (PPS) is a validated tools for venous thromboembolism (VTE) risk assessment. However, its clinical value in COVID-19 patients' evaluation was unclear. METHODS: We prospectively evaluated the VTE risk of COVID-19 patients using PPS. Demographic and clinical data were collected. Association of PPS with 28-day mortality was analyzed by multivariate logistic regression and Kaplan-Meier analysis. RESULTS: Two hundred and seventy-four continuous patients were enrolled, with total mortality of 17.2%. Patients in high PPS group, with significantly abnormal coagulation, have a higher levels of interleukin 6 (25.27 vs. 2.55 pg/ml, P < 0.001), prophylactic anticoagulation rate (60.7% vs. 6.5%, P < 0.001) and mortality (40.5% vs. 5.9%, P < 0.001) when compared with that in low PPS group. Critical patients showed higher PPS (6 vs. 2 score, P < 0.001) than that in severe patients. Multivariate logistic regression revealed the independent risk factors of in-hospital mortality included high PPS [odds ratio (OR): 7.35, 95% confidence interval (CI): 3.08-16.01], increased interleukin-6 (OR: 11.79, 95% CI: 5.45-26.20) and elevated d-dimer (OR: 4.65, 95% CI: 1.15-12.15). Kaplan-Meier analysis indicated patients with higher PPS had a significant survival disadvantage. Prophylactic anticoagulation in higher PPS patients shows a mild advantage of mortality but without statistical significance (37.1% vs. 45.7%, P = 0.42). CONCLUSION: Higher PPS associated with in-hospital poor prognosis in COVID-19 patients. Prophylactic anticoagulation showed a mild advantage of mortality in COVID-19 patients with higher PPS, but it remain to need further investigation.

[Novel coronavirus pneumonia (COVID-19) CT distribution and sign features].

Objective: To investigate the imaging findings of 2019 novel coronavirus pneumonia (COVID-19). Methods: From January 20 to February 5, 2020, a total of 130 patients diagnosed with COVID-19 from seven hospitals in China were collected. The imaging data were reviewed and analyzed in detail. Results: (1) Distribution: the lesion detected in the lung unilaterally in 14 cases (10.7%) and bilaterally in 116 cases (89.3%). According to the distribution in the lobes of the lung, all cases could be classified into subpleural distribution (102 cases, 78.4%), centrilobular distribution (99 cases, 76.1%) and diffused distribution (8 cases, 6.1%). (2) Number of lesions: single lesion 9 cases (6.9%); multiple lesions 113 cases (86.9%), diffuse lesions 8 cases (6.1%). (3) Imaging density: 70 cases (53.8%) of ground-glass opacity (GGO), 60 cases (46.2%) of GGO+consolidation. (4) Accompanying signs: 100 cases (76.9%) with vascular thickening, 98 cases (75.3%) with "pleural parallel sign" ; " intralobular septal thickening" in 100 cases (76.9%); "halo sign" in 13 cases (10%); "reversed-halo sign" in 6 cases (4.6%); pleural effusion in 3 cases (2.3%), and pneumatocele in 2 cases (1.5%); no case with pulmonary cavity. Among 35 patients that underwent follow-up CT, 21 patients (60%) improved while 14 (40%) exacerbated. Conclusions: COVID-19 imaging characteristic mainly has subpleural, centrilobular and diffused distribution. The first two distributions can overlap or progress to diffused distribution. In the later period, it was mainly manifested as organizing pneumonia and fibrosis. The most valuable characteristic is the pleural parallel sign.

Investigating ultrasound-induced acoustic softening in aluminum and its alloys.

Ultrasonic vibration has been observed to lower the flow stress necessary to initiate plastic deformation, a phenomenon known as "acoustic softening". This unique effect of ultrasound has been extensively applied in welding, machining, forming of metals, and ultrasonic additive manufacturing to lower the yield stress necessary to initiate plastic deformation, it nevertheless lacks fundamental investigation. Some prior studies showed experimental errors due to the design of experimental setups and the associated testing methods that have been introduced, leading to questions about their observations and conclusions. Therefore, an experimental setup described in this paper is designed to minimize the constraints identified from the setups in prior studies. Three types of aluminum are studied: Al 1100-O a commercially pure aluminum, Al 6061-O an aluminum alloy without precipitate strengthening, and Al 6061-T6 a precipitate-strengthened aluminum alloy. The acoustic softening and residual effect are compared based on the similarities and differences in microstructures of the three types of aluminum. In both acoustic softening and residual effect, linear relations are obtained between stress change and ultrasound intensities. The slope defined by the linear relations, i.e. the acoustic softening factor, depends on the microstructure of the specific material. The underlying mechanism of acoustic softening is associated with the activation of dislocations by ultrasonic energy and subsequently their interactions with other dislocations and precipitates, whereas the residual effects are attributed to the permanent changes in dislocation density due to dislocation annihilation, dynamic annealing, and dislocation-precipitate interaction.

Identification of two novel anti-HCV E2 412-423 epitope antibodies by screening a Chinese-specific phage library.

The hepatitis C virus (HCV) E2 412-423 linear epitope has been found to be highly conserved across multiple HCV genotypes. The antibodies against this epitope have broadly neutralizing activity. Considering the poor immunogenicity of the epitope in humans and significant diversity in the global distribution of HCV genotypes, the aim of this study was to construct an anti-HCV phage library by using a series of optimal strategies to screen novel broadly neutralizing antibodies from Chinese donors. mRNA was isolated from peripheral blood samples of 39 patients who were anti-HCV positive. A phage library was constructed by inserting a single-chain variable fragment (scFv) gene repertoire into the T7Select10-3b vector. A synthetic peptide representing the HCV E2 N-terminal 412-423 region was used as "bait" for bio-panning. The binding affinities of phage clones to the synthetic peptide were evaluated through peptide-ELISA. Two scFv clones (R3-19 and R4-85) showing the strongest binding affinities were selected. The complementarity-determining regions (CDRs) of these clones were aligned with those of other previously reported broadly neutralizing anti-HCV antibodies, and multiple conserved amino acid sites were found. The optimized procedures ensured that two novel scFv antibodies were isolated from a constructed phage library and showed specific binding to the poorly immunogenic HCV E2 412-423 linear epitope. Keywords: phage antibody library; hepatitis C virus; broadly neutralizing antibody; synthetic peptide.

MiR-376a functions as tumor suppressor by targeting SGK3 in renal cell carcinoma.

OBJECTIVE: Emerging evidence showed that microRNA-376a (miR-376a) functions as a crucial role in human cancers. However, its role in renal cell carcinoma (RCC) remains unclear. MATERIALS AND METHODS: MiR-376a expression in RCC cell lines was analyzed by quantitative real time-polymerase chain reaction (qRT-PCR). The target of miR-376a was validated using the luciferase activity reporter assay, and the effects of miR-376a expression on RCC cell behaviors were investigated in vitro. RESULTS: MiR-376a expression was downregulated in RCC cell lines in comparison with HK-2 cell line. Low miR-376a expression was correlated with poor overall survival of RCC patients. Serum/glucocorticoid regulated kinase family member 3 (SGK3) was validated as a direct target of miR-376a. The overexpression of miR-376a inhibits RCC cell proliferation, migration, and invasion through regulating SGK3. CONCLUSIONS: Taken together, these results demonstrated the tumor suppressive role of miR-376a via targeting SGK3 in RCC and indicated that miR-376a might represent a novel therapeutic target for RCC treatment.

Effects of neuroblastoma breakpoint family member 1 (NBPF1) gene on growth and Akt-p53-Cyclin D pathway in cutaneous squamous carcinoma cells.

Neuroblastoma breakpoint family member 1 (NBPF1) is involved in the occurrence and development of tumors. However, only a limited number of studies were conducted on NBPF1 and cutaneous squamous cell carcinoma (SCC). This study mainly explored the expression and mechanism of NBPF1 in SCC. SCC tissue and adjacent tissues samples were randomly selected. NBPF1 gene was overexpressed in the A431 cell line using plasmid transfection technique. Cell viability was tested by cell counting kit-8 (CCK-8) assay. Flow cytometry was used to determine cell cycle and apoptosis. Western blot and RT-qPCR were respectively performed to determine the expression levels of proteins and mRNAs. The NBPF1 gene was lowly expressed in SCC tissues. The expression level of NBPF1 gene was the lowest in A431 cell line. The cell viability of A431 was reduced after transfection. Overexpression of NBPF1 not only arrested A431 cells in G1 phase and promoted apoptosis, but also up-regulated the expressions of Bax and p53 mRNA and protein and down-regulated the expressions of Bcl-2, Survivin and Cyclin D1. Akt-p53-Cyclin pathway was inhibited when NBPF1 gene expression was up-regulated. Upregulation of NBPF1 might promote apoptosis of A431 cells and block cell cycle via inhibiting the activation of Akt-p53-Cyclin signaling pathway.

Dose dependency PM2.5 aggravated airway inflammation in asthmatic mice via down-regulating expression of ITGB4.

OBJECTIVE: We aimed to investigate whether PM2.5 has the potential to exacerbate neutrophil airway inflammation and to analyze the underlying mechanisms. MATERIALS AND METHODS: The high-volume air sampler (Laoying 2033B, Qingdao, China) was used to collect PM2.5 from January 01, 2016 to December 21, 2016 in Yantai, Shandong Province, China. BALB/c mice were divided into the following four groups: control group, ovalbumin (OVA) group, low-dose PM2.5 group and high-dose PM2.5 group. Mice except for control group were sensitized and challenged by OVA, and those in low-dose PM2.5 group and high-dose PM2.5 group were intranasally administered by PM2.5 suspension. Airway responsiveness of mice was measured. Enzyme-linked immunosorbent assay (ELISA) kit was used to evaluate the expressions of interleukin 17 (IL-17) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and serum samples. Cell counting in BALF and histological examination were measured to explore PM2.5-induced airway inflammation. Protein expression of Integrin ß4 (ITGB4) was assessed by Western blot. RESULTS: Airway hyperresponsiveness (AHR) exacerbated in PM2.5 exposed asthmatic mice in progressively increased doses of acetylcholine chloride (ACH). Levels of IL-17 and TNF-αin BALF and serum increased significantly in PM2.5 groups compared with other groups with significant differences between two PM2.5 groups. PM2.5 exposure exacerbated inflammatory cell infiltration and mucus secretion in airways of asthmatic mice. Percentage of neutrophils in PM2.5 groups was significantly higher in dose-dependent manner. OVA and PM2.5 co-exposure inhibited the expression of ITGB4. In particular, ITGB4 expression in mice of high-dose PM2.5 group was significantly lowered than the low-dose PM2.5 group. CONCLUSIONS: We showed that PM2.5 exposure exacerbates neutrophil airway inflammation in asthmatic mice though up-regulating expressions of IL-17 and TNF-α but down-regulating the expression of ITGB4.

[Outcomes of splenectomy in relapsed/refractory autoimmune hemolytic anemia].

Objective: To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA). Methods: Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up. Results: Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years. Conclusion: The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.