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  • 简介:AbstractObjective:Pemphigus is a life threatening autoimmune bullous disease which involves the skin and mucous membranes of the stratified squamous epithelium. The global distribution of Pemphigus varies according to genetic, ethnic, socioeconomic, and cultural backgrounds. The purpose of our study is to evaluate the epidemiological features of pemphigus a single center in Morocco and compare our results with those reported elsewhere.Methods:A retrospective analysis was conducted of 302 pemphigus patients seen between 1990 and 2020 in the Dermatology Department of Ibn Sina Hospital (Rabat, Morocco). We further collected all the Moroccan scientific researches published by now to compare.Results:The average annual incidence was 0.32/100,000 inhabitants. The incidence doubled to 0.72 in 2020. The most common variant was pemphigus vulgaris (125 cases) followed by pemphigus erythematosus (99 cases), pemphigus foliaceous (40 cases), and vegetans (27 cases). The female to male ratio was 0.75, the average age at onset was 53 years old and the mean duration of the disease before diagnosis was 13.36 months.Conclusion:This study joins the main characteristics of pemphigus in the Maghreb and around the world (pemphigus vulgaris most frequent subtype). In 2020, an epidemiological peak occurred during the coronavirus disease 2019 pandemic; probably related to stress and delayed time consultation for fear of contracting the severe acute respiratory syndrome coronavirus 2.

  • 标签: pemphigus epidemiology Rabat Morocco autoimmune bullous disease desmoglein
  • 简介:AbstractObjective:Human immunodeficiency virus (HIV) p24 antigen and antibody and herpes simplex virus 2 IgM are seromarkers indicating infection with HIV and herpes simplex virus-2 (HSV-2), respectively, whereas tumor necrosis factor α is an inflammatory biomarker that can be triggered by infections. Female children of single parents are faced with many socio-economic challenges that make them vulnerable to sexual influences and prone to sexually transmitted infections. The goal of this work was to determine HIV p24 antigen/antibody, HSV-2 IgM and tumor necrosis factor-α plasma levels in adult female children living in single-parent households.Methods:In this case-control observational study, 100 adult female children living with a single parent (50 living with a single mother and 50 living with a single father; age: 18-22 years) and 100 age-matched women living with both parents were recruited to serve as the test and control groups, respectively. All subjects were negative for acid-fast bacilli, plasmodium, hepatitis C virus, and hepatitis B virus. Human tumor necrosis factor α, HSV-2 IgM, antibody to hepatitis C virus, hepatitis B surface antigen and human immunodeficiency virus p24 antigen and antibody (HIV p24 Ag/Ab) levels were determined by ELISA, while the detection of acid-fast bacilli in sputum and Plasmodium in blood was carried out by optical microscopy. This work was carried out in the Owo/Ose Federal Constituency in Ondo State that shares boundaries with Edo State. The study protocol was approved by the Research and Ethical Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/2020/127) on August 27, 2020.Results:HIV p24 Ag/Ab was detected in 0 adult female children living with a single mother, 1 (2%) adult female child living with a single father and 1 (1 %) adult female child living with both parents. HSV-2 IgM was detected in 9 (18%) adult female children living with a single mother, 13 (26%) adult female children living with a single father, and 5 (10%) adult female children living with both parents.Conclusion:This work shows that adult female children of single parents are vulnerable to sexual influences, and thereby more prone to HSV-2 and possibly HIV, especially adult female children of single fathers.

  • 标签: adult female children HIV p24 Ag/Ab HSV-2 IgM single-parent household tumor necrosis factor α
  • 简介:AbstractBackground:Glioma is a common malignant brain tumor. The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma.Methods:SPI1 expression in glioma was identified using qRT-PCR and Western blotting. Cell proliferation was assessed using the CCK8 assay. Transwell and wound healing assays were utilized to evaluate cell migration. Additionally, cell cycle and apoptosis were detected using flow cytometry.Results:We observed that the expression level of SPI1 was up-regulated in glioma tissues, compared to normal tissues. Furthermore, we found that SPI1 is able to promote proliferation and migration of glioma cells in vitro. Flow cytometry results demonstrate that, compared to si-NC cells, si-SPI1 cells stagnated in the G1 phase, and downregulation of SPI1 expression is able to increase rates of apoptosis. Double luciferase activity and chromatin immunoprecipitation assay results indicated that SPI1 can bind to the promoter sites and promote the proliferation and migration of glioma cells by regulating the expression of oncogenic PAICS.Conclusions:Our results suggest that SPI1 can promote proliferation and migration of glioma. Furthermore, SPI1 can be utilized as a potential diagnostic marker and therapeutic target for glioma.

  • 标签: Glioma SPI1 PAICS proliferation migration
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  • 简介:AbstractObjective:The current study aimed to profile the demographics, hematological index, and extrinsic factors of patients treated for frostbite in a single center in Southwest China.Methods:We collected the clinical data of patients with frostbite admitted to a regional hospital from January 1st, 2009 to January 1st, 2019. The baseline information was summarized, and the causes and hematological indexes of frostbite were analyzed.Results:The study cohort comprised 27 patients. The median patient age was 22 years (range 14-81 years). All frostbite injuries occurred between September 22nd and April 27th. Half of the patients were Tibetans. Cold injuries in Tibetan patients were associated with pilgrimage (70%, 9/13) and grazing (15%, 2/13), while the leading causes of frostbite in Han residents of the Southwest China basin were mandatory fieldwork without protection (36%, 5/14) and loss of consciousness (36%, 5/14). The hematological examination findings did not significantly differ between amputees and those who did not undergo amputation. Several hematological indexes significantly differed between patients with good outcomes versus those with poor outcomes.Conclusion:To avoid severe frostbite damage, routine mandatory activities like pilgrimage should be conducted under proper protection in extreme weather. Hematological indexes such as the red blood cell count, hematocrit, and hemoglobin level should be monitored closely by first-line medical personnel during hospitalization, as these indexes might indicate the outcome of frostbite. Further research is needed to improve the management of patients with frostbite in Southwest China.

  • 标签: frostbite amputation prognosis Southwest China
  • 简介:AbstractNon-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.

  • 标签: Nonalcoholic fatty liver disease Hepatocyte nuclear factor 4α Lipogenesis Inflammation Fibrosis Liver Lipotoxicity Apoptosis
  • 简介:AbstractThe coronavirus disease 2019 (COVID-19) pandemic has been an unmitigated disaster for society and the economy worldwide. However, much remains unknown about the pathogenesis of, treatment methods for, and preventive measures against COVID-19. Single-cell sequencing is a novel sequencing technology whose use has recently become prevalent in various life-science fields. This high-resolution technology is being used to analyze the COVID-19 pandemic at a single-cell level. In this review, we summarize the application of single-cell sequencing technology to the field of COVID-19-related research, including the biology of severe acute respiratory syndrome coronavirus 2, clinical concerns associated with COVID-19, neutralizing antibody screening, and vaccine development. We also address challenges to, and improvements in, existing single-cell research related to COVID-19.

  • 标签: COVID-19 neutralizing antibody SARS-CoV-2 single-cell sequencing vaccine
  • 简介:AbstractBackground:Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice.Methods:In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo.Results:Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway.Conclusion:In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.

  • 标签: Hepatocyte growth factor Acute respiratory distress syndrome Endothelial barrier mTOR/STAT3 pathway Permeability
  • 简介:AbstractBackground:Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods:The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results:A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DM vs. 19.3% in non-DM, P = 0.026) and N3b status (18.8% in DM vs. 12.8% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P= 0.011) and N3b status (OR= 1.752, P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1-2: 2.2% vs. 4.9%, T3: 29.0% vs. 20.3%, T4a: 38.9% vs. 25.8%, T4b: 50.0% vs. 36.6%; ELN16-29: 8.6% vs. 10.4%, ELN30-44: 27.9% vs. 20.5%, ELN ≥ 45: 37.7% vs. 25.3%), N3b status (DM vs. non-DM, T1-2: 0% vs. 1.7%, T3: 16.1% vs. 5.1%, T4a: 27.8% vs. 19.1%, T4b: 44.0% vs. 28.0%; ELN16-29: 8.6% vs. 7.9%, ELN30-44: 18.0% vs. 11.8%, ELN ≥ 45: 26.4% vs. 17.3%), and the number of MLN (DM vs. non-DM, T1-2: 0.4 vs. 1.1, T3: 8.6 vs. 5.2, T4a: 9.7 vs. 8.6, T4b: 17.0 vs. 12.8; ELN16-29: 3.6 vs. 4.6, ELN30-44: 5.8 vs. 5.5, ELN ≥ 45: 12.0 vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN.Conclusions:DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.

  • 标签: Diabetes mellitus Gastric cancer Lymph node Metastasis
  • 简介:AbstractCell-cell communication is the basis of physiological processes and cell signals. The disease occurs when the cells do not adequately communicate and the messages are blocked. With ligand-receptor interaction databases and single-cell RNA sequencing (scRNA-seq) databases, we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types. This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19. We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes, such as carcinogenesis and SARS-CoV-2 infection.

  • 标签: Cell-cell communication Ligand-receptor pair Single-cell RNA sequencing Carcinogenesis COVID-19
  • 简介:AbstractBackground:To analyze clinically and radiologically the surgical outcome like residual disease, progression of disease, recurrence, disabilities, event-free survival (EFS), and mortality of different infra-tentorial tumor subtypes in children and adults of a strictly non-migratory and ethnic population.Methods:The 410 histologically proved, out of 589, infra-tentorial brain tumor patients were analyzed clinically and by the imaging post-surgically in a single tertiary center for an ethnic region. In this analytico-observational study, retrospectively postoperative records of 589 infra-tentorial brain tumors from November 1998 to December 2018 (20 years) were retrieved, scrutinized, and compiled. The post-operative clinic-radiological records of 410 patients with proved histopathological examination results were included. Statistical law of variance was applied where-ever necessary.Results:The 63.2% of the all 410 operated infra-tentorial brain tumors were males while females predominated in meningiomas and pineoblastomas. About 31.7% infra-tentorial tumors were children (below 18 years). About 54.1% cases were histologically malignant. The residual tumors comprised 40.2% and symptoms of disease-progression occurred in 10.9%. The tumor recurrence occurred in 14.3% while 6.0% patients developed severe disability. The overall mortality was 11.4% but 18.9% in malignant tumors. The event-free survival (EFS) for all the patients was 66.0%, patients with malignancies had 47.7% and benign group had 87.7%.Conclusion:The study, surgical outcome of infra-tentorial brain tumor subtypes in children and adults (approx. 1/3rd of patients being children), conducted in a tertiary center at a remote land-locked location with non-migratory ethnic population as its catchment area, has a significant epidemiological value for the community and the region.

  • 标签: Infra-tentorial brain tumors Histological subtypes Ethnic population Surgical outcome
  • 简介:AbstractObjective:Endoscopic repair of large anterior skull base (ASB) defects has excellent results when using multilayered repairs with a nasoseptal flap. However, in extensive intranasal tumors, a nasoseptal flap may not always be available. One alternative option is a flexible single-layer ASB repair. Initial studies indicate low cerebrospinal fluid leak rates with a single-layer repair. However, the level of frontal lobe support, particularly the propensity for a significant inferior displacement of the frontal lobe, is not known. The goal of this study is to determine the frontal lobe position after single-layer acellular dermal allograft repair in large ASB defects.Study Design:Retrospective cohort study.Setting:Tertiary care medical center.Subjects and Methods:This cohort study compares the frontal lobe position in adults who underwent endoscopic endonasal ASB tumor resection and single-layer cadaveric dermal matrix repair (ASB cohort) with control subjects without intracranial abnormalities (control cohort). The ASB cohort includes subjects with an ASB defect of ≥5 cm anterior/posterior and ≥1.5 cm wide and who had imaging at least 2 months after surgery. The frontal lobe position is measured on sagittal CT/MRI using a reference line from the base of the sella to the nasion. A value of zero indicates that the inferior-most aspect of the frontal lobe is at the level of the nasion-sellar line. A positive value indicates that the frontal lobe is inferior to the nasion-sellar line. The ASB cohort frontal lobe position is compared with the control cohort using the Mann-Whitney U test. A priori we set an absolute difference of 5 mm as a clinically significant difference.Results:The ASB cohort includes 47 subjects who are 57% male with an average age of 60 years (range: 31-89 years). The most common ASB pathology is esthesioneuroblastoma (n = 21) and 81% of the ASB cohort had postoperative radiation. The control cohort includes 20 subjects who are 60% male, with a mean age of 45 years (range: 19-74 years). The majority of controls underwent imaging for head trauma (n = 13). The ASB mean frontal lobe position is -0.2 mm superior to the nasion-sellar line (range: -9.2 to 10.4 mm), while the control's mean frontal lobe position is 1.1 mm inferior to the nasion-sellar line. This difference is not statistically significant (P= 0.13) and does not reach our a priori definition of clinical significance. The frontal lobe position of ASB subjects who had radiation is closer to the nasion-sellar line as compared with those who did not undergo radiation.Conclusions:Single-layer acellular dermal graft repair maintains frontal lobe support and position in large ASB defects.

  • 标签: anterior skull base cohort study frontal lobe skull base repair skull base tumor
  • 简介:AbstractBackgrounds:At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios.Methods:We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups.Results:The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6%, [84/141] P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57-2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8% [11/141], P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7%, [1/141] P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96-22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07-2.14), body mass index (BMI) >30 kg/m2 (aOR: 2.98, 95% CI: 1.10-8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12-5.50).Conclusions:Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m2, large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.

  • 标签: Borderline oligohydramnios Induction of labor Single-balloon catheter Dinoprostone Nuchal cord
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  • 简介:摘要BackgroundDelayed encephalopathy (DE) is the most severe complication after acute carbon monoxide (CO) poisoning, which seriously affects the outcome of patients and leads to a high disability rate. Prior studies have shown that hyperbaric oxygen (HBO2) therapy is therapeutic for DE due to reducing immune-mediated neuropathology and thus improving cognitive performance.MethodsIn our present perspective study, five DE patients were treated regularly with HBO2 therapy. The mini-mental state examination (MMSE) and Barthel index (BI) were intermittently collected during their hospitalization for mental and physical status evaluation, the peripheral bloods were serially sampled to determine the concentration changes of circulating stem cells, as well as corresponding BDNF and neural markers.ResultsMMSE and BI showed series of improvements after multiple HBO2 therapies. The CD34+/CD90+ and CD34+/CD133+ dual positive cells, which were categorized as circulating stem cells, were observed an overall up-regulation since the beginning of the DE onset upon the application of HBO2 therapy. Characteristic neurotrophin BDNF, neural markers such as nestin and synaptophysin (SYP) were also up-regulated after exposure of HBO2. Conclusion The application of HBO2 therapy is of significance in improving the cognition of DE patients, along with mobilized circulating stem cells.ConclusionWe primarily infer that the CD34+/CD90+ and CD34+/CD133+ cells were mobilized by HBO2 exposure and have played a positive role in cognition improvement on DE patients by up-regulation of BDNF, nestin and SYP. The altering amount of circulating stem cells mobilized in peripheral blood could be a potential marker on predicting the outcome of DE.

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  • 简介:AbstractBackground:Response to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients.Methods:The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People’s Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated.Results:Forty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs. 15.5 months, P = 0.0005) and OS (11.1 months vs. not reached, P = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs. 15.5 months, P = 0.0532) rather than OS (P = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs. 4.3 months, P = 0.1894). More metastatic organs involved were associated with inferior PFS (P = 0.0052) but not OS (P = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[φ]: 0.516, P = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4).Conclusions:Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.

  • 标签: Metastatic sites Immunotherapy Liver metastases Bone metastasis Non-small-cell lung cancer Tumor response
  • 简介:AbstractBackground:Head and neck cancers (HNCs) are a heterogeneous group of tumors that progress owing to varied enviromental and genetic risk factors. Viral infections are threatening and adept at altering the expression of cellular transcription factors such as nuclear factor kappa B (NF-κB) and deregulation of other cellular proteins like NF kappa B inhibitor alpha (IκBα). The present study was conducted to detect high-risk genotypes of human papillomavirus (HPV) and protein expression of NF-κB signaling pathway in HNC patients with HPV infection.Methods:For HPV detection, genomic DNA from 152 HNC tumors was extracted formalin-fixed paraffin-embedded tissue DNA kit. For genotyping, polymerase chain reaction (PCR) using a general primer, HPV type-specific primers and agarose gel electrophoresis were performed. Immunohistochemistry (IHC) was also performed on 4-μm thick tissue sections using HPV E6 monoclonal antibody. Protein expression analysis of NF-κB signaling pathway including p50, p65, and IκBα was performed using IHC.Results:PCR analysis showed that 24.3% (37/152) of HNC cases were HPV positive. Among HPV positive, 86.5% (32/37) were tobacco users, while among HPV negative, 66.9% (77/115) were tobacco users. A significant association of HPV positivity and tobacco user was observed by univariate analysis [P < 0.01; odds ratio (OR): 0.310, 95% confidence interval (CI): 0.110 to 0.870]. More HPV positive patients were with poor oral hygiene (78.3%) when compared with patients with good oral hygiene (21.6%) [P < 0.03, OR: 2.440, 95% CI: 1.650 to 3.600]. The results of the logistic regression analysis showed that age, tobacco use and oral hygiene are significant predictors (P < 0.02). PCR and IHC staining results confirmed that HPV16 was predominant among HNC cases (64.8%) when compared with HPV18 (35.2%). Expression of NF-κB proteins (p50, p65, and IκBα inhibitor) were also observed in HPV and non-HPV infected HNC tissues. IHC expression of p50, and p65 showed nuclear staining, while IκBα inhibitor showed cytoplasmic staining. Protein expression in HPV cases was higher as compared to HPV naive cases (P < 0.05).Conclusions:From the study, it can be established that the use of tobacco, oral hygiene, and HPV infection may be synergistically involved in modulating the expression of NF-κB signaling pathway for the development and progression of HNC in the Pakistani population.

  • 标签: Human papillomavirus NF-kappa B p50 p65 IκBα inhibitor Polymerase chain reaction Immunohistochemistry Head and neck cancer Pakistani population
  • 简介:AbstractObjective:It remains unclear whether adjuvant chemoradiotherapy (CRT) improves survival outcome of pancreatic ductal adenocarcinoma (PDAC) patients after surgery. This study aimed to investigate the efficacy and safety of tegafur/gimeracil/oteracil (S-1)-based adjuvant concurrent chemoradiotherapy in resected PDAC patients with defined high-risk pathological features.Methods:We conducted a single-arm, prospective, and interventional study at Zhongshan Hospital Fudan University from December 2012 to December 2019 and the last follow-up was conducted in December 2021. This study was approved by the Ethics Committee of Zhongshan Hospital Fudan University on December 27, 2012 (approval No. B2012-139). Resected PDAC patients with high-risk pathological features, including positive resection margin, pathological T3-4N1-2M0 disease, peripancreatic fat invasion, microvascular invasion, and perineural invasion, were recruited. Primary endpoint was overall survival and secondary endpoints were disease-free survival, treatment toxicity, and 2-, 5-year survival rates.Results:A total of 54 patients were recruited. Mean age was 63.6 years old (±7.2). The distribution of T and N stages were 24.1% for T1, 46.3% for T2, 27.8% for T3, 1.9% for T4, 33.3% for N1, and 11.1% for N2. Seven patients had R1 resection. The median overall survival and disease-free survival were 27.1 and 13.7 months, respectively, while no fatal adverse events were recorded. Subgroup analyses showed differences in survival outcomes among patients with microvascular invasion, different N stages, and preoperative CA 19-9 levels. Further, a Cox proportional hazard model demonstrated associations of lymph node metastases, CA 19-9 level, and microvascular invasion with overall survival and disease-free survival.Conclusion:S-1 -based adjuvant CRT showed promising efficacy and manageable toxicity in resected PDAC patients with highrisk pathological features.

  • 标签: Adjuvant chemoradiotherapy Pancreatic cancer Pathology S-1 Surgery