Noninvasive prediction of lymph node metastasis in pancreatic cancer using an ultrasound-based clinicoradiomics machine learning model.

OBJECTIVES: This study was designed to explore and validate the value of different machine learning models based on ultrasound image-omics features in the preoperative diagnosis of lymph node metastasis in pancreatic cancer (PC). METHODS: This research involved 189 individuals diagnosed with PC confirmed by surgical pathology (training cohort: n = 151; test cohort: n = 38), including 50 cases of lymph node metastasis. Image-omics features were extracted from ultrasound images. After dimensionality reduction and screening, eight machine learning algorithms, including logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), random forest (RF), extra trees (ET), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to establish image-omics models to predict lymph node metastasis in PC. The best omics prediction model was selected through ROC curve analysis. Machine learning models were used to analyze clinical features and determine variables to establish a clinical model. A combined model was constructed by combining ultrasound image-omics and clinical features. Decision curve analysis (DCA) and a nomogram were used to evaluate the clinical application value of the model. RESULTS: A total of 1561 image-omics features were extracted from ultrasound images. 15 valuable image-omics features were determined by regularization, dimension reduction, and algorithm selection. In the image-omics model, the LR model showed higher prediction efficiency and robustness, with an area under the ROC curve (AUC) of 0.773 in the training set and an AUC of 0.850 in the test set. The clinical model constructed by the boundary of lesions in ultrasound images and the clinical feature CA199 (AUC = 0.875). The combined model had the best prediction performance, with an AUC of 0.872 in the training set and 0.918 in the test set. The combined model showed better clinical benefit according to DCA, and the nomogram score provided clinical prediction solutions. CONCLUSION: The combined model established with clinical features has good diagnostic ability and can be used to predict lymph node metastasis in patients with PC. It is expected to provide an effective noninvasive method for clinical decision-making, thereby improving the diagnosis and treatment of PC.

A 3-year follow-up clinical study on the preservation for vitality of involved tooth in jaw cysts through an innovative method.

Jaw cysts commonly affect the oral and maxillofacial region, involving adjacent tooth roots. The management of these teeth, particularly regarding root canal therapy and apicoectomy, lacks consensus. This study introduces a novel treatment concept and refined surgical approach to preserve pulp viability in teeth involved in jaw cysts. The objective was to investigate the effectiveness and potential benefits of this approach over a 36-month follow-up period. A conservative management approach prioritized vitality preservation, reserving root canal treatment and apicectomy for cases with post-operative discomfort. A comprehensive follow-up of 108 involved teeth from 36 jaw cyst cases treated with the modified method was conducted. Clinical observation, X-ray imaging, cone-beam computed tomography (CBCT), and pulp vitality testing assessed changes in cyst size, tooth color, pulp vitality, root structure, and surrounding alveolar bone. After 36 months, our modified surgical approach successfully preserved tooth vitality in 84 involved teeth. Adverse symptoms in 19 teeth, such as redness, swelling, fistula, and pain, resolved with postoperative root canal therapy. Follow-up was lost for five teeth in two cases. No cyst recurrences were observed, and in 34 cases, the bone cavity gradually disappeared, restoring normal bone density during long-term follow-up. Our modified surgical method effectively preserves tooth vitality in jaw cysts. This innovative approach has the potential to improve the management of teeth involved in jaw cysts.

Upregulated CANT1 is correlated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: CANT1, as calcium-activated protein nucleotidase 1, is a kind of phosphatase. It is overexpressed in some tumors and related to poor prognosis, but few studies explore its function and carcinogenic mechanism in hepatocellular carcinoma (HCC). METHODS: The expression of CANT1 mRNA and protein was analyzed by the Cancer Genome Atlas (TCGA) database and immunohistochemistry(IHC) staining. The relationship between CANT1 expression and clinicopathology was evaluated by various public databases. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of CANT1 by the area under curve (AUC). Univariate, multivariate Cox regression and Kaplan-Meier curves were applied to evaluate the predictive value of CANT1 on the prognosis of HCC. Methsurv was used to analyze gene changes and DNA methylation, and its impact on prognosis. The enrichment analysis of DEGs associated with CANT1 revealed the biological process of CANT1 based on Gene Set Enrichment Analysis (GSEA). The relationship between immune cell infiltration level and CANT1 expression in HCC was investigated using the single-sample GSEA (ssGSEA) method and the Tumor Immune Estimation Resource (TIMER) database. Finally, the association between CANT1 and immune checkpoints and drug sensitivity was also analyzed. RESULTS: CANT1 was highly expressed in 22 cancers, including HCC, and CANT1 overexpression in HCC was confirmed by IHC. The expression of CANT1 was correlated with clinical features, such as histologic grade. Highly expressed CANT1 caused poor overall survival (OS) of HCC patients. Univariate and multivariate regression analysis suggested that CANT1 was an independent prognostic marker. Of the 31 DNA methylation at CpG sites, three CpG sites were associated with the prognosis of HCC. GSEA indicated that CANT1 was mainly involved in the cell cycle, DNA replication, and etc. Moreover, CANT1 expression was correlated with immune cell infiltration and independently associated with the prognosis of HCC patients. Finally, CANT1 expression was correlated with most immune checkpoints and drug sensitivity. CONCLUSION: CANT1 may be a latent oncogene of HCC, and associated with immune cells and immune checkpoints, which may assist in HCC treatment.

Clinicopathological Features of Hepatocellular Carcinoma with Metabolic Risk Factors.

Objective: This study aims to explore the pathological characteristics of metabolic-related hepatocellular carcinoma (HCC) and its correlation with metabolic factors. Methods: Fifty-one patients with liver cancer of unknown causes were enrolled. Biopsy of the liver and staining of the liver tissues with hematoxylin-eosin as well as special and immunohistochemical stains were performed. The histological subtypes of HCC were diagnosed based on the WHO Classification of Malignant Hepatocellular Tumors. The NAFLD activity score system was adopted for assessing the surrounding non-neoplastic liver tissues. Results: Of the total, 42 (82.4%) patients were diagnosed with HCC, 32 had metabolic risk factors, 20 patients met the diagnostic criteria of the metabolic-associated fatty liver disease (MAFLD)-related HCC, and 40.6% (13/32) had liver cirrhosis. The incidence of cirrhosis (p = 0.033) and diabetes mellitus type 2 (p = 0.036) in patients with MAFLD-related HCC was notably higher than that in HCC patients with only metabolic risk factors. Among the 32 HCC cases with metabolic risk factors, trabecular type was the most prevalent, followed by steatohepatitis type, scirrhous type, solid type, pseudoglandular type, clear-cell type, and macrotrabecular type. The degree of tumor cells' swelling and ballooning was found to be positively related to the degree of fibrosis in the surrounding liver tissues (p = 0.011) as well as the proportion of cirrhosis (p = 0.004). Moreover, the degree of fibrosis in the surrounding liver tissues showed a negative correlation with the levels of serum cholesterol (p = 0.002), low-density lipoprotein (p = 0.002), ApoA1 (p = 0.009), ApoB (p = 0.022), total protein (p = 0.015), WBC count (p = 0.006), and PLT count (p = 0.015). Conclusion: Pathological characteristics of the tumor and adjacent non-neoplastic liver tissues of HCC with metabolic risk factors were found to be correlated with metabolic abnormalities.

The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma.

BACKGROUND: RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. METHOD: The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan-Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis（DCA）analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. RESULT: The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. CONCLUSION: We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies.

Efficacy of single-stage posterior surgery for HIV-positive patients with thoracolumbar tuberculosis.

OBJECTIVE: We aimed to observe the clinical effect of single-stage posterior surgery on HIV-positive patients with thoracolumbar tuberculosis. METHODS: From October 2015 to October 2019, 13 HIV-positive patients with thoracolumbar tuberculosis who underwent single-stage posterior surgery were retrospectively analyzed (observation group), and 13 HIV-negative patients with thoracolumbar tuberculosis who were matched with the gender, age, operative site, and surgical approach during the same period were selected as the control group. Postoperative complications, hemoglobin, albumin, CD4+T lymphocyte count, operative site, operative time, and blood loss were recorded between the two groups. The clinical efficacy was evaluated by the visual analog scale (VAS), American Spinal Injury Association (ASIA) scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), kyphotic angle, correction rate of kyphosis, angle loss, and bone graft fusion time. RESULTS: In the observation group, 7 patients had postoperative complications, including 1 patient with cerebrospinal fluid leakage, 1 patient with nerve root irritation, 1 patient with an opportunistic infection, and 4 with delayed wound healing. In the control group, 2 patients developed postoperative complications, including 1 with nerve root irritation and 1 with delayed wound healing. There was no statistically significant difference in the incidence of postoperative complications between the two groups (P > 0.05). CD4+T lymphocyte count, hemoglobin, and albumin in HIV-positive patients with postoperative complications were statistically different from those without postoperative complications (P all < 0.05). No tuberculosis recurrence was found at the last follow-up, ESR and CRP returned to normal, and there were no statistically significant differences in bone graft fusion time, VAS score, ASIA scale, correction rate of kyphosis, and angle loss between two groups (P all > 0.05). CONCLUSION: Single-stage posterior surgery for HIV-positive patients with thoracolumbar tuberculosis could achieve satisfactory clinical efficacy through comprehensive preoperative evaluation, standardized perioperative antiviral and anti-tuberculosis treatments, and prevention of postoperative complications.

Compliance with Oral Nutritional Supplementation among Gastric Cancer Patients at Nutritional Risk: A Cross-Sectional Study.

AIMS: To explore compliance with oral nutritional supplementation (ONS) and to identify the risk factors for noncompliance among gastric cancer patients based on the health belief model (HBM). METHODS: This prospective, observational study included gastric cancer patients at nutritional risk who were prescribed ONS from July to September 2020. Demographic factors, clinical factors, ONS-related factors, social factors and variables derived from the HBM were collected. The outcome of interest was compliance with ONS, which was measured by self-reported intake of ONS. Uni- and multivariate analyses of potential risk factors for noncompliance were performed. RESULTS: A total of 162 gastric cancer patients in the preoperative and adjuvant chemotherapy periods were analyzed. The compliance rate with ONS was 24.7%. Univariate analysis identified thirteen variables as risk factors for decreased compliance. Multivariate logistic analysis indicated that ONS compliance was independently associated with the treatment period, perceived barriers to ONS, the motivation to take ONS, and the timing of taking ONS. CONCLUSION: This study showed that overall ONS compliance among gastric cancer patients was notably low. Patients in the chemotherapy treatment period who took ONS at random times each day perceived more barriers to taking ONS and had a lower level of motivation were associated with lower compliance with ONS.

Cytopathological analysis of bronchoalveolar lavage fluid in patients with and without HIV infection.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) infection can lead to a broad spectrum of lung diseases, including infectious diseases and tumors. Recently, with the wide application of bronchoscopes and cytopathology of bronchoalveolar lavage fluid (BALF), the diagnostic efficiency of lung diseases has improved. The present study focuses on analyzing the cytopathologic characteristics of BALF in the diagnosis of HIV/AIDS-related lung disease and comparing the lung disease spectrum between HIV and HIV-uninfected patients. METHODS: BALF specimens were collected from 2211 patients. Using ThinPrep liquid-based technology, the cytologic smears were prepared by staining with Hematoxylin and Eosin (HE), Gomori's methenamine silver (GMS), and Periodic Acid Schiff (PAS), acid-fast and immunocytochemical (ICC) staining. Real-time PCR was used to detect cytomegalovirus (CMV) and Mycobacterium tuberculosis (M. tuberculosis) in the remaining BALF. PCR-reverse dot hybridization was used for mycobacterial species identification. RESULTS: From the 2211 BALF specimens, 1768 (79.96%) were specimens from HIV-infected patients, and 443 (20.04%) were speciments from HIV-uninfected patients. The HIV-infected patients with a median age of 38.5 ± 11.3 years were markedly younger than the HIV-uninfected patients (52.9 ± 14.9 years) (p < 0.01). We found that 1635 (92.5%) HIV-infected patients were males, showing a prominently higher proportion than those without HIV infection (71.1%) (p < 0.01). Meanwhile, 1045 specific lesions were found in 1768 HIV-infected patients (59.1%), including 1034 cases of infectious diseases and 11 neoplastic lesions, also exhibiting a distinctly higher proportion compared to the HIV-uninfected patients (12.2%) (p < 0.001). For the HIV-infected group, a distinctly higher proportion of single infection lesions (724/1768, 41%) was noted than the HIV-uninfected group (14/443, 3.2%) (p < 0.001). Among single infection lesions, the most common was Cytomegalovirus(CMV) infection (20.9%) for the HIV-infected group, followed by Pneumocystis jiroveci(PJ) (13.0%), Fungal (3.5%), and Mycobacterial infections (3.4%), of which M. tuberculosis infection accounted for 3.1%. Double infections (300/1768, 17.0%) and Triple infections (10/1768, 0.6%) were found only among the patients with HIV. The malignancies among HIV-infected patients included adenocarcinomas (0.22%), small cell carcinomas (0.2%), squamous cell carcinomas (0.1%), and diffuse large B-cell lymphoma (0.1%). HIV-infected patients exhibited a significantly lower incidence of neoplastic lesions (0.6% vs. 9.0%) than the HIV-uninfected patients (p < 0.001). CONCLUSIONS: There was a significant difference in the spectrum of lung diseases between HIV-infected and non-infected patients diagnosed by BALF cytopathology.

Cytomegalovirus cell tropism and clinicopathological characteristics in gastrointestinal tract of patients with HIV/AIDS.

BACKGROUND: Cytomegalovirus (CMV) has been recognized as one of the frequently occurring opportunistic infections (OIs) reported in the patients having human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In addition, it has been identified as the factor leading to gastrointestinal (GI) tract disorder among HIV/AIDS population. CMV exhibits broad cell tropism in different organs. This study evaluated the CMV cell tropism and clinicopathological characteristics of CMV infection in the different GI regions in HIV/AIDS cases. METHODS: Using nucleic acid in situ hybridization (ISH), CMV was detected in the gastrointestinal mucosal biopsy samples. The paraffin-embedded samples were stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC), respectively. RESULTS: A total of 32 HIV/AIDS patients were enrolled in this study. Fourteen of these patients underwent gastroscopy, while the remaining eighteen received colonoscopy. CMV-infected cells were observed at 46 GI sites. Among them, the colon was the region with the highest susceptibility to GI CMV infection (n = 12, 26.1%). The CMV giant cell inclusion bodies were detected in epithelial cells and mesenchymal cells, including histiocytes, smooth muscle cells, fibroblasts, and endothelial cells. In the duodenum, there were markedly more positive epithelial cells than mesenchymal cells (p = 0.033). In contrast, in the esophagus (p = 0.030), cardia (p = 0.003), rectum (p = 0.019), colon (p < 0.001), and cecum (p < 0.001), there were notably less positive epithelial cells than mesenchymal cells. The expression levels of PDGFRα and Nrp2 in the mesenchymal cells were higher than the epithelial cells in cardia, cecum, colon, sigmoid, and rectum, especially in the areas with ulcers. However, Nrp2 in the epithelial cells was higher than that in the duodenum. Moreover, the positive CMV DNA in peripheral blood was related to the CMV-positive cell count, as well as the ulceration in GI tract (p = 0.035 and 0.036, respectively). CONCLUSIONS: The colon has been identified as the GI site with the highest susceptibility to CMV infection. There are different CMV-infected cells in the different sites of the GI that relate to the expression level of PDGFRα and Nrp2. CMV DNA positive in the blood is related to the positive CMV cell count, as well as ulceration in the GI tract.

[Study on the Effect of Polystyrene-Polyvinylpyrrolidone Electrospun Fibre in Inhibiting the Adhesion of Porphyromonas gingivalis].

OBJECTIVE: To explore the effect of polystyrene (PS) and PS-polyvinylpyrrolidone (PVP) electrospun materials on the adhesion ability of Porphyromonas gingivalis( P. gingivalis), a common periodontal pathogen. METHODS: PS and PS-PVP electrospun materials were prepared with stainless steel needles in high-voltage electric field. The growth and adhesion of P. gingivalis on the surface of different materials were observed with scanning electron microscope (SEM). The changes in the amount of P. gingivalis biofilm formed on the surface of different materials were measured according to viable colony forming units (CFU). The effect of surface charge of the different materials on the adhesion ability of P. gingivalis was determined through changing the charge properties on the surface of the electrospun materials. RESULTS: SEM images showed that both PS and PS-PVP can be used to form electrospun fibers with a diameter of 0.2 µm. SEM images and CFU counts of the biofilm at 24 h and 48 h showed that there was a smaller amount of P. gingivalis biofilm on the surface of the two materials ( P<0.05). After treatment with tetrabutylammonium bromide (TBAB), the surface charge of the PS-PVP electrospun material changed from being negatively charged to being positively charged, and the amount of bacterial adhesion on the surface increased significantly in comparison to that of untreated PS and PS-PVP materials ( P<0.05). CONCLUSION: PS and PS-PVP electrospun materials can be used to reduce the adhesion ability of P. gingivalis on the surface of different materials, and this ability may be related to the surface charge properties of the materials.

Nicotine Causes Mitochondrial Dynamics Imbalance and Apoptosis Through ROS Mediated Mitophagy Impairment in Cardiomyocytes.

Nicotine contained in traditional cigarettes, hookahs, and e-cigarettes is an important risk factor for cardiovascular disease. Our previous study showed that macroautophagic flux impairment occurred under nicotine stimulation. However, whether nicotine influences mitochondrial dynamics in neonatal rat ventricular myocytes (NRVMs) is unclear. The purpose of this study was to explore the effects and potential mechanism of nicotine on mitophagy, mitochondrial dynamics, apoptosis, and the relationship between these processes in NRVMs. Our results showed that nicotine exposure increased mitochondria-derived superoxide production, decreased mitochondrial membrane potential, and impaired PINK1/Parkin-mediated mitophagic flux in NRVMs. Interestingly, nicotine significantly promoted dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and suppressed mitofusin (MFN)-mediated fusion, which was also observed in the bafilomycin A1-treated group. These results suggest that mitophagic flux impairment may contribute to Drp-1-mediated mitochondrial fission. Finally, nicotine caused excessive mitochondrial fission and contributed to apoptosis, which could be alleviated by mdivi-1, an inhibitor of Drp1. In addition to CTSB, as we previously reported, the enzyme activity of cathepsin L (CTSL) was also decreased in lysosomes after stimulation with nicotine, which may be the main cause of the hindered mitophagic flux induced by nicotine in NRVMs. Pretreatment with Torin 1, which is an inhibitor of mTOR, activated CTSL and ameliorated nicotine-induced mTOR activation and mitophagy impairment, decreased mitochondria-derived superoxide production, and blunted mitochondrial fission and apoptosis. Pretreatment with the ROS scavenger N-acetyl-cysteine (NAC) or inhibitors of p38 and JNK, which could also alleviate mitophagy impairment, exhibited similar effects as Torin1 on mitochondria. Taken together, our study demonstrated that nicotine treatment may lead to an increase in Drp1-mediated mitochondrial fission by blocking mitophagic flux by weakening the enzyme activity of CTSL and activating the ROS/p38/JNK signaling pathway. Excessive mitochondrial fission induced by nicotine ultimately leads to apoptosis. Torin1 restored the decreased CTSL enzyme activity by removing excessive ROS and alleviated the effects of nicotine on mitophagic flux, mitochondrial dynamics, and apoptosis. These results may provide new evidence on the relationship between mitophagic flux and mitochondrial dynamics and new perspectives on nicotine's effects on mitochondrial dynamics in cardiomyocytes.

Diagnostic value of real-time PCR of brain mass lesion in HIV-associated toxoplasmic encephalitis: a case series.

BACKGROUND: Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE. METHODS: A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service. RESULTS: There were 8 male and 1 female patients; their age ranged from 26 to 56 years-old. The main symptom was intracranial hypertension (6/9). Six patients presented multiple brain lesions, which were mainly located in the supratentorial area (7/9). CD4+ count ranged from 11 to 159 cells/µl (median 92 cells/µl), and serological HIV viral load 0-989190 copies/ml (median 192836 copies/ml). IgG and IgM against serum TG were positive in 7 and 1 patients, respectively. Moreover, regarding CSF, IgG against TG was positive in 3 patients, while all patients were negative for IgM. The neuroimaging features on MRI showed no specificity. Four patients were diagnosed with TE by histopathological findings. After receiving anti-Toxoplasma therapy, 8 (8/9) patients improved clinically to a considerable extent. CONCLUSIONS: The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS.

BACKGROUND: Cytomegalovirus (CMV) is among the most common opportunistic infections identified in patients with HIV/AIDS. CMV often targets the colon in such patients. However, the role of regulatory T cells (Tregs) and Programmed death-1 (PD-1) in intestinal CMV infection is unclear. In this study, we evaluate the expression of programmed death -1 (PD-1) and its association with regulatory T cells (Tregs) in patients with HIV/AIDS having CMV colitis. METHODS: CMV was detected in the intestinal mucosal biopsy samples via nucleic acid in situ hybridization. PD-1, CD4, CD8, and Treg-specific marker as well as the winged-helix transcription factor and forkhead box P3 (FoxP3) were detected by immunohistochemical methods. RESULTS: Intestinal CMV diease was identified in 20 out of 195 patients with HIV/AIDS enrolled in our study. CMV was diagnosed microscopically by the presence of giant cell inclusion bodies in epithelial cells, histiocytes, and fibroblasts. Levels of immunoreactive PD-1 detected in mucosal biopsies from patients with HIV/AIDS having CMV colitis were significantly higher than CMV-negative control group (p = 0.023). FoxP3+ cells were detected in the CMV colitis group slight more than that in the control group. CD4+ T lymphocyte counts in the peripheral blood and intestinal mucosal biopsies from CMV colitis group were all notably decreased compared with those with control group (p < 0.001 for both). PD-1 had a significant negative correlation with CD4 counts in intestinal mucosa (p = 0.016). CD8+T lymphocyte counts in peripheral blood and intestinal mucosa were slightly lower than those in the control group, although the differences were not statistically significant. CONCLUSIONS: CMV colitis with HIV/AIDS is associated with significant changes in T lymphocyte populations. These findings may have important implications for disease pathogenesis and progression.

[Application of computer virtual design to assist the accuracy of socket preparation during tooth autotransplantation].

PURPOSE: It was aimed to apply computer virtual design and digital surgical templates to simulate postoperative position of tooth and guide the accuracy of socket preparation during tooth autotransplantation. METHODS: The study enrolled 10 patients who underwent tooth autotransplant surgery. Cone-bean CT (CBCT) data were imported into Proplan CMF 3.0 software. The donor tooth was transferred to the recipient site according to the occlusion and space situation. A digital template was designed to guide socket preparation. Computer-aided rapid prototyping (RP) technique was used to print the surgical template and tooth model. RESULTS: With computer virtual design and digital template, it was possible to accurately guide socket preparation in recipient site. The six-month follow-up results showed the periodontal space in the radiographs was continuous and intact. There was no mobility in all cases and the probing depth of the tooth was <4 mm. The related data showed a favorable survival and success rates of the donor teeth. CONCLUSIONS: Computer virtual design can successfully simulate postoperative position in tooth autotransplantation while simplifying the surgical procedure, and enhance the accuracy of socket preparation.

Analysis of the causes of cervical lymphadenopathy using fine-needle aspiration cytology combining cell block in Chinese patients with and without HIV infection.

BACKGROUND: Cervical lymphadenopathy refers to a frequently observed clinical presentation in numerous pathological conditions. A wide spectrum of diseases can cause cervical lymphadenopathy, irrespective of the fact that the patients are infected with HIV or not. The present study focuses on validating whether the causes of cervical lymphadenopathy differ significantly in HIV and non-HIV patients by using fine-needle aspiration cytology (FNAC) combining cell block. METHODS: A total of 589 patients with cervical lymphadenopathy were recruited in the FNA clinic. The samples were obtained by an auto-vacuumed syringe that benefited the sampling more materials. The cytological smears were prepared by Hematoxylin and Eosin (HE), Periodic Acid Schiff (PAS), Gomori's methenamine silver (GMS) and acid-fast staining. Cell blocks were made if required, and immunohistochemistry stain was performed on the cell block section. RESULTS: The study found 453 (76.9%) patients with HIV and 136 (23.1%) patients without HIV infection. The average age of HIV-infected patients was 34.8 ± 10.2 years, which was significantly lower than that of non-HIV-infected patients (42.9 ± 18.1 years) (p < 0.01). Of all patients infected with HIV, 390 (86.1%) were males. This proportion was significantly higher than that of non-HIV-infected patients [65/136 (47.8%)] (p < 0.01). The major causes of cervical lymphadenopathy in HIV positive patients were mycobacterial infection (38.4%), reactive hyperplasia (28.9%), non-specific inflammation (19.9%), and malignant lesions (4.2%). In contrast, the most common causes in HIV negative patients were reactive hyperplasia (37.5%), malignancy (20.6%), non-specific inflammation (19.1%) and mycobacterial infection (12.5%). Opportunistic infections such as non-tuberculous mycobacteria (4.2%), cryptococcosis (1.5%), Talaromyces marneffei (1.5%) and other fungi (0.4%) were found only in HIV-infected individuals. Non-Hodgkin's lymphoma (2.4%) was the most common malignant lesion in patients with HIV infection, followed by Kaposi's sarcoma (0.9%) and metastatic squamous cell carcinomas (0.7%). However, the most common malignancy in non-HIV-infected patients was metastatic carcinomas (14%) including small cell carcinomas, adenocarcinomas, squamous cell carcinomas and hepatocellular carcinoma, which were noticeably greater than the HIV patients (p < 0.01). CONCLUSIONS: There were significantly different causes of cervical lymphadenopathy in HIV infected and non-HIV infected patients. FNAC was a useful diagnostic method for differential diagnosis of cervical lymphadenopathy.

[Evaluation of using Proplan virtual software in teaching of orthognathic surgery].

PURPOSE: Using Proplan virtual software to construct a virtual teaching platform for orthognathic surgery, and to explore an effective teaching model for orthognathic surgery. METHODS: One-hundred grade four students of stomatology in Fujian Medical University were divided into two groups. Traditional orthognathic surgery teaching method and Proplan virtual software teaching method were employed to teach the two groups of students, respectively. Orthognathic-surgery-related paper test was used to evaluate how the two groups of students understand orthognathic surgery; then the students were switched to the other teaching method, respectively. A follow-up questionnaire survey was conducted to further evaluate students' acceptance of the two teaching methods. Finally, a comprehensive statistical analysis was performed for students understanding of orthognathic surgery using SPSS 11.0 software package. RESULTS: According to the test scores, students in the experimental group scored higher than the control group, the difference was significant (P<0.01). The acceptance of different teaching methods displayed remarkable difference between the two groups. Token together, our finding showed that virtual model surgery teaching was an easier teaching method for students to understand and accept. CONCLUSIONS: Proplan virtual software teaching improves the teaching efficiency of orthognathic surgery and deserves further promotion.

Downregulation of GEP100 Improved the Growth Inhibition Effect of Erlotinib Through Modulating Mesenchymal Epithelial Transition Process in Pancreatic Cancer.

OBJECTIVE: The epidermal growth factor receptor is overexpressed in the majority of pancreatic cancer. Epidermal growth factor receptor tyrosine kinase inhibitor erlotinib was approved to treat patients combining with gemcitabine. However, the sensitivity is low. Here, we try to reveal the regulatory role of guanine nucleotide exchange protein 100 (GEP100) in erlotinib sensitivity. METHODS: We investigated the correlation between GEP100 expression and sensitivity to erlotinib in different pancreatic cancer cell lines, followed by examination of the effect of GEP100 on erlotinib sensitivity by establishing the stable knocked-down cell line. The expression level of epithelial mesenchymal transition-related protein was examined by Western blot, and the regulatory mechanism was investigated by short hairpin RNA. Xenograft experiment was also performed in nude mice. RESULTS: We identified a significant correlation between sensitivity to erlotinib and expression of GEP100. GEP100 downregulation increased its sensitivity to erlotinib. E-cadherin short hairpin RNA treatment inhibited this sensitivity. Immunohistochemical staining showed a mutual exclusive expression pattern of GEP100 and E-cadherin in human pancreatic cancer tissues. Xenograft showed that downregulation of GEP100 enhanced the growth inhibition of erlotinib in nude mice. CONCLUSIONS: Our results suggested that GEP100 and E-cadherin have the predictive value for responsiveness to erlotinib in pancreatic cancer.

An experimental study addressing the promotion of mandibular defect repair through the intermittent subcutaneous injection of parathyroid hormone.

PURPOSE: Parathyroid hormone (PTH) is a major regulator of bone metabolism. Various animal studies and clinical trials have addressed the treatment of osteoporosis and fracture healing with the intermittent administration of PTH, whereas few studies have investigated the effects of PTH on mandibular defect repair. This study sought to examine the feasibility of using recombinant human PTH (rhPTH) to promote the repair of mandibular defects and to provide a preliminary investigation of the underlying mechanisms of this phenomenon. MATERIALS AND METHODS: A mandibular defect model was established using Japanese white rabbits. The experimental animals were randomly divided into a control group that received postoperative subcutaneous injections of normal saline on alternate days and an experimental group that received postoperative subcutaneous injections of rhPTH 25 µg on alternate days. The experimental animals were sacrificed at 1, 2, 3, and 4 weeks after the operation to perform x-ray imaging and bone histomorphometric examinations of the defect areas. Changes in serum levels of bone-specific alkaline phosphatase (bALP) and osteoprotegerin (OPG) over time were examined. RESULTS: Compared with the control group, the experimental group exhibited newly generated bone matrix in the mandibular defect area at earlier stages. In the experimental group, the bone trabeculae were arranged in an orderly manner, and uniform calcification was observed. Marked hyperplasia of osteoblasts was observed in the new bone tissue of the experimental group, but significantly less hyperplasia of osteoblasts was observed in the control group. In the 2 groups, the average serum bALP and OPG levels increased after the operation and then gradually decreased. In the experimental group, levels of bALP and OPG at 1 week and 2 weeks after the operation were significantly different from preoperative levels. In the control group, the OPG level at 2 weeks after the operation was significantly different from the preoperative OPG level. A comparison of serum bALP and OPG levels at each examined time point showed no significant difference between the 2 groups. CONCLUSION: The intermittent subcutaneous injection of rhPTH 25 µg/day promotes the healing of mandibular defects in rabbits. The application of rhPTH may facilitate mandible regeneration by increasing quantities of osteoblasts, accelerating bone turnover metabolism, and upregulating OPG levels.

Down-regulation of GEP100 causes increase in E-cadherin levels and inhibits pancreatic cancer cell invasion.

AIMS: Invasion and metastasis are major reasons for pancreatic cancer death and identifying signaling molecules that are specifically used in tumor invasion is of great significance. The purpose of this study was to elucidate the role of GEP100 in pancreatic cancer cell invasion and metastasis and the corresponding molecular mechanism. METHODS: Stable cell lines with GEP100 knocked-down were established by transfecting GEP100 shRNA vector into PaTu8988 cells and selected by puromycin. qRT-PCR and Western blot were performed to detect gene expression. Matrigel-invasion assay was used to detect cancer cell invasion in vitro. Liver metastasis in vivo was determined by splenic injection of indicated cell lines followed by spleen resection. Immunofluorescence study was used to detect the intracellular localization of E-cadherin. RESULTS: We found that the expression level of GEP100 protein was closely related to the invasive ability of a panel of 6 different human pancreatic cancer cell lines. Down-regulation of GEP100 in PaTu8988 cells significantly decreased invasive activity by Matrigel invasion assay, without affecting migration, invasion and viability. The inhibited invasive activity was rescued by over-expression of GEP100 cDNA. In vivo study showed that liver metastasis was significantly decreased in the PaTu8988 cells with GEP100 stably knocked-down. In addition, an epithelial-like morphological change, mimicking a mesenchymal to epithelial transition (MET) was induced by GEP100 down-regulation. The expression of E-cadherin protein was increased 2-3 folds accompanied by its redistribution to the cell-cell contacts, while no obvious changes were observed for E-cadherin mRNA. Unexpectedly, the mRNA of Slug was increased by GEP100 knock-down. CONCLUSION: These findings provided important evidence that GEP100 plays a significant role in pancreatic cancer invasion through regulating the expression of E-cadherin and the process of MET, indicating the possibility of it becoming a potential therapeutic target against pancreatic cancer.