Screening and early diagnosis of chronic obstructive pulmonary disease: a population study.

BACKGROUND AND OBJECTIVE: Although chronic obstructive pulmonary disease (COPD) is a common disease leading to further morbidity and significant mortality, there is still limited data on screening for COPD. The purpose of this study was to establish an early chronic obstructive pulmonary disease (COPD) screening system for the community and hospitals in Nanshan District in Shenzhen City, to improve the rate of early diagnosis and treatment of patients with COPD. METHODS: We identified individuals at high risk of COPD using a questionnaire survey and analyzed the relevant influencing factors in the early stages of COPD in high-risk groups. RESULTS: We collected a total of 5,000 COPD screening questionnaires, and a total of 449 patients were diagnosed with COPD by pulmonary function examination. The prevalence of COPD in people aged 20 and above in Nanshan District of Shenzhen City was estimated to be 8.98%, with a base of 5000. The severity classification as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria was as follows: GOLD I accounted for 34.74%; GOLD II accounted for 37.64%; GOLD III accounted for 16.04%; and GOLD IV accounted for 11.58%. Common features of early COPD that we identified were: (1) patients were mainly males, accounting for 68.0%; (2) COPD was common among people aged 50-59 years, comprising 31%; (3) 96.0% of patients often had severe respiratory symptoms and had frequent coughs when they did not have a cold; (4) 57.2% of patients experienced shortness of breath when walking quickly on level ground or climbing gentle slopes; (5) 72.6% of patients had a family history of bronchial asthma and COPD. Multivariate ordinal multi-classification logistic regression showed that gender, age, shortness of breath, and the use of firewood, grass, and coal stoves were all influencing factors in pulmonary function grading. CONCLUSION: A screening questionnaire combined with a pulmonary function test should be adopted as a COPD screening strategy to be implemented at the primary level as a public health priority in China to reduce the incidence, disability, and mortality from COPD.

The correlation between a Th1/Th2 cytokines imbalance and vitamin D level in patients with early chronic obstructive pulmonary disease (COPD), based on screening results.

Objective: This study explored the correlation between a Th1/Th2 cytokines imbalance and 25-hydroxy-vitamin D (vit D) level in early chronic obstructive pulmonary disease (COPD), provided experimental rationales for the role of vit D in the prevention and control of COPD, and elucidated the potential anti-inflammatory mechanism involved. Methods: This study was based on the results of the "Screening and Early Diagnosis of COPD" public health project conducted through Shenzhen Municipal Qianhai Shekou Free Trade Zone Hospital. Patients with early COPD were selected as study participants. A prospective, randomized, and controlled method was employed for assigning eligible participants into three groups, i.e., a COPD lung function (LF) I, COPD LF II, and a healthy group, respectively (n = 40 each). The serum content of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin 4 (IL-4), and IL-6 were measured by enzyme-linked immunosorbent assay, and the ratio of IFN-γ/IL-4 treated as a marker for Th1/Th2. The serum concentration of 25-hydroxyl-vit D (25 [OH]D) was quantified by a chemiluminescence assay. Statistical processing was performed, and the correlations between changes in the above parameters with vit D level and LF parameters were examined. Results: There were differences in FEV1pred%, FEV1/FVC, IFN-γ, IL-4, IL-6 and IFN-γ/IL-4 between the healthy group, the COPD LF I group and the COPD LF II group (p < 0.05). In early COPD, Th1/Th2 cytokines was positively correlated with forced expiratory volume/expected value (FEV1pred%) (r = 0.485, p < 0.001) and forced expiratory volume/forced vital capacity (FEV1/FVC) (r = 0.273, p = 0.018); Th1/Th2 cytokines levels positively correlated with vit D level (r = 0.27, p = 0.02), and 25(OH)D level positively correlated with FEV1pred% (r = 0.695, p < 0.001). Conclusion: Vitamin D deficiency was ubiquitous in patients with early COPD. It was positively correlated with the FEV1pred% and FEV1/FVC LF parameters. Accordingly, this study provides experimental rationales for the role of vit D in the prevention and control of COPD and the potential anti-inflammatory mechanisms involved.

Metabolic status indicators and influencing factors in non-obese, non-centrally obese nonalcoholic fatty liver disease.

Non-obese nonalcoholic fatty liver disease (NAFLD) is characterized by metabolic disorders and related complications. This study aimed to provide an integrated description of clinical, metabolic, and influencing factors for a specific category of patients with non-obese NAFLD. A total of 36 participants with body mass index (BMI) < 28 kg/m2 and visceral adipose tissue < 100 cm2 were classified into 2 groups: the non-obese, non-centrally obese control group (n = 17) and non-obese, non-centrally obese NAFLD group (n = 19). Hypertriglyceridemia, impaired fasting glucose, low high-density lipoprotein cholesterol levels, and hypertension were used to determine whether participants were metabolically abnormal. Based on a logistic regression model, odds ratios for the factors influencing NAFLD with 95% confidence intervals were calculated. Insulin resistance (IR) and fasting plasma glucose (FPG) levels were higher in the NAFLD group than in the control group (P < .05). The NAFLD group had a higher metabolic abnormality rate than the healthy control group (36.84% vs 5.88%, P = .044). Correlation analysis showed that IR was positively correlated with FPG and triglyceride (P < .05). BMI was the main influencing factor of NAFLD (regression coefficient ß = 0.631; odds ratio = 1.879; 95% confidence interval, 1.233-2.863). NAFLD patients with a BMI < 28 kg/m2 and visceral adipose tissue < 100 cm2 had more apparent IR, higher FPG, and a higher metabolic abnormality rate. IR may be affected by FPG and triglyceride. Even in non-obese and non-centrally obese individuals, BMI should be controlled to avoid NAFLD.

Multifactorial Analysis of Clinical Prognosis of Liver Metastasis and Vascular Intervention Combined with Ablation in Colorectal Cancer.

Colorectal cancer is one of the leading causes of deaths in China. The initial stages of colorectal cancer can be treated by surgery, radiation, and chemotherapy. However, in the advanced stages, it warrants an application of multimodality treatment. With advances in the medical field, there are applications of new modality of treatment that could possibly provide the appropriate treatment for the advanced stage tumours. The first site of metastasis after colorectal cancer is the liver and the conventional treatment to cure the metastatic lesion involves the administration of chemotherapy. With further advancement, chemotherapy has been directly administered at the thorough transarterial chemoembolization (TACE) which is a vascular intervention. With further advancement, the nonvascular intervention, such as radiofrequency ablations (RFAs), has been administered to the patients. A large amount of data support the use of vascular intervention (TACE) with ablation for hepatic carcinoma; there is no sufficient literature to support the application of the modality in the metastatic liver lesion. In this prospective observational study, we have enrolled 80 patients with metastatic liver lesion from the adenocarcinoma of colon or rectum, treated the patients with a combination of the TACE and ablation therapy, and followed up the patients for a period of 3 years. A multivariate analysis of the various factors that influence the prognosis and outcome has been studied and it has been concluded that the combination therapy is medically beneficial for individuals with aggressive liver lesions, improving overall as well as progression-free life span.

Effect of infection after liver cancer interventional therapy on T lymphocyte subsets and Toll-like receptors in peripheral blood mononuclear cells and its mechanism.

BACKGROUND: The T lymphocyte subset levels are an indicator used to evaluate the immune status of the body. In recent years, many studies have investigated the correlation between T lymphocyte subset levels and postoperative infection. OBJECTIVES: To investigate the incidence of infection after liver cancer interventional therapy and its influence on T lymphocyte subset levels and toll-like receptors (TLRs). MATERIAL AND METHODS: A total of 325 patients with primary liver cancer receiving interventional therapy were divided into an infection group (n = 37) and a non-infection group (n = 288). The infection site and the distribution of pathogenic bacteria in the infection group were observed. The serum T lymphocyte subset level and TLR2 and TLR4 levels in peripheral blood mononuclear cells were compared. The clinical value of the postoperative TLR2 and TLR4 levels in evaluating infection was analyzed using receiver operating characteristic (ROC) curves. RESULTS: Among 51 strains of pathogens isolated from the infected patients, strains of Escherichia coli (27.45%) and Pseudomonas aeruginosa (19.61%) were the most commonly observed. After surgery, the levels of CD3+, CD4+ and CD4+/CD8+ decreased, while the level of CD8+ increased in both groups; the levels of TLR2 and TLR4 decreased in the non-infection group, while the levels of TLR2 and TLR4 increased in the infection group (all p < 0.05). Furthermore, the decreases and increases were more significant in the infection group than in the non-infection group (all p < 0.001). The area under the curve of postoperative TLR2 and TLR4 levels in evaluating infection were greater than 0.700 (p < 0.001). CONCLUSIONS: Gram-negative bacteria account for the majority of infections in patients after liver cancer interventional therapy, and the main infection sites are the lung and abdomen. The infected patients show changes in T lymphocyte level and decreased immune function. The TLR2 and TLR4 can be used as auxiliary indicators to evaluate infection after surgery.

Long noncoding RNA HCG18 up-regulates the expression of WIPF1 and YAP/TAZ by inhibiting miR-141-3p in gastric cancer.

BACKGROUND: Accumulating works show that lncRNAs play critical roles in the development of gastric cancer (GC). LncRNA HLA complex group 18 (HCG18) was implicated in the progression of bladder cancer and glioma, but its role in GC is unknown. METHODS: RT-PCR was used to detect HCG18 and miR-141-3p expression in GC specimen. GC cell lines (AGS and MKN-28) were exploited as cell model. The biological effect of HCG18 on cancer cells was probed by CCK-8, colony formation, flow cytometry, Transwell and wound-healing experiments in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Interaction between HCG18 and miR-141-3p was determined by bioinformatics analysis, RT-PCR, and luciferase reporter experiments. Downstream gene expression of miR-141-3p, including Wiskott-Aldrich syndrome protein interacting protein family member 1 (WIPF1), Yes associated protein 1 (YAP), and tafazzin (TAZ) were detected using Western blot. RESULTS: HCG18 was markedly up-regulated in GC specimens, while miR-141-3p was markedly down-regulated. Down-regulation of HCG18 inhibited viability, migration, and invasion of GC cells, while miR-141-3p transfection led to opposite effect. HCG18 could down-regulate miR-141-3p through adsorbing it, and a negative association between HCG18 and miR-141-3p was found in GC specimens. HCG18 promoted WIPF1, YAP and TAZ expression, nonetheless, such influence was reversed by co-transfecting with miR-141-3p. CONCLUSION: HCG18 was aberrantly up-regulated in GC tissues, and it indirectly regulated the activity of Hippo signaling through counteracting miR-141-3p expression.

High-dimensional single-cell analysis delineates radiofrequency ablation induced immune microenvironmental remodeling in pancreatic cancer.

Radiofrequency ablation (RFA) is an effective local therapy approach for treating solitary tumor of many types of malignancy. The impact of RFA on the tumor immune microenvironment on distant tumors after RFA treatment is still unclear. In this study, by using syngeneic tumor models and single-cell RNA and T-cell receptor sequencing, we have investigated the alterations of tumor-infiltrating immune cells in distant non-RFA tumors. Single-cell RNA sequencing identified six distinct lymphoid clusters, five distinct monocyte/macrophage clusters, three dendritic cells clusters, and one cluster of neutrophils. We found that RFA treatment reduced the proportions of immunosuppressive cells including regulatory T cells, tumor-associated macrophages and tumor-associated neutrophils, whereas increased the percentages of functional T cells in distant non-RFA tumors. Moreover, RFA treatment also altered gene expressions in single-cell level in each cell cluster. By using pseudo-time analysis, we have described the biological processes of tumor-infiltrating CD8+ T cells and monocytes/macrophages based on the transcriptional profiles. In addition, the immune checkpoints including PD-1 and LAG3 were upregulated in the T cells in distant non-RFA tumors after RFA treatment. In conclusion, our data indicate that RFA treatment induced remodeling of tumor immune microenvironment in distant non-RFA tumors in pancreatic cancer mouse model and suggest that combining RFA with immune checkpoint inhibitors may be an effective treatment approach.

Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer.

BACKGROUND: Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We investigated if targeting CD47 with a monoclonal antibody could enhance the response of PDAC to ICPi by altering the TME. METHODS: Using immunohistochemistry, we examined tumor-infiltrating CD68+ pan-macrophages (CD68+ M) and CD163+ M2 macrophages (CD163+ M2) and tumor expression of CD47 and PD-L1 proteins in 106 cases of PDAC. The efficacy of CD47 blockade was examined in xenograft models. CD45+ immune cells from syngeneic tumor models were subjected to single-cell RNA-sequencing (scRNA-seq) by using the 10x Genomics pipeline. RESULTS: We found that CD47 expression correlated with the level of CD68+ M but not CD163+ M2. High levels of tumor-infiltrating CD68+ M, CD163+ M2, and CD47 expression were significantly associated with worse survival. CD47high/CD68+ Mhigh and CD47high/CD163+ M2high correlated significantly with shorter survival, whereas CD47low/CD68+ Mlow and CD47low/CD163+ M2low correlated with longer survival. Intriguingly, CD47 blockade decreased the tumor burden in the Panc02 but not in the MPC-83 syngeneic mouse model. Using scRNA-seq, we showed that anti-CD47 treatment significantly remodeled the intratumoral lymphocyte and macrophage compartments in Panc02 tumor-bearing mice by increasing the pro-inflammatory macrophages that exhibit anti-tumor function, while reducing the anti-inflammatory macrophages. Moreover, CD47 blockade not only increased the number of intratumoral CD8+ T cells, but also remodeled the T cell cluster toward a more activated one. Further, combination therapy targeting both CD47 and PD-L1 resulted in synergistic inhibition of PDAC growth in the MPC-83 but not in Panc02 model. MPC-83 but not Panc02 mice treated with both anti-CD47 and anti-PD-L1 showed increased number of PD-1+CD8+ T cells and enhanced expression of key immune activating genes. CONCLUSION: Our data indicate that CD47 targeting induces compartmental remodeling of tumor-infiltrating immune cells of the TME in PDAC. Different PDAC mouse models exhibited differential response to the anti-CD47 and anti-PD-L1 blockade due to the differential effect of this combination treatment on the infiltrating immune cells and key immune activating genes in the TME established by the different PDAC cell lines.

Risk Factors of Regional Lymph Node Metastasis in Patients with Cervical Cancer.

OBJECTIVES: To explore the risk factors related to regional lymph node metastasis in cervical cancer and analyze the value of independent risk factors in predicting regional lymph node metastasis. METHODS: We retrospectively analyzed the clinical data of 699 patients who underwent surgery for stage IB1-IIA2 cervical cancer in Quanzhou First Hospital affiliated to Fujian Medical University from 2010 to 2016. The patients were divided into metastasis (n = 92) and non-metastasis (n = 607) groups based on the postoperative pathology of regional lymph node status. The relevant clinicopathological features of the metastasis and non-metastasis groups were compared through variance analysis and chi-square tests. Logistic regression was adopted to screen relevant independent risk factors of regional lymph node metastasis. RESULTS: In univariate analysis, International Federation of Gynecology and Obstetrics (FIGO) stages, serum squamous cell carcinoma antigen (SCC-Ag), histological type of squamous carcinoma and maximal tumor diameter were related factors for lymphatic metastasis in patients with cervical cancer. In multivariate analysis, SCC-Ag and histological type of squamous carcinoma were independent prognostic factors for lymphatic metastasis in patients with cervical cancer. Pre-treatment SCC-Ag serum levels, as a predictor of lymph node metastasis of cervical cancer, revealed a sensitivity of 62.07% (95% confidence interval (CI): 51.03-72.62%), specificity of 65.15% (59.07-70.89%), and area under the receiver operating characteristic (ROC) curve of 0.69 (95% CI: 0.61-0.76). CONCLUSIONS: Cervical cancer patients whose pathological type is squamous carcinoma with high levels of SSC-Ag pre-operation are more likely to be diagnosed with regional lymph node metastasis. Standardized lymph node dissection should be implemented during operation.

A novel three-dimensional-printed paranasal sinus-skull base anatomical model.

PURPOSE: A novel precision three-dimensional (3D)-printed paranasal sinus-skull base anatomical model was generated with a commercial grade desktop 3D printer. A specific page-turning pattern was employed in this model, to display the internal spatial structure of the paranasal sinus. METHODS: The CT image data of paranasal sinus were imported into the Mimics software to construct a 3D digital paranasal sinus-skull base model. Then, the model was sliced in the coronal position and loaded into the 3D printer to print each slice of the paranasal sinus-skull base model at a ratio of 1:1 in size. Based on CT image data, nine senior doctors assessed the simulation and accuracy of the anatomical structure features of the paranasal sinus-skull base, and the advantages and educational value of the 3D printing model using a seven-point Likert scale. RESULTS: A life-like 3D paranasal sinus-skull base structural model was successfully printed, with its internal spatial details clearly displayed. Nine senior doctors all thought that the profile of the printed anatomical structure was similar to that displayed by CT scan; however, the model provided more 3D spatial visual information. In addition, the model was considered to be of great value in the anatomy teaching and complicated surgery of the paranasal sinus-skull base, which had a material cost of only 3 dollars. CONCLUSIONS: The 3D printed paranasal sinus-skull base model has 3D visual functions, which provides a novel tool for anatomical studies on paranasal sinus, resident training, pre-surgical education and surgical planning.