Integrating network pharmacology and Mendelian randomization to explore potential targets of matrine against ovarian cancer.

BACKGROUND: Matrine has been reported inhibitory effects on ovarian cancer (OC) cell progression, development, and apoptosis. However, the molecular targets of matrine against OC and the underlying mechanisms of action remain elusive. OBJECTIVE: This study endeavors to unveil the potential targets of matrine against OC and to explore the intricate relationships between these targets and the pathogenesis of OC. METHODS: The effects of matrine on the OC cells (A2780 and AKOV3) viability, apoptosis, migration, and invasion was investigated through CCK-8, flow cytometry, wound healing, and Transwell analyses, respectively. Next, Matrine-related targets, OC-related genes, and ribonucleic acid (RNA) sequence data were harnessed from publicly available databases. Differentially expressed analyses, protein-protein interaction (PPI) network, and Venn diagram were involved to unravel the core targets of matrine against OC. Leveraging the GEPIA database, we further validated the expression levels of these core targets between OC cases and controls. Mendelian randomization (MR) study was implemented to delve into potential causal associations between core targets and OC. The AutoDock software was used for molecular docking, and its results were further validated using RT-qPCR in OC cell lines. RESULTS: Matrine reduced the cell viability, migration, invasion and increased the cell apoptosis of A2780 and AKOV3 cells (P< 0.01). A PPI network with 578 interactions among 105 candidate targets was developed. Finally, six core targets (TP53, CCND1, STAT3, LI1B, VEGFA, and CCL2) were derived, among which five core targets (TP53, CCND1, LI1B, VEGFA, and CCL2) differential expressed in OC and control samples were further picked for MR analysis. The results revealed that CCND1 and TP53 were risk factors for OC. Molecular docking analysis demonstrated that matrine had good potential to bind to TP53, CCND1, and IL1B. Moreover, matrine reduced the expression of CCND1 and IL1B while elevating P53 expression in OC cell lines. CONCLUSIONS: We identified six matrine-related targets against OC, offering novel insights into the molecular mechanisms underlying the therapeutic effects of matrine against OC. These findings provide valuable guidance for developing more efficient and targeted therapeutic approaches for treating OC.

Exploring the Mechanism of Zilongjin in Treating Lung Adenocarcinoma Based on Network Pharmacology Combined with Experimental Verification.

Zilongjin (ZLJ) is a common traditional Chinese medicine for lung adenocarcinoma (LUAD) treatment. However, its mechanisms of action remain to be elucidated. Network pharmacology was used to explore the underlying mechanisms of ZLJ on LUAD treatment. The disease-related targets were determined from the Gene-Cards and DisGeNET databases. Active compounds and targets of ZLJ were obtained from the HIT, TCMSP, and TCMID databases. Then the protein-protein interaction (PPI) network was built by the STRING database to identify core-hub targets of ZLJ in LUAD. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enriched regulatory pathways of targets. Molecular docking analysis was used to evaluate interactions between potential targets and active compounds. Finally, qRT-PCR was used to further verify the results of network pharmacology. A total of 124 LUAD-related targets of ZLJ and 5 active compounds of ZLJ from the relevant databases were screened out. Among these target proteins, JUN, CDH1, PPARG, and FOS were core hub-genes in the PPI network. GO and KEGG pathway enrichment analysis indicated that these targets might regulate the PPAR signaling pathway in LUAD. JUN, PPARG, and FOS levels were upregulated, while CDH1 level was downregulated in LUAD cells. This study discerned that ZLJ may target genes such as JUN, FOS, PPARG, and CDH1 via the PPAR signaling pathway in LUAD, offering foundational insights for further exploration of ZLJ in clinical applications.

Headache alleviation with nasal irrigation following endoscopic endonasal surgery for pituitary adenomas.

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. RESULTS: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. CONCLUSIONS: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.

Management of dermatologic adverse events associated with tumor treating fields in patients with glioblastoma multiforme: A 27-case series.

Objective: This study summarized the clinical management of 27 patients with glioblastoma multiforme who tumor treating fields therapy for the healthcare providers. Methods: Glioblastoma multiforme patients who experienced dermatologic adverse events after tumor treating fields therapy from April 2019 to May 2021 were included. The clinical management involved educating patients and their caregivers on the prevention of dermatologic adverse events, scalp assessment and preparation, and removal and replacement of the transducer array. Informed consent for participating in the study including the taking of pictures was obtained from all patients. Results: The dermatologic adverse events were successfully managed in all 27 patients, with no severe dermatologic adverse events were reported. Conclusions: Data on tumor treating fields-related dermatologic adverse events is rarely reported, and published reports of management of scalp dermatologic adverse events are lacking. This case series summarizes a clinically individualized management for tumor treating fields-related dermatologic adverse events.

Intelligent Monitoring of Care Status for COPD Patients Based on Deep Learning.

To discuss the application method and effect of COPD patients in deep learning in intelligent monitoring, two groups were used under a reasonable selection of antibiotics specifically including reasonable and effective oxygen administration, atomization, sputum discharge treatment, psychotherapy, and rehabilitation training and treatment. Results were indicated, and there were significant differences between the lung function evaluation index and the two groups. Its intelligent monitoring mode was 97.5% and 80.0%, while the red blood cell ratio, arterial oxygen partial pressure (PaO2), pulse blood oxygen saturation (SpO2), arterial carbon dioxide partial pressure (PaCO2), and symptom improvement were better than artificial and were statistically significant (P < 0.05). Therefore, the training of the anti-inspiratory muscle can effectively improve the lung function and dyspnea symptoms of COPD patients at the stable stage, thus greatly improving their respiratory function and ensuring the quality of life of patients, which is worthy of clinical application.

Risk factors for postoperative cerebrospinal fluid leakage after transsphenoidal surgery for pituitary adenoma: a meta-analysis and systematic review.

OBJECTIVE: Postoperative cerebrospinal fluid (CSF) leakage represents a challenge even for experienced pituitary surgeons. We aimed to quantitatively synthesize data from studies regarding the risk factors for postoperative CSF leakage after transsphenoidal surgery (TSS) for pituitary adenoma (PA). METHODS: PubMed, Web of Science, The Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database were searched for case-control and cohort studies, focusing on the risk factors associated with postoperative CSF leakage after TSS for PA. Pooled odds ratios (ORs) and 95% confidence intervals were calculated to determine the risk factors. RESULTS: A total of 34 case-control and cohort studies involving a total of 9,144 patients with PA were included in this systematic review. The overall rate of postoperative CSF leakage after TSS for PA was 5.6%. Tumor size, adenoma consistency, revision surgery, and intraoperative CSF leakage were independent risk factors for postoperative CSF leakage (ORs, 3.18-6.33). By contrast, the endoscopic approach showed a slight protective benefit compared with the microscopic approach in TSS (OR, 0.69). CONCLUSIONS: This review provides a comprehensive overview of the quality of the evidence base, informing clinical staff of the importance of screening risk factors for postoperative CSF leakage after TSS for PA. More attention should be paid to PA patients at high risk for CSF leakage after TSS to reduce complications and improve prognosis.

Convolutional Neural Network-Processed MRI Images in the Diagnosis of Plastic Bronchitis in Children.

Objective: The study focused on the features of the convolutional neural networks- (CNN-) processed magnetic resonance imaging (MRI) images for plastic bronchitis (PB) in children. Methods: 30 PB children were selected as subjects, including 19 boys and 11 girls. They all received the MRI examination for the chest. Then, a CNN-based algorithm was constructed and compared with Active Appearance Model (AAM) algorithm for segmentation effects of MRI images in 30 PB children, factoring into occurring simultaneously than (OST), Dice, and Jaccard coefficient. Results: The maximum Dice coefficient of CNN algorithm reached 0.946, while that of active AAM was 0.843, and the Jaccard coefficient of CNN algorithm was also higher (0.894 vs. 0.758, P < 0.05). The MRI images showed pulmonary inflammation in all subjects. Of 30 patients, 14 (46.66%) had complicated pulmonary atelectasis, 9 (30%) had the complicated pleural effusion, 3 (10%) had pneumothorax, 2 (6.67%) had complicated mediastinal emphysema, and 2 (6.67%) had complicated pneumopericardium. Also, of 30 patients, 19 (63.33%) had lung consolidation and atelectasis in a single lung lobe and 11 (36.67%) in both two lung lobes. Conclusion: The algorithm based on CNN can significantly improve the segmentation accuracy of MRI images for plastic bronchitis in children. The pleural effusion was a dangerous factor for the occurrence and development of PB.

Increased number and activation of peripheral basophils in adult-onset minimal change disease.

Nowadays, the pathogenesis of minimal change disease (MCD) is still not well-known, and the current understanding on MCD is mainly based on data derived from children, and very few adults. Here, we comprehensively analysed the correlation between the changes of peripheral basophils and the incidence rate and relapse of adult-onset MCD. The results showed that in patients at the onset of MCD, the ratio and activation of basophils were all higher than those of healthy controls (all P < .05). In vitro test results showed that basophils from healthy controls can be activated by the serum taken from patients with MCD. Among 62 patients at the onset of MCD, with complete remission after treatment and 1 year of follow-up, the relative and absolute basophil counts before treatment were higher in the long-term remission group (n = 33) than that of the relapse group (n = 29). The basophil counts were significantly higher in the infrequent relapse group (n = 13) than that of the frequent relapse group (n = 16; P < .05). These findings suggested that basophil may play a pathogenic role in adult-onset MCD, and the increased number and activation of peripheral basophils could predict recurrence in adult MCD.

Metformin: the updated protective property in kidney disease.

Metformin is a frontline hypoglycemic agent, which is mainly prescribed to manage type 2 diabetes mellitus with obesity. Emerging evidence suggests that metformin also exerts protective effects against various kidney diseases. Some postulate that kidney disease is actually a metabolic disease, accompanied by nonresolving pathophysiologic pathways controlling oxidative stress, endoplasmic reticulum stress, inflammation, lipotoxicity, fibrosis, and senescence, as well as insufficient host defense mechanisms such as AMP-activated protein kinase (AMPK) signaling and autophagy. Metformin may interfere with these pathways by orchestrating AMPK signaling and AMPK-independent pathways to protect the kidneys from injury. Furthermore, the United States Food and Drug Administration declared metformin is safe for patients with mild or moderate kidney impairment in 2016, assuaging some conservative attitudes about metformin management in patients with renal insufficiency and broadening the scope of research on the renal protective effects of metformin. This review focuses on the molecular mechanisms by which metformin imparts renal protection and its potential in the treatment of various kidney diseases.

[Dynamic changes of chest CT imaging in patients with COVID-19].

OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare,the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.

Updated advances of linking psychosocial factors and sex hormones with systemic lupus erythematosus susceptibility and development.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that primarily affects women, especially those of reproductive age. Genetics, environment, and gene-environment interactions play key roles in the development of SLE. Despite the numerous susceptibility genes of SLE identified to date, gene therapy is far from a clinical reality. Thus, more attention should be paid to the risk factors and underlying mechanisms of SLE. Currently, it is reported that psychosocial factors and sex hormones play vital roles in patients with SLE, which still need further investigated. The purpose of this review is to update the roles and mechanisms of psychosocial factors and sex hormones in the susceptibility and development of SLE. Based on review articles and reports in reputable peer-reviewed journals and government websites, this paper summarized psychosocial factors (e.g., alexithymia, depression, anxiety, negative emotions, and perceived stress) and sex hormones (e.g., estrogens, progesterone, androgens, and prolactin) involved in SLE. We further explore the mechanisms linking these factors with SLE susceptibility and development, which can guide the establishment of practical measures to benefit SLE patients and offer new ideas for therapeutic strategies.

Cross-regulation between exosomal and autophagic pathways: promising therapy targets in disease.

Exosomes are vesicles secreted by a variety of cell types. They can release their cargo into the extracellular environment or transfer their contents to other cells, as a form of intercellular communication. Therefore, exosomes are vital to both physiological and pathological functions. Autophagy is a process of intracellular degradation of unnecessary or dysfunctional cellular components such as damaged organelles and misfolded proteins. It is initiated by various environmental stressors and mediated by lysosomes. Under physiological conditions, autophagy exists in cells at basal levels to support cellular metabolism and help maintain self-homeostasis. In other circumstances, autophagy can contribute to the initiation and progression of disease. Recent studies have revealed that exosomal and autophagic pathways can be regulated by each other and play important roles in health and disease. However, the cross-regulation between these pathways is highly intricate, and the effects on exosomal trafficking and autophagy are environment-dependent. Here, we summarize the recent advances in understanding the cross-regulation between the exosomal and autophagic pathways, and their involvement in multiple diseases, which can help develop novel strategies for their prevention and treatment. From the evidence summarized in this review, we conclude: 1) exosomal trafficking plays a beneficial or harmful role in disease through the regulation of autophagy; 2) autophagy is vital in disease by regulating the generation of exosomes; and 3) the cross-regulation between exosomal and autophagic pathways may be promising targets for disease prevention and treatment, while this needs to be clarified in future investigations.

Current mechanistic insights into the role of infection in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by inflammation and abnormal production of autoantibody, but the mechanisms of the aberrant immune responses are currently unknown. Recently, growing evidence has suggested that infection plays a pivotal role in SLE. Here, we investigate the role of infectious agents (e.g., Epstein-Barr virus, parvovirus B19, human T-lymphotropic virus type 1, human immunodeficiency virus type 1, and endogenous retroviruses) in the pathogenesis of SLE. More importantly, we explore the known mechanisms underlying the involvement of infectious agents in the pathogenesis of SLE, including molecular mimicry, epitope spreading, superantigen production, bystander activation, persistent viral infection, altered apoptosis, clearance deficiency, and epigenetic alterations (e.g., DNA methylation and microRNAs). However, some infectious agents (e.g., malaria parasites, hepatitis B virus, Toxoplasma gondii, and Helicobacter pylori) may exert protective effects on SLE. Therefore, the relationship between infection and SLE is multifaceted and multidirectional, including causative and/or protective associations, which warrant further investigation in the future.

MicroRNA-370 inhibits the growth and metastasis of lung cancer by down-regulating epidermal growth factor receptor expression.

Abnormal microRNA-370 (miR-370) expression has been frequently reported in several types of cancers, including lung cancer. However, the role and molecular mechanisms of miR-370 in regulating the growth and metastasis of lung cancer have not been clarified. Here, we show higher levels of epidermal growth factor receptor (EGFR), but lower levels of miR-370 expression in most human lung cancer cells and non-tumor cells. Induction of miR-370 over-expression significantly reduced the levels of EGFR expression and the EGFR 3'untranslated region (UTR)-regulated luciferase activity in XWLC-05 and H157 cells, suggesting that miR-370 may bind to the 3'UTR of EGFR mRNA. Compared with the control cells, induction of miR370 overexpression significantly inhibited the proliferation, clone formation capacity, migration and invasion of XWLC-05 and H157 cells while miR-370 inhibitor over-expression enhanced their tumor behaviors in vitro. Furthermore, miR-370 over-expression down-regulated the EGFR and hypoxia-inducible factor (HIF)-1α expression, and attenuated the extracellular single-regulated kinase (ERK)1/2 and AKT phosphorylation in XWLC-05 and H157 cells. In contrast, miR370 inhibitor over-expression increased the EGFR and HIF-1α expression as well as the ERK1/2 and AKT phosphorylation in XWLC-05 and H157 cells. Moreover, miR-370 over-expression significantly reduced the levels of EGFR and CD31 expression and inhibited the growth and lung metastasis of xenograft NSCLC tumors in mice. Our study indicates that miR-370 may bind to the 3'UTR of EGFR to inhibit EGFR expression and the growth, angiogenesis and metastasis of non-small cell lung cancer by down-regulating the ERK1/2 and AKT signaling.

Impact of cellular immune function on prognosis of lung cancer patients after cytokine-induced killer cell therapy.

AIMS: To investigate changes in cellular immune function of patients with lung cancer before and after cytokine- induced killer (CIK) cell therapy and to identify variation effects on overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: A total of 943 lung cancer patients with immune dysfunction were recruited from January 2002 to January 2010, 532 being allocated to conventional therapy and 411 to CIK therapy after a standard treatment according to the NCCN Clinical Practice Guidelines. All the patients were investigated for cellular immune function before and after therapy every three months. and clinical prognostic outcomes were analyzed. RESULTS: After six courses of treatment, immune function was much improved in patients receiving CIK cells therapy as compared to controls. The percentages of recurrence and/or metastases for patients undergoing CIK cell therapy was 56.2% and 49.1% respectively but 78.6% and 70.3% among controls (p<0.001). The median OS times for CIK cell therapy and control groups were 48 and 36 months respectively. The OS rates at 12, 36, 60, 84 months in CIK treated patients were 97.8%, 66.9%, 27.7%, and 4.1% while they were 92.3%, 44.5%, 9.2%, and 1.5% in controls. OS and PFS were significantly different by log rank test between the two groups and across the three immune improvement classes. CONCLUSIONS: The immune function of lung cancer patients was improved by CIK cell therapy, associated with an increase in the OS rate and extension of the time to recurrence and/or metastasis.

[Targeted Sox4 gene-knock-down suppresses xenograft growth of Xuanwei female lung cancer cell line XWLC-05 cells in nude mice].

OBJECTIVE: To study the effect of targeted Sox4 gene-knock-down on the growth of xenografts of Xuanwei female lung cancer cell line XWLC-05 cells in nude mice. METHODS: Recombinant plasmid pGFP-V-RS-Sox4 shRNA was constructed and transfected into XWLC-05 cells. Real-time quantitative PCR and Western blot were applied to confirm the effect of Sox4 gene-knock-down. XWLC-05 cells stably transfected with the plasmids were inoculated into nude mice to establish the xenograft model. The nude mouse status, tumor formation and tumor growth were observed, and the tumor inhibition rate was calculated. CT scan was performed to assess the metastasis of xenografts. Immunohistochemical staining was applied to detect Sox4 and ki-67 protein expression. RESULTS: Recombinant plasmid pGFP-V-RS-A-Sox4 shRNA which can effectively knocking-down Sox4 gene was successfully constructed and the stable transfected cells were selected by puromycin-screening. The success rate of tumor cell inoculation was 100% in the mice of all groups except those inoculated with saline. The body weight of all mice inoculated with parental XWLC-05 cells (blank control), pGFP-V-RS-scram shRNA trsfected XWLC-05 cells (negative control), and pGFP-V-RS-Sox4 shRNA transfected XWLC-05 cells was increased to a varying degree, but there was no significant difference among the groups (P > 0.05 ). The growth of xenografts was significantly inhibited after silencing the Sox4 gene expression when compared with that of the blank and negative controls (P < 0.05) . The volume of removed tumors of the Sox4 gene-inhibited mice was (2.30 ± 0.34) cm(3) , significantly smaller than that of the negative control (3.99 ± 0.45) cm(3) and the blank control (4.03 ± 0.42) cm(3) (P < 0.05) . The weight of removed tumors of Sox4 gene-inhibited mice was (0.86 ± 0.14) g, significantly lower than that of the negative control (1.84 ± 0.27) g and blank control (1.86 ± 0.22) g, (P < 0.05). Immunohistochemical staining showed that Sox4 and ki-67 proteins mainly expressed in cell nuclei. The staining was significantly decreased in xenografts of Sox4-inhibited mice when compared with the negative and blank controls (P < 0.05). No distant metastasis was found in any mouse by CT imaging and pathological examination during the observation period. CONCLUSIONS: The xenograft model of Xuanwei female lung cancer cell line XWLC-05 cells in nude mice is successfully established. Knocking-down of Sox4 gene can suppress the xenograft tumor growth.

[Expression of transcription factor SOX4 and its clinical significance in female lung cancer patients in Xuanwei area, Yunnan Province].

OBJECTIVE: To investigate the expression of transcription factor SOX4 in lung cancer tissues of female patients in Xuanwei area, Yunnan Province, and explore its correlation with clinicopathological characteristics and prognosis of the female patients. METHODS: Real-time PCR was applied on lung cancer specimens and their corresponding normal lung tissues from 96 female cases of Xuanwei area to assess the expression of SOX4 mRNA. Immunohistochemical staining was performed to investigate the SOX4 protein expression, and further to elucidate its correlation with clinicopathological characteristics and prognosis. RESULTS: The expression level of SOX4 mRNA in the cancer tissues (2.53 ± 1.65) was significantly higher than that of matched normal tissues (1.43 ± 1.14, P = 0.003). Immunohistochemical staining showed that there were 53.1% (51/96) positive expression of SOX4 protein in the cancer tissue and only 26.0% (25/96) in matched normal tissue (P < 0.001). The expression of SOX4 protein had a significant correlation with clinical stage, lymph node metastasis and differentiation of tumor (P < 0.05). The survival analysis by Kaplan-Meier method showed that patients with positive expression of SOX4 protein, lymph node metastasis and advanced tumor stage had a significantly shorter median survival time (P < 0.05). Cox regression survival analysis showed that pathological grade was a significant independent factor affecting prognosis. CONCLUSIONS: The expressions of SOX4 mRNA and protein are significantly up-regulated in Xuanwei female lung cancer patients. Patients with positive SOX4 expression have a shorter median survival time. SOX4 protein expression level combined with pathological grade can be used as a prognostic indicator of female lung cancer patients in Xuanwei area, Yunnan Province.

Moderating effects and maintenance of lung cancer cellular immune functions by CIK cell therapy.

AIMS: To study the CIK cell treatment effects on regulation of cellular immune function disorders in patients with lung cancer, and to analyze the time characteristics. METHODS: Cellular immune function was assessed by FCM, and patients with functional disorders were randomly divided into two groups, one given CIK cell therapy within 18 months (5 courses) and the other the controls, which were followed up for 1 year with cellular immune functions tested once a month. RESULTS: There were 5 types of cellular immunity, 4 of which are disorders; after CIK treatment, the improvement rate of the 4 groups were 79.1%, 70.8%, 76.0% and 70.0%, intergroup differences not being statistically significant (P=0.675), all significantly higher than in the control group (P=0.000). The median maintenance times for the 4 groups were 10.4 months (9.76-11.04), 8.4 months (7.86-8.94), 9.8 months (9.20-10.4) and 7.9 months (6.25-9.55), respectively. CONCLUSIONS: CIK cells were able to improve the immune functions of patients with lung cancer, the rate of improvement and maintenance time being related to the immune function before the treatment and CIK-cell-therapy courses.

[An oral DNA vaccine against VEGFR2 inhibits angiogenesis of Lewis lung carcinoma in C57BL/6 mice].

BACKGROUND: It has been known that vascular endothelial growth factor (VEGF) and its receptor (VEGFR2) play important roles in tumor angiogenesis. The aim of this study is to investigate whether an oral DNA vaccine against VEGFR2 has the inhibition effect on tumor growth and angiogenesis, and explore its mechanism in vivo. METHODS: C57BL/6 mice were respectively given the DNA vaccine encoding VEGFR2 (vaccine group), pcDNA3.1 (plasmid group) and saline (saline group). All the mice were then inoculated with Lewis lung carcinoma 3LL cells. Weight, size and microvessel density (MVD) of transplanted tumors were observed. The levels of CD3+ and CD8+ T cells in peripheral blood of mice were detected by flow cytometry. RESULTS: Weight of transplanted tumors in vaccine group was significantly smaller than those in plasmid and saline groups (P < 0.05), and MVD was significantly lower in vaccine group than that in plasmid and saline groups (P < 0.05). After inoculated with 3LL cells, CD3+ and CD8+ T cell levels of vaccine group were markedly higher than those of plasmid and saline groups (P < 0.05). CONCLUSIONS: The oral DNA vaccine can significantly inhibit angiogenesis and growth of transplanted tumor in mice. It may act through killing endothelial cells of tumor.

[Inhibitory effect of Periplaneta Americana extract on 3LL lung cancer in mice].

BACKGROUND: It has been known that Kangfuxin, a drug derived from Periplaneta Americana, can induce cell apoptosis of many cancer cell lines in vitro. The aim of this study is to investigate the inhibitory effect and mechanism of Periplaneta Americana extract (PAE) on 3LL lung cancer in mice. METHODS: The C57BL/6J mice transplanted with 3LL lung cancer were divided into normal saline (NS), PAE high dose (PAE-H) and PAE low dose (PAE-L) groups. The body weight changes and inhibitory rate of tumor growth in each group were observed. In addition, the cell cycle, apoptosis index (AI) and the expression of apoptosis associated genes were analysed by flow cytometry (FCM). RESULTS: The body weights were decreased in PAE-L and PAE-H treated group compared with NS group and the inhibitive rate of tumor growth was 41.24% and 81.08% respectively. FCM assay indicated that PAE could induce apoptosis of lung cancer cell, and the apoptosis rate was concentration-dependent. At the same time, the number of S and G2/M phase cells was decreased, most of the cells were arrested in G1/G1 phase. The result of TUNEL showed that there were apoptosis and necrosis associated with upregulated expression of Fas, FasR and p53 genes, and downregulated expression of Bcl-2. CONCLUSIONS: PAE may inhibit the growth of 3LL lung cancer in mice and induce apoptosis of 3LL lung cancer cells. It might be related to its effects on the regulation of apoptotic gene expression.