Objective: To explore the mechanism of action of Zangjiangzhi capsule (ZJZC) in treating hyperlipidemia (HLP). Methods: The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS/MS). Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment. The SwissTargetPrediction database was used to predict compound targets, and GeneCards, DisGeNet, OMIM, and DRUGBANK databases were used to identify HLP-related targets. Protein–protein interaction diagrams were constructed using the STRING database. The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The “herb-ingredient-target” network was visualized using Cytoscape. Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay. Results: Ninety compounds were identified in ZJZC, including 34 flavonoids, 12 phenols, 10 terpenoids, 10 alkaloids, 8 organic acids, 8 anthraquinones, and 9 other compounds. In total, 904 targets were identified for these compounds. Among them, 158 targets intersected with the HLP target network. Network pharmacology analysis showed that MAPK1, PPAR-α, RXRA, HSP90AA1, PIK3R1, AKT1, PIK3CA, IL6, TNF, and ESR1 are the key targets of action. KEGG enrichment analysis identified 164 pathways. Among these, the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis pathways, regulation of lipids in adipocytes, and insulin resistance are related to HLP. Molecular docking showed good affinity between the key targets and ingredients. Further, ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-α protein, which have been shown to be strongly associated with HLP. Conclusions This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP, providing evidence at the molecular level for its clinical application in the treatment of HLP.

BACKGROUND:Mesenchymal stem cell-derived exosomes may play a crucial role in tissue damage repair,and miRNA is an important component of exosomes for therapeutic effects.Among them,miR-29b-3p has the effect of reducing cell apoptosis,promoting axonal regeneration,and angiogenesis. OBJECTIVE:To study the protective effect of adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p on a neural cell injury model simulated by H2O2-treated PC12 cells,and explore the relevant mechanisms. METHODS:(1)First,the collagenase digestion method was used to extract rat adipose-derived mesenchymal stem cells.Adipose-derived mesenchymal stem cells were transfected with miR-29b-3p mimics and inhibitors.Exosomes were extracted from the culture supernatant by ultracentrifugation and identified so as to construct adipose-derived mesenchymal stem cell-derived exosomes with high expression and knockdown miR-29b-3p.(2)By constructing a neural cell injury model simulated by PC12 cells treated with H2O2,the relevant mechanisms of the protective effect of adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p on the simulated neuronal cell injury model were studied. RESULTS AND CONCLUSION:(1)Adipose-derived mesenchymal stem cell-derived exosome had a typical cup-shaped shape and a diameter distribution in the range of 50-140 nm,expressed membrane proteins Alix,CD63,and TSG101,which were specific markers on the surface of exosomes,and could be successfully ingested by PC12 cells.(2)Adipose-derived mesenchymal stem cell-derived exosome pretreatment could reduce cell apoptosis induced by H2O2 treatment in PC12 cells,and this protective effect was enhanced with the increase of miR-29b-3p expression in the exosomes and weakened with the decrease of miR-29b-3p expression in the exosomes.The mechanism of its effect was related to adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p promoting the expression of anti-apoptotic protein Bcl-2 and inhibiting the expression of apoptotic protein Bax.

With the progress of targeted therapy and immunotherapy for lung cancer, the clinical demand for lung biopsy is increasing. An ideal biopsy specimen can be used not only for histopathological diagnosis, but also for biomarker detection. The ideal biopsy specimen should meet two requirements, including more than 60 mm2 of tumor tissue and containing more than 20% of tumor cells. In order to obtain ideal lung cancer biopsy specimens, advanced imaging techniques are needed to help. In this article, we reviewed the requirements for biopsy specimens based on biomarker detection, as well as the current status and research progress of using imaging techniques for preoperative planning and intraoperative real time guidance of lung cancer biopsy.
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Humans ; Lung Neoplasms/diagnostic imaging* ; Biopsy ; Biomarkers ; Immunotherapy

BACKGROUND: Lung cancer is the most common neoplasmas with a poor prognosis and a low 5-year survival rate. Early screening is an important measure for the prevention and treatment of lung cancer. At present, different countries have issued corresponding lung cancer screening guidelines, but China still lacks guidelines based on Chinese population research. Therefore, the National Cancer Center launched a Multi-center Cancer Screening Program in Urban China. This study analyzed the evaluation of lung cancer risk assessment model and screening effect in urban China of Yunnan, so as to explore the evaluation model of high-risk lung cancer population suitable for China's national conditions and develop lung cancer screening guidelines for Chinese. METHODS: A questionnaire survey and lung cancer risk assessment were conducted on 165,337 people in 36 street offices in 4 main urban areas of Kunming, Yunnan Province, using cluster sampling method from January 2015 to December 2019. People with high-risk of lung cancer conducted low-dose computed tomography (LDCT) screening of chest. What's more, all participants were followed up by active or passive follow-up. RESULTS: There were 264 patients were diagnosed lung cancer by pathology, and the overall incidence of lung cancer was 0.16% (264/165,337). The high-risk group (0.31%, 116/37,914) was higher than the non-high-risk group (0.12%, 148/127,423), and the difference was statistically significant (P<0.001). The incidence of lung cancer in the high-risk group was higher than the non-high-risk group among the male, female, and lower 50-year-old or more than 50-year-old subgroups, with statistical differences (P<0.001), but there was no statistical difference in the group without LDCT screening (P=0.73). The sensitivity of the lung cancer high-risk population assessment model was 43.94% (116/264) and the specificity was 77.10% (127,275/165,073). The early diagnosis rate of the screening group was 72.97% (54/74), which was significantly higher than that of the non-screening group [28.48% (43/151)]. CONCLUSIONS The lung cancer high-risk population assessment model of National Key Public Health Program: Cancer Screening Program in Urban China can detect high-risk populations and improve the early diagnosis rate of lung cancer effectively.

Objective:To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment.Methods:Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital.Results:The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men ( P<0.001) and displayed a downward trend with age ( P=0.03). The mutation rate of ethnic minorities was higher than Han ( P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history ( P<0.001), and patients without drinking history was higher than patients with drinking history ( P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history ( P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types ( P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients ( P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples ( P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area ( P<0.001). Multivariate analysis showed that gender ( P<0.001), age ( P=0.036), smoking history ( P<0.001), pathological type ( P<0.001), specimen type ( P<0.001), and whether or not Xuanwei area ( P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area ( P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han ( P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities ( P=0.005). Conclusions:The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.

Objective:To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas.Methods:A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions.Results:The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender ( P<0.001), smoking history ( P<0.001), age ( P<0.001), pathological type ( P<0.001), and whether the Xuanwei area ( P=0.027), but not related to the nationality ( P=0.748) and family history of lung cancer ( P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males ( P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females ( P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority ( P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area ( P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area ( P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area ( P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history ( P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history ( P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history ( P=0.008). Conclusions:The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.

Objective:To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment.Methods:Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital.Results:The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men ( P<0.001) and displayed a downward trend with age ( P=0.03). The mutation rate of ethnic minorities was higher than Han ( P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history ( P<0.001), and patients without drinking history was higher than patients with drinking history ( P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history ( P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types ( P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients ( P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples ( P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area ( P<0.001). Multivariate analysis showed that gender ( P<0.001), age ( P=0.036), smoking history ( P<0.001), pathological type ( P<0.001), specimen type ( P<0.001), and whether or not Xuanwei area ( P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area ( P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han ( P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities ( P=0.005). Conclusions:The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.

Objective:To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas.Methods:A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions.Results:The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender ( P<0.001), smoking history ( P<0.001), age ( P<0.001), pathological type ( P<0.001), and whether the Xuanwei area ( P=0.027), but not related to the nationality ( P=0.748) and family history of lung cancer ( P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males ( P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females ( P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority ( P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area ( P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area ( P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area ( P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history ( P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history ( P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history ( P=0.008). Conclusions:The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.

Objective To determine clinical features and rupture risk of anterior communicating artery (AComA) aneurysms in different age groups. Methods The clinical data of 519 consecutive patients with AComA aneurysms in the First Affiliated Hospital of Wenzhou Medical University between December 2007 and February 2015 were reviewed and divided into younger group (<65 years) and older group (≥65 years). The clinical characteristics and aneurysm morphologies were compared between the two groups. Results There were 390 aneurysms in younger group, and 129 in older groups. For the younger group, hypertension,the size of the aneurysms, maximum height, perpendicular height, size ratio (SR), aspect ratio (AR), aneurysm angle, A1 segment configuration, morphology showed significantly differences in ruptured aneurysms group compared with those in unruptured aneurysms (P<0.05). The multivariate analysis showed that significant difference between the two groups was aneurysm size ( OR＝1.461,95% CI 1.027-2.079, P＝0.035). For the older group, there were statistically significant differences in hypertension,size of the aneurysms, maximum height, perpendicular height, SR, aneurysm angle, vessel size and the distribution of aneurysm projection between the ruptured aneurysms group and unruptured aneurysms group (P<0.05). The multivariate analysis showed that SR ( OR＝11.516,95% CI 1.782-74.445,P＝0.01) was the only significant predictor of aneurysm rupture. Between the younger and older groups,the distributions of sex, hypertension, smoke, vessel size and SR were statistically significant (P < 0.05). Conclusions For younger people, the males who smoked are more likely to have AcomA aneurysms and the size of the aneurysms is independent risk of aneurysm rupture. For older people, the females with hypertension also more often have AcomA aneurysms and the SR is independently associated with aneurysm rupture.

Objective: To explore the value of dual-energy CT-based volumetric iodine-uptake (VIU) in the evaluation of chemotherapy efficacy in advanced gastric cancer. Methods: Inclusion criteria of subjects: (1) without previous systematic therapy; (2) with complete clinical information before and after chemotherapy; (3) without contraindications of chemotherapy. Exclusion criteria of subjects: (1) unfinished duration and times of chemotherapy; (2) unmeasurable primary lesions; (3) poor imaging quality or poor gastric filling. Clinical and image data of 52 patients with advanced gastric cancer who were diagnosed by pathology from gastroscopic biopsy, and needed chemotherapy evaluated by imaging and clinical information in the First Affiliated Hospital of Wenzhou Medical University from February 2017 to February 2018 were collected and analyzed. Of 52 patients, 38 were male and 14 were female with the median age of 65 (31-88) years old. All the patients underwent a dual-energy, dual phase-enhanced CT scanning before chemotherapy and after the third chemotherapy session. The parameters of the lesions measured before and after chemotherapy in portal vein phase were as follows: the maximum diameter (the largest diameter among those measured in the cross-sectional, coronal, and sagittal planes), average CT value (the regions of interest were manually pinpointed under cross-sectional planes with largest diameter of the tumor, which did not include regions less than 2 mm to the edge of the tumor) and VIU (lesion volume × iodine concentration). The change rates of maximum lesion diameter, average CT value and VIU before and after chemotherapy were calculated [(post-chemotherapy parameters-pre-chemotherapy parameters)/ pre-chemotherapy parameters]. The efficacy of chemotherapy was evaluated by RECIST 1.1 (the change of maximum tumor diameter after chemotherapy), Choi (the change of average CT value after chemotherapy) and VIU (the change of VIU after chemotherapy), respectively, which was categorized by complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients with CR, PR, and SD were assigned to the effective group, while those with PD were classified as the ineffective group. Paired t - test or Wilcoxon signed ranks test was used to compare the changes of parameters before and after chemotherapy, whereas Spearman correlation analysis and Kappa test were used for the correlation analysis and the consistency test between the three evaluation criteria (Kappa≥0.75 indicated good consistency). Results: After chemotherapy, the average CT value [(74.01±16.75) HU vs. (81.06±15.87) HU, t=2.202, P=0.030] and median VIU (668.53×10² μg vs. 272.52×10² μg, Z=4.761, P<0.001) decreased significantly, while the difference of the maximum diameter was not statistically significant [(66.71±34.49) mm vs. (78.45±35.62) mm, t=1.708, P=0.091]. The median change rate of VIU (–53.33%) was greater than that of CT values (–5.75%) with significant difference (Z=-5.408, P<0.001). According to the RECIST 1.1 criteria, 47 patients (90.4%, including 19 with PR and 28 with SD) were effective and 5 patients (9.6%) were ineffective. According to the Choi criteria, 45 patients (86.5%, including 37 with PR and 8 with SD) were effective and 7 patients (13.5%) were ineffective. According to the VIU criteria, 46 patients (88.5%, including 41 with PR and 5 with SD) were effective and 6 patients (11.5%) were ineffective. Efficacy comparison among these three criteria showed no significant difference (χ²=0.377, P=0.828). As compared to RECIST 1.1 evaluation, the proportion of PR evaluated by Choi and VIU was significantly higher (χ²=16.861, P<0.001), whereas the proportion of SD was significantly lower (χ²=24.089, P<0.001). There was no significant difference in the proportions of PR and SD between VIU and Choi criteria (χ²=0.887, P=0.346). Consistency and correlation analysis showed that the VIU and Choi evaluation criteria presented the highest consistency and correlation (Kappa=0.912, P<0.001; r=0.916, P<0.001). Conclusion VIU is a feasible parameter for the evaluation of chemotherapy efficacy in advanced gastric cancer, and may be more sensitive than the evaluation criteria based on maximum diameter or change of CT value in the tumor.