Background and objective Lung squamous cell carcinoma(LUSC)is a subtypes of non-small cell lung cancer(NSCLC).It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway.Protocadherin-gamma subfamily B4(PCDHGB4)as a family member in LUSC was rarely reported.The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC us-ing bioinformatics methods.Methods The Cancer Genome Atlas(TCGA),cBioPortal and UALCAN databases were used to analyze the expression,prognosis,clinicopathological features,immune cell infiltration,immune regulatory genes,immune checkpoint inhibitors(ICIs),and methyltransferases of PCDHGB4 in LUSC.At the single cell level,we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations.In addition,we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis.Finally,enrichment analysis was performed based on the differentially expressed genes.Results Bioinformat-ics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues.Sur-vival analysis showed that increased PCDHGB4 expression was associated with poor prognosis.Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells,monocytes or macrophages,and dendritic cells.It was further found that PCD-HGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints,immune regulatory genes,and methyltransferases.Besides,enrichment analysis revealed that PCDHGB4 was involved in mul-tiple cancer-related pathways.Conclusion The expression of PCDHGB4 was low in LUSC.PCDHGB4 was related to the poor prognosis of patients,and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells.PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.

Objective To study the key genes and immune biomarkers of gout and to explore potential target Chinese medicine,which can provide new directions for the clinical treatment of gout.Methods The gout microarray dataset was downloaded from the GEO database,the differential genes were screened using R software,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on these differential genes.The STRING database was applied to analyze the protein interaction network of the differential genes,and the Cytoscape was used to screen the key genes.The protein expression levels of key genes were validated using the ELISA method.Furthermore,the xCell was used to estimate the relative expression and correlation of immune cells in gout.Finally,the significantly enriched immune-related biological processes and key target genes of Chinese medicine were predicted by Coremine Medical database.Results A total of 852 differential gout genes were screened.GO enrichment analysis was mainly enriched in the leukocyte chemotaxis,interleukin-2 production,and regulation of vasculature development;KEGG pathway was mainly enriched in IL-17 signaling pathway,Chemokine signaling pathway,and TNF signaling pathway.Ten key genes,including TNF,IL-6,IL-1β,CXCL8,FOS,and VEGFA etc,were selected.The experimental validation showed that the protein expression levels of key genes were consistent with the expression trends of the chip data.Immune infiltration showed that monocytes,memory B cells,CD8+T-cells and IDC were closely associated with gout.Herbal predictions had identified Ginseng,Panax notoginseng,Scutellaria,Baicalensis,Saururus chinensis,and Salvia miltiorrhiza as potential drugs for the treatment of gout.Conclusion This study identified possible key genes and immune mechanisms contributing to the pathogenesis of gout,and discovered potential targetable traditional Chinese medicine.These key genes and herbs are expected to offer new insights and methods for the treatment of gout.

Objective:To evaluate the effect of selective cerebral mild hypothermia on the expression of histone deacetylase 1-3 (HDAC1-3) during focal cerebral ischemia-reperfusion (I/R) in rats.Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 240-260 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (S group), focal cerebral I/R group (I/R group), selective cerebral mild hypothermia group (SCH group), and normothermia group (N group). Only the cervical vessels were isolated in S group. In the other three groups, sutures were inserted into the internal carotid artery to block the middle cerebral artery for 2 h, and then the sutures were pulled out to restore perfusion for 24 h. A focal cerebral I/R model was prepared. Normal saline at 20 ℃ and 37 ℃ was infused into the internal carotid artery at a rate of 0.6 ml/min for 10 min starting from the time point immediately after removal of the sutures in SCH group and N group respectively. Cerebral temperature and rectal temperature were continuously monitored during the operation. The modified neurological severity score (mNSS) was assessed at 24 h of reperfusion. The rats were then sacrificed under deep anesthesia and brains were obtained for determination of cerebral infarct size (by TTC staining). The tissues of the cerebral ischemic penumbra were taken for determination of the apoptosis rate of neurons (by TUNEL method) and lactylation modification and expression of HDAC1-3 (by Western blot) and for observation of the morphology of neurons (by HE staining). Results:Compared with S group, the mNSS, cerebral infarct size and apoptosis rate of neurons were significantly increased, HDAC1-3 expression was down-regulated, and the lactylation modification was increased in the other three groups ( P<0.05). Compared with I/R and N groups, the mNSS, cerebral infarct size and apoptosis rate of neurons were significantly decreased, HDAC1-3 expression was up-regulated, and the lactylation modification was decreased in SCH group ( P<0.05). There was no statistically significant difference in the aforementioned parameters between I/R group and N group ( P>0.05). HE staining showed that the morphology of neurons was intact and well-defined in S group, a large number of cells with edema and irregularly solidified nuclei were found in I/R group and N group, and the nuclear shrinkage and morphological changes of neurons were alleviated in SCH group. Conclusions:The mechanism by which selective cerebral mild hypothermia alleviates cerebral I/R injury may be related to up-regulation of HDAC1-3 expression in rats.

BACKGROUND: Lung cancer is the most common malignant tumor in China, lung adenocarcinoma (LUAD) is the main type of lung cancer, which is a serious threat to people's life and health. At present, there are fewer studies on the role of Dikkopf1 (DKK1) in lung adenocarcinoma. The aim of this study was to investigate the role and potential prognostic value of DKK1 in the development of lung adenocarcinoma by bioinformatics methods. METHODS: Several databases, such as genotype-tissue expression (GTEx), The Cancer Genome Atlas (TCGA) and tumor-immune system interactions database (TISIDB), were used to analyze the expression, clinicopathological features, immune cell infiltration, prognosis and methylation of DKK1 in lung adenocarcinoma. Then, linked immune cell infiltration Omics database was used to analyze the co-expressed genes of DKK1 and their functional enrichment. Finally, 59 pathological samples of paraffin-embedded lung adenocarcinoma patients who underwent surgery at the Affiliated Cancer Hospital of Xinjiang Medical University between 2016 and 2017 were collected for the validation of the prognostic value of expression by immunohistochemistry (IHC) test. RESULTS: The results of bioconfidence analysis showed that the expression level of DKK1 in lung adenocarcinoma tissues was higher than that in normal tissues, the expression in advanced cancers was higher than that in early stages, and the experimental validation revealed that among 59 cases of lung adenocarcinoma, there were 15 cases of negative expression (25.4%), 18 cases of weakly positive expression (30.5%), and 26 cases of strongly positive expression (44.1%). The different expression of DKK1 is related to methylation, prognosis and the activities of various immune cells. Functional enrichment shows that DKK1 may be involved in skin development and cell-substrate junction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis shows that DKK1 is related to ABC transporters. Bioinformatics analysis and clinical case specimens showed that high DKK1 expression was associated with poorer prognosis in patients with lung adenocarcinoma. CONCLUSIONS High expression of DKK1 in lung adenocarcinoma is associated with poor prognosis. DKK1 is closely associated with tumor immune cell infiltration and pathways. DKK1 can be considered as a potential prognostic marker and a novel target for immunotherapy of lung adenocarcinoma.

[摘 要] 目的：采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷（HRD）检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法：共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例，HRD状态采用基因组瘢痕评分法（GSS）（主要依据拷贝数的长度、类型、位置及基因组断片）或HRD评分法（杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和）进行评估，当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果：248名卵巢癌患者中70.97%的患者HRD呈阳性，其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率（均P<0.01），HRD评分更高的患者其合并其他基因突变的频率也越高（P<0.05）。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联（均P<0.01）。结论：云南地区卵巢癌患者HRD阳性率较高，HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶（PARP）抑制剂治疗中获得更大的收益。

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Objective:To investigate the role of DDX3 up-regulation in the proliferation of human cervical cancer cells and its correlation with clinical prognosis.Methods:Expression levels of DDX3 in the 59 specimens of cervical cancer and adjacent non-neoplastic tissue collected at Henan Provincial People′s Hospital from April 2012 to March 2013 were detected using immunohistochemistry. A lentivirus-mediated DDX3-over-expression cell line was constructed based on HeLa cells of cervical cancer. CCK-8 assay was used to evaluate cell survival rate. Boyden chamber was used to measure the cell migration and invasion. Real-time fluorescence quantitative PCR was used to detect DDX3 expression level and Western blot was used to detect the expression of EMT and PI3K/Akt signal pathway-related proteins. Results:DDX3 overexpression was associated with FIGO stage, depth of cervical invasion and lymph node metastasis ( P<0.05). Kaplan-Meier analysis revealed that cervical cancer patients with high expression of DDX3 had a poor overall survival ( P<0.05). Compared with the cells transfected with pLVX-Con vector, the expression of DDX3 protein and mRNA was significantly increased in the cells transfected with pLVX-DDX3 (all P<0.01). Cell proliferation was significantly increased following transfection with pLVX-DDX3 for 72 h in HeLa cells compared with that transfected with pLVX-Con ( P<0.05). Compared with the controls, DDX3 overexpression significantly promoted the migration and invasion of HeLa cells ( P<0.05), and increased the expression of N-Cadherin, vimentin and Snail in HeLa cells ( P<0.05). In pLVX-DDX3 group, the expression levels of β-catenin, phosphorylated Akt, and pAkt′s downstream target p-GSK3β were significantly higher than those of pLVX-Con group ( P<0.05). The expression levels of p-Akt, p-GSK3β and β-catenin were decreased when the PI3K/Akt pathway was blocked using the PI3K inhibitor LY294002 ( P<0.05), and the expression levels of N-Cadherin, vimentin and Snail were also significantly decreased ( P<0.05). Conclusions:DDX3 overexpression promotes proliferation, migration and invasion of cervical cancer cells, and induces epithelial-mesenchymal transition (EMT). Its mechanism may be related to activation of the PI3K/Akt signaling pathway.

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.