Objective:To investigate the expression of heat shock factor binding protein 1 (HSPB1) in endometrial carcinoma and its clinical significance.Methods:The pan-cancer dataset after standardization and unification was downloaded from the University of California Santa Cruz (UCSC) Genome database (updated to December 6, 2019), and the expression of HSPB1 in pan-cancer was analyzed. The transcriptome data of endometrial carcinoma of the uterus from the Cancer Genome Atlas (TCGA) database were downloaded (updated to July 21, 2016), including 552 cases of endometrial carcinoma and 35 cases of corresponding adjacent tissue samples. The clinical data of 543 patients with endometrial cancer were obtained. The differences in the expression levels of HSPB1 in patients with different clinicopathological features were compared. R 4.3.1 software maxstat was used to calculate the optimal critical value (>46.30) of HSPB1 expression, and the patients were divided into HSPB1 low expression group (<46.30) and HSPB1 high expression group (≥46.30). Kaplan-Meier method was used to analyze the difference in prognosis between the 2 groups, and log-rank test was performed. The top 50 genes with positive and negative correlation with HSPB1 were screened by LinkedOmics database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on HSPB1. The interaction network of HSPB1 protein was analyzed by STRING database and Cytoscape 3.9.1 software. The correlation between HSPB1 expression and various immune cell infiltration levels was analyzed by using the TIMER2.0 database.Results:The expression of HSPB1 in 27 kinds of tumor tissues was higher than that in paracancerous tissues, and the expression of HSPB1 in 2 kinds of tumor tissues was lower than that in paracancerous tissues (all P < 0.05). In the transcriptome data of 552 cases of endometrial cancer and 35 cases of corresponding paracancerous tissues in the TCGA database, the relative expression level of HSPB1 in endometrial cancer tissues was higher than that in corresponding paracancerous tissues ( t = -2.90, P = 0.005). The result of the comparison of relative expression level of HSPB1 in endometrial cancer patients with different clinicopathological features showed that patients aged < 65 years had higher expression level compared to those aged ≥ 65 years, patients at clinical stage Ⅰ-Ⅱ had higher expression level compared to those at stage Ⅲ-Ⅳ, patients with Grade grading G 1-G 2 had higher expression level compared to those with G 3, and patients with pathological type I had higher expression level compared to those with type Ⅱ (all P < 0.05). Of the 543 patients, 2 were lost to follow-up, and the overall survival of the remaining 541 patients with high HSPB1 expression was better than that of those with the low expression ( HR = 0.532, 95% CI: 0.333-0.849, P = 0.008). HSPB1 and its related genes were mainly involved in estrogen signaling, p53 signaling and other pathways; HSPB1 was involved in cysteine-type endopeptidase inhibitor activity and calcium-dependent protein binding. The top 10 genes with the strongest correlation with HSPB1 in protein-protein interaction analysis were DSG3, EVPL, PKP1, DSC3, PKP3, PPL, KRT5, IVL, TGM1 and CSTA. The expression of HSPB1 was negatively correlated with tumor purity ( r = -0.025, P < 0.01), and positively correlated with CD4 + T cells ( r = 0.204, P < 0.01), CD8 + T cells ( r = 0.225, P < 0.01), B cells ( r = 0.285, P < 0.01), NK cells ( r = 0.269, P < 0.01), macrophages ( r = 0.234, P < 0.01) and dendritic cells ( r = 0.354, P < 0.01). Conclusions:The high expression of HSPB1 is associated with clinicopathological features, prognosis and immune infiltration in patients with endometrial carcinoma. It may be one of the reference indexes for predicting the prognosis of patients with endometrial cancer.

Objective:To investigate the expression of heat shock factor binding protein 1 (HSPB1) in endometrial carcinoma and its clinical significance.Methods:The pan-cancer dataset after standardization and unification was downloaded from the University of California Santa Cruz (UCSC) Genome database (updated to December 6, 2019), and the expression of HSPB1 in pan-cancer was analyzed. The transcriptome data of endometrial carcinoma of the uterus from the Cancer Genome Atlas (TCGA) database were downloaded (updated to July 21, 2016), including 552 cases of endometrial carcinoma and 35 cases of corresponding adjacent tissue samples. The clinical data of 543 patients with endometrial cancer were obtained. The differences in the expression levels of HSPB1 in patients with different clinicopathological features were compared. R 4.3.1 software maxstat was used to calculate the optimal critical value (>46.30) of HSPB1 expression, and the patients were divided into HSPB1 low expression group (<46.30) and HSPB1 high expression group (≥46.30). Kaplan-Meier method was used to analyze the difference in prognosis between the 2 groups, and log-rank test was performed. The top 50 genes with positive and negative correlation with HSPB1 were screened by LinkedOmics database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on HSPB1. The interaction network of HSPB1 protein was analyzed by STRING database and Cytoscape 3.9.1 software. The correlation between HSPB1 expression and various immune cell infiltration levels was analyzed by using the TIMER2.0 database.Results:The expression of HSPB1 in 27 kinds of tumor tissues was higher than that in paracancerous tissues, and the expression of HSPB1 in 2 kinds of tumor tissues was lower than that in paracancerous tissues (all P < 0.05). In the transcriptome data of 552 cases of endometrial cancer and 35 cases of corresponding paracancerous tissues in the TCGA database, the relative expression level of HSPB1 in endometrial cancer tissues was higher than that in corresponding paracancerous tissues ( t = -2.90, P = 0.005). The result of the comparison of relative expression level of HSPB1 in endometrial cancer patients with different clinicopathological features showed that patients aged < 65 years had higher expression level compared to those aged ≥ 65 years, patients at clinical stage Ⅰ-Ⅱ had higher expression level compared to those at stage Ⅲ-Ⅳ, patients with Grade grading G 1-G 2 had higher expression level compared to those with G 3, and patients with pathological type I had higher expression level compared to those with type Ⅱ (all P < 0.05). Of the 543 patients, 2 were lost to follow-up, and the overall survival of the remaining 541 patients with high HSPB1 expression was better than that of those with the low expression ( HR = 0.532, 95% CI: 0.333-0.849, P = 0.008). HSPB1 and its related genes were mainly involved in estrogen signaling, p53 signaling and other pathways; HSPB1 was involved in cysteine-type endopeptidase inhibitor activity and calcium-dependent protein binding. The top 10 genes with the strongest correlation with HSPB1 in protein-protein interaction analysis were DSG3, EVPL, PKP1, DSC3, PKP3, PPL, KRT5, IVL, TGM1 and CSTA. The expression of HSPB1 was negatively correlated with tumor purity ( r = -0.025, P < 0.01), and positively correlated with CD4 + T cells ( r = 0.204, P < 0.01), CD8 + T cells ( r = 0.225, P < 0.01), B cells ( r = 0.285, P < 0.01), NK cells ( r = 0.269, P < 0.01), macrophages ( r = 0.234, P < 0.01) and dendritic cells ( r = 0.354, P < 0.01). Conclusions:The high expression of HSPB1 is associated with clinicopathological features, prognosis and immune infiltration in patients with endometrial carcinoma. It may be one of the reference indexes for predicting the prognosis of patients with endometrial cancer.

Objective:To investigate the distribution characteristics of conjugate eye deviation on MRI in patients with posterior circulation ischemic stroke (PCIS) presenting as isolated acute vestibular syndrome (AVS), and its relationship with infarct lesions.Methods:Patients with PCIS presenting as isolated AVS admitted to Weihai Central Hospital Affiliated to Qingdao University from January 2022 to June 2024 were included retrospectively. The infarct distribution and eye deviation were detected by MRI within 3 days of admission. If the gaze deviation of both eyes horizontally towards the same side is observed, it was defined as radiological conjugate eye deviation (RCED); if one eye was deviated while the other eye was not; it was defined as radiological non-conjugate eye deviation (RDED). Multivariate logistic regression analysis was to determine the independent influencing factors of RCED. Results:A total of 82 patients with PCIS presenting with isolated AVS were included. Among them, there were 61 males (74.4%), mean aged 66.20±12.50 (range, 31-91) years. Seventy-two patients (87.8%) had cerebellar infarction, 9 (11.0%) had medullary infarction, 2 (2.4%) had caudal pontine infarction, 1 had both cerebellar and medullary infarction. MRI revealed RCED in 42 cases (51.2%), RDED in 22 cases (26.8%), and no deviation in 18 cases (22.0%). Of the 42 patients with RCED, 32 had cerebellar infarction, accounting for 44.4% of all patients with cerebellar infarction; there were 2 patients with caudal pontine infarction and 9 with medullary infarction. All 22 patients with RDED had cerebellar infarction. Univariate analysis showed that there was significant difference between the RCED group and the non-RCED group in age and the proportion of patients with lesions involving the cerebellar hemisphere and medullary infarction (all P<0.05). Multivariate logistic regression analysis showed that the lesion involvement in the cerebellar hemisphere was an independent influencing factor for RCED (odds ratio 0.169, 95% confidence interval 0.033-0.876; P=0.034). Conclusions:Cerebellar infarction is the most common in patients with PCIS presenting as isolated AVS. Both patients with medullary infarction and pontine infarction present with RCED, while the incidence of RCED in patients with cerebellar infarction is 44.4%. RDED is only seen in patients with cerebellar infarction. Compared with RCED, RDED is more common in patients with infarction involving the cerebellar hemisphere.

Objective:To investigate clinical features, imaging characteristics, etiology, and potential mechanisms of medullary "comma-shaped" infarctions.Methods:Patients with common-shaped infarction treated at Weihai Central Hospital Affiliated to Qingdao University from January 2020 to September 2023 were retrospectively collected, and their clinical manifestations, imaging findings, treatment, and outcome were analyzed and summarized.Results:A total of 9 patients with medullary common-shaped infarction were enrolled, including 3 males, aged 67.22±14.66 years (ranging from 39 to 83 years). Main clinical symptoms and signs included the decreased pain and temperature sensation on the contralateral limb (66.67%, 6/9), coughing or choking while drinking liquids/dysphagia (66.67%, 6/9), ipsilateral pharyngopalatine muscle paralysis (66.67%, 6/9), and dizziness (66.67%, 6/9). Seven patients (77.78%, 7/9) had severe stenosis or occlusion at the ipsilateral vertebral artery, one (11.11%, 1/9) had occlusion at the left middle cerebral artery, and one (11.11%, 1/9) did not have large vessel stenosis. At 90 days after onset, the follow-up showed that the modified Rankin Scale scores were all <2.Conclusions:Medullary comma-shaped infarctions are rare in clinical practice, its main manifestations include the decreased pain and temperature sensation on the contralateral limb, coughing or choking while drinking liquids/dysphagia, ipsilateral pharyngopalatine muscle paralysis, dizziness, etc. The pathogenesis is mainly hypoperfusion caused by vertebral artery stenosis.

Objective To investigate the structure of deoxyhypusine synthase(DHS)in Saccharomyces cerevisiae(Dys1)and unravel the molecular mechanism of hypusine lysine modification,providing a theoretical basis for the treatment of highly proliferative diseases such as human immunodeficiency virus type 1(HIV-1)replication.Meth-ods Using the E.coli BL21 expression system,an in vitro expression vector was constructed and used to express the protein of Dys1.Dys1 protein samples were purified using methods such as affinity chromatography and molecu-lar sieving to achieve protein purification and isolation.The crystals of Dys1 were obtained using the crystallized so-lution containing 6％Polyethylene Glycol(PEG)8000,0.1 mol/L N-2-hydroxyethylpiperazine-N-ethane-sulphoni-cacid(Hepes)pH 6.5,and 8％ethylene glycol.The crystal structure of Dys1 was resolved at a resolution of 2.8 ? using X-ray crystallography.The structural analysis was performed with CCP4i and Coot software.Results The overall structure of Dys1 was a tetramer,each monomer containing a catalytic site and a cofactor NAD+binding site.The core region of the monomer adopted a Rossmann fold.The amino acid residues involved in the substrate binding sites were highly conserved among eukaryotes.Conclusion The crystal structure of Dys1 is being resolved for the first time.It reveals the binding mode of the cofactor NAD+to the enzyme and confirms that the enzyme functions as a tetramer,with the N-terminus serving as an essential modulator for its catalytic activity.

Objective: This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods: A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results: Gallic acid was confirmed as a direct thrombin inhibitor with IC

Objective To observe the genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy (PDR) in Chongqing Han population.Methods 400 type 2 diabetes (T2D) patients (case group) and 600 age-and sex-matched healthy controls (control group) were enrolled in this study.There were 8 PDR patients in case group.All the subjects were Han ethnic people.The immune-related representative SNP locus of C5 gene including rs2269067,rs7040033,rs7027797 were screened by linkage disequilibrium analysis.Locus rs1017119 was selected by TagSNP and was around the above three loci.Subjects' peripheral venous blood was collected and DNA was extracted.Genotyping was examined by PCR-restriction fragment length polymorphism method.The level of C5 plasma protein was measured by enzyme-linked immunoabsorbent assay.Results The frequency of GG genotype of rs2269067 was significantly increased in PDR patients in cases group compared with controls (Pc=3.4 × 10-5,OR=1.87,95％CI=1.43-2.44;P=3.1 × 10-6).There was no differences in frequency of G,CC and CG genotype of rs2269067 between two groups (P=1.4 × 10-4,1.000,1.0 × 10-6).There were no differences in frequency of G,CC,CG,GG genotype of rs7040033,rs1017119,and rs7027797 between two groups (P＞0.05).The production of C5 plasma protein was significantly increased in case group as compare with control group (P=0.0004).An increased production of C5 plasma protein was observed in rs2269067 GG genotype cases compared to CG or CC cases (P=0.003,0.001).Conclusion C5 rs2269067 GG genotype may be associated with the PDR of T2D in Chongqing Han population.