ObjectiveThis study explores the methods of lung tissue extraction and fixation required for pathological studies of fetal rats, based on the unique physiological structure of fetal rat lung tissue and existing lung tissue fixation techniques for adult rats. MethodsSix pregnant adult SD rats at 20.5 days of gestation were subjected to cesarean section to obtain fetal rats. Four healthy fetal rats with similar body weight, vital signs, and respiratory status were selected from each pregnant rat, and they were randomly divided into the following groups using a random number table: direct lung infiltration group, lung infiltration group after intratracheal infusion, whole-body infiltration group of fetal rats, and whole-body infiltration group after intratracheal infusion of fetal rats. To systematically compare and analyze the anatomical morphology under different fixation methods, lung tissues from four groups of fetal rats were harvested, perfused, and fixed, and the gross morphology of lung tissues in each group was observed. Paraffin sections were prepared and stained with Hematoxylin-Eosin (H&E). The histological morphology of the whole lung, alveoli, and bronchi was further examined under optical microscopy. ResultsIn the direct lung infiltration group, the hilar structures were unclear, lung lobation was indistinct, the shape was irregular, lung cavities were small, and alveoli and bronchi were shrunken. In the lung infiltration group after intratracheal infusion, the hilar structures were clear, lobation was pronounced, the shape was regular, lung cavities were large, and alveoli and bronchi were full. Both the whole-body infiltration group and whole-body infiltration group after intratracheal infusion of fetal rats exhibited visible lungs, hearts, skins, and other organs. The lung tissues of both groups showed obvious lobulation, irregular shape, and damage at the margins of lung lobes. In the whole-body infiltration group, the thoracic cavities of the fetus were flattened, lung cavities were small, and alveoli and bronchi were shrunken. In the whole-body infiltration group after intratracheal infusion of fetal rats, the fetal thoracic cavities were full, lung cavities were large, and alveoli and bronchi were relatively full. ConclusionThe lung infiltration after intratracheal infusion method for fetal rat lung tissue fixation outperforms direct lung infiltration, whole-body infiltration of fetal rats, and whole-body infiltration after intratracheal infusion of fetal rats in terms of preservation of the lung tissue's original morphology, paraffin sectioning, staining, and pathological observation and analysis. The embedding, sectioning, and staining processes are also simple and save consumables. Therefore, intratracheal infusion followed by lung infiltration method is recommended for fixation in histopathological observation of fetal rat lung tissue.

Objective:To explore whether multi-parametric MRI (mpMRI) combined with 68Ga-prostate specific membrane antigen (PSMA) PET/CT can improve the detection efficiency of clinically significant prostate cancer (csPCa). Methods:Clinical and imaging data of 152 patients (age (68.5±8.5) years) who underwent mpMRI and 68Ga-PSMA PET/CT examination for suspected prostate cancer in the First Affiliated Hospital of the Air Force Medical University from January 2021 to November 2022 were retrospectively analyzed, with the histopathological results from transrectal ultrasound guided biopsy as reference. Lesions with Gleason scores (GS) ≥3+ 4 from the biopsy were diagnosed with csPCa, and lesions with negative biopsy or GS 6 were diagnosed with non-csPCa. MpMRI was evaluated independently by two radiologists according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The radioactive uptake of 68Ga-PSMA PET/CT in prostate lesions was evaluated by SUV max. The independent-sample t test, Mann-Whitney U test and χ2 test were used to compare differences between the two groups, and then multivariate logistic regression analysis was performed. ROC curves analysis was used to analyze the diagnostic efficacies of individual and combined factors and Delong test was used. Results:There were 85 csPCa and 67 non-csPCa confirmed. Prostate specific antigen (PSA), PI-RADS score and SUV max were significantly different between the csPCa group and the non-csPCa group ( χ2=68.06, U values: -7.66, -8.98, all P<0.001). Multivariate logistic regression analysis indicated that PI-RADS score (odds ratio ( OR)=3.424, 95% CI: 1.651-7.100) and SUV max ( OR=1.931, 95% CI: 1.403-2.658) were independent predictors of csPCa (both P<0.001). ROC curves analysis revealed that the cut-off value for diagnosing csPCa was 4 for PI-RADS score and 5.6 for SUV max. The accuracy of mpMRI and PET/CT alone in csPCa diagnosis was 80%(122/152) (AUC of 0.789(95% CI: 0.711-0.866) with the sensitivity and specificity of 91%(77/85) and 67%(45/67)), and 87%(132/152) (AUC of 0.876(95% CI: 0.817-0.936) with the sensitivity and specificity of 81%(69/85) and 94%(63/67)), respectively. Several joint models incorporating 68Ga-PSMA PET/CT with mpMRI data were investigated, the model of PI-RADS 5 or PI-RADS 3-4 and SUV max>5.6 showed better performance than mpMRI and PET/CT alone and other joint models ( z values: 2.01-3.64, all P<0.05), with the accuracy of 91%(138/152) (AUC of 0.910(95% CI: 0.857-0.962) with the sensitivity and specificity of 89%(76/85) and 93%(62/67)). Conclusion:MpMRI combined with 68Ga-PSMA PET/CT can significantly improve the detection efficiency of csPCa, with the principal effect being improved in risk stratification of PI-RADS 3-4 lesions in mpMRI.

Acute decompensated cirrhosis is a stage of end-stage liver disease during which patients often experience decompensated complications and rapid progression. Systemic inflammatory response is characterized by excessive secretion of inflammatory factors caused by bacterial infection of local tissue and rapid spread to the whole body, thereby affecting the physiological activities of the body and causing organ damage or disorder, and it is a relatively serious inflammatory state. This article elaborates on the occurrence of systemic inflammation, the factors affecting the severity of systemic inflammation, the manifestation of systemic inflammation in different stages of decompensated cirrhosis, and the role of systemic inflammation in complications, in order to gain a deeper understanding of systemic inflammation and apply it in the research and development of new therapies and drugs.

Fusobacterium nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. The two-component system plays an important role in the regulation and expression of genes related to pathogenic resistance and pathogenicity. In this paper, we focused on the CarRS two-component system of F. nucleatum, and the histidine kinase protein CarS was recombinantly expressed and characterized. Several online software such as SMART, CCTOP and AlphaFold2 were used to predict the secondary and tertiary structure of the CarS protein. The results showed that CarS is a membrane protein with two transmembrane helices and contains 9 α-helices and 12 β-folds. CarS protein is composed of two domains, one is the N-terminal transmembrane domain (amino acids 1-170), the other is the C-terminal intracellular domain. The latter is composed of a signal receiving domain (histidine kinases, adenylyl cyclases, methyl-accepting proteins, prokaryotic signaling proteins, HAMP), a phosphate receptor domain (histidine kinase domain, HisKA), and a histidine kinase catalytic domain (histidine kinase-like ATPase catalytic domain, HATPase_c). Since the full-length CarS protein could not be expressed in host cells, a fusion expression vector pET-28a(+)-MBP-TEV-CarS_cyto was constructed based on the characteristics of secondary and tertiary structures, and overexpressed in Escherichia coli BL21-Codonplus(DE3)RIL. CarS_cyto-MBP protein was purified by affinity chromatography, ion-exchange chromatography, and gel filtration chromatography with a final concentration of 20 mg/ml. CarS_cyto-MBP protein showed both protein kinase and phosphotransferase activities, and the MBP tag had no effect on the function of CarS_cyto protein. The above results provide a basis for in-depth analysis of the biological function of the CarRS two-component system in F. nucleatum.
Humans ; Histidine Kinase/metabolism* ; Fusobacterium nucleatum/metabolism* ; Automobiles ; Protein Kinases/genetics* ; Escherichia coli/metabolism* ; Colorectal Neoplasms

[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。

Objective: To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT). Methods: Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3′untranslated region (3′UTR) of GNA11 gene, respectively. Results: Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)]. Conclusion The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.

Objective To preliminarily verify the feasibility of utilizing TG119 report to commission the volumetric modulated arc therapy (VMAT) plans.Methods Based on the test cases mentioned in TG119 report,7-/9-field intensity-modulated radiation therapy (IMRT) and dual-arc VMAT plans were devised by using two types of beam energy (6 MV and 10 MV) in the Eclipse TPS system according to the requirement of this report.All the plans were verified using 0.125cc semiflex thimble ionization chamber,MatriXX and Delta 4,respectively.The final results were statistically compared with the results measured by multiple institutions in the TG119 report.Results The resuhs of both IMRT and VMAT plans met the requirement of the TG119 report.The discrepancy of point dose in the high/low dose region of VMAT plans using different photon beams was ranged from-2.55％ to 2.55％,and ± 1.85％ for the IMRT plans.The percentage of γ passing points (±3％/3 mm) for the IMRT plans using 6 MV and 10 MV photon beams was 99.38％ and 99.53％,99.32％ and 99.46％ for the VMAT plans.The γ passing rate of the compound field exceeded 98％.Conclusions The VMAT plans with 6 MV and 10 MV photon beams meet the requirement of the TG119 report.TG119 report provides certain guidance for establishing a benchmark for dosimetry verification of the VMAT plans.

Objective To investigate the impact of four different collimator angle optimization techniques on the planning target volume (PTV) and organ at risk (OAR) during intensity-modulated radiotherapy (IMRT) for gastric cancer.Methods Ten patients with gastric cancer undergoing IMRT in Zhongnan Hospital of Wuhan University from 2015 to 2016 years were recruited in this study.All IMRT plans were designed by conventional five fields (330°,10°,45°,90°and 180°).In the Eclipse treatment planning system,four different collimator angle optimization techniques with consistent planning optimization parameters were employed to design the IMRT plan.Collimator angle optimization techniques included the following aspects.The collimator angle was set at 0 degree (CL0),collimator angle was set at 90 degree (CL90),Eclipse automatic collimator angle optimization (CLA) was adopted and collimator angle was set as the angle when the distance between X-Jaws and PTV (CLx) was the shortest.The dosimetric parameters mainly included the conformal index (CI) of PTV,the homogeneity index (HI),the mean dose (Mean),and the dosage of OAR.The treatment time (Time),monitor unit (MU),control point (CP),split field (SF) and conformal distance (Fx) were also considered.Results Regarding CL0 as the control,the CI,HI and Mean did not significantly differ among four collimator angle optimization techniques (all P＞0.05),whereas CLx could significantly increase the average dose of PTV in the target area (P＜0.05);CLx optimization reduced the liver (V30 reduction by 1.54％),left kidney (V12 decrease by 1.46％),right kidney and other OARs,whereas it slightly increased the maximum dose of the small intestine and spinal cord (＜1％).CLgo and CLA optimization elevated the dose of OAR in gastric cancer.Among four different collimator angle optimization techniques,CLx optimization reduced the MU (25.02％),CP (26.03％),Fx (20.27％) and SF (by 1.3separate fields on average) and treatment time (10.03％).CLgo and CLA optimization could decrease the MU,CP,Fx and SF.CL90 optimization had certain advantages in shortening the treatment time,whereas CLA optimization could prolong the treatment time by 5.04％.Conclusions During IMRT for gastric cancer,CL90,CLA and CLx collimator angle optimization techniques can obtain comparable dosimetry distribution to CL0 optimization technique,which can reduce the MU,decrease the radiation leakage,shorten the treatment time and improve treatment efficiency.

in view of the emphasis on disease management and clinical research, the authors introduced the evaluation and construction methods of the departments based on disease management. Introduction to the selection process of the evaluation and construction methods of such departments, the authors expounded the construction thought of clinical research evaluation system. This paper analyzed the important role of clinical scientific research in the formation of hospital characteristic advantage and leading position, then suggested that hospitals should take research-type diseases as the basis, promote steady breakthroughs in their medical services and scientific research level, and fully reflect the responsibilities of tertiary hospitals.

Objective To analyze the influencing factors on clinical response to conbercept for diabetic maeular edema (DME).Methods A total of 51 patients (51 eyes) with DME who underwent intravitreal injection of conbercept were included in this retrospective study.The general information (age,sex,body mass index,smoking history,drinking history),blood glucose indicators (duration of diabetes,fasting blood glucose,HbA 1 c),blood pressure indicators (history of hypertension,systolic blood pressure,diastolic blood pressure),lipid indicators [total cholesterol (TC),high-density lipoprotein (HDL),apolipoprotein A (APOA)],biochemical indicators [neutrophil concentration,hemoglobin (HB),serum creatinine (Scr)] were collected.The best corrected visual acuity (BCVA) and macular central macular thickness (CMT) before and after treatment were comparatively analyzed.CMT reduced not less than 20％ and BCVA increased by 2 lines as effective standards.Univariate analysis and multivariate logistic regression analysis were used to determine the factors affecting the efficacy ofintravitreal injection ofconbercept in patients with DME.Results Univariate analysis showed that diastolic blood pressure,HDL,serum neutrophil concentration,baseline CMT and baseline BCVA were associated with edema regression (P＜ 0.05);HbA 1 c was associated with vision improvement (P＜ 0.05).Multivariate logistic regression analysis showed that there was a history of smoking (OR=0.122,95％ CI 0.017-0.887),low diastolic blood pressure (OR=0.850,95％CI 0.748-0.966),low HDL (OR=0.007,95％CI 0.000 1-0.440),thin baseline CMT (OR=0.986,95％CI 0.977-0.995) were independent risk factors for failure outcome of edema regression (P＜0.05);long duration of diabetes (OR=1.191,95％CI 1.011-1.404),high APOA (OR=l.007,95％ CI 1.000-1.013) were independent risk factors for failure outcome of vision improvement.Age,fasting blood glucose,systolic blood pressure,TC,HB,Scr and other indicators had no effect on the efficacy of edema regression and vision improvement after treatment (P＞ 0.05).Conclusions Smoking history,long duration of diabetes,low diastolic blood pressure,low HDL level,high APOA level and thin baseline CMT are independent risk factors for the treatment of DME with intravitreal injection of conbercept.