Objective:To investigate the prognostic value of systemic inflammatory score (SIS) in prognostic assessment of patients with unresectable metastatic colorectal cancer (mCRC).Methods:The clinical data of 130 patients with unresectable mCRC in Affiliated Haikou Hospital of Xiangya Medical College of Central South University from January 2014 to December 2016 were retrospectively analyzed. The relationship between SIS and clinicopathological characteristics of unresectable mCRC patients was also analyzed. The survival analysis was made by using Kaplan-Meier. The risk factors affecting the prognosis of unresectable mCRC patients were analyzed by using Cox regression model to make univariate and multivariate analysis.Results:According to SIS results, patients were divided into 0-score group (40 cases), 1-score group (58 cases), and 2-score group (32 cases). There were no significant differences in different SIS constitution patients stratified by age, gender, primary tumor location, functional status score, tissue type, RAS gene status, number of metastatic organs, peritoneal spread and molecular targeted therapy (all P > 0.05). Kaplan-Meier survival analysis showed that the 5-year overall survival rates of SIS 0-score, 1-score and 2-score group were 37.5%, 19.0%, 6.3%, respectively; and the difference was statistically significant ( χ2 = 3.152, P<0.01). Cox regression survival analysis showed that female, primary tumor location in right side and SIS (scores of 1-2) were independent risk factors for overall survival in patients with unresectable mCRC (all P<0.05). Conclusion:SIS may be an important indicator for prognostic assessment of patients with unresectable mCRC, and patients with high SIS have poor prognosis.

ObjectiveTo evaluate the diagnostic value of “taller-than-wide sign” of thyroid malignancy in transverse and longitudinal plane using ultrasound.Methods708 thyroid lesions including 302 benign nodules and 406 malignant nodules ( 390 papillary carcinomas,12 medullary carcinomas,4 follicular carcinomas) that were diagnosed at surgery were included in this study.The sensitivity and specificity of “taller-than-wide sign” in transverse (A/TC ≥ 1 ) and longitudinal plane (A/TL ≥ 1 ) were evaluated using ultrasound.All thyroid malignant lesions were divided into three groups according to size of the nodules:group A≤1 cm; group B≤2 cm,group C＞2 cm.The sensitivity of each group was also evaluated.ResultsThe constituent ratio of “taller-than-wide sign” between benign and malignant nodules was significantly different (P＜0.001 ).The differences of sensitivity of A/TL ≥ 1 and A/TC ≥ 1 among three groups were also found( P ＜0.001),and the sensitivity of A/Tc≥1 was higher than A/TL≥1.ConclusionsA/TC≥1 found by ultrasound contributes to differentiate the thyroid carcinoma from benign nodules.For a large thyroid lesion,other indicators are needed to diagnose thyroid carcinoma.

Objective To discuss the imaging features of parietal bones atrophy,and to improve the understanding of this disease. Methods Clinical and imaging data of 8 patients with parietal bones atrophy were analyzed retrospectively.Age ranged 66-90 years with median age 76 years.CT scans were performed in all cases,and CT enhanced examination in 1 case.MRI examination were performed in 3 cases,in which MRI enhanced examination in 2 cases.Imaging characteristics were analyzed along with a review of the current literature.Results Bilateral parietal sympathetic involvements were found in 4 cases,unilateral parietal involvement in 4 cases,in which the left parietal bone was found in 2 cases and the right side in other 2 cases.The lesions ranged from 2.4 cm to 7.1 cm.On CT and MRI images,the external table of the parietal bones showed symmetrical impression,the diploe revealed thinner and the inner table was intact,which presented"Step change".Two of these patients were followed up,in which 1 case become severe atrophy,and the other case was no significant change.Nothing was showed in the relative scalp and soft tissue.Conclusion According to different degrees of thinning of parietal bones,combined with specific age,symmetrical parietal bone impression should be considered.

Clinical data from 11 previously diagnosed and treated patients with hyperthyroidism(Graves′ disease) complicated by liver failure were collected. Among them, 4 cases were drug-induced liver injury leading to liver failure, 1 case had a history of schistosomal liver cirrhosis combined with hyperthyroidism, and 6 cases had hyperthyroidism-induced liver injury(HILI) leading to liver failure. During hospitalization, all patients received supportive therapy and symptomatic treatment with β-blockers. Nine patients were treated with glucocorticoids and artificial liver support therapy. Among the 11 patients, 2 died, 8 patients achieved normal thyroid and liver function within 1-12 months after treatment, and 1 patient with liver cirrhosis had stable liver function in the later stage. After improvement in liver function, 7 patients received isotope therapy, 1 patient underwent total thyroidectomy, and 1 patient received medication. These results indicate that the clinical characteristics differ for drug-induced liver injury and HILI-related liver failure. Early initiation of artificial liver support therapy, in addition to β-blockers and glucocorticoids, is important in alleviating thyroid toxicity and liver damage, thus creating an opportunity for subsequent radioactive iodine or surgical treatment.

With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Objective:To analyze the characteristics of lung function in patients with spinal muscular atrophy (SMA) to provide evidence for multidisciplinary management of SMA.Methods:A total of 30 patients with SMA treated in the SMA multidisciplinary clinic of the Children′s Hospital, Zhejiang University School of Medicine from July 2019 to March 2021 were enrolled, including 1 child with type I, 18 patients with type Ⅱ and 11 children with type Ⅲ.There were 17 males and 13 females; the age ranged from 4 years to 21 years and 10 months old.A retrospective study was conducted to analyze the clinical features, spinal imaging findings and lung functions of patients with different clinical types of SMA and explore the factors influencing the lung functions of patients with SMA.Pulmonary function was measured by forced expiratory flow-volume curve.Forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), FEV 1/FVC and peak expiratory flow (PEF) were measured.The results were expressed as the percentage of the measured value to predicted value.The Cobb angle was measured to evaluate scoliosis. Pearson correlation analysis and multiple linear regression analysis were used to evaluate the relationship between lung function and age and Cobb angle in patients with type Ⅱ SMA. Pearson correlation analysis and univariate linear regression analysis were used to evaluate the relationship between Cobb angle and age in patients with type Ⅱ SMA. Results:Pulmonary function in 1 type I patient showed decreased FVC and FEV 1; Among 18 patients with type Ⅱ, 14 cases had abnormal lung function (77.8%): FVC decreased in 12 patients (66.7%), FEV 1 decreased in 10 patients (55.6%), PEF decreased in 12 patients (66.7%). Among 11 patients with type Ⅲ, one had decreased FVC (9.1%). FVC, FEV 1 and PEF of patients with type Ⅱ were significantly lower than those of patients with type Ⅲ [(62.4±31.8)% vs.(90.8±11.0)%, (66.3±33.3)% vs.(97.8±9.9)%, (65.3±30.1)% vs.(98.6±21.1)%, all P<0.01]. Pearson correlation analysis showed that FVC of patients with type Ⅱ SMA was correlated with age and Cobb angle ( r=-0.864, -0.865, all P<0.001), FEV 1 was correlated with age and Cobb angle ( r=-0.878, -0.863, all P<0.001), PEF was correlated with age and Cobb angle ( r=-0.831, -0.783, all P<0.001), and Cobb angle was related to age ( r=0.922, P<0.001). Multiple linear regression analysis indicated that FVC of patients with type Ⅱ SMA was linearly correlated with Cobb angle ( R2=0.748, P<0.001), FEV 1 was linearly correlated with age ( R2=0.770, P<0.001), PEF was linearly related to age ( R2=0.690, P<0.001). Univariate linear regression analysis revealed that Cobb angle of patients with type Ⅱ SMA was linearly related to age ( R2=0.851, P<0.001). Conclusions:FVC, FEV 1 and PEF may decrease in patients with SMA.The degree of lung function damage is different in different types of SMA patients.With the increase of age, Cobb angle increases and FVC, FEV 1 and PEF decrease in patients with type Ⅱ SMA.Understanding the factors influencing the pulmonary function damage in patients with SMA is conductive to carrying out individual multidisciplinary management.

OBJECTIVES: The high morbidity and mortality of colorectal cancer (CRC) have posed great threats to human health. Circular RNA (circRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been found to play vital roles in carcinogenesis. This paper aims to construct a circRNA/miRNA/mRNA regulatory network so as to explore the molecular mechanism of CRC. METHODS: The sequencing data of circRNA from CRC were obtained from Gene Expression Omnibus (GEO). The differential circRNA was screened and its structure was identified by Cancer-specific CircRNA Database (CSCD); the sequencing data of miRNA and messenger RNA (mRNAs) were downloaded from The Cancer Genome Atlas (TCGA) database and the differentially expressed genes were screened; the corresponding miRNA of differential circRNAs were predicted by CircInteractome database; DIANA, Miranda, PicTar, and TargetScan databases were used to predict the target genes of different miRNAs; the target genes from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched by R language; String database combined with Cytoscape 3.7.2 software was used to construct protein-protein interaction (PPI) network and hub genes were screened; the expressions of mRNAs in the Top10 hub genes were verified in CRC. The network diagrams of circRNAs/miRNAs/mRNAs and circRNAs/miRNAs/Top10 hub mRNAs were constructed by Cytoscape3.7.2. Real-time PCR was used to examine the expression levels of hsa_circRNA_0065173, hsa-mir-450b, hsa-mir-582, adenylate cyclase 5 (ADCY5), muscarinic acetylcholine receptor M2 (CHRM2), cannabinoid receptor 1 (CNR1), and lysophosphatidic acid receptor 1 (LPAR1) in the CRC tissues and the adjacent normal tissues. RESULTS: A total of 14 differential circRNAs were identified, and 8 were found in CSCD; 34 miRNAs targeted by circRNAs were obtained. The PPI network was constructed, and the Top10 hub genes were identified, which were CHRM2, melanin concentrating hormone receptor 2 (MCHR2), G-protein gamma 3 subunit (GNG3), neuropeptide Y receptor Y1 (NPY1R), CNR1, LPAR1, ADCY5, adenylate cyclase 2 (ADCY2), gamma 7 (GNG7) and chemokine 12 (CXCL12), respectively. The expressions of Top 10 hub genes were also verified, and the results showed that the Top 10 hub genes were down-regulated in CRC; the constructed network diagram showed that hsa_circRNA_0065173 may regulate ADCY5, CHRM2, and Hsa-mir-450b by modulating hsa-mir-450b and hsa-mir-582. CNR1 and LPAR1 genes might serve as potentially relevant targets for the treatment of CRC. Real-time PCR results showed that the expression levels of hsa_circRNA_0065173, ADCY5, CHRM2, CNR1 and LPAR1 in the CRC tissues were significantly reduced compared with the adjacent normal tissues (all P<0.05); the expression levels of hsa-mir-450b and hsa-miR-582 were significantly increased (both P<0.05). CONCLUSIONS In this study, a potential circRNAs/miRNAs/mRNAs network is successfully constructed, which provides a new insight for CRC development mechanism through ceRNA mediated by circRNAs.
Colorectal Neoplasms/genetics* ; Computational Biology/methods* ; Gene Regulatory Networks ; Humans ; MicroRNAs/genetics* ; RNA, Circular/genetics* ; RNA, Messenger/genetics*

Transcriptional regulation is crucial for regulated gene expression. Due to the complexity, it has been difficult to engineer eukaryotic transcription factor (TF) and promoter pairs. The few availabilities of eukaryotic TF and promotor pairs limit their practical use for clinical or industrial applications. Here, we report a de novo construction of synthetic inhibitory transcription factor and promoter pairs for mammalian transcriptional regulation. The design of synthetic TF was based on the fusion of DNA binding domain and Kruppel associated box transcription regulating domain (KRAB). The synthetic promoter was constructed by inserting the corresponding TF response element after SV40 promoter. We constructed and tested five synthetic inhibitory transcription factor and promoter pairs in cultured mammalian cells. The inhibition capability and orthogonality were verified by flow cytometry. In summary, we demonstrate the feasibility of constructing mammalian inhibitory TF and promoter pairs, which could be standardized for advanced gene-circuit design and various applications in the mammalian synthetic biology.
Animals ; Gene Expression Regulation ; Gene Regulatory Networks ; Mammals ; Promoter Regions, Genetic ; Transcription Factors ; Transcription, Genetic

OBJECTIVE: To observe the clinical characteristics of mild and common COVID-19 patients infected with the Omicron variant, and to analyze related factors affecting the time to negative conversion of viral nucleic acid detection. METHODS: Clinical data of 1781 patients with coronavirus disease 2019 (COVID-19) admitted to a cabin hospital in Shanghai from April 12 to May 26, 2022, were retrospectively analyzed, including age, gender, height, weight, clinical symptoms, comorbid diseases, COVID-19 vaccination, treatment, and nucleic acid negative conversion time. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of nucleic acid negative conversion time. RESULTS: Among the 1781 patients, 995 were male and 786 were female, with a median age of 39 (30, 52) years. There were 727 patients (40.8%) with overweight and obesity [body mass index (BMI) > 24 kg/cm ²) and 413 patients (23.2%) had comorbid diseases. 205 cases (11.5%) were not vaccinated while 1576 cases were vaccinated. There were 1233 cases (69.2%) with one or more symptoms. The main clinical symptoms were cough (60.3%), expectoration (50.4%) and fever (36.9%). 1444 cases (81.0%) were treated with Chinese medicine, 78 cases (4.4%) were treated with western medicine, 14 cases (0.8%) were treated with integrated Chinese and western medicine, and 245 cases (13.8%) did not receive any medical treatment. All patients improved and were discharged. The median nucleic acid negative conversion time was 10.3 (7.4, 12.4) d. Univariate and multivariate analysis showed that, age ≥ 60 years ( OR＝1.537, 95% CI: 1.116 - 2.115, P<0.01), BMI > 24 kg/cm ² ( OR＝1.344, 95% CI: 1.106 - 1.634, P<0.01 ) and hypertension ( OR＝1.518, 95% CI: 1.094 - 2.106, P<0.05) were independent risk factors for prolonged nucleic acid negative conversion. COVID-19 vaccination ( OR=0.548, 95% CI: 0.398 - 0.755, P<0.01) was a protective factor, that is, vaccination shortened the time for the nucleic acid test to become negative. CONCLUSIONS The symptoms of the Omicron variant infection were relatively mild and occult. Age ≥ 60 years old, comorbid hypertension, no vaccination and BMI > 24 kg/cm ² are independent influencing factors for prolonged nucleic acid negative conversion.
Humans ; Female ; Male ; Middle Aged ; SARS-CoV-2 ; COVID-19/epidemiology* ; COVID-19 Vaccines ; Retrospective Studies ; China ; Hypertension/epidemiology* ; Nucleic Acids

OBJECTIVES: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). METHODS: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. RESULTS: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. CONCLUSIONS Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.
Male ; Female ; Humans ; Child ; Albuterol/therapeutic use* ; Prospective Studies ; Muscular Atrophy, Spinal/drug therapy* ; Spinal Muscular Atrophies of Childhood/drug therapy* ; Treatment Outcome