Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

OBJECTIVE：To study the anti- inflammatory effect and mechanism of Jingulian capsule on inflammatory model rats. METHODS ：Totally 48 rats were randomly divided into blank control group ，model group ，Jingulian capsule low-dose ， medium-dose and high-dose groups （0.66，1.32，2.64 g/kg），dexamethasone group （positive control ，0.945 mg/kg），with 8 rats in each group. Blank control group and model group were given constant volume of water intragastrically ，and other groups were given relevant medicine intragastrocally ，twice a day ，for consecutive 3 days. Thirty minutes after last administration ，model group and administration groups were given lipopolysaccharide （10 mg/kg）intraperitoneally to induce inflammatory model. Six hours after intraperitoneal injection ，the contents of TNF-α，IL-1β，IL-6，PGE2 in serum were detected by ELISA. The wet to dry weight （W/D）ratio of lung tissue were determined. HE staining was used to observe the pathological changes of lung tissue . RT-PCR was used to detect the mRNA expression of TNF-α，IL-6，PGE2 and IL- 1β in lung tissue. Western blot assay was used to detect the phosphorylation of NF-κB p65 protein and the expression of IκBα protein in lung tissue. RESULTS：Compared with blank ； control group ，the contents of TNF-α，IL-1β，IL-6 and PGE 2 in serum ，the W/D ratio of lung tissue ，the expression of TNF-α，IL-1β，IL-6 and PGE 2 mRNA and the phosphorylation level of NF-κB p65 protein in lung tissue of model group weresignificantly increased ，and the expression of IκBα proteinwas significantly decreased （P＜0.05 or P＜0.01）；a large number of alveolar atrophy and collapse ，alveolar wall thickening ，lung consolidation ，and a large number of inflammatory cell infiltration could be seen in lung tissue. Compared with model group ，the contents of TNF-α，IL-1β（except for low-dose group ）， IL-6 and PGE 2 in serum ，as well as the expression of TNF-α（except for high-dose group ），IL-1β，IL-6（except for low-dose ， high-dose groups ）and PGE 2 mRNA in lung tissue were decreased significantly in Jingulian capsule groups （P＜0.05 or P＜0.01）； the W/D ratio of lung tissue was decreased significantly in Jingulian high-dose group （P＜0.05 or P＜0.01）；the expression of phosphorylation level of NF-κB p65 protein in lung tissue of Jingulian medium-dose group were decreased significantly （P＜0.05 or P＜0.01），while the expression of IκBα protein was increased significantly（P＜0.05）；the alveolar structure was clear ，the alveolar wall was slightly thickened ， and a small amount of inflammatory cell infiltration was seen in lung tissue. CONCLUSIONS：Jingulian capsule has good anti-inflammatory effect on inflammatory model rats ，the mechanism of which may be related to the inhibition of NF-κB signal pathway.

Objective:To explore the performance of the commonly used whole blood C-reactive protein (CRP) detection systems and give related recommendation on the performance requirements of detection systems.Methods:A total of 7 540 venous blood samples from 26 maternal, child and children′s hospitals were collected to conduct this multi-center study on the analytical performance of 5 commonly used whole blood CRP detection systems from March to April in 2019. The blank check, carryover, repeatability, intermediate precision, linearity, sample stability, influence of hematocrit/triglyceride/bilirubin, comparison with SIEMENS specific protein analyzer and trueness were evaluated. The 5 systems included BC-5390CRP autohematology analyzer, AstepPLUS specific protein analyzer, Ottoman-1000 Automated Specific Protein POCT Workstation, i-CHROMA Immunofluorometer equipment Reader and Orion QuikRead go detecting instrument. The 5 systems were labeled as a, b, c, d and e randomly.Results:Within the 5 systems, all values of blank check were less than 1.00 mg/L, the carryovers were lower than 1.00%. The repeatability of different ranges of CRP concentrations including 3.00-10.00, 10.00-30.00 and>30.00 mg/L were less than 10.00%, 6.00% and 5.00%, respectively, and the intermediate precision was less than 10.00%. The linearity correlation coefficients of the 5 systems were all above 0.975, while the slope was within 0.950-1.050. Whole blood samples were stable within 72 hours both at room temperature (18-25 ℃) and refrigerated temperature (2-8 ℃). The CRP results were rarely influenced by high triglyceride or bilirubin, except for the immmunoturbidimetric test based on microparticles coated with anti-human CRP F(ab) 2 fragments. When triglyceride was less than 15.46 mmol/L, the deviation of CRP was less than 10.00%. When bilirubin was less than 345.47 μmol/L, the deviation of CRP was less than 10.00%. CRP was more susceptible to Hct on the systems without Hct correction. The deviation of CRP between different Hct dilution concentration and 40% dilution concentration can reach as high as 67.48%. The correlation coefficients ( r) of 5 systems were all more than 0.975 in the range of 0-300.00 mg/L compared with Siemens specific protein analyzer. All systems passed the trueness verification using the samples with specified values of 12.89 and 30.60 mg/L. Conclusion:The performance of 5 systems can basically meet the clinical needs, but it is suggested that the whole blood CRP detection system without automatic Hct correction should be modified manually.

The occurrence and progression of thyroid cancer are related to a series of molecular changes and the activation of signaling pathways, which is the basis of targeted therapy. For inoperable locally advanced, metastatic and refractory thyroid cancer, especially anaplastic thyroid cancer, the efficacy of targeted therapies, particularly tyrosine kinase inhibitors (TKIs) , has been demonstrated in clinical trials. TKIs can relieve clinical symptoms, improve patients’quality of life, prolong the progress free survival, and even create opportunities for radical operation or reoperation. This article reviews and summarizes the key molecular events in tumorigenesis and progression of thyroid cancer, and analyzes the results of clinical studies on the efficacy and safety of different TKIs in refractory advanced thyroid cancer, in order to provide reference and assistance for individualized targeted therapy of patients.

Objective:To investigate the clinical efficacy of laparoscopic sleeve gastrec-tomy (LSG) in the treatment of obesity associated nonalcoholic fatty liver disease (NAFLD).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with obesity associated NAFLD who were admitted to Xijing Hospital of Digestive Diseases of Air Force Medical University from January 2018 to June 2019 were collected. There were 19 males and 21 females, aged (27±8)years. Patients underwent LSG after preoperative examinations and evaluations. Observation indicators: (1) surgical and postoperative conditions; (2) follow-up. Follow-up was conducted by telephone interview, WeChat, and outpatient review to detect the liver function, glucose and lipid metabolism-related status as well as the relief of comorbidities of patients at 6 and 12 months after LSG. The follow-up was up to June 2020. Measurement data with normal distribu-tion were represented as Mean± SD. Repeated measurement data were analyzed by the repeated measures ANOVA. Count data were represented as absolute numbers, and chi-square test was used for comparison between groups. Results:(1) Surgical and postoperative conditions: 40 patients underwent LSG successfully, without intraoperative conversion to laparotomy or death. The operation time, volume of intraoperative blood loss, and duration of postoperative hospital stay were (83±12)minutes, (19±7)mL and (3.7±0.7)days. Among the 40 patients, 1 case had fat liquefac-tion after LSG and 2 had abdominal distension within a month, who were improved after symp-tomatic and supportive treatment. (2) Follow-up: 40 patients were followed up at postoperative 6 and 12 months. The body mass of 40 patients was (112±17)kg, (85±16)kg, (73±11)kg before operation, at postoperative 6 and 12 months, respectively. The body mass index was (39.7±4.2)kg/m 2, (30.0±4.5)kg/m 2, (25.9±2.9)kg/m 2 before operation, at postoperative 6 and 12 months, respectively. The alanine aminotransferase was (56.40±39.51)U/L, (30.15±17.93)U/L, (26.45±9.44)U/L before operation, at postoperative 6 and 12 months, respectively. The aspartate amino-transferase was (34.03±19.62)U/L, (28.20±10.27)U/L, (24.90±8.44)U/L before operation, at post-operative 6 and 12 months, respectively. The gamma-glutamyltransferase was (48.68±28.45)U/L, (43.30±18.56)U/L, (32.80±12.09)U/L before operation, at postoperative 6 and 12 months, respectively. The fasting blood-glucose was (6.51±2.38)mmol/L, (5.64±1.51)mmol/L, (4.98±0.91)mmol/L before operation, at postoperative 6 and 12 months, respectively. The triglyceride was (1.81±0.95)mmol/L, (1.48±0.57)mmol/L, (1.17±0.44)mmol/L before operation, at postoperative 6 and 12 months, respectively. The total cholesterol was (4.77±0.98)mmol/L, (4.58±0.75)mmol/L, (4.10±0.68)mmol/L before operation, at postoperative 6 and 12 months, respectively. The low density lipoprotein cholesterin was (2.99±0.81)mmol/L, (2.79±0.54)mmol/L, (2.48±0.40)mmol/L before operation, at postopera-tive 6 and 12 months, respectively. The high density lipoprotein cholesterin increased was (1.08±0.20)mmol/L, (1.15±0.18)mmol/L, (1.45±0.21)mmol/L before operation, at postoperative 6 and 12 months, respectively. Compared with preoperative indicators, there were significant differences in postoperative body mass, body mass index, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, fasting blood-glucose, triglyceride, total cholesterol and low density lipoprotein cholesterin ( F=472.439, 533.730, 26.791, 11.029, 25.545, 27.994, 27.534, 36.220, 18.596, P<0.05), showing a downward trend. There was a significant difference between preoperative and postoperative high density lipoprotein cholesterin ( F=68.974, P<0.05), showing a upward trend. The excess weight loss of 40 patients at 6 months and 12 months after LSG were 61%±18% and 85%±15%. The preoperative ultrasonography of 40 patients showed no, mild, moderate and severe fatty liver in 0, 2, 15 and 23 cases, respectively. The above indicators were 8, 9, 12, 11 cases at post-operative 6 months, and 23, 11, 6, 0 cases at postoperative 12 months, respectively. There was a significant difference of the grade of NAFLD between patients before and after surgery ( χ2=68.210, P<0.05). Conclusion:LSG has an accurate short-term clinical efficacy for obesity associated NAFLD, which can reduce body mass, improve liver function, alleviat the disorders of glucose and lipid metabolism and the severity of medium-severe fatty liver.

The studies on infectiousness of person infected with SARS-CoV-2 at different stages of illness are an important basis for making effective prevention and control measures such as investigating the infectious source, determining the scope of close contacts and the timing of case isolation. This review discusses the infectiousness of cases infected with SARS-CoV-2 in the incubation period, symptomatic period and convalescent period by reviewing national and international literatures, technical and professional guidelines. Existing researches suggest that the infectious viruses could be isolated at the end of the incubation period as well as since illness onset, and viral load in upper respiratory tract swabs reached the peak on day 4-6 after illness onset and thereafter began to decline, implying the infectiousness was relatively strong at the end of incubation period and within one week after illness onset. Although there were a few cases who tested positive for SARS-CoV-2 after recovery, no evidence was found to indicate these cases can cause the transmission.

Objective:To compare the efficacies of MRI, X-ray mammography (XMG) and Ultrasound (US) in detecting and diagnosing breast ductal carcinoma in situ (DCIS).Methods:Two hundred and forty one consecutive patients with pathology-confirmed DCIS were retrospectively recruited from January 2011 to December 2017 in PLA General Hospital. The imaging examination modalities included MRI and/or XMG and/or US.The breast imaging reporting and data system (BI-RADS) categorizations by MRI, XMG and US were compared and their sensitivities of detecting DCIS were calculated. The causes of underestimation on MRI were interpreted with the information of XMG and US. Chi-square test was used to compare the differences.Results:The diagnostic sensitivity of XMG, US and MRI was 65.9% (29/44), 71.6% (101/141) and 91.2% (145/159), respectively, with statistical significant differences (χ2 =24.034, P<0.001). Breast density and lesion type would influence the sensitivity of XMG. And the sensitivity of US was decreased because of non-mass lesion. Of the 14 cases under-evaluated as BI-RADS category 1 to 3 on MRI, 5 were corrected by XMG and/or US to BI-RADS category 4. The cause of underestimation on MRI was the coexistence of DCIS with adenoma or other benign lesion. Conclusion:The retrospective comparison of MRI, XMG and US in this study showed that MRI had significant higher sensitivity in detecting breast DCIS, while the false negative rates of XMG and US were un-negligible.

Objective:To summarize the surgical treatment of malignant carotid body tumor (MCBT).Methods:A retrospective analysis of 14 MCBT patients admitted at our hospital from Mar 2005 to Nov 2019 was made, and the imaging data, surgical records, perioperative complications and follow-up data were collected.Results:There were 8 males and 6 females, with an average age of (40.8±11.3) years. 10 patients underwent surgical resection of CBT, with one case undergoing tumor enucleation only, nine cases underwent internal carotid artery reconstruction, and all patients underwent intraoperative lymph node biopsy.Tumors were completely removed in all 10 patients. No perioperative death or cerebral infarction occurred. The intraoperative blood loss was (955±658.5) ml. Four patients had permanent nerve injury after surgery. The follow-up time ranged 1-132 months. There were no cases of cerebral infarction or death, and the reconstructed graft remained patent. Apart from the 2 patients who developed tumor metastasis after surgery, other patients recovered uneventfully with no disease progression.Conclusions:Surgery is still the main treatment for MCBT, but MCBT is large and Shamblin class is more advanced. Therefore, complete tumor removal and reconstruction of the carotid arteries are difficult. Surgery should seek to completely remove the tumor and neck lymph node biopsy should be performed to determine the lymph node metastasis.

Objective:To compare the accuracy of influenza-like illness (ILI) surveillance by automatic computer analysis based on electronic medical records and by doctor’s report.Methods:A total of 3 542 patients who presented to Yichang Central Hospital fever clinic, respiratory department or emergency department between April to October 2019 with an ICD-10 code for acute respiratory illness (J00-J22) and complete electronic medical information of ILI related syndromes were drawn as the study sample. Taking the classification of the study sample according to the ILI case definition by influenza surveillance professionals as the gold standard, draw the receiver operating characteristic (ROC) curve and calculate sensitivity, specificity, diagnostic consistency to compared the accuracy of ILI surveillance by automatic computer analysis and by doctor's report.Results:Median age of 3 542 cases was 30 (24, 38) years old; 1 179 cases (33.29%) compliance with the case definition, ILI reported by doctors was 1 306 cases (36.87%), and computer automatic identification ILI were 1 150 cases (32.47%); 1 391 (39.27%) cases were men. The results of automatic computer analysis and doctor report consistency of kappa values with gold standard judgment were 0.97 and 0.66 respectively; area under the ROC curve was 0.98 and 0.84, respectively. And the sensitivity and specificity of automatic computer analysis were higher than that of doctor's report (all P values were <0.001), the sensitivity was 96.95% and 82.27%, and the specificity was 99.70% and 85.78%, respectively. Conclusion:The automatic computer analysis based on electronic medical records can identified ILI cases with good sensitivity and specificity in ILI case surveillance.

Objective:To compare the accuracy of influenza-like illness (ILI) surveillance by automatic computer analysis based on electronic medical records and by doctor’s report.Methods:A total of 3 542 patients who presented to Yichang Central Hospital fever clinic, respiratory department or emergency department between April to October 2019 with an ICD-10 code for acute respiratory illness (J00-J22) and complete electronic medical information of ILI related syndromes were drawn as the study sample. Taking the classification of the study sample according to the ILI case definition by influenza surveillance professionals as the gold standard, draw the receiver operating characteristic (ROC) curve and calculate sensitivity, specificity, diagnostic consistency to compared the accuracy of ILI surveillance by automatic computer analysis and by doctor's report.Results:Median age of 3 542 cases was 30 (24, 38) years old; 1 179 cases (33.29%) compliance with the case definition, ILI reported by doctors was 1 306 cases (36.87%), and computer automatic identification ILI were 1 150 cases (32.47%); 1 391 (39.27%) cases were men. The results of automatic computer analysis and doctor report consistency of kappa values with gold standard judgment were 0.97 and 0.66 respectively; area under the ROC curve was 0.98 and 0.84, respectively. And the sensitivity and specificity of automatic computer analysis were higher than that of doctor's report (all P values were <0.001), the sensitivity was 96.95% and 82.27%, and the specificity was 99.70% and 85.78%, respectively. Conclusion:The automatic computer analysis based on electronic medical records can identified ILI cases with good sensitivity and specificity in ILI case surveillance.