Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective:To analyze the epidemic characteristics of reported tuberculosis incidence in Kashgar from 2015 to 2022, and use the seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence, providing references for the local control of pulmonary tuberculosis.Methods:The reported incidence data of tuberculosis in the Kashgar area of Xinjiang from January 2015 to August 2023 were collected through the"Infectious Disease Monitoring System", a subsystem of the "Chinese Disease Prevention and Control Information System". The epidemic characteristics of reported incidence in this area from 2015 to 2022 were analyzed. Two SARIMA models of monthly reported incidence number and rate were established. The prediction performance of the two models was evaluated using the reported incidence data of tuberculosis from January 2023 to August 2023. The χ2 test was used to analyze population characteristics, and the Cochran-Armitage trend test was used to analyze annual incidence. Results:From 2015 to 2022, 133 972 cases of pulmonary tuberculosis were reported in Kashgar, with a yearly reported incidence rate of 383.64/100 000, showing a rising trend ( TCA=77.03, P<0.001) and then a declining trend ( TCA=176.16, P<0.001). The proportion of pathogenic positive pulmonary tuberculosis had increased yearly ( TCA=132.66, P<0.001). The reported onset time was concentrated from January to June each year, with a peak in April. Yengisar County, Zepu County and Yopurga County had the highest reported incidence rate in Kashgar. The sex ratio of men to women was 1.03∶1, and the reported incidence rate of men was higher than that of women ( χ2=27.04, P<0.001). The reported incidence rate of the group aged 60 years and older was the highest. The patient′s occupation was mainly farmers (84.99%). The average relative errors of the SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model in predicting the reported monthly incidence number and rate were 11.67% and -9.81%, respectively. Both models had good prediction accuracy (MAPE=33.55%, MAPE=38.22%). Conclusion:The average reported incidence rate of pulmonary tuberculosis in the Kashgar area shows a rising trend first and then a declining trend. The patients are mainly men and farmers, and attention should be paid to the prevention and control of tuberculosis among the elderly in winter and spring. The SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model can fit the trend of reported tuberculosis incidence in the Kashgar area well and have good predictive performance.

Objective:To analyze the epidemic characteristics of reported tuberculosis incidence in Kashgar from 2015 to 2022, and use the seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence, providing references for the local control of pulmonary tuberculosis.Methods:The reported incidence data of tuberculosis in the Kashgar area of Xinjiang from January 2015 to August 2023 were collected through the"Infectious Disease Monitoring System", a subsystem of the "Chinese Disease Prevention and Control Information System". The epidemic characteristics of reported incidence in this area from 2015 to 2022 were analyzed. Two SARIMA models of monthly reported incidence number and rate were established. The prediction performance of the two models was evaluated using the reported incidence data of tuberculosis from January 2023 to August 2023. The χ2 test was used to analyze population characteristics, and the Cochran-Armitage trend test was used to analyze annual incidence. Results:From 2015 to 2022, 133 972 cases of pulmonary tuberculosis were reported in Kashgar, with a yearly reported incidence rate of 383.64/100 000, showing a rising trend ( TCA=77.03, P<0.001) and then a declining trend ( TCA=176.16, P<0.001). The proportion of pathogenic positive pulmonary tuberculosis had increased yearly ( TCA=132.66, P<0.001). The reported onset time was concentrated from January to June each year, with a peak in April. Yengisar County, Zepu County and Yopurga County had the highest reported incidence rate in Kashgar. The sex ratio of men to women was 1.03∶1, and the reported incidence rate of men was higher than that of women ( χ2=27.04, P<0.001). The reported incidence rate of the group aged 60 years and older was the highest. The patient′s occupation was mainly farmers (84.99%). The average relative errors of the SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model in predicting the reported monthly incidence number and rate were 11.67% and -9.81%, respectively. Both models had good prediction accuracy (MAPE=33.55%, MAPE=38.22%). Conclusion:The average reported incidence rate of pulmonary tuberculosis in the Kashgar area shows a rising trend first and then a declining trend. The patients are mainly men and farmers, and attention should be paid to the prevention and control of tuberculosis among the elderly in winter and spring. The SARIMA ( 1, 1, 2) ( 0, 1, 1) 12 model and SARIMA ( 0, 1, 1)( 0, 1, 1) 12 model can fit the trend of reported tuberculosis incidence in the Kashgar area well and have good predictive performance.

The purpose of this paper is to review the research on the influence and mechanism of intolerance of uncertainty （IU） on anxiety both at home and abroad in recent years. IU refers to the individual's disgust response due to the intolerance of perceived lack of prominent， critical or sufficient information， and it has individual tendency. IU plays an important role in the occurrence and development of anxiety， but the specific process and mechanism remain unclear. This paper reviews the influence of IU on anxiety， and clarifies its mechanism of action on the generation and development of anxiety from the perspectives of cognition， emotion and behavior， so as to provide references for preventing the development of general anxiety into anxiety disorders and developing new psychological intervention and treatment strategies.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective To observe the clinical characteristics of 2 patients with mucolipidosis type Ⅲ. Methods Two sibling patients (a sister and a brother) with mucolipidosis type Ⅲ symptoms and other family members were the research objects, and the changes of their features of hand bone imaging, blood indexes [blood glucose, cholesterol, triacylglycerol (TG), total protein (TP), albumin (Alb)] and body composition were analyzed. Results Except the 2 patients, the bone morphology, blood indexes and body compositions in other 7 family members were under normal conditions. The phalanx intervals of both hands in 2 patients with mucolipidosis type Ⅲwere widened significantly, among them the thumb manifestation was more obvious; the distal segments of phalanxes in both hands became pointed and curved presenting a "claw-like hand" deformity; the metacarpal and distal carpal metaphysis were obviously enlarged, and scaphoid, lunate, trianglar, orbicular, and trapezium and trapezoid bones were loosely arranged at the wrist; the distal ends of ulna and radius were markedly enlarged. Compared to healthy people, the triglyceride levels of serum in the 2 patients were obviously reduced (the percentage of reduction: 57.14% and 41.07% respectively); body mass indexes (BMI), total fat and visceral fat were significantly lowered (BMI reduction percentage:26.81% and 14.55%, total fat reduction percentage: 38.12% and 44.95%, visceral fat reduction percentage: 62.25% and 67.74%, respectively) in the two patients. Conclusion The purpose of studying the biochemistry indexes, imaging characteristics and body compositions is to more deeply understand the clinical symptoms and signs of the 2 sibling patients with mucolipidosis type Ⅲ in a family to provide a theoretical reference.

Objective To compare the characteristics of connective tissue disease-associated interstitial lung disease (CTD-ILD) and idiopathic pulmonary fibrosis(IPF). Methods Patients with a diagnosis of ILD from June 2014 to December 2015 were selected in this study and patients with known other causes of ILD were excluded. The clinical manifestation, autoantibody, high resolution chest computed tomography (CT) and blood gas analysis were retrospectively analyzed. Results Six hundred and twenty-eight patients were included in this study. The prevalence of CTD-ILD and IPF were 459 (73.09%) and 169(26.91%) respectively. The age in IPF group was higher than that in CTD-ILD group:(67.10 ± 13.13) years vs. (52.10 ± 14.23) years, and there was significant difference (t =-10.092, P =0.000). The rate of male in IPF group was higher than that in CTD-ILD group: 75.15%(127/169) vs. 28.32%(130/459), and there was significant difference (P=0.000). Autoantibodies were commonly seen in CTD-ILD group and only antinuclear antibody, and anti-SSA antibody and anti-Ro-52 antibody were seen in IPF group. The most common chest images were honeycombing, bullae of lung and pneumonectasis in CTD-ILD group, while the presence of consolidation and small nodular shadow were more common in IPF group. The concurrence of respiratory failure was higher in IPF group compared with that in CTD-ILD group:49.11%(83/169) vs. 13.07%(60/459), and there was significant difference (P<0.01). Conclusions Patients with CTD-ILD and IPF possess distinct characteristics. Overall assessment of clinical manifestation, autoantibody serology, high resolution chest CT and other indicator will be conducive to the differential diagnosis and treatment of ILD.

Objective To prospectively evaluate the efficacy and safety of Computed Tomography (CT)-guided microcoil localization for pulmonary small solid nodules and ground-glass opacity prior to thoracoscopic resection.And to investigate the indication for CT-guided microcoil localization for small solid pulmonary nodules and ground-glass opacity.Methods From December 2012 to February 2014,85 enrolled patients with pulmonary solid nodules and ground-glass opacity underwent CT guided microcoil localization prior to video assisted thoracoscopic surgery.The procedures of localization were performed by trailing method or routine method under CT guided percutaneous pneumocentesis.For Trailing method,the microcoil was placed with the distal part coiled adjacent to the lesion and the proximal end coiled beyond the parietal pleura.By routine method,the entire microcoil was injected adjacent to the lesion.Results CT-guided microcoil placements were successful in all ninety-one lesions,including 15 solid nodules,15 mixed ground glass opacity,and 61 pure ground glass opacity,with an average diameter of 8.75mm(5-26 mm).The Complication rate of the localization procedure was 23.5％ (20/91),with 13 cases of asymptomatic pneumothorax,and 7 cases of pulmonary hematoma.None patient required surgical intervention,nor severe Complication occurred.All patients underwent video assisted thorascopic surgery on the same day or the next few days after microcoil localization.VATS removal of the pulmonary lesions was successful in all patients.However,two of 91 microcoils were found displaced during VATS resection.The success rate of microcoil marking VATS resection for pulmonary small solid nodules and ground-glass opacity was 97.8％.Microcoil marking was required for 84.6 percent of all the resected lesions.Conclusion Preoperatively CT-guided microcoil localization for pulmonary small solid nodules and ground-glass opacity is a feasible safe and effective marking technique for video assisted thoracoscopic resection.The indication for microcoil localization in our study meet the requirement of VATS resection.

Objective To study the variation characteristics of peripheral blood β-catenin and DKK1 levels in patients with rheumatoid arthritis (RA) and the correlation with bone and joint damage.Methods One hundred and eight patients with RA (observation group) and 110 healthy individuals (control group) were selected.The bone mineral density(B MD) in the femur (femur neck,Ward area,greater trochanter,total femur area) and lumbar spine (L2,3,4) were measured by dual-energy X-ray absorptiometry instrument.X-ray for two hands were evaluated according to the Sharp score.The peripheral blood β-catenin and DKK1 levels were detected by enzyme-linked immunosorbent assay (ELISA).Multiple analysis was completed by multiple linear regression and Logistic regression.Results The peripheral blood DKK1 level in observation group was significantly higher than that in control group [(8.2 ±5.0) mg/L vs.(6.1 ±4.2)mg/L],there was statistical difference (t =2.452,P =0.025),but there was no statistical difference in β-catenin level between the 2 groups (t =15.947,P =0.142).Compared to control group,patients with RA had lower BMD at femur and lumbar spine (P ＜ 0.01).The incidence of osteoporosis in observation group was significantly higher than that in control group [31.5％ (34/108) vs.15.5％ (17/110)],there was statistical difference (x2 =9.289,P =0.005).The correlation analysis results showed that the peripheral blood DKK1 was positive correlation with erythrocyte sedimentation rate (ESR),28-jonit disease activity score (DAS28),alkaline phosphatase (AKP) and two hands X-ray joint narrowing space score in patient with RA (P ＜ 0.01 or ＜ 0.05) ;the peripheral blood β-catenin level was positively correlated with ESR and AKP (P ＜ 0.01 or ＜ 0.05).The multiple linear regression results showed that the disease duration,health assessment questionnaires (HAQ),DKK1 influenced two hands X-ray joint narrowing space score; but the age,disease duration,HAQ influenced two hands X-ray bony erosion score.The multiple Logistic regression results showed that the two hands X-ray Sharp score was the risk factor of osteoporosis at femur in patients with RA; but the age was the risk factor of osteoporosis at lumbar in patients with RA.Conclusions Peripheral blood DKK1 level in patients with RA increases significantly,while there is no apparent alteration in β-catenin level.Peripheral blood DKK1 level is correlated with disease activity and joint space narrow score.

Objective To analysis the clinical radiologic features of intrapulmonary lymph nodes,and to improve the diagnostic rate of intrapulmonary lymph nodes.Methods From May 2008 to September 2011,16 cases of pulmonary nodules were proved pathologically as intrapulmonary lymph nodes,including 9 males and 7 females,with an average age of 58.2 years (39-73 years).All patients accepted chest X-ray and HR CT scan prior to operation,identified of 11 solitary nodules,3 multiple nodules,and other 2 cases of multiple nodules with synchronous ipsilateral lung cancer.We retrospectively review the data as follows:the population and clinical characters,the subjective imaging diagnosis,the imaging characters of the nodule location,size,texture,shape,border,distance from the nearest pleural surface,and the appearance of the surrounding pulmonary parenchyma et al.Results Clinically,six of all the 16 patients are or were cigarette smokers or had an exposure history of inhaled particles,three patients else were all from a same oilfield area although they denied having the Aforementioned history of smoke or exposure.Lung cancer,metastatic tumor,lung cancer intrapulmonary metastasis were the common subjective imaging diagnosis,with a misdiagnosis rate of 56.3％.Radiologically,these intrapulmonary nodules could be seen in the chest X-ray in half of the 16 patients,with a discovery rate of 50％ in chest X- ray screening.The median size of the intrapulmonary lymph nodes was 7.1 mm (4 - 11 mm),all nodules located below the level of the carina,87.5％ ( 14/16 cases) were solid nodules,68.75％ ( 11/16 cases) were round or ovate in shape with a sharp border.87.5％ ( 14/16 cases) were attached to the pleura or within 1 cm from the nearest pleural surface,87.5％ ( 14/16 cases) appeared linear densities extending from the intrapulmonary lymph nodes.The linear denshy referred to the CT imaging feature that a linear soft-tissue density extended from the intrapulmonary lymph nodes,distinct from the normal lung marking like interlobular septa and bronchovascular bundles,with a diameter less than 5 mm; spiculation were detected in only 2 of the 16 patients ; no calcification and mediestinal lymphadenopathy was detect in all the nodules.Pathologically,All nodules contained anthracotic pigment,and follicular hyperplasia were seen in 8 cases.Conclusion Intrapulmonary lymph nodes are rare benign pulmonary nodules possessing certain clinical and radiologic features.Intrapulmonary lymph nodes should be suspected for small subpleural nodules below the level of the carina.