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.

BACKGROUND:Mouse osteogenic potential is regulated by the JAK-STAT signaling pathway,and interleukin-9 can regulate multiple cellular functions through the JAK-STAT pathway,which has the potential to be a novel cytokine that regulates osteogenic potential. OBJECTIVE:To investigate the effect of interleukin-9 deficiency on osteogenic potential in mice METHODS:The femurs collected from 2-month-old wild-type and interleukin-9 knockout mice were subjected to Micro-CT scanning to analyze the changes in bone mass.Then,hematoxylin-eosin staining,Masson staining,and immunohistochemical staining of type Ⅰ collagen were performed on the slices of the femurs of mice.Bone marrow cells from 2-month-old wild-type and interleukin-9 knockout mice were extracted for colony-forming assay and detection of osteogenic gene expression in bone marrow mesenchymal stem cells.To further verify whether interleukin-9 worked through the JAK-STAT pathway,the expression of STAT3 protein was detected by western blot. RESULTS AND CONCLUSION:Micro-CT results showed the bone mass of interleukin-9 knockout mice decreased significantly compared with that of wild-type mice.In addition,the bone mineral density,bone volume fraction,trabecular number significantly decreased and trabecular separation markedly escalated in interleukin-9 knockout mice.The findings of hematoxylin-eosin staining were consistent with Micro-CT results.Interleukin-9 knockout mice had lower bone trabecular density.Type I collagen immunohistochemistry staining and Masson staining indicated the number of type Ⅰ collagen positive osteoblasts was significantly reduced and the capacity of collagen formation was damaged in interleukin-9 knockout mice.The results of colony-forming assay indicated that the mineralization capacity of osteoblast in interleukin-9 knockout mice were significantly lower than that in wild-type mice.Western blot results showed that osteogenesis induction activated STAT3 signaling,and the pSTAT3 level in wild-type mice with osteogenic induction was significantly higher than that in interleukin-9 knockout mice with osteogenic induction.These findings suggest that interleukin-9 regulates osteogenesis through the JAK-STAT3 pathway and interleukin-9 deficiency inhibits osteoblast differentiation and function,which may lead to reduced bone mass in interleukin-9 knockout mice.

Glioma is the most common type of cancer in the brain and central nervous system,mainly originated from glioma cells or neuronal cells.It is characterized by high prevalence,recurrence rate and mortality.Among aggressive brain tumors,the incidence of glioma is the highest.Long non-coding RNA(lncRNA)is one of the most popular non-coding RNAs in tumor research.It has a variety of biological functions and regulates gene expression at the transcription,post-transcription and genetic levels.It was found that lncRNA was abnormally expressed in cancer patients,and abnormally expressed lncRNA was also found in glioma.lncRNA regulates the occurrence and development of gliomas through different signaling pathways,and affects the heterogeneity and invasiveness of gliomas through the glycolytic pathway.In addition,immune-related lncRNAs are valuable in evaluating the diagnosis,treatment and prognosis of gliomas.In this article,the role of lncRNA in glioma will be reviewed from three aspects including regulation of signaling pathway,glycolytic pathway and immunoregulation.

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 investigate the clinicopathological features and treatment strategy of pseudomyxoma peritonei (PMP) of ex-tra-appendiceal origin. Methods: Clinical data of 34 patients diagnosed with PMP of extra-appendiceal origin who were treated by cy-toreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the Aerospace Center Hospital from September 2011 to February 2019 were retrospectively analyzed. Clinical and imaging features were summarized and the Log-rank test was used for survival analysis. Results: The clinical manifestations of the 34 patients with PMP of extra-appendiceal origin were mainly abdomi-nal distension (58.8%) and abdominal pelvic mass (52.9%), which are very similar to those of appendiceal PMP. The incidence of main complications after CRS and HIPEC was 14.7%. During the follow-up period of a median of 12 months (range 1-46 months), 9 patients died, and the 1-and 3-year overall survival rates were 69.6% and 53.5%, respectively. In the univariate analysis, peritoneal cancer in-dex (PCI)>20, no HIPEC, and non-radical surgery were significant risk factors for poor prognosis, while gender, age, origin, and patho-logical type did not show significant correlations. Conclusions: The clinical features of PMP of extra-appendiceal origin are not differ-ent to those of PMP originating from the appendix. It is difficult to ascertain the primary lesion before the operation; however, regard-less of the origin, CRS combined with HIPEC is always a safe and effective treatment choice.

Objective: To explore the molecular mechanism of miR-17-5p regulating the proliferation and invasion of nasopharyngeal carcinoma cells by regulating the expression of breast cancer metastasis suppressor 1 like (BRMS1-like or BRMS1L) gene. Methods:A total of 40 cases of nasopharyngeal carcinoma tissues and corresponding paracancerous tissues resected from nasopharyngeal carcinoma patients, who were admitted to the General Hospital of Pingdingshan Shenma Medical Group during January 2014 to December 2017, were included in this study; in addition, nasopharyngeal carcinoma cell lines CNE 2, HONE 1, C666-1 and nasopharyngeal immortalized epithelial cell line NP69 were also collected for this study. The expression of miR-17-5p in nasopharyngeal carcinoma tissues and cell lines was detected by qPCR. The targeted relationship between BRMS1L and miR-17-5p was predicted by the StarBase and verified by the Dual luciferase reporter gene assay. Effects of transfection of miR-17-5p mimics and inhibitors on the expression of BRMS1Lin CNE2 cells were detected by WB assay. CCK-8, Transwell and Flow cytometry were used to detect the effects of miR-17-5p/BRMS1L axis on the proliferation, migration, invasion and apoptosis of CNE 2 cells. Results: miR-17-5p was highly expressed in nasopharyngeal carcinoma tissues and cell lines (P<0.05 or P<0.01). Knockdown of miR-17-5p significantly inhibited proliferation, invasion and migration of CNE2 cells but promoted apoptosis (P<0.05 or P<0.01); miR-17-5p targeted BRMS1Land down-regulated its expression. Over-expression of BRMS1Lsignificantly inhibited the proliferation, invasion and migration of CNE2 cells but promoted apoptosis (all P<0.01); while simultaneous over-expression of miR-17-5p and BRMS1L reversed the above effects (all P<0.01). Conclusion: miR-17-5p promoted proliferation, invasion, migration and inhibited apoptosis of CNE 2 cells by down-regulating the expression of BRMS1L.

Objective To investigate the mechanism of cerebral protection by treatment of butylphthalide (NBP) and its effect to mitochondria in a porcine model of cardiac arrest (CA) after cardiopulmonary resuscitation (CPR). Methods Healthy Wuzhishan pigs weighting (30±2) kg were divide into three groups randomly(random number): The sham group (n=6), the control group (n=12) and the NBP group (n=12). Operation was performed in the sham group. Cardiac arrest of ventricular fibrillation was induced by programed electrical stimulation in the control and NBP group. After CPR, asynchronous defibrillation of 150J was performed to achieve the restoration of spontaneous circulation. NBP was injected at the rate of 2.5 mg?kg-1 in the NBP group. Hemodynamics were recorded at baseline, 1 hr, 2 hr, 3 hr and 4 hr after CPR. The number of injured neurons, apoptosis index and evaluation of mitochondrial injury were calculated under light and electrical microscope respectively. Mitochondria were separated by differential centrifugation. Mitochondrial respiratory function was measured with oxygen consumption of R3 and R4, respiratory control rate (RCR), ADP/oxygen. Mitochondrial permeability transition pore (MPTP) open was tested by colorimetric. Results After CPR, the mean artery pressure, coronary perfusion pressure and cardiac output decreased significantly, whereas no significant differences were found between the control and NBPgroup (P>0.05). Significant cerebral injury was found after CPR. The number of injured neurons, apoptosis index and evaluation of mitochondrial injury were improved significantly by the NBP treatment (P<0.05). Compared with the sham group, oxygen consumption of R3 and R4, R3/R4 and ADP/O decreased significantly in the cerebral frontal cortex mitochondria of the control group (P<0.01), whereas they were increased in the NBP group (P<0.01). MPTP increased in the control group, which could be improved by the NBP treatment. Conclusions NBP can improve the neurologic outcome after CPR and decrease the apoptosis of neurons by improving the respiratory function of mitochondria and inhibiting the MPTPopening.