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 elucidate the prediction ability of monocyte monolayer assay(MMA)used in hemolytic dis-ease of fetus and newborn(HDFN)caused by IgG anti-M.Methods Plasma from eight pregnant women containing IgG an-ti-M were collected,and were divided into two groups(4 cases with HDFN,with severe clinical symptoms such as fetal hy-drops,and 4 cases without HDFN)according to the clinical outcomes.M antigen positive cells were sensitized with dithioth-reitol(DTT)treated plasma from eight pregnant women respectively.MMA was performed by coincubation with monocytes and sensitized M cells,along with negative and positive control set up.T-test was conducted to compare the difference in phagocytic efficiency between two groups.Results The phagocytic efficiency in group with HDFN were 15.37%,13.05%,9.17%and 24.50%respectively,with the mean value of 15.52%,while the group without HDFN were 8.74%,11.07%,5.12%and 6.23%respectively,with the mean value of 7.79%.There was no significant difference in phagocytic efficiency between two groups(P>0.05).The mean values of both groups were not significantly different from the negative control(P>0.05),but both were significantly lower than positive control(P<0.05).Conclusion The low phagocytic efficiency couldn't convince that the MMA is an effective predictor for the HDFN caused by IgG anti-M,indicating that another mech-anism might be responsible for it rather than monocyte phagocytosis.The assessment of the peak systolic velocity in middle cerebral artery of the fetal should be considered in the management for pregnant women who produce IgG anti-M to estimate the situation of fetal anemia.

【Objective】 To explore the correlation between body mass index (BMI) and lipid indexes with prostate volume in patients with benign prostatic hyperplasia (BPH) so as to provide reference for the clinical prevention of this disease. 【Methods】 Clinical data of 578 patients admitted to the Department of Urology of Chinese PLA General Hospital during Jan.2014 and Dec.2022 were collected.The patients underwent initial prostate puncture biopsy or prostatectomy and BPH was confirmed pathologically.The patients’ age, time of onset of the disease, BMI, past medical history and biochemical indexes were analyzed.According to the total prostate volume (TPV) grading, the patients were divided into TPV>75 mL and TPV≤75 mL groups.The general data of the two groups were compared, and predictors of TPV were determined with linear regression analysis.The samples were stratified with BMI to observe the differences in the effects of apolipoprotein B (ApoB) on TPV. 【Results】 There were 215 cases in the TPV>75 mL group and 363 cases in the TPV≤75 mL group.The levels of BMI, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) were higher in the TPV>75 mL group (P<0.01).Multivariate linear regression analysis showed that age (β=0.604, P=0.003), BMI (β=2.000, P<0.001), ApoB (β=23.792, P<0.001) and TPV had a significant positive linear correlation; after adjusting for the confounders of age and BMI, ApoB was not linearly correlated with TPV in BPH population with BMI<24 (P>0.05), and ApoB predicted prostate volume growth in overweight and obese BPH population respectively (β=26.411, P=0.011; β=47.602, P=0.017). 【Conclusion】 Age, ApoB and BMI can be used as predictors of volume growth in BPH patients, which can help further research on the pathogenesis and progression of BPH.

Objective To propose a modified lung ultrasound score(LUS),and to observe its value for evaluation on severity of acute respiratory distress syndrome(ARDS).Methods Data of lung ultrasound,chest X-ray and so on in 33 sudden ARDS patients were retrospectively analyzed.The patients were divided into moderate-severe group(n=16)and mild group(n=17)according to oxygenation index(OI).The outcomes of LUS,modified LUS and radiographic assessment of lung edema(RALE)score were compared between groups.Receiver operating characteristic(ROC)curves were drawn,the area under the curves(AUC)were calculated to evaluate the efficacy of various image scores for evaluating the severity of ARDS.Pearson correlation analysis was performed to explore the correlations of various image scores with OI,of RALE score with LUS and modified LUS in ARDS patients.Results LUS and modified LUS in moderate-severe group were both higher than those in mild group(both P＜0.05).No significant difference of RALE score was found between groups(P＞0.05).AUC of LUS,modified LUS and RALE score for evaluating the severity of ARDS was 0.809,0.853 and 0.640,respectively.LUS and modified LUS in ARDS patients were moderately negatively correlated with OI(r=-0.570,P=0.001;r=-0.708,P＜0.001),while no obvious correlation of RALE score and OI was found(r=-0.229,P=0.201).RALE score of ARDS patients was moderately positively correlated with both LUS and modified LUS(r=0.588,P＜0.001;r=0.502,P=0.003).Conclusion The above mentioned modified LUS could effectively evaluate severity of ARDS,with better efficacy than LUS and RALE score.

[Purpose]To analyze the incidence and mortality trends,and survival of gallbladder cancer in Nantong City of Jiangsu Province from 2013 to 2017.[Methods]The gallbladder cancer incidence and mortality data from 2013 to 2017 were collected from Nantong cancer registries.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese and world standard population(ASIRC/ASMRC,ASIRW/ASMRW)were calculated by sex,age and regions(urban and rural).Joinpoint software was used to analyze the incidence and mortality trends of gallbladder cancer.The observed survival rate and relative survival rate were calculated by using life table method and Ederer Ⅱ method.[Results]From 2013 to 2017,the gallbladder cancer crude incidence and mortality rates were 6.36/105 and 4.91/105,ASIRC and ASMRC were 2.62/105 and 1.94/105,respectively.The crude incidence and mortality,and ASMRC showed an upwards trend(all P＜0.05).The ASIRC for men and women was 2.43/105 and 2.83/105,the ASMRC for men and women was 1.74/105 and 2.16/105,respectively.ASIRC and ASMRC in women were higher than those in men.The ASIRC in urban and rural areas was 2.40/105 and 2.69/105,and the ASMRC was 1.61/105 and 2.05/105,respectively.ASIRC and ASMRC in rural areas were higher than those in urban areas.The average age of onset was 70.33 years old and the average age of death was 71.86 years old.The 5-year observed survival rate was 12.90％,and the 5-year relative survival rate was 14.47％.Both the 5-year observed survival rate and relative survival rate showed an upwards trend(both P＜0.05).[Conclusion]The incidence and mortality rates of gall-bladder cancer in Nantong City are relatively high and the survival rate is generally low.It is sug-gested that targeted prevention and control measures of gallbladder cancer in Nantong City should be strengthened,particularly in rural areas and for middle-aged and elderly women.

Objective:To evaluate the role of sphingosine-1-phospho-1 receptor 1 (S1PR1) in remifentanil-induced hyperalgesia in rats with incisional pain and the relationship with KCNQ2/3 potassium channels in the dorsal root ganglia (DRG).Methods:Forty-eight male Sprague-Dawley rats with successful caudal vein catheterization, aged 2-3 months, weighing 260-280 g, were divided into 6 groups ( n=8 each) using a random number table method: control group (group C), S1PR1 inhibitor group (FTY720) group (group F), remifentanil group (group R), remifentanil + S1PR1 inhibitor (FTY720) group (group RF), remifentanil + incision pain group (group RI) and remifentanil + incision pain + S1PR1 inhibitor (FTY720) group (group RIF). In group C, normal saline 0.1 ml· kg -1·min -1 was intravenously infused for 60 min. In group F, FTY720 3 nmol was intrathecally injected at 10 min before normal saline injection, and 0.1 ml · kg -1·min -1 normal saline was infused into the caudal vein for 60 min. Remifentanil 1.0 μg· kg -1·min -1 was infused for 60 min through the caudal vein in group R. In RF group, FTY720 (3 nmol) was intrathecally injected, and 10 min later remifentanil 1.0 μg· kg -1·min -1 was infused via the caudal vein for 60 min. The incisional pain model was established, and remifentanil 1.0 μg· kg -1·min -1 was infused via the caudal vein for 60 min in RI group. In RIF group, FTY720 3 nmol was intrathecally injected at 10 min before remifentanil infusion, then the incisional pain model was developed, and remifentanil 1.0 μg· kg -1·min -1 was infused via the caudal vein at the same time for 60 min. The mechanical paw withdraw threshold (MWT) and thermal paw withdraw latency (TWL) were measured at 24 h before remifentanil or normal saline infusion (T 0) and 2, 6, 24 and 48 h after remifentanil or normal saline infusion (T 1-4). The rats were sacrificed after the last measurement of pain threshold, and the L 4-6 segments of the DRG were taken for determination of the expression of S1PR1, KCNQ2 and KCNQ3 protein and mRNA in the DRG by Western blot and real-time polymerase chain reaction. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-4, the expression of S1PR1 protein and mRNA in the DRG was up-regulated, the expression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was down-regulated ( P<0.05), and no significant change was found in each parameter in R and RI groups ( P>0.05). Compared with group R, the MWT was significantly decreased, and the TWL was shortened at T 1-4, the expression of S1PR1 protein and mRNA in the DRG was up-regulated, and the expression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was down-regulated in group RI, and the MWT was significantly increased, and the TWL was prolonged at T 1-4, the expression of S1PR1 protein and mRNA in the DRG was down-regulated, and the expression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was up-regulated in group RF ( P<0.05). Compared with group RI, the MWT was significantly increased, and the TWL was prolonged at T 1-4, the expression of S1PR1 protein and mRNA in the DRG was down-regulated, and the expression of KCNQ2 and KCNQ3 protein and mRNA in the DRG was up-regulated in group RIF ( P<0.05). Conclusions:S1PR1 is involved in the process of remifentanil-induced hyperalgesia in rats with incisional pain, which is related to the inhibition of KCNQ2/3 potassium channel expression in the DRG.

Objective:To analyze the correlation between MRI indicators and clinical features of multifidus degeneration in patients with unilateral lumbar disc hemiation. Method:Eighty-six eligible patients with unilateral lumbar disc hemiation admitted to our hospital from Janu-ary 2018 to December 2021 with complete clinical data were retrospectively analyzed and divided into three groups according to the level and number of lumbar disc hemiation:27 patients in group A were treated with L4/5 disc hemiation only,30 patients in group B were treated with L5/S1 disc hemiation only,and 29 pa-tients with multi-level lumbar disc hemiation in group C.All patients underwent lumbar MRI scans,and the measurements included the ratio of the total cross-sectional area of the unaffected and affected sides of the multifidus muscle at L4/5 and L5/S1 levels,the degree of bilateral multifidus muscle atrophy,and the propor-tion of fatty infiltration.The lumbar visual analogue scale(VAS),Oswestry disability index(ODI)and other clinical features of patients with lumbar disc herniation were obtained from the medical records,and Spearman correlation was used to analyze the correlation between the ratio of the total cross-sectional area of the unaffect-ed and affected sides of the multifidus muscle at L4/5 and L5/S1 levels and the proportion of fatty infiltration. Result:There was no significant difference in age,gender and body mass index(BMI)between the groups(P＞0.05);the total cross-sectional area ratio of the unaffected and affected sides of the multifidus muscle in the three groups was positively correlated with the VAS score(P＜0.05)and not correlated with the ODI score(P＞0.05);the degree of bilateral multifidus muscle atrophy and the proportion of fatty infiltration were posi-tively correlated with the ODI score(P＜0.05)and not correlated with the VAS score(P＞0.05). Conclusion:In patients with unilateral lumbar disc herniation,the degree of asymmetry in the left and right cross-sectional areas of the multifidus muscle was associated with lumbar pain,whereas the degree of bilateral multifidus muscle atrophy and the proportion of fatty infiltration were associated with ODI scores.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.