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 assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To compare the changes of alveolar bone thickness and height in patients with bimaxillary dentoalveolar protrusion after the treatment with labial straight wire appliance and personalized lingual appliance for the retraction of anterior teeth.Methods:31 cases of labial fixed orthodontic treatment and 31 of personalized lingual orthodontic treatment were included.CBCT images were taken before and after treatment,the thickness and height of the alveolar bone on both sides of the upper anterior teeth were measured and statistically analyzed.Results:After the upper anterior teeth were retracted with labial aligner,the thick-ness of the alveolar bone in the labial root middle 1/2 and apical region of the upper incisors increased,the thickness of the alveolar bone in the cervical region of the labial side of the upper canine increased(P＜0.05),whereas the thickness and height of the alve-olar bone in the palatal side of the upper anterior teeth decreased,and the total thickness of the alveolar bone in the apical region decreased(P＜0.05).After the anterior teeth retracted with lingual aligners,the alveolar bone thickness of the labial cervical of the upper middle incisors and lateral incisors decreased,the alveolar bone thickness of the apical region of the upper middle incisors and upper canine increased,and the thickness and height of the palatal alveolar bone of the upper anterior teeth decreased,with the total thickness of the apical region decreased(P＜0.05).The reduction of alveolar bone thickness of the labial neck and root middle 1/2 of the upper incisors and alveolar bone height of the palatal side of the upper canine in the lingual appliance group was more than that in the laial group(P＜0.05).Conclusion:Labial straight wire appliance and personalized lingual appliance are effective in the retraction of the anterior teeth and the alveolar bone remodeling based on bone resorption,labial appliance is more effective.

Objective:To compare the changes of alveolar bone thickness and height in patients with bimaxillary dentoalveolar protrusion after the treatment with labial straight wire appliance and personalized lingual appliance for the retraction of anterior teeth.Methods:31 cases of labial fixed orthodontic treatment and 31 of personalized lingual orthodontic treatment were included.CBCT images were taken before and after treatment,the thickness and height of the alveolar bone on both sides of the upper anterior teeth were measured and statistically analyzed.Results:After the upper anterior teeth were retracted with labial aligner,the thick-ness of the alveolar bone in the labial root middle 1/2 and apical region of the upper incisors increased,the thickness of the alveolar bone in the cervical region of the labial side of the upper canine increased(P＜0.05),whereas the thickness and height of the alve-olar bone in the palatal side of the upper anterior teeth decreased,and the total thickness of the alveolar bone in the apical region decreased(P＜0.05).After the anterior teeth retracted with lingual aligners,the alveolar bone thickness of the labial cervical of the upper middle incisors and lateral incisors decreased,the alveolar bone thickness of the apical region of the upper middle incisors and upper canine increased,and the thickness and height of the palatal alveolar bone of the upper anterior teeth decreased,with the total thickness of the apical region decreased(P＜0.05).The reduction of alveolar bone thickness of the labial neck and root middle 1/2 of the upper incisors and alveolar bone height of the palatal side of the upper canine in the lingual appliance group was more than that in the laial group(P＜0.05).Conclusion:Labial straight wire appliance and personalized lingual appliance are effective in the retraction of the anterior teeth and the alveolar bone remodeling based on bone resorption,labial appliance is more effective.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0～40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P＜0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P＜0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P＜0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective    By applying the mutual corroboration in the diagnosis, we aimed to improve the accuracy of preoperative imaging diagnosis, select the appropriate timing of operation and guide the follow-up time for patients with pulmonary nodules. Methods    Clinical data of 1 368 patients with pulmonary nodules undergoing surgical treatment in our department from July 2016 to October 2019 were summarized. There were 531 males and 837 females at age of 44 (21-67) years. The intraoperative findings, images and pathology were classified and analyzed. The imaging pathology and pathological changes of pulmonary nodules were shown as a dynamic process through mutual collaboration and interaction. Results    Of 1 368 patients with pulmonary nodules, 376 (27.5%) were pure ground-glass nodules, 729 (53.3%) were mixed ground-glass nodules and 263 (19.2%) were solid nodules. Among the pure ground-glass nodules, adenocarcinoma in situ (AIS) accounted for the highest proportion (156 patients), followed by microinvasive adenocarcinoma (MIA, 90 patients), atypical adenomatous hyperplasia (AAH, 85 patients), and benign tumors (20 patients). Among mixed ground-glass nodules, 495 patients were invasive adenocarcinoma (IA) and 207 patients of MIA. no patient was featured by AAH, AIS or MIA. Conclusion    The mutual collaboration and interaction can improve the accuracy of preoperative diagnosis of pulmonary nodules, and it supports the choice of operation timing and the judgment of follow-up time.

Objective To determine the clinical characteristics in elderly patients with Guillain-Barré syndrome ( GBS) and explore the relationship between glucose metabolism and severity and prognosis of disease. Methods Records of patients with GBS admitted between January 2004 and February 2017 from Affiliated Hospital of Jiangsu University were evaluated, including antecedent infection, initial symp-toms, cranial nerve palsy, subgroup analysis, Hughes score and Medical Research Council ( MRC) score at nadir and when discharged. Results The incidence of ocular palsy (6. 4％ vs 27. 0％, P=0. 02) and of facial palsy (18. 8％ vs 45. 8％, P =0. 016 ) were both lower in older group, compared to non-elderly group. MRC score at nadir (32 vs 44, P=0. 020), rate of severe type (80. 6％ vs 47. 9％, P=0. 004) and rate of poor prognosis when discharged (67. 7％ vs 29. 2％,P=0. 001) in elderly group were higher than non-elderly group. As to the distribution of subtype in these two groups, no significant difference was found (P=0. 691). Hyperglycemia wasn't prognostic factor of severe type (OR =0. 531,P =0. 321) or poor short-term prognosis (OR=0. 519,P=0. 261). Conclusions The clinical characteristics of elderly patients with GBS are distinct from non-elderly patients. Hyperglycemia wasn 't predictor of severe type or poor short-term prognosis of GBS.

Objective To compare the advantages and disadvantages of non-irrigation and irrigation in the surgical approach of chronic subdural hematoma (CSDH),thus to provide reference for clinical treatment of CSDH.Methods Clinical data of 102 patients with CSDH were retrospectively analyzed.According to the different operation methods,the patients were divided into the non-irrigation group(52 cases) and the irrigation group(50 cases).The blood loss during the procedure,operative time,length of stay and postoperative complication rate between the two groups were compared,and the causes of postoperative complications were analyzed.Results The blood loss during the procedure,operative time and length of stay in the non-irrigation group were (6.73 ± 1.17) mL,(15.06 ± 2.64) min and (10.74 ± 2.20) d,respectively,which in the irrigation group were (19.52 ± 3.18) mL,(38.54 ± 6.95) min and (10.44 ± 2.07)d,respectively,there were statistically significant differences between the two groups in the blood loss during the procedure and the operative time (t =-27.11,-22.72,all P ＜ 0.05),there was no statistically significant difference between the two groups in the length of stay (t =0.70,P ＞ 0.05).The incidence rates of postoperative complication in the non-irrigation group and irrigation group were 8.00％ and 7.69％,respectively,there was no significant difference between the two groups (x2 =0.003,P ＞ 0.05).Conclusion Each of the two methods has its own advantages and disadvantages in the treatment of CSDH.Compared with burr hole irrigation,burr hole non irrigation has the advantages of less blood loss and shorter operative time.However,burr hole non-irrigation is more likely to suffer serious complication.We should select suitable surgical approach by the specific circumstances of the patients.The causes of postoperative complications of CSDH are varied.In particular,there is an important relationship between the non-standard operation and postoperative complications.