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.

Helicobacter pylori(H.pylori)can colonize the gastric mucosa of humans and animals,leading to persistent infection,chronic inflammation,and tissue damage.To understand the preva-lence of H.pylori in dogs,this study designed specific primers targeting a unique region of the H.pylori virulence gene vacA and established a SYBR Green Ⅰ-based real-time PCR(qPCR)method.The specificity,sensitivity,and repeatability of this method were evaluated.Using the es-tablished method,alongside conventional PCR and H.pylori stool antigen(HpSA)detection,we conducted an epidemiological survey of H.pylori infection in pet dogs in urban Hangzhou.The re-sults showed that the standard curve demonstrated a good linear relationship within the concentra-tion range of 3.26×106 to 3.26×101 copies/μL.The method specifically detected H.pylori,with a minimum detection limit of 3.26×101 copies/μL.The intra-and inter-assay coefficients of variation ranged from 0.84％to 1.87％and 0.96％to 1.93％,respectively.Applying this method to canine fe-cal samples collected in Hangzhou from 2023 to 2024 revealed an overall H.pylori positive rate of 25.21％.In comparison,the detection rates by conventional PCR and HpSA were 10.68％and 8.97％,respectively.These results indicate that the established qPCR method is suitable for detec-ting H.pylori infection in dogs,providing a rapid,sensitive,specific,and reproducible quantitative detection method.Additionally,this study confirms the significant prevalence of H.pylori infection in household dogs.Given the widespread dissemination of H.pylori and its potential zoonotic risk,So recommend implementing risk communication and ongoing regional monitoring programs to protect the health of both humans and pets.

Sepsis refers to a life-threatening organ dysfunction caused by a dysregulated host response to infection,with persistently high morbidity and mortality,posing a significant healthcare burden.As integral components of innate and adaptive immunity,macrophages exhibit high plasticity and can differentiate into distinct phenotypes(M1 pro-inflammatory and M2 anti-inflammatory)in response to various environmental stimuli,playing crucial roles in both the hyperinflammatory phase and late immunosuppressive phase of sepsis.The metabolic profile of M2 macrophages has gradually become a research focus,and it is regulated by a variety of enzymes and signaling pathways,including adenosine 5'-monophosphate-activated protein kinase,peroxisome proliferator-activated receptor and protein kinase RNA-like ER kinase pathways.These pivotal signaling pathways and enzymes can promote the polarization of M2 macrophages and enhance their anti-inflammatory functions by modulating the metabolism of glucose,lipid,and amino acid,thereby conferring protective effects against sepsis and providing new ideas for the targeted treatment.

Objective:To analyze the relationship between neck pain severity and duration and cervical sagittal parameters in non-specific neck pain (NNP) patients from a real world data, and to initially explore the relationship between NNP and cervical sagittal position sequence.Methods:The clinical data of 126 patients with main complaint of neck pain in the outpatient department of Beijing Friendship Hospital, Capital Medical University from January to September 2023 were retrospectively analyzed. This cohort included 84 female and 42 male patients with a mean age of (42.21±14.88) years (aged from 15 to 76 years). According to the duration of neck pain was more than 3 month or not, patients were divided into acute neck pain group ( n=57) and chronic neck pain group ( n=69). Patients were divided into mild neck pain group ( n=72) and moderate and severe neck pain group ( n=54) according to the severity of neck pain. The duration and visual analogue scale (VAS) of neck pain for each patient was recorded. Cervical sagittal related parameters, including cervical lordosis (C 2-C 7 Cobb′ angle, CL), C 2-C 7 sagittal vertical axis (cSVA), T 1 slope (TS) were measured by cervical lateral X-ray, and the value of T 1 slope minus cervical lordosis (TS-CL) was calculated. At the same time, cervical lateral X-ray was used to record whether the patient had cervical kyphosis and whether the patient was associated with ossification of the nuchal ligament (ONL). The VAS score of neck pain was expressed as the median (interquartile) [ M( Q1, Q3)]. Measurement data with normal distribution were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data were represented as cases and percentage, and was conducted by Chi-square test. Spearman correlation analysis was used to investigate the correlation of VAS score and duration of neck pain with age, gender, imaging parameters (CL, cSVA, TS, TS-CL), cervical kyphosis and ONL. Results:The median VAS score of all patients with neck pain was 4(3, 5). For all patients, VAS score of neck pain was significantly correlated with cSVA ( P=0.029) and TS-CL ( P=0.028). There was no correlation between VAS score and CL ( P=0.235), TS ( P=0.355), with cervical kyphosis or not ( P=0.988), or with ONL or not ( P=0.181). The TS-CL values of acute neck pain group and chronic neck pain group were (11.80±8.38)° and (8.77±7.61)°, respectively, with a significant difference ( P=0.035). There was no significant difference in the incidence of cSVA, CL, TS, ONL and cervical kyphosis between the two groups ( P>0.05). The cSVA of mild neck pain group and moderate and severe neck pain group were (1.16±0.94) cm and (1.80±1.04) cm, respectively. CL was (12.25±10.76)° and (8.27±9.08)°, respectively. The TS-CL values were (8.11±7.54)° and (12.84±8.04)°, respectively, and the differences between the two groups were statistically significant ( P<0.05). The incidence of ONL in moderate and severe neck pain group was significantly higher (35.2% vs 19.4%), and the difference was statistically significant ( P<0.05). Conclusions:The severity of NNP was significantly correlated with cSVA, the more severe the neck pain, the more the mismatch between TS and CL was presented. Compared with chronic neck pain, patients with acute neck pain tended to appear TS and CL mismatch. There was a large value of cSVA and TS-CL in moderate and severe neck pain patients. The incidence of ONL was significantly increased in patients with moderate and severe neck pain.

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.

Objective:To explore the risk factors of cement leakage into the spinal canal in percutaneous vertebroplasty (PVP) for spinal metastases.Methods:A retrospective analysis was conducted on the case data of 211 patients with spinal metastases who underwent PVP in the Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University from January 2016 to June 2024. According to the presence or absence of intraspinal bone cement leakage after surgery, the patients were divided into the leakage group ( n=45) and the non-leakage group ( n=166). The clinical data of the two groups, including gender, age, bone mineral density T-score, American Society of Anesthesiologists (ASA) classification, operation time, and bone cement injection volume, were collected and statistically analyzed. Measurement data were expressed as mean±standard deviation ( ± s), and the independent samples t-test was used for comparison between groups; count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Univariate analysis was used to explore the possible risk factors for intraspinal bone cement leakage after PVP, and then the indicators with statistically significant differences in the univariate analysis were included in the multivariate Logistic regression analysis to identify the independent risk factors. Results:A total of 45 patients out of 211 patients with PVP surgery had cement leakage into the spinal canal after surgery, with an incidence rate of 21.3%. There were statistically significant differences between the leakage group and the non-leakage group in terms of whether the posterior wall of the vertebral body was broken, operation time, the injection volume of bone cement, distribution of injured vertebrae, and viscosity of bone cement ( P<0.05). The results of multivariate Logistic regression analysis showed that the broken posterior wall of the vertebral body, large injection volume of bone cement, and low viscosity of bone cement were the independent risk factors for the occurrence of cement leakage into the spinal canal in PVP for spinal metastases ( P<0.05). Conclusion:When PVP surgery is used to treat spinal metastases, broken posterior wall of the vertebral body, large injection volume of bone cement, and low viscosity of bone cement can increase the incidence of postoperative intravertebral cement leakage, and the operation should be performed with caution.

Objective To investigate the changes in coagulation system in acute decompensated cirrhosis(ADC)patients with or without sepsis and the association of these changes with short-term prognosis.Methods A prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023,among whom there were 86 patients with sepsis and 30 patients without sepsis,and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group.Thromboelastography(TEG)and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients.The data including TEG results and short-term prognosis were collected,and a correlation analysis was performed.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman correlation coefficient was calculated to investigate the correlation between different variables.The Logistic regression model was used to perform the univariate and multivariate analyses.Results For the ADC patients with sepsis,the lungs and bloodstream were the main infection sites,and bacteria were the main pathogenic microorganism.TEG results showed that compared with the patients with sepsis alone,the patients with ADC and sepsis had a significant reduction in median maximum amplitude(MA),a significant increase in coagulation time(K time),and a significant reduction in α angle(all P<0.05);the patients with ADC and sepsis had a significantly longer reaction time(R time)than those with ADC alone(P=0.02),and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis(P=0.04).There was no correlation between MA and platelet count in the patients with ADC and sepsis(r=-0.133,P=0.057),while there was a significant correlation between MA and platelet count in the patients with sepsis alone(r=0.595,P=0.001).SOFA score was negatively correlated with MA in sepsis patients with or without ADC(r=-0.503 and-0.561,both P<0.001),and for the patients with ADC and sepsis,R time,K time,and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT(all P<0.05).The patients with ADC alone all survived within 90 days,and compared with the death group,the patients with sepsis alone who survived had significantly higher values of MA and α angle(all P<0.05);there was a significant difference in α angle on day 90 between the survival group and the death group,no matter whether the patients were comorbid with ADC or not(both P<0.01),while for the patients with ADC and sepsis,there was no significant difference in MA value on day 90 between the survival group and the death group(P>0.05).Conclusion For ADC patients comorbid with sepsis,coagulation function assessment and monitoring should be taken seriously in clinical practice,and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023， among whom there were 86 patients with sepsis and 30 patients without sepsis， and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected， and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis， the lungs and bloodstream were the main infection sites， and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone， the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA）， a significant increase in coagulation time （K time）， and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02）， and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133， P=0.057）， while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595， P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561， both P<0.001）， and for the patients with ADC and sepsis， R time， K time， and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days， and compared with the death group， the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group， no matter whether the patients were comorbid with ADC or not （both P<0.01）， while for the patients with ADC and sepsis， there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. ConclusionFor ADC patients comorbid with sepsis， coagulation function assessment and monitoring should be taken seriously in clinical practice， and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

Objective:Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy.Methods:Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS).Results:Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS ( P＜0.05). Multivariate analysis showed that initial radiotherapy dose ( HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence ( HR=4.106, 95% CI: 1.228-13.728), and RFI ( HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose ( HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence ( HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions:The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.

Objective To investigate the characteristics of lens diameter in different axial positions and their rela-tionship with ocular biometric parameters using swept-source optical coherence tomography.Methods A total of 180 pa-tients(180 eyes)with age-related cataract who were scheduled for phacoemulsification combined with intraocular lens im-plantation from July to December 2023 were included,and the operated eyes were used as the observation eyes.The lens diameter data of patients were obtained by scanning at 16 axial positions using the swept-source optical coherence tomo-graphy device CASIA2.The patients were divided into three groups according to the scanning axial positions of the maxi-mum and minimum lens diameters:horizontal group,oblique group,and vertical group.The distribution differences of the maximum and minimum lens diameters among the three groups were compared.Ocular biometric parameters,including ax-ial length(AL),white-to-white distance,anterior chamber depth(ACD),and lens thickness(LT),were measured using the IOL Master 700.Correlation analysis was used to assess the relationship between lens diameter and age,ocular biomet-ric parameters.Multiple linear regression analysis was used to evaluate the impact of age and ocular biometric parameters on lens diameter.Results The maximum lens diameter[10.13(9.20,10.80)mm]was significantly larger than the min-imum lens diameter[9.26(8.21,9.91)mm],with a statistically significant difference(Z=-7.387,P＜0.001).There were no statistically significant differences in the maximum and minimum lens diameters among the three groups(H=1.575,P=0.455;H=0.927,P=0.629).The distribution difference of the maximum lens diameters between the oblique group and the horizontal group was statistically significant(x2=6.035,P=0.014);differences in other group comparisons were not statistically significant(all P＞0.022).The proportion of the maximum lens diameter occurring in the oblique group(55.2％)was significantly higher than that in the horizontal group(38.0％).The maximum lens diameter was more commonly found in the oblique group.The lens diameter was positively correlated with age and LT(rs=0.217,P＜0.05;rs=0.538,P＜0.001),and negatively correlated with ACD(rs=-0.379,P＜0.001).Comparison of standardized regres-sion coefficients(β')showed that LT had the greatest impact on lens diameter,followed by AL;both LT and AL had a sig-nificant positive impact on lens diameter(β'=0.483,P＜0.001;β'=0.314,P＜0.001).Conclusion The distribution frequency of the maximum lens diameter in the oblique group(30°-60° and 120°-150°)was significantly higher than that in the horizontal group.There was a positive correlation between lens diameter and age and LT,and a negative correlation between lens diameter and ACD.Among all the factors affecting lens diameter,LT and AL are the most critical factors,with LT having a more significant impact on lens diameter than AL.