Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

Objective To analyze the correlation between vertebral artery asymmetry and vertebral artery origin stenosis(VAOS)lesions in population without risk factors for cardiovascular and cerebrovascular diseases.Methods A total of 6 423 participants without cardiovascular and cerebrovascular high-risk factors who underwent cervical atherosclerosis ultrasound screening in the"standardized evaluation database for cerebral vascular ultrasound screening in the high-risk population of stroke"from December 2019 to December 2021 were consecutively enrolled.The general information of the participants was collected before the examination,including gender,age,body mass index(BMI),and bilateral vertebral artery ultrasound parameters,i.e.,the internal diameter of the intervertebral segment(V2 segment)and the degree of VAOS(mild,moderate,severe,and occlusion)assessed by hemodynamic parameters(peak systolic flow velocity[PSV],end-diastolic flow velocity[EDV],and PSVinitiation/PSVintervertebral segment).According to the ultrasound results,the participants were divided into VAOS group and no stenosis group(non-VAOS group).Vertebral artery diameter ≤ 2.0 mm was defined as vertebral artery hypoplasia(VAH).According to the difference in the inner diameter of the V2 segment of the bilateral vertebral arteries,the participants were classified as vertebral artery dominance(VAD)group(inner diameter difference ≥1.2 mm)and non-VAD group(inner diameter difference＜1.2 mm).In the final statistical analysis,if there is a side involved,each group will be counted by the number of cases,and if no side differentiation is involved,each group will be counted by the number of cases.Taking the occurrence of VAOS as the dependent variable,the general information and anatomical factors(VAH,VAD)were analyzed by univariate Logistic regression.The item of P＜0.05 was used as the independent variable,and the independent influencing factors of VAOS were further analyzed by multivariate Logistic regression.Results A total of 6 423 participants were included,including 1 985 males and 4 438 females,with an average age of(43±13)years from 19 to 80 years.There were 628 cases in the VAD group and 5 795 cases in the non-VAD group.(1)Compared with the VAD group,the proportion of females in the non-VAD group was higher(69.9％vs.61.3％,P＜0.01),and the age was younger([43±13]vs.[45±14]years,P＜0.01),and the proportion of those aged＜40 years was higher than that in the VAD group(46.3％vs.38.4％,P＜0.01).The proportion of VAH patients and the incidence of VAOS were lower than those in the VAD group(0.6％vs.17.2％and 1.5％vs.4.0％,respectively,both P＜0.01).(2)Univariate Logistic regression analysis of the incidence of VAOS among participants without cardiovascular and cerebrovascular risk factors showed that the proportion of male,age,BMI,VAH and VAD ratios in the VAOS group were higher than those in the non-VAOS group,with statistical significance(all P＜0.05).Multivariate Logistic regression analysis showed that male(OR,1.92,95％CI 1.30-2.85,P=0.001),age(OR,1.12,95％CI1.10-1.14,P＜0.01)and VAD(OR,2.14,95％CI 1.30-3.40,P=0.002)were independent risk factors for VAOS in participants without cardiovascular and cerebrovascular risk factors.Conclusions The occurrence of VAD is affected by gender and age.VAD is an independent risk factor for VAOS in population without cardiovascular and cerebrovascular risk factors.

Objective To investigate the association between vertebral artery origin stenosis(VAOS)and the degree of bilateral vertebral artery diameter asymmetry caused by vertebral artery dominance(VAD)in patients cardiovascular and cerebrovascular disease risk factors and the optimal diameter difference(△D)cutoff value for diagnosing VAD.Methods A total of 6 404 subjects without vertebral artery occlusion and risks factors of cerebrovascular disease including hyperlipidemia,hypertension,diabetes,obesity(body mass index[BMI]≥ 28 kg/m2),smoking history,and drinking history were retrospectively enrolled from the Standardized Evaluation Database for Screening of High-risk Groups for Stroke from December 2019 to December 2021.The age,sex,BMI,bilateral vertebral artery△D,and VAOS evaluated by the systolic peak velocity and end-diastolic velocity of the vertebral artery origin and intervertebral segment were collected.Subjects with stenosis rate≥50％were divided into VAOS group,and the rest were divided into control group.The general data and △D of the two groups were compared.The items with statistically significant differences were enrolled into multivariable Logistic regression analysis in which ≥50％VAOS was used as the dependent variable.The VAOS group and the control group were matched at a ratio of 1∶5 using propensity score matching.The receiver operating characteristic(ROC)curve was drawn based on ≥50％VAOS as the outcome indicator and △D as the independent variable after matching.The area under the curve(AUC)was calculated.The Youden index was used to calculate the optimal cutoff value of △D.Results Among the 6 404 patients included,there were 1 975 males and 4 429 females.Among them,46 patients were in the VAOS group,and the incidence of VAOS was 0.72％.(1)The results of univariate Logistic regression analysis showed that the male proportion,age,BMI and △D in the VAOS group were higher than those in the control group(P＜0.05).The above variables were further included in the multivariate Logistic regression analysis and the results showed that male(OR,2.49,95％CI 1.36-4.67,P=0.003),age(OR,1.14,95％CI 1.11-1.17,P＜0.01)and △ D(OR,1.81,95％CI 1.06-2.97,P=0.024)were risk factors for VAOS.(2)After propensity score matching,46 cases were included in the VAOS group and 230 cases were included in the control group,for a total of 276 cases.The inter-group comparison showed that the △D in the VAOS group was higher than that in the control group(0.65[0.30,1.20]mm vs.0.40[0.20,0.80]mm,P=0.009).There were no significant differences in the other baseline data between the groups(P＞0.05).(3)Based on 276 subjects matched by propensity score,the ROC curve analysis with the occurrence of VAOS as the outcome indicator and △D as the independent variable showed that the AUC of △D for predicting ≥50％VAOS was 0.622,the optimal cutoff value was 0.800 mm,the specificity was 78.3％,and the sensitivity was 41.3％.Conclusions The difference in the diameter of the bilateral vertebral arteries in patients without cardiovascular and cerebrovascular disease risk factors is associated with the occurrence of ≥50％VAOS.The optimal cutoff value of the diameter difference is 0.800 mm,which can be used as a reference standard for defining VAD.The diameter difference 0.800mm indicates a higher risk of VAOS with stenosis rate ≥50％(specificity 78.3％,sensitivity 41.3％).The results of this study need to be further verified.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To study the application of 3D printing technology in multi-center fenestrated/branched endovascular repair (F/B-EVAR) for endovascular repair of abdominal aortic diseases.Methods:From Feb 2018 to Mar 2023, The clinical and followup data of 316 cases of abdominal aortic lesions undergoing repair with F/B-EVAR at 69 medical centers nationwide using 3D printing technology to guide physician-modified stent graft were retrospectively analyzed.Results:The mean follow-up time of the patients was 23 months (2-60 months), and 24 cases were lost to follow up, the follow-up rate was 92.4% (292/316), the mean postoperative hospitalization time was (8.2±4.9) days. A total of 944 main abdominal branch arteries were reconstructed. Intraoperative reconstruction of 11 branches failed, with a success rate of 98.8% (933/944). Within 30 days after surgery, 8 patients died (2.5%), and 6 patients died during follow-up, a total of 14 patients died (4.4%). There were 11 cases (3.5%) of spinal cord ischemia and no patient suffered from permanent paraplegia. There were 19 patients (6.0%) with postoperative renal function injury. Internal leakage was found in 26 patients, and the rate of internal leakage was 8.2%.Conclusion:3D printing technology can accurately locate the location of branch arteries, simplifing the surgical process, shortening the learning curve , and improving clinical efficacy.

Objective:To review the risk factors for early and medium-term complications of fenestration-branch endovascular thoracic aortic repair (F/B-TEVAR) in patients with complex aortic arch disease.Methods:The clinical and follow-up data of 202 patients undergoing F/B-TEVAR treatment from Feb 2019 to Sep 2023 in these centers were retrospectively analyzed .Results:There were 46 cases suffering from postoperative complications (22.8%). The risk factors with statistical significance included aortic atherosclerotic plaque [ OR=2.843; 95% CI (1.4-5.6); P<0.01], aortic intramural thrombosis [ OR=2.358; 95% CI (1.2-4.6), P=0.011], the aortic dilatation [ OR=4.219; 95% CI (1.6-11.3), P<0.01], the history of stroke [ OR=2.088; 95% CI (1.1-4.1), P=0.032], smoking history [ OR=2.680; 95% CI: (1.3-5.5); P<0.01], duration of surgery [ OR=1.9; 95% CI: (1.2-2.9); P=0.042].While the application of 3D printing assistive technology [ OR=0.392; 95% CI: (0.2-0.9); P=0.048] was in a negative correlation with postoperative complication. Conclusions:The independent risk factors for complications after F/B-TVAR included aortic atherosclerotic plaque, aortic intramural thrombosis, the aortic dilatation, the history of stroke, smoking history,duration of surgery.The application of 3D printing technology can effectively reduce the complication rate.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

The article analyzes chief physician SUN Wuquan's empirical characteristics in treating neck-type cervical spondylosis:disease differentiation combined with pattern differentiation,emphasizing the assessment of tendons and bones,with DING's Tuina(Chinese therapeutic massage)manipulations and static Gongfa(Qigong exercise)as the predominant treatment,inherits the academic features of DING's Tuina school,"paying equal attention to tendons and bones,putting function first";thus provides a reference for treating neck-type cervical spondylosis with Tuina therapy.

OBJECTIVE: To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL). METHODS: A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed. RESULTS: The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(r_s=-0.32，r_s=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (r_s=0.79，r_s=0.54，r_s=0.58； r_s=0.72，r_s=0.63，r_s=0.45), but not with WBC, CD4⁺ T cells and CD8⁺T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (r_s=0.53). CONCLUSION Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Interleukin-9 ; Clinical Relevance ; T-Lymphocytes, Helper-Inducer/pathology* ; Cytokines

Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.