ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63^-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63^-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.

Objective To investigate the expression of Excision repair cross-complementation group 6-like(ERCC6L)in non-small cell lung cancer(NSCLC),and evaluate its prognostic value.Methods From September 2016 to 2019,144 cases of NSCLC tissues and adjacent tissues(non-tumor tissues at least 5 cm away from cancerous tissues)were admitted.The expression of ERCC6L protein in NSCLC tissues and their adjacent tissues were detected using immunohistochemistry(IHC)method.The clinicopathological data of patients with high and low expression of ERCC6L were compared,and the Kaplan-Meier curves and Cox proportional hazards regression model were used to evaluate the relationship between ERCC6L expression and overall survival(OS)of NSCLC patients.Results The data of IHC staining showed that high expression of ERCC6L was detected in 42.4％(61/144)of NSCLC tissues,which was higher than in their adjacent tissues(37.7,％,37/144)(x2=8.909,P＜0.05).High expression of ERCC6L was frequently detected in poorly differentiated carcinoma(x2=38.660,P＜0.001),T2/T3 stage(x2=6.528,P=0.011)and TNM stage Ⅲ(x2=12.522,P＜0.05).In addition,patients with high expression of ERCC6L had higher rates of lymph node metastasis(x2=5.802,P＜0.05),lymphovascular invasion(x2=29.899,P＜0.05)and pleural invasion(x2=7.942,P＜0.05)than those with low expression(P＜0.05).Survival analysis revealed that patients with high expression of ERCC6L had a worse prognosis than those with low expression,and the 5-year overall survival(OS)rate of two patient groups was 44.8％and 70.5％,respectively(x2=15.919,P＜0.05).Univariate and multivariate Cox regression analysis demonstrated that high expression of ERCC6L(HR=2.106,95％CI=1.087-4.079,P＜0.05)was an independent prognostic factor for NSCLC patients.Conclusion High expression of ERCC6L is closely correlated to tumor aggressive features,and it might be a valuable prognostic biomarker for NSCLC patients.

Objective To investigate the status and developmental trends of clinical trials for weight control drugs in China,and to provide data support for sponsors,researchers,and regulatory authorities.Methods The drug clinical trial registration and information platform of the National Medical Products Administration was utilized to search for registered clinical trials of weight control drugs from November 2012 to June 2024.The search employed"overweight","obesity",and"weight loss"as keywords.The information collected included project registration time,drug name,dosage form,drug classification,indications,trial staging,study progress,design type,lead unit,and sponsor.Microsoft Office Excel software was employed for data entry,organization,and extraction.Results A total of 95 registered clinical trials of weight control drugs were identified,comprising 40 domestic multicenter trials,47 domestic single-center trials,and 8 international multicenter trials.Regarding trial phasing,46(48.4％)were phase Ⅰ clinical trials,17(17.9％)were phase Ⅱ clinical trials,19(20.0％)were phase Ⅲ clinical trials,and 13(13.7％)were bioequivalence trials.The drug categorization encompassed 22 chemical drugs,20 biological products,and 1 traditional Chinese medicine/natural drug.Concerning drug dosage forms,there were 32 items of injectable dosage forms,8 items of tablets,2 items of capsules,and 1 item of chewable tablets.Conclusions Registered clinical trials for weight-loss medications in China are predominantly concentrated in regions with developed medical resources.Injectable biologics constitute most test drugs,with most drugs in the early stages of research and development.The examination of the safety and efficacy of these drugs remains to be substantiated,and it is anticipated that a considerable period will elapse before their approval and market introduction.

Objective:To present a set of clinically representative quality assurance (QA) test cases for stereotactic radiosurgery (SRT) plans of multiple intracranial metastases, in order to assess the plan quality and machine execution capabilities.Methods:Based on the clinical characteristics of multiple brain metastases, four groups of test cases with three target volumes (TVs), six TVs, nine TVs, and TVs near organs at risk (OARs) were designed. For these cases, SRT plans were developed, and plan quality was assessed using metrics including the Radiation Therapy Oncology Group conformality index (RTOG CI), gradient index (GI), homogeneity index (HI), and the volume of normal brain tissue receiving a dose of 24 Gy ( V24 Gy), which was defined as the volume enclosed by the 24 Gy isodose line around the Brain-PTV ( V24 Gy of Brain-PTV). Verification plans were generated for each test case, including the verification of point doses, planar doses (PD), and SRS MapCHECK (SMC) semiconductor matrix planar doses. Compared with the calculated result of the treatment planning system (TPS), the criteria for the γ analysis of planar doses were set at 1 mm/2% and 2 mm/2%. Results:For the four groups of test cases, the mean CI, GI, HI, and V24 Gy of Brain-PTV were 1.04±0.03, 3.79±0.40, 0.73±0.01 and (7.46±3.80) cm 3, respectively. The mean deviations of the point doses were 0.88%±0.98%, 1.47%±0.79%, 1.52%± 0.76%, and 1.17% ± 0.38%, respectively. The mean γ passing rates of the single fields for PDs were greater than 98% at 2 mm/2% and exceeding 96% at 1 mm/2%, and the mean γ pass rates of the SMC semiconductor matrix for PDs were 97.75% ± 2.31% and 99.33% ± 0.62%, at 1 mm/2% and 2 mm/2% respectively. Conclusions:The proposed QA test cases for SRT of multiple intracranial metastases allow for the effective assessments of the plan quality and machine execution capabilities and, thus, can assist various centers in clinical applications.

Spectral computed tomography (CT) has triggered a technological revolution in radiodiagnosis while demonstrating its increasing application value in radiotherapy. Employing dual-energy techniques for material decomposition, spectral CT provides optimized solutions for several critical aspects of radiotherapy. Based on a review of the application situation of spectral CT in radiotherapy, this study delved into spectral CT′s significant advantages in image quality improvement, precise dose calculation, and comprehensive quantitative assessment. Furthermore, this study envisioned the development orientations and application prospects of spectral CT.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.

Objective:To establish daily quality assurance workflow based on self-developed phantom to ensure MR-linac performance such as beam accuracy, MR image guidance accuracy, and the clinical treatment workflow to enhance the efficiency of daily quality assurance (QA).Methods:The self-developed phantom was made by 3D printer and used in conjunction with Daily QA-MR detector array. After CT-sim scanning, a treatment plan was designed and transmitted to the accelerator, tests were performed such as image guidance accuracy, beam output and beam quality, the differences in daily QA results between the self-developed phantom and standard phantom recommended by the manufacturer were analyzed by using paired t-test. Results:A total of 24 sets results were collected, the image guide accuracy in the X, Y and Z directions between standard and self-made phantom were (0.1±0.4), (-0.14±0.16), (0.07±0.05) mm and (0±0.02), (-0.02±0.02), (0.02±0.01) mm, respectively, and the differences were statistically significant ( P<0.001, =0.001 and <0.001). Daily QA-MR detector array beam measurement results including output, symmetry, beam quality and field size were -0.11%±0.20%, -0.10%±0.19%, -0.01%±0.08%, (0.4±0.1) mm and (0.2±0.1) mm, respectively. The new process saved 25% (approximately 9 min) of the time compared to the standard process. Conclusions:The new daily QA process for MR-linac is performed based on self-developed phantom and Daily QA-MR detector array. The accuracy and sensitivity meet the requirements and can improve the QA efficiency.

OBJECTIVE: To explore the effect of nano-hydroxyapatite/collagen composite (nHAC) on bone graft fusion after anterior cervical discectomy and fusion (ACDF) in patients with cervical spondylosis and low bone mass. METHODS: A retrospective analysis was conducted on 47 patients with low bone mass who underwent ACDF from 2017 to 2021. They were divided into the nHAC group and the allogeneic bone group according to different bone graft materials. The nHAC group included 26 cases, with 8 males and 18 females;aged 50 to 78 years old with an average of (62.81±7.79) years old;the CT value of C₂-C₇ vertebrae was (264.16±36.33) HU. The allogeneic bone group included 21 cases, with 9 males and 12 females;aged 54 to 75 years old with an average of (65.95±6.58) years old;the CT value of C₂-C₇ vertebrae was (272.39±40.44) HU. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) spinal cord function score were compared before surgery, 1 week after surgery, and at the last follow-up to evaluate the clinical efficacy. Imaging assessment included C₂-C₇ Cobb angle, surgical segment height, intervertebral fusion, and whether the cage subsidence occurred at 1 week after surgery and the last follow-up. RESULTS: The follow-up duration ranged from 26 to 39 months with an average of (33.27±3.34) months in the nHAC group and 26 to 41 months with an average of (31.86±3.57) months in the allogeneic bone group. At 1 week after surgery and the last follow-up, the VAS, NDI scores, and JOA scores in both groups were significantly improved compared with those before surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the C₂-C₇ Cobb angles in the nHAC group and the allogeneic bone group were (14.26±10.32)° and (14.28±8.20)° respectively, which were significantly different from those before surgery (P<0.05). At the last follow-up, the C₂-C₇ Cobb angles in both groups were smaller than those at 1 week after surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the height of the surgical segment in the nHAC group was (31.65±2.55) mm, and that in the allogeneic bone group was (33.63±3.26) mm, which were significantly different from those before surgery (P<0.05). At the last follow-up, the height of the surgical segment in both groups decreased compared with that at 1 week after surgery, with statistically significant differences (P<0.05). At the last follow-up, 39 surgical segments were fused and 6 cages subsided in the nHAC group;40 surgical segments were fused and 7 cages subsided in the allogeneic bone group;there was no statistically significant difference between the two groups (P>0.05). Compared with the CT value of vertebrae without cage subsidence, the CT value of vertebrae with cage subsidence in both groups was significantly lower, with a statistically significant difference (P<0.05). CONCLUSION The application of nHAC in ACDF for patients with low bone mass can achieve effective fusion of the surgical segment. There is no significant difference in improving clinical efficacy, intervertebral fusion, and cage subsidence compared with the allogeneic bone group. With the extension of follow-up time, the C₂-C₇ Cobb angle decreases, the height of the surgical segment is lost, and the cage subsides in both the nHAC group and the allogeneic bone group, which may be related to low bone mass. Low bone mass may be one of the risk factors for cervical spine sequence changes, surgical segment height loss, and cage subsidence after ACDF.
Humans ; Male ; Female ; Middle Aged ; Spondylosis/physiopathology* ; Spinal Fusion/methods* ; Cervical Vertebrae/surgery* ; Aged ; Diskectomy ; Durapatite ; Retrospective Studies ; Collagen/chemistry*

Objective To investigate the status and developmental trends of clinical trials for weight control drugs in China,and to provide data support for sponsors,researchers,and regulatory authorities.Methods The drug clinical trial registration and information platform of the National Medical Products Administration was utilized to search for registered clinical trials of weight control drugs from November 2012 to June 2024.The search employed"overweight","obesity",and"weight loss"as keywords.The information collected included project registration time,drug name,dosage form,drug classification,indications,trial staging,study progress,design type,lead unit,and sponsor.Microsoft Office Excel software was employed for data entry,organization,and extraction.Results A total of 95 registered clinical trials of weight control drugs were identified,comprising 40 domestic multicenter trials,47 domestic single-center trials,and 8 international multicenter trials.Regarding trial phasing,46(48.4％)were phase Ⅰ clinical trials,17(17.9％)were phase Ⅱ clinical trials,19(20.0％)were phase Ⅲ clinical trials,and 13(13.7％)were bioequivalence trials.The drug categorization encompassed 22 chemical drugs,20 biological products,and 1 traditional Chinese medicine/natural drug.Concerning drug dosage forms,there were 32 items of injectable dosage forms,8 items of tablets,2 items of capsules,and 1 item of chewable tablets.Conclusions Registered clinical trials for weight-loss medications in China are predominantly concentrated in regions with developed medical resources.Injectable biologics constitute most test drugs,with most drugs in the early stages of research and development.The examination of the safety and efficacy of these drugs remains to be substantiated,and it is anticipated that a considerable period will elapse before their approval and market introduction.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.