OBJECTIVE: To evaluate the feasibility and accuracy of cone-beam CT (CBCT) images for radiotherapy dose calculation in pelvic tumors. METHODS: An improved volumetric density coverage method was used to establish CT value-relative electron density (RED) curves for CBCT images. The planning CT plans were transferred to the CBCT images, and the constructed density curves were applied to calculate doses for CBCT plans while maintaining the optimization parameters unchanged. Dose calculation deviations between the two plans were analyzed. RESULTS: The mean differences in dosimetric parameters for the target volume and organs at risk (OAR) between the two plans were less than 1% and 1.5%, respectively. The target conformity index (CI), homogeneity index (HI), and gamma passing rates were highly consistent, with no statistically significant differences. CONCLUSION CBCT images corrected by this method can be used for dose calculation in pelvic tumor radiotherapy planning.
Cone-Beam Computed Tomography/methods* ; Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Pelvic Neoplasms/diagnostic imaging*

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Objective: To analyze the association between latent class of health-risk behaviors and depressive symptoms among middle school students, so as to provide the evidence for the prevention and intervention of depressive symptoms among middle school students. Methods: Students in two junior high schools, two senior high schools and one vocational high school in Yinzhou District, Ningbo City, Zhejiang Province, were selected using a stratified multi-stage cluster sampling method. Demography and health-risk behaviors were collected using questionnaire surveys, depressive symptoms were investigated using the Center for Epidemiological Studies Depression-10 Scale, and latent class analysis was conducted for health-risk behaviors. The association between different latent classes and depressive symptoms was analyzed using a multivariable logistic regression model. Results: A total of 1 247 students were surveyed, including 641 boys (51.40%) and 606 girls (48.60%). There were 452 junior high school students (36.25%), 532 high school students (42.66%) and 263 vocational high school students (21.09%). Latent class analysis showed that health-risk behaviors in students were classified into three groups, namely healthy behavior group (52.93%), poor diet group (39.94%) and high-risk behavior group (7.14%), and the detection rates of depressive symptoms were 7.12%, 18.88% and 52.81%, respectively, with a statistically significant difference between groups (P<0.05). Multivariable logistic regression analysis showed that after adjusting for age, gender, native place, only child and living on campus, the poor diet group (OR=3.107, 95%CI: 2.086-4.627) and high-risk behavior group (OR=15.401, 95%CI: 9.031-26.262) had higher risks of depressive symptoms compared with the healthy behavior group. Conclusion Having high-risk behaviors and poor diet may increase the risk of developing depressive symptoms among middle school students.

Objective To compare the influence between self-monitoring of blood gluocose(SMBG)combined with digital diabetes management and traditional management mode on the related clinical indexes in the patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM treated in the endocrinology and metabolism outpatient department of this hospital from January 2022 to June 2022 and meeting the inclusion criteria of this study were successively included.They were divided into the experimental group and control group.The experimental group was managed by SMBG combined with digital diabetes man-agement mode,while the control group adopted the traditional management mode,the outpatient clinic follow up once a month.After 6 months of follow-up,fasting blood glucose,glycosylated hemoglobin(HbA1c),low density lipoprotein cholesterol(LDL-C)and urinary microalbumin/creatinine ratio(UACR)were compared between the two groups.Results The FBG,HbA1c,LDL-C,and UACR of the experimental group decreased after intervention when compared with baseline.Compared with the control group,the FBG[8.7(7.7,9.2)mmol/L vs.10.8(8.8,12.7)mmol/L,Z=-4.660,P＜0.001],HbA1c[6.3％(5.3,7.8)％vs.8.5％(7.2,10.0)％,Z=-5.130,P＜0.001],LDL-C[2.6(1.8,3.1)mmol/L vs.3.3(2.6,4.0)mmol/L,Z=-4.112,P＜0.001],UACR[16.1(3.5,46.5)mg/g vs.58.4(11.9,108.0)mg/g,Z=-2.220,P=0.026]for patients in the expriemental group after intervention were significantly decreased.Conclusion SMBG combined with digital diabetes management model can significantly improve the clinical indicators of patients.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decy-sin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online da-tabases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcino-ma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancre-atic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling path-way agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migra-tion.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,N-cadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related pro-teins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the prolifera-tion,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

Objectives:To explore the clinicopathological characteristics and prognostic risk factors in differentiated thyroid cancer (DTC) patients with lung metastasis.Methods:Patients of differentiated thyroid cancer with lung metastasis in Tianjin Medical University Cancer Institute & Hospital were enrolled from Jan 1, 2010 to Dec 31, 2016. The clinicopathological characteristics and risk factors affecting the prognosis were analyzed retrospectively.Results:A total of 65 DTC patients with lung metastasis were collected in this study, including 56 patients with papillary thyroid carcinoma and 9 patients with follicular thyroid carcinoma; 23 patients died and 42 patients survived. Median follow-up time was 99.4 months. There were 18 males, 47 females. Age 14-73 years, median age 51.0 years. High incidence of DTC lung metastasis was 50-59 years for males and 40-49 years for females. Based on AJCC 8th edition TNM staging, there were 37 patients in stage Ⅱ (age <55 years) and 28 patients in stage Ⅳb (age ≥55 years). The number of 131Ⅰ treatments performed ranged from 1 to 13 times, with a mean of 3.9 times. Firty-five patients were with lung metastasis alone, and 10 patients with lung metastasis and distant metastasis in other organs. Eleven patients suffered from hypoparathyroidism after 131Ⅰ treatment. COX multifactorial regression analysis found that age was independent risk factor affecting prognosis, multiple organs distant metastasis and pathologic subtype were relative risk factors affecting prognosis. There was no correlation between gender, number of 131Ⅰ treatments and poor prognosis. Conclusions:DTC has a high survival even with the occurrence of lung metastasis, but the prognosis is poor when combined with multi-organ metastasis. Age and multiple organ distant metastatic are independent risk factors affecting prognosis.

ObjectiveThe hygroscopic properties of Mume Flos decoction pieces were studied from the perspectives of macroscopic［water activity（A_w）］ and microscopic（water molecular mobility）， which provided a theoretical basis for the determination of the safe storage moisture content. MethodAdsorption isotherm of Mume Flos decoction pieces was obtained by static weighing method， and seven common hygroscopic models were fitted and estimated. The best model was selected according to the principle that determination coefficient（R²） was closer to 1， residual sum of squares（RSS） was closer to 0 and Akaike information criterion（AIC） was smaller. According to the optimal model， the absolute and relative safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ was calculated. Low-field nuclear magnetic resonance（LF-NMR） was used to measure the water molecular mobility in the hygroscopic process of Mume Flos decoction pieces. ResultThe best model to describe the adsorption isotherm of Mume Flos decoction pieces was the Peleg model. According to the model expression， the absolute safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ were 9.59%， 7.96% and 7.68%， and the relative safe moisture contents were 13.05%， 11.99%， 11.77%， respectively. Mume Flos decoction pieces all contained two water states during the process of hygroscopic absorption at different temperatures， namely bound water T₂₁ and free water T₂₂. During the process of hygroscopic absorption， bound water had the largest increase in peak area. The sum of peak areas of the bound water and free water had a good linear relationship with the moisture contents， and the R² were 0.959 9， 0.911 8 and 0.974 7 at 25， 35， 45 ℃， respectively. When A_w<0.57， T₂₁ did not change， and the water molecular mobility remained unchanged. When A_w>0.57， T₂₁ showed an increasing trend， and the water molecular mobility increased. The moisture contents of Mume Flos decoction pieces were 8.44%， 6.81% and 6.25% when the water molecular mobility increased at 25， 35， 45 ℃， respectively. ConclusionCombined with the theory of water activity and water molecular mobility， 6.25% is recommended as the safe storage moisture content of Mume Flos decoction pieces， this study can provide reference for determining the safe storage moisture content of other decoction pieces.

Long non-coding RNA (lncRNA) is an RNA molecule that does not code to express proteins, and plays an important role in the occurrence and development of a variety of tumors. As an lncRNA, SPRY4-IT1 is highly expressed in breast cancer tissues, and can be used as an upstream and downstream regulator of breast cancer, promoting the progression of breast cancer, and is closely related to breast cancer stage and prognosis. In-depth study of the molecular mechanism associated with SPRY4-IT1 and breast cancer can provide new ideas for discovering biomarkers for early diagnosis of breast cancer, assessing disease prognosis and finding targeting sites.