Factorial design is an important method for optimizing complex strategies in implementation science. This paper systematically elucidates the origin, types, and core concepts of the factorial design, and then use a brief smoking cessation intervention project as an example to illustrate its specific applications in identifying key factors and testing interactions. Factorial design has the following typical advantages: it can test synergistic and antagonistic effects between factors, provide effect estimates that are broadly valid across the experimental conditions, and offer high statistical efficiency. At the same time, it also has certain limitations, including that its complexity is positively correlated with the number of factors, the need for large sample sizes to detect interactions, the potential for insufficient acceptability of some strategy combinations due to ethical concerns or participant burden, and the complexity of the analytical methods required. In future research, its application should be further optimized by appropriately controlling the number of factors, clearly defining research objectives, and evaluating intervention acceptability, in order to promote the development of precision implementation science.

Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To explore the genes related to primary myelofibrosis (PMF) and signaling pathways as well as the possible clinical significance.Methods:A total of 3 mRNA expression datasets of PMF (GSE26049, GSE61629 and GSE53482) were downloaded from Gene Expression Omnibus (GEO) database, including the data of peripheral blood samples from 55 PMF patients and 58 controls. The differentially expressed genes (DEG) between PMF patients and the controls were identified by using online tool GEO2R. Gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the common DEG of the 3 datasets, and then protein interaction (PPI) network was constructed. The key nodes of the common DEG in PPI network were calculated by using MCC method and Degree method in cytoHubba program; finally the top 10 hub genes were selected and the hub genes shared by the 2 methods were obtained. Peripheral blood samples of 25 PMF patients and 10 controls (normal hematopoietic stem cell transplant donors or iron deficiency anemia patients) admitted to the Second Hospital of Shanxi Medical University from September 2017 to June 2021 were retrospectively collected. Reverse transcription-fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of 10 screened common hub genes in each sample, and the expressions of all genes at transcriptional level of the two groups were compared.Results:A total of 239 common DEG between PMF patients and the controls were screened out in the 3 datasets, including 153 downregulated DEG and 86 upregulated DEG. The GO enrichment analysis showed that the common downregulated DEG were significantly enriched in negative regulation of transcription, translation and fibroblast proliferation, while the upregulated DEG were mainly enriched in protein ubiquitination and ubiquitin-dependent protein catabolic process. The KEGG pathway analysis indicated that the upregulated common DEG and downregulated common DEG were both enriched in PI3K/Akt signaling pathway, cancer pathways and transcriptional misregulation in cancer. There were 8 common hub genes shared by the 2 methods among the top 10 genes ranked by MCC and Degree methods, including 6 downregulated common DEG (TP53, MYC, ATM, FYN, PTPRC and ATRX) and 2 upregulated common DEG (VEGFA and FOXO3). These above 8 common hub genes were mainly involved in PI3K/Akt signaling pathway, cell cycle and cancer transcriptional regulation signaling pathways. RT-qPCR detection of clinical peripheral blood samples showed that the relative expression levels of mRNA in 6 downregulated common DEG of PMF patients were lower compared with those in controls, while the differences were not statistically significant (all P > 0.05); the relative expression levels of mRNA in 2 upregulated common DEG of PMF patients were higher compared with those in controls, and the differences were statistically significant ( U value was 33.00, 36.00, respectively; P value was 0.021, 0.033, respectively). Conclusions:Bioinformatics and clinical sample verification show that VEGFA and FOXO3 are up-regulated in PMF patients, which are mainly involved in the PI3K/Akt signaling pathway, cell cycle and cancer transcriptional regulation signaling pathway. Both genes may be related to the development of PMF and may become potential therapeutic targets.

Objective To observe the value of ultrasound radiomics for distinguishing early and middle-late stage endometrial cancer(EC).Methods A total of 294 women with EC were retrospectively enrolled,including 196 in early stage and 98 in middle-late stage.The patients were randomly divided into training set(n=206)and validation set(n=88)at the ratio of 7∶3.Clinical data were compared between different stages,and a clinical model was constructed.Radiomics features were extracted and screened based on ultrasound data,and radiomics models were constructed with logistic regression(LR),random forest(RF),support vector machine(SVM),Gaussian naive Bayes(GNB)and extreme gradient boosting(XGBoost),respectively.Finally,a clinical-radiomics model was constructed.The value of each model for distinguishing early and middle-late stages EC was observed.Results Significant differences of age of consultation,menstrual disorders,abdominal pain and proportion of menopause were found between patients with early and middle-late stage EC(all P＜0.05).Among these 5 radiomics models,RF model had the highest area under the curve(AUC)for distinguishing early and middle-late stage EC.Pairwise comparison of clinical model,RF radiomics model and clinical-RF radiomics model showed that significant differences of AUC were found between each 2 models(all P＜0.05),and clinical-RF radiomics model had the highest AUC.Conclusion Ultrasound radiomics based on RF were helpful for distinguishing early and middle-late stage EC,and better diagnostic efficacy could be obtained through combining with clinical data.

Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

Objective To compare the correlation and consistency of liquid chromatography-tandem mass spectrometry(LC-MS/MS)and electrochemiluminescence immunoassay(ECLIA)in the determination of se-rum 25-hydroxyvitamin D[25(OH)D],in order to guide the clinical selection of appropriate detection meth-ods.Methods A total of clinical serum samples were collected from the laboratory,and 25(OH)D levels were detected by LC-MS/MS and ECLIA,respectively.Passing-Boblok regression was used to analyze the correla-tion between the two methods,and Bland-Altman and Mountain plot were used to evaluate the agreement be-tween the two methods.Serum 25(OH)D<20.0 ng/mL was defined as vitamin D deficiency,and serum 25(OH)D as 20.0-<30.0 ng/mL was defined as vitamin D insufficiency.Kappa analysis was used to determine the coincidence rate of the two methods in the diagnosis of vitamin D nutritional status.Results The 25(OH)D levels detected by LC-MS/MS and ECLIA were(26.67±4.79)ng/mL and(39.33±4.09)ng/mL,respec-tively.The regression equation of the two methods was YECLIA=-4.558 1+1.719 8XLC-MS/MS,the slope was 1.719 8(95%CI 1.586 3-1.828 4),excluded 1,and the intercept was 4.558 1(95%CI-7.692 2--2.122 1),excluded 0,prompt system difference or ratio differences of the two methods.There were system-atic or proportional differences between the two methods.The Bland-Altman figure showed two methods aver-ages was 12.7,and the difference of out points(ratio)was 3.19%.The peak value of the mountain plot was-9.17 ng/mL,with more deviations from 0,indicating poor agreement between the results measured by the two methods.The Kappa coefficient of the two methods for judging vitamin D deficiency was 0.875,and the diagnostic coincidence rate was 94.68%.The Kappa coefficient of the two methods for judging vitamin D in-sufficiency was 0.538,and the diagnostic coincidence rate was 75.53%.Conclusion The agreement between ECLIA and LC-MS/MS is poor,but the agreement between ECLIA and LC-MS/MS in the diagnosis of vita-min D deficiency and insufficiency based on nutritional status is high.

Objective:To investigate the advantage of three dimensional(3D)-printed tissue compensators in radiotherapy for superficial tumors at irregular sites.Methods:A subcutaneous xenograft model of prostate cancer in nude mice was established. Mice were randomly divided into no tissue compensator group( n=6), common tissue compensator group( n=6), and 3D-printed tissue compensator group( n=6). Computed tomography (CT) images of nude mice in the 3D-printed tissue compensator group were acquired. Compensator models were made using polylactic acid, and material properties were evaluated by measuring electron density. CT positioning images of the three groups after covering the corresponding tissue compensators were acquired to delineate the gross tumor volume (GTV). Nude mice in the three groups were irradiated with 6 MV X-rays at the prescribed dose. The prescribed dose for the three groups was 1 500 cGy. The dose distribution in the GTV of the three groups was calculated and compared using the analytical anisotropic algorithm in the Eclipse 13.5 treatment planning system. The metal-oxide-semiconductor field-effect transistor was used to verify the actual dose received on the skin surface of nude mice. Results:The air gap in the 3D-printed tissue compensator group and the common tissue compensator group was 0.20±0.07 and 0.37±0.07 cm 3, respectively ( t=4.02, P<0.01). For the no tissue compensator group, common tissue compensator group, and 3D-printed tissue compensator group, the D95% in the target volume was (1 188.58±92.21), (1 369.90±146.23), and (1 440.29±45.78) cGy, respectively ( F=9.49, P<0.01). D98% was (1 080.13±88.30), (1 302.76±158.43), and (1 360.23±48.71) cGy, respectively ( F=11.17, P<0.01). Dmean was (1 549.08±44.22), (1 593.05±65.40), and (1 638.87±40.83) cGy, respectively ( F=4.59, P<0.05). The measured superficial dose was (626.03±26.75), (1 259.83±71.94), and (1 435.30±67.22) cGy, respectively ( F=263.20, P<0.001). The percentage variation in tumor volume growth after radiation was not significantly different between the common tissue compensator group and the 3D-printed tissue compensator group ( P>0.05). Conclusions:3D-printed tissue compensators fit well to the body surface, which reduces air gaps, effectively increases the dose on the body surface near the target volume, and provides ideas for radiotherapy for superficial tumors at some irregular sites.