Objective:To investigate the radiation field distribution characteristics in a 9 MeV electron FLASH (e-FLASH) linear accelerator treatment room.Methods:The Geant4 Monte Carlo program was employed for physical simulating of the radiation field distribution inside and outside the treatment room under a single-beam delivery condition with a total dose of 50 Gy at the reference point and a dose rate of 250 Gy/s. High-sensitivity radiation detectors (AT1123) were used to validate the measurements at key points.Results:The dose rate at the reference point was approximately 9×10 11 μSv/h. Due to the scattering and shielding effects, the deviation of the attenuation rate from the inverse-square law was observed and the isodose lines exhibited spatial drift. Measured dose rates at key points showed good agreement with the simulation result, with a maximum deviation within 30%. Conclusions:The complex radiation field distribution can be effectively simulated using Geant4 in an e-FLASH treatment room. This indicated the Geant4 is not only applicable for the shielding calculations in e-FLASH radiotherapy facilities, but also for the design optimization through, reduction of trial-and-error iterations and engineering costs.

OBJECTIVE To construct and evaluate nomogram prediction model for refractory chemotherapy-induced nausea and vomiting （CINV）. METHODS The data of malignant tumor patients who received chemotherapy at the Third People’s Hospital of Zhengzhou from January 2017 to December 2023 were collected. These patients were categorized into the occurrence group and the non-occurrence group according to the occurrence of refractory CINV. Multivariate Logistic regression analysis was employed to screen predictive factors for refractory CINV and constructing a nomogram prediction model. Model performance was assessed via receiver operating characteristic curve analysis. Model calibration was evaluated using Bootstrap resampling. Decision curve analysis （DCA） was used to determine the clinical net benefit of three strategies under different risk thresholds. Clinical impact curves were utilized to assess the clinical value of the model at different risk thresholds. Shapley additive explanations （SHAP） analysis was performed to evaluate individual factor contributions to the predictive model. RESULTS A total of 388 patients were included， with 219 experiencing refractory CINV. Multivariate Logistic regression identified 11 predictive factors for refractory CINV， including gastrointestinal disease history， anticipated nausea and vomiting， chemotherapy-induced emetic risk classification， and electrolyte levels， etc. The model’s area under the curve was 0.80 [95% confidence interval （0.76， 0.84）]， with a mean error of 0.036. DCA demonstrated the prediction model had higher clinical net benefit when the risk threshold was between 0.05 and 0.85. SHAP analysis revealed the top three predictive factors as gastrointestinal disease history （0.924）， chemotherapy- induced emetic risk classification （0.866）， and electrolyte levels （0.581）. CONCLUSIONS Eleven factors， including gastrointestinal disease history， anticipated nausea and vomiting， chemotherapy-induced emetic risk classification， and electrolyte levels， are identified as predictors of refractory CINV. The model based on these factors has good predictive ability， which can be used to predict the risk of refractory CINV.

Objective:To investigate the radiation field distribution characteristics in a 9 MeV electron FLASH (e-FLASH) linear accelerator treatment room.Methods:The Geant4 Monte Carlo program was employed for physical simulating of the radiation field distribution inside and outside the treatment room under a single-beam delivery condition with a total dose of 50 Gy at the reference point and a dose rate of 250 Gy/s. High-sensitivity radiation detectors (AT1123) were used to validate the measurements at key points.Results:The dose rate at the reference point was approximately 9×10 11 μSv/h. Due to the scattering and shielding effects, the deviation of the attenuation rate from the inverse-square law was observed and the isodose lines exhibited spatial drift. Measured dose rates at key points showed good agreement with the simulation result, with a maximum deviation within 30%. Conclusions:The complex radiation field distribution can be effectively simulated using Geant4 in an e-FLASH treatment room. This indicated the Geant4 is not only applicable for the shielding calculations in e-FLASH radiotherapy facilities, but also for the design optimization through, reduction of trial-and-error iterations and engineering costs.

Objective:To investigate the prognosis of rectal cancer patients with wait and see strategy after near clinical complete response(near-cCR) to neoadjuvant therapy and influencing factors for tumor recurrence.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 463 patients with low advanced rectal cancer who underwent neoadjuvant therapy, including 89 cases in Shanxi Provincial People's Hospital and 374 cases in Shanxi Cancer Hospital, from January 2013 to December 2017 were collected. There were 258 males and 205 females, aged (62±7)years. Patients received efficacy evaluation at 6 weeks after neoadjuvant therapy, in which patients with near-cCR who adhered to wait and see strategy received 6 cycles of additional adjuvant chemotherapy after comprehensive reexaminations. Observation indicators: (1)situations of neoadjuvant therapy; (2) influencing factors for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy; (3) prognostic analysis. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to draw survival curve, and the log-rank test was used for survival analysis. The binary logistic regression model was used for univariate and multivariate analyses. Results:(1)Situations of neoadjuvant therapy. There were 136 patients achieving near-cCR after neoadjuvant therapy, including 86 cases adhering to wait and see strategy and 50 cases undergoing laparoscopic radical resection of rectal cancer. Of 86 cases with wait and see strategy, 29 cases were in clinical stage Ⅱ and 57 cases were in stage Ⅲ. There were 27 cases of scar type, 16 cases of ulcer type, 20 cases of nodule type, 23 cases of inflammatory edema type based on endoscopic tumor regression. (2) Influencing factors for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy. Results of multivariate analysis showed that age was an indepen-dent protective factor for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy ( odds ratio=0.88, 95% confidence interval as 0.81-0.97, P<0.05). Compared with scar type, the ulcer type was an independent risk factor ( odds ratio=4.22, 95% confidence interval as 1.01-17.64, P<0.05). (3) Prognostic analysis. All the 136 patients achieving near-cCR were followed up for 65(range, 60-72)months. The 5-year overall survival rate was 84.9% of 86 patients with wait and see strategy, versus 76.0% of 50 patients undergoing laparoscopic radical resection of rectal cancer, showing no significant difference between them ( χ2=1.94, P>0.05). Of 86 patients with wait and see strategy, the 5-year overall survival rate was 81.5%, 75.0%, 85.0%, 95.7% for cases of scar type, ulcer type, nodule type, inflammatory edema type, showing no significant difference among them ( χ2=3.64, P>0.05). Conclusions:Compared with laparoscopic radical resec-tion of rectal cancer, wait and see strategy is safe and feasible for rectal cancer patients after near-cCR to neoadjuvant therapy. Age is an independent protective factor for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy. Compared with scar type, ulcer type is an independent risk factor.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

Objective:To investigate the prognosis of rectal cancer patients with wait and see strategy after near clinical complete response(near-cCR) to neoadjuvant therapy and influencing factors for tumor recurrence.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 463 patients with low advanced rectal cancer who underwent neoadjuvant therapy, including 89 cases in Shanxi Provincial People's Hospital and 374 cases in Shanxi Cancer Hospital, from January 2013 to December 2017 were collected. There were 258 males and 205 females, aged (62±7)years. Patients received efficacy evaluation at 6 weeks after neoadjuvant therapy, in which patients with near-cCR who adhered to wait and see strategy received 6 cycles of additional adjuvant chemotherapy after comprehensive reexaminations. Observation indicators: (1)situations of neoadjuvant therapy; (2) influencing factors for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy; (3) prognostic analysis. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to draw survival curve, and the log-rank test was used for survival analysis. The binary logistic regression model was used for univariate and multivariate analyses. Results:(1)Situations of neoadjuvant therapy. There were 136 patients achieving near-cCR after neoadjuvant therapy, including 86 cases adhering to wait and see strategy and 50 cases undergoing laparoscopic radical resection of rectal cancer. Of 86 cases with wait and see strategy, 29 cases were in clinical stage Ⅱ and 57 cases were in stage Ⅲ. There were 27 cases of scar type, 16 cases of ulcer type, 20 cases of nodule type, 23 cases of inflammatory edema type based on endoscopic tumor regression. (2) Influencing factors for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy. Results of multivariate analysis showed that age was an indepen-dent protective factor for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy ( odds ratio=0.88, 95% confidence interval as 0.81-0.97, P<0.05). Compared with scar type, the ulcer type was an independent risk factor ( odds ratio=4.22, 95% confidence interval as 1.01-17.64, P<0.05). (3) Prognostic analysis. All the 136 patients achieving near-cCR were followed up for 65(range, 60-72)months. The 5-year overall survival rate was 84.9% of 86 patients with wait and see strategy, versus 76.0% of 50 patients undergoing laparoscopic radical resection of rectal cancer, showing no significant difference between them ( χ2=1.94, P>0.05). Of 86 patients with wait and see strategy, the 5-year overall survival rate was 81.5%, 75.0%, 85.0%, 95.7% for cases of scar type, ulcer type, nodule type, inflammatory edema type, showing no significant difference among them ( χ2=3.64, P>0.05). Conclusions:Compared with laparoscopic radical resec-tion of rectal cancer, wait and see strategy is safe and feasible for rectal cancer patients after near-cCR to neoadjuvant therapy. Age is an independent protective factor for tumor recurrence of rectal cancer patients with wait and see strategy after near-cCR to neoadjuvant therapy. Compared with scar type, ulcer type is an independent risk factor.

Objective:To investigate the risk factors affecting pathological diagnosis upgrading after resection of colorectal laterally spreading tumor (LST).Methods:From June 2018 to December 2022, the clinical data of 256 patients with LST (297 lesions) admitted to Shanxi Provincial Cancer Hospital were retrospectively included as an modeling group.From January 2023 to January 2024, 125 patients with LST (129 lesions) were collected as an external validation group. The pathological diagnosis of endoscopic forceps biopsy (EFB) samples and the resected LST tissue of modeling group were compared, and the patients were divided into pathological non-difference group and pathological upgrading group. The clinical data such as gender, age, body mass index (BMI), pre-resection carcinoembryonic antigen levels, drinking history, smoking history, family history of colorectal cancer, and whether complicated with underlying diseases as well as endoscopic surface morphological features such as lesion size, morphological features, and lesion location were compared between the two groups. Chi-square test was used for statistical analysis, and multivariate logistic regression analysis was used to identify the risk factors for pathological diagnosis upgrading after resection. Based on the independent risk factors, the prediction models were established and validated by nomogram. The receiver operating characteristic curve (ROC) of repeated samples within the modeling group and external validation growp was plotted, and the area under the curve (AUC) was used to evaluate the predictive value of the model.Results:The proportion of patients with family history of colorectal cancer in the pathological upgrading group was higher than that of the pathological non-difference group (38.7%, 12/31 vs. 22.2%, 50/225), and the difference was statistically significant ( χ2=4.04, P=0.045). There were statistically significant differences in lesion size (63.9% (23/36) and 44.4% (116/261) lesions with long diameter ≥2 cm, respectively), surface morphological characteristics (flat elevated type accounted for 8.3% (3/36) and 22.6% (59/261), granular uniform type accounted for 11.1% (4/36) and 28.0% (73/261), nodular mixed type accounted for 44.4% (6/36) and 24.9% (65/261), pseudo-depressed type accounted for 36.1% (13/36) and 24.5% (64/261)), and lesion location (distal colon accounted for 22.2% (8/36) and 33.3% (87/261), proximal colon accounted for 16.7% (6/36) and 28.7% (75/261), and rectum accounted for 61.1% (22/36) and 37.9% (99/261)) between the pathological upgrading group and the pathological non-difference group ( χ2=4.80, 12.62 and 7.08, all P<0.05). The results of multivariate logistic regression analysis showed that family history of colorectal cancer ( OR=2.211, 95% confidence interval (95% CI) 1.005 to 4.861, P=0.049), lesion length ≥ 2 cm ( OR=2.212, 95% CI 1.074 to 4.555, P=0.031), nodular mixed subtype ( OR=4.841, 95% CI 1.343 to 17.455, P=0.016), pseudo-depressed subtype ( OR=3.995, 95% CI 1.084 to 14.721, P=0.037), and lesion in rectum ( OR=2.417, 95% CI 1.024 to 5.705, P=0.044) were independent risk factors for pathological diagnosis upgrading after LST resection. A nomogram was established based on these four risk factors, with a ROC AUC of 0.833 (95% CI 0.752 to 0.913). The external validation results demonstrated that the ROC AUC was 0.848 (95% CI 0.736 to 0.960), the sensitivity was 0.737, the specificity was 0.972, the maximum Youden index was 0.712, and the overall accuracy was 0.868. Conclusions:Family history of colorectal cancer, lesion length ≥ 2 cm, lesion in rectum, and nodular mixed or pseudo-depressed subtypes may affect the accuracy of pathological diagnosis of LST lesions by EFB, and leading to pathological diagnosis upgrading after resection. The prediction model based on these four factors has good predictive efficacy in pathological diagnosis upgrading after LST resection.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

Objective:To preliminarily explore the related factors that affect chimera mosaicism in in vitro fertilization (IVF) treatment. Methods:A case-control study was conducted to retrospectively analyze the clinical data of 2252 blastocysts in 579 preimplantation genetic testing (PGT) cycles in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2020. Biopsy cells were analyzed by next generation sequencing (NGS). According to the analysis results, all embryos were divided into mosaicism group and non-mosaicism group. Mosaicism types included euploid-aneuploid mosaicism, aneuploid-aneuploid mosaicism and complex mosaicism. The population characteristics and laboratory-related parameters of the two groups of embryos were compared, and single-factor and multi-factor analysis of the incidence of mosaicism were performed to evaluate the related factors that affect the development of mosaic embryos.Results:A total of 2252 blastocysts in 579 cycles were included in this study, 905 embryos (40.2%) were euploid, 923 (41.0%) were aneuploid, and 424 (18.8%) were mosaicism. Among them, 228 (10.1%) were euploid-aneuploidy mosaicism, 59 (2.6%) were aneuploidy-aneuploidy mosaicism, and 137 (6.1%) were complex mosaicism. NGS technology was performed in 4 institutions, and the mosaicism rate fluctuated between 7.6% and 26.2%. After adjusting the confounding factors (the age of the male and female partners, the quality of the male partner's sperm, the ovarian stimulation protocols, the type of culture medium, the indications of PGT, the different biopsy operators and the developmental stage of the blastocyst), it was found that the blastocyst trophectoderm cell (TE) score (grade C vs. grade A, P=0.014) and the genetic testing institutions (institution 2 vs. early stage of institution 1, P<0.001; late stage of institution 1 vs. early stage of institution 1, P<0.001) had a significant effect on the occurrence of mosaicism. Compared with the TE score of grade A, the chance of mosaicism in grade C increased by 66% (a OR=1.66, 95% CI=1.11-2.50, P=0.014). Compared with the early stage of institution 1, the incidence of mosaicism in institution 2 and late stage of institution 1 was 2.28 times (a OR=2.28, 95% CI=1.71-3.04, P<0.001), and late stage of institution 1 was 2.17 times that of the early stage (a OR=2.17, 95% CI=1.41-3.34, P<0.001). Conclusion:The incidence of mosaicism during IVF treatment is related to NGS genetic testing institutions and the quality of trophectoderm cells

Objective:To analyze the value of dual energy CT parameters combined with serum procollagen Ⅰ N-terminal propeptide (PⅠNP) and beta C-terminal cross-linked telopeptide of type Ⅰ collagen (β-CTX) in differential diagnosis of spinal bone metastasis from lung cancer and myeloma.Methods:The clinical data of 54 patients with spinal bone metastasis from lung cancer and 50 patients with myeloma in Jincheng People′s Hospital from October 2019 to March 2021 were analyzed retrospectively. All patients were examined by dual energy CT on the day of admission, and the CT values at the energy levels of 40 to 80 keV (energy interval of 10 keV) were recorded. The serum PⅠNP and β-CTX levels were detected by chemiluminescent assay before treatment. The pathological examination results were taken as gold standard, and the CT values at the energy levels of 40 to 80 keV by dual energy CT and serum PⅠNP and β-CTX levels were compared between 2 groups. Receiver operating characteristic (ROC) curve was used to analyze the differential diagnosis value of the CT values at the energy levels of 40 to 80 keV, serum PⅠNP and β-CTX levels alone and combination.Results:The CT values at the energy levels of 40 to 80 keV by dual energy CT and serum PⅠNP and β-CTX levels in patients with spinal bone metastasis from lung cancer were significantly higher than those in patients with myeloma: 79.86 (61.20, 116.32) HU vs. 58.29 (46.92, 64.03) HU, 64.48 (50.27, 90.08) HU vs. 45.78 (38.59, 56.75) HU, 57.35 (43.31, 78.04) HU vs. 43.62 (36.91, 54.06) HU, 52.05 (42.98, 75.79) HU vs. 41.26 (32.84, 51.76) HU, 45.52 (38.55, 63.59) HU vs. 36.68 (28.72, 49.83) HU, 66.35 (31.15, 81.97) μg/L vs. 31.38 (27.76, 34.50) μg/L and 0.61 (0.48, 0.67) μg/L vs. 0.49 (0.47, 0.52) μg/L, and there were statistical differences ( P<0.05 or <0.01). ROC curve analysis result showed that the sensitivity of the combination of the CT values at the energy levels of 40 to 80 keV by dual energy CT was higher than those alone (83.33% vs. 59.26%, 61.11%, 62.96%, 64.81% and 66.67), the area under the curve (AUC) was also higher than those alone (0.882 vs. 0.798, 0.811, 0.817, 0.801 and 0.773), and there were statistical differences ( P<0.01 or <0.05); the sensitivity of the combination of serum PⅠNP and β-CTX levels was higher than those alone (81.48% vs. 57.41% and 62.96%), the AUC was higher than those alone (0.829 vs. 0.753 and 0.729), and there were statistical differences ( P<0.01 or <0.05); the sensitivity of all indexes combined in the differential diagnosis of spinal bone metastasis from lung cancer and myeloma was higher than those of the combination of the CT values at the energy levels of 40 to 80 keV by dual energy CT, the combination of serum PⅠNP and β-CTX levels (98.15% vs. 83.33% and 81.48%), the same as AUC (0.976 vs. 0.882 and 0.829), and there were statistical differences ( P<0.01); there were no significant differences in the specificity of each index alone and combination ( P>0.05). Conclusions:Compared with myeloma, the CT values at the energy levels of 40 to 80 keV by dual energy CT, serum PⅠNP and β-CTX levels in patients with spinal bone metastasis from lung cancer are increased, and the combination of the above indexes has ideal value in differential diagnosis of the two diseases.