Objective The results of ASTRUM-007 reveal the clinical benefits of PD-L1-positive esophageal squamous cell carcinoma(ESCC)patients.This study aims to analyze the economics of first-line treatment of PD-L1-positive ESCC with brucella combined with chemotherapy from the perspective of China's health system.Methods A three-state partitioned survival model(PSM)including progression-free survival(PFS),disease progression(PD),and death(D)was established to evaluate the economy of serplulimab combined with chemotherapy,the first-line treatment for PD-L1 positive advanced ESCC,compared with the placebo combination chemotherapy.The cycle period was two weeks,the horizon of the simulation was a lifetime,and the annual discount rate was set to 5%.The main outcome parameters are total cost,quality-adjusted life year(QALY),and incremental cost-effectiveness ratio(ICER).One-way sensitivity analysis(OWSA),probability sensitivity analysis(PSA),and scenario analysis were used to evaluate the impact of the change of important parameters in the model on ICER.Results The basic results showed that the incremental effect and incremental cost of the serplulimab combined with chemotherapy compared with the placebo combination chemotherapy were 1.281 QALYs and 266 573.26 yuan,respectively,and the ICER was 208 166.24 yuan/QALY.OWSA showed that the price of serplulimab was the most sensitive parameter to ICER;PSA showed that when the WTP threshold was three times China's per capita GDP in 2022,Serplulimab combined with chemotherapy was significantly more economical than the placebo combination chemotherapy;scenario analysis revealed that according to the ASTRUM-007 study in the Central Asian group and the charitable drug donation program of serplulimab:in patients with PD-L1 1≤CPS<10,ICER was 205 056.83 yuan/QALY;with 218 022.59/QALY in patients with PD-L1 CPS≥10,and the mean value of ICER was lower than three times of China's per capita GDP.The ICER of all patients was 59 046.65 yuan/QALY,with 68 294.42 yuan/QALY of patients with PD-L1 1≤CPS<10,44 744.02 yuan/QALY of patients with PD-L1 CPS≥10.The ICER value was lower than China's per capita GDP.Conclusion Serplulimab combined with chemotherapy is more economical than placebo combined with chemotherapy in the treatment of PD-L1-positive ESCC patients.

ObjectiveTo investigate the mechanism of Biejiajian Wan in the intervention of primary liver cancer based on long non-coding RNA SNHG5 （lncRNA SNHG5）/micro RNA-26a-5p （miRNA-26a-5p）/glycogen synthase kinase-3β （GSK-3β） signal axis. MethodDouble luciferase reporting assay was used to verify the targeted interaction between lncRNA SNHG5 and miRNA-26a-5p， miRNA-26a-5p， and GSK-3β in HepG2 cells. Nude-mouse transplanted tumor model of human HepG2 were established and randomly divided into model group， Biejiajian Wan low-dose group （0.5 g·kg^-1）， medium-dose group （1.0 g·kg^-1）， and high-dose group （2.0 g·kg^-1）， and sorafenib group （100 mg·kg^-1）， with 10 mice in each group. The mice were given intragastric administration of normal saline or drug for 28 days， and the tumor volume was measured at different time. Hematoxylin-eosin （HE） staining was used to observe the histological changes of tumors. The nucleic acid levels of lncRNA SNHG5， miRNA-26a-5p， GSK-3β， and β-catenin mPNA in tumor tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of GSK-3β and β-catenin in tumor tissue were detected by western blot. ResultCompared with the SNHG5-WT （wild type） + miRNA NC （negative control） group， the relative luciferase activities of the SNHG5-WT + miRNA-26a-5p mimic group were decreased （P<0.05）. Compared with the GSK-3β-WT + miRNA NC group， the relative luciferase activity of the GSK-3β-WT + miRNA-26a-5p mimic group was decreased （P<0.05）. Compared with the model group， the tumor volume of Biejiajian Wan low-dose， medium-dose， and high-dose groups was significantly decreased （P<0.05， P<0.01）. Compared with the model group， the cells in the tumor tissue of nude mice in each dose group of Biejiajian Wan were sparsely arranged with necrocytosis， which showed concentration-dependent changes. Compared with the model group， the expression levels of lncRNA SNHG5， GSK-3β， and β-catenin were decreased （P<0.05， P<0.01）， while the expression of miRNA-26a-5p was increased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. Compared with the model group， the protein expression levels of GSK-3β and β-catenin were decreased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. ConclusionBiejiajian Wan may affect the necrosis of liver cancer cells through lncRNA SNHG5/miRNA-26a-5p/GSK-3β signal axis and thus play an anti-tumor role. This research will provide more theoretical basis for the clinical application of Biejiajian Wan.

Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P＜0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P＜0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P＞0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P＜0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P＜0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.

OBJECTIVE To evaluate the cost-effectiveness of sintilimab combined with chemotherapy than single-use chemotherapy in the first-line treatment of advanced， recurrent or metastatic esophageal squamous cell carcinoma （ESCC） from the perspective of health system of our country， and provide reference for rational use of drug in clinic. METHODS Based on ORIENT-15 study data， TreeAge Pro 2011 software was used to establish a three-state Markov model of non-progressive survival （PFS）， disease progression and death for cost-utility analysis. The model period was 3 weeks， the research time limit was 10 years， and the discount rate was 5%. The main outputs of the model were total cost， quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER）. The 1-3 times of China’s GDP per capita in 2021 was taken as the threshold of willing- ness to pay （WTP）. The uncertainty of the parameters was analyzed by single factor sensitivity analysis and probability sensitivity analysis， and the cost-effectiveness of the two schemes was discussed under three situations： different discount rates， comparison with other similar treatment schemes and charitable drug donation schemes. RESULTS The results of basic analysis showed that compared with chemotherapy plan alone， the ICER of sintilimab combined with chemotherapy was 64 208.75 yuan/QALY， which was less than WTP threshold. The results of single factor sensitivity analysis show that PFS state utility value， cycle cost of sintilimab and discount rate had relatively great influence on the results. Probability sensitivity analysis showed that when WTP≥120 000 yuan， the economic probability of sintilimab combined with chemotherapy plan was 100%. The results of situational analysis showed that sintilimab combined chemotherapy was more cost- effective than single-use chemotherapy. CONCLUSIONS Sintilimab combined with chemotherapy is more cost-effective than single-use chemotherapy in the first-line treatment of advanced， recurrent or metastatic ESCC.

Objective:To investigate the effect of ethephon exposure on sperm quality of adolescent male SD rats and the influence mechanism.Methods:A total of 40 45-day-old male SD rats were divided into control group and low, middle and high experimental groups according to the random number table method, 10 rats in each group.The said 4 groups were given 9 g/L normal saline, 100 mg/kg, 200 mg/kg, and 400 mg/kg ethephon aqueous solution for 28 days, respectively.One epididymal tail was taken to prepare sperm suspension, the sperm concentration and motility were detected.The testis and epididymis tissues were stained with HE, and their pathological changes were observed under light microscope.The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) content in the testis were detected.Enzyme linked immunosorbent assay kit was used to mea-sure the epididymal α-glucosidase activity, L-carnitine (LC) content, nuclear factor erythroid 2-related factor 2 (Nrf2) and organic cation transporter 2 (OCTN2) expression levels.Then the oxidative damage caused by ethephon to epididymis was evaluated.SPSS 26.0 software was used for data analysis.Data were compared by One- way ANOVA among groups and LSD method between 2 groups. Results:The sperm concentration of the control group, low, medium and high dose groups were (40.21±1.94)×10 9/L, (35.23±2.53)×10 9/L, (23.61±2.62)×10 9 /L, and (18.86±2.16)×10 9 /L, respectively.The sperm activity rate were (70.98±3.01)%, (57.96±3.75)%, (45.71±2.41)%, and (31.23±2.26)%, respectively.The concentration and vitality of epididymal sperms in the experimental group were significantly lower than those in the control group (all P<0.01). In the control group, low, medium and high dose groups, the SOD activity were (46.48±2.21) U/mg prot, (38.49±2.56)U/mg prot, (33.80±1.73) U/mg prot, and (27.65±2.05) U/mg prot, respectively.The GSH-Px activity in said 4 groups were (21.41±1.95) U/mg prot, (17.32±1.28) U/mg prot, (15.09±0.94) U/mg prot, and (14.08±1.23) U/mg prot, respectively.The MDA content in said 4 groups were (1.41±0.09) nmol/mg prot, (1.59±0.09) nmol/mg prot, (1.81±0.09) nmol/mg prot, and (2.16±0.14) nmol/mg prot, respectively.Compared to the control group, the experimental groups had significantly lower SOD and GSH-Px activities and significantly higher MDA content (all P<0.05). α-glucosidase levels in the control group, low, middle and high experimental groups were (15.46±0.71) U/mL prot, (12.95±0.72) U/mL prot, (11.34±0.65) U/mL prot, and (8.76±0.60) U/mL prot, respectively.LC levels in the control group, low, middle and high dose groups were(6.21±0.31) μg/L, (5.89±0.13) μg/L, (5.02±0.12) μg/L, (4.38±0.07) μg/L, respectively, compared with those of the control group, the concentration of α-glucosidase and LC in experimental groups decreased significantly (all P<0.01). The expression levels of Nrf2 in epididymis of the control group, low, middle and high dose groups were (1.34±0.05) ng/L, (1.25±0.04) ng/L, (1.08±0.06) ng/L, (0.92±0.04) ng/L, respectively; the expression levels of OCTN2 in epididymis of the control group, low, middle and high dose groups were (4.55±0.12) ng/L, (4.23±0.11) ng/L, (3.20±0.24) ng/L, (2.59±0.05) ng/L, respectively, compared with those of the control group, the expression levels of Nrf2 and OCTN2 in experimental groups decreased significantly (all P<0.01). Conclusions:Ethephon exposure leads to excessive generation of reactive oxygen and oxidative stress in reproductive organs.Ethephon exposure may activate the Keap1-Nrf2/ARE signal pathway, resulting in a decrease in the number, vitality and quality of sperms, and impaired fertility.

Objective: To understand the prevalence of sexual abuse among rural children and its association with family cohesion and adaptability, and to explore factors that may affect household functions of the victims. Methods: A total of 1 666 rural middle school students in Hanchuan and Yunxi, Hubei were recruited with stratified cluster sampling method, multivariate Logistic regression was used to analyze associated factors of the household functions of the victims. Results: A total of 175 (10.50%) reported non-contact sexual abuse and 44 (2.64%) reported contact sexual abuse. Compared with control group, sexual abuse victims reported lower scores of family cohesion (F=8.97，P<0.01) and adaptability (F=4.09，P=0.02). Among the victims, maternal absence was a risk factor for poor family cohesion(OR=0.20，P<0.01), higher parental educational level and appropriate parenting methods(P<0.05) were protective factors for family cohesion and family adaptability. Conclusion Household functions of children sexual abuse victims in rural areas are generally poor, especially for victims with mothers absence, low parental education and improper parenting style. More attention should be paid to such children to minimize the impact of negative events such as sexual abuse.

Objective: To understand nutrient intake and dietary structure among migrant children in primary schools in Hongshan District of Wuhan, so as to carry out dietary nutrition intervention and evaluate the effectiveness of the intervention. Methods: Stratified random sampling was used to select children in grade 3-6 who were randomly assigned to the intervention group (n=218) and the control group (n=222) from primary schools with a large number of migrant children in Hongshan District of Wuhan. After the baseline survey, the intervention group was given a two month diet intervention with "nutrition class" and knowledge lecture, and the caregivers of the intervention group were also given an intervention. Results: At baseline, both groups had inadequate nutrient intake, with adequate intake rate of calcium, selenium, vitamin B 1 and vitamin B 2 less than 5%; children were lack of dietary diversity with adequate intake of vegitable, milk and milk product less than 5%. After intervention, the intake of energy, three main macronutrients, calcium, vitamin A, and vitamin C in the intervention group were higher than that of before intervention, as well as than the control group, differences were statistically significant (Z=2.22-8.65，2.62-8.46，P<0.05). In terms of dietary structure, adequate intake rate of cereals and miscellaneous beans increased from 55.5% to 68.8%, livestock and poultry meat increased from 45.9% to 56.4%, which were higher than that of the control group (56.3% and 44.6%) (χ 2=5.29-13.25，4.39-14.13，P<0.05). Conclusion Inadequate nutrient intake and unreasonable dietary structure of migrant children can be improved through short term dietary intervention including nutrition education to both parents and children.

Objective: To investigate the picky eating behavior among school-age children and to analyze its association with their health status, providing scientific basis for health promotion of school-age children in China. Methods: A total of 796 students of grade 3 to grade 6 from two primary schools in Hongshan, Wuhan were selected through cluster sampling. Statistical analysis was conducted according to the results of the 3-day food record and questionnaire survey on children and their caregivers. Results: In the current study, 40.58% of the children had picky eating problems, the incidence of picky eating behaviors of migrant children was higher than that of local children(χ2=3.92, P<0.05). Most of the picky eaters(23.87%) tended to reject vegetables. Compared to the others, picky eaters had lower intake of vitamin B 2 [(0.49±0.01)(0.46±0.01)mg] and vitamin C [(57.35±0.76)(54.32±0.90)mg] (t=2.03, 2.57, P<0.05) and had a higher risk of stunting(OR=1.42, P<0.05). Conclusion Picky eating behaviors are common among school-age children, which is significantly associated with stunting. Nutritional education for children (especially migrant children) are urgently needed to improve their dietary structure and promote healthy growth and development.

Objective:To analyze the clinicopathological features of chordoid glioma.Methods:A total of 12 cases of chordoid gliomas from 2009 to 2020 in Xuanwu Hospital of Capital Medical University and General Hospital of Chinese People′s Liberation Army were retrospectively analyzed. The clinical and imaging characteristics, pathologic and molecular characteristics were analyzed, and the relevant literature was reviewed.Results:All 12 patients (4 males and 8 females) aged from 25 to 67 years (mean 39 years) and mainly had a history of headache or/and vision loss. MRI showed that the lesions located in the third ventricle, and they showed abnormal enhancement. Pathologically, these 12 cases displayed the morphologic characteristics of chordoid gliomas, including papillary structures in two cases. Immunohistochemically, GFAP and vimentin were expressed in all 12 cases (12/12). TTF1 was also expressed in all cases (10/10). CD34 and CKpan were seen in 11 cases (11/12). EMA with dot-and/or-ring like positivity was seen in 9 cases (9/10). Tissues were available in nine chordoid gliomas for Sanger sequencing to detect PRKCA and IDH gene mutation, and eight cases (8/9) showed PRKCA gene D463H mutation. None of these cases showed IDH1 R132 and IDH2 R172 mutation. All 12 patients underwent surgery, and four were lost to follow up. The remaining eight patients were progression or recurrence free at last follow-up in January 2021.Conclusions:Chordoid gliomas have relatively distinguishing clinical and histopathological features. PRKCA gene mutation in chordoid gliomas can be considered as a biomarker for the diagnosis and differential diagnosis of chordoid gliomas, and may provide a direction for future targeted therapy.

Objective: To study the clinicopathological features, differential diagnosis and prognosis of primary histiocytic sarcoma of central nervous system(CNS). Methods: Three cases of CNS histiocytic sarcoma were collected at Chinese People′s Liberation Army General Hospital from 2005 to 2018. Their clinicopathological characteristics were analyzed, and the related literature reviewed. Results: The three patients included two females and one male, aged 36, 44, 58 years (median 44 years). MRI showed heterogeneously enhancing lesions which were considered meningioma, high-grade glioma or metastatic carcinoma. Histopathologically there were moderately pleomorphic, mitotically active tumor cells with a loose arrangement, effacing the normal brain tissue. These cells possess abundant eosinophilic cytoplasm, highly atypical nuclei, predominant nucleoli, and hemophagocytosis; multinucleated or spindled forms were also seen, as was background reactive inflammation. The tumor cells were typically positive for CD68, CD163, vimentin and lysozyme, S-100 protein, two of three cases were positive for BRAF V600E,one of three cases was partly positive for CD45, CD45RO, CD4, CD34, and negative for GFAP, Olig-2, CK, EMA, SSTR2, CD99, CD117, MPO, CD1a, Langerin, CD21, CD23, CD35, CD15, CD30, CD38, and CD138. The index of Ki-67 was 30%-75%. Rich reticular fiber network was seen in all cases; BRAF V600E mutation was present in two cases. Conclusions CNS histiocytic sarcoma is a rare malignant tumor; histopathologic and immunohistochemical examination are necessary for the diagnosis and to exclude other primary CNS and hematolymphopoietic tumors. Primary CNS histiocytic sarcoma is treated by surgery, chemotherapy and radiation therapy, but the prognosis is poor. Complete resection combined with high dose focused radiotherapy can improve the prognosis.