This study examines the effects of zearalenone(ZEA)on the survival and function of lu-teinized granulosa cells,and studies the role of activating transcription factor 6(ATF6)in regula-ting apoptosis and functional abnormalities of luteinized granulosa cells induced by ZEA.An in vitro model of luteinized granulosa cells was utilized to examine the effects of ZEA treatment on apoptosis,hormone secretion,and the expression of relevant proteins.Furthermore,the expression of ATF6 was manipulated using siRNA to elucidate its regulatory function in the ZEA-induced damage of luteinized granulosa cells in mice.Our findings revealed that ZEA inhibited the activity of luteinized granulosa cells and reduced the secretion of estradiol(E2)and progesterone(P4)in a dose-dependent manner.The expression levels of p-IRE1,ATF6 and StAR in both low(20 pmol/L)and high(40 μmol/L)ZEA groups were significantly increased after 24 h(P＜0.05).GRP78 had no significant change at low concentration treatment(P＞0.05),but significantly increased at high concentration treatment(P＜0.05).Similarly,ATF4 and p-EIF2α had no significant change at low concentration treatment(P＞0.05),but significantly decreased at high concentration treat-ment(P＜0.05).HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).After 48 h of treatment,ATF6 and GRP78 were significantly increased in both low and high concentration treatments(P＜0.05).p-IRE1 was significantly de-creased at low concentration treatment(P＜0.05),but remained unchanged at high concentration treatment(P＞0.05).ATF4,p-EIF2α,HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).St AR was significantly increased in both low and high concentration treatments(P＜0.05).Interference with the expression of ATF6 could sig-nificantly reduce the apoptosis induced by low concentration group(P＜0.05),and enhanced the hormone secretion in both high and low concentration groups(P＜0.05).In conclusion,ZEA can cause damage to luteinized granulosa cells and activate ATF6 signaling pathway.Interference with ATF6 can alleviate apoptosis and hormone secretion disturbance induced by low concentration ZEA,but has limited effect on damage caused by high concentration ZEA.

Objective:To investigate the expression characteristics of Zeste enhancer of Zeste homolog 2 (EZH2) in breast cancer tissue and its influence on tumor progression and prognosis.Methods:Transcriptome data of breast cancer tissue and normal breast tissue adjacent to cancer as well as clinical data of patients were obtained from the cancer genome atlas (TCGA) database, gene expression comprehensive database and European genome phenotype archives database, and the difference of EZH2 expression was analyzed using TIMER 2.0 platform. The survival information of breast cancer patients was obtained from the Kaplan Meier Plotter database, and the overall survival time, relapse free survival time and distant metastasis free survival time of breast cancer patients with low EZH2 expression and high EZH2 expression were compared. Select 14 nude mice were selected and randomly divided into si-EZH2 group and control group, with 7 mice in each group.MCF7 culture suspensions transfected with EZH2 knockdown plasmid and control plasmid were inoculated for corresponding group. The body mass and tumor volume of two groups of nude mice inoculated with MCF7 cells were compared at different times. On the 28th day, the nude mice were euthanized and the tumors were dissected to compare the tumor mass of the two groups of nude mice. The normally distributed quantitative data was represented by xˉ ± s. Two independent sample t-tests were used for comparison between two groups, repeated measures ANOVA was used for comparison of body mass and tumor volume between two groups of nude mice at different times, and Bonferroni test was used for pairwise comparison. The comparison of survival rates was conducted using log rank test. Results:A total of 1085 breast cancer tissues and 291 normal adjacent breast tissues were included in the TCGA database. EZH2 expression in breast cancer tissues was higher than that in normal adjacent breast tissues ( P<0.05). In the Kaplan Meier Plotter database, the total survival time, relapse free survival time, and distant metastasis free survival time of breast cancer patients in the EZH2 overexpression group were shorter than those in the EZH2 low expression group ( P=0.013, <0.001, <0.001). After 7 days of inoculation with MCF7 culture suspension, significant subcutaneous tumors were observed on the left back of both groups of nude mice. On the first day, there were no statistically significant difference in body mass between the two groups of nude mice ( P>0.05); On day 7, 13, 19, 25, and 28, the body mass and tumor volume of both groups of nude mice gradually increased (nude mouse body mass: within group F=29.31, P<0.001, between groups F=234.32, P<0.001, Finteraction=16.83, P<0.001; Tumor volume: within group F=34.00, P<0.001, between groups F=193.17, P<0.001, Finteraction=35.61, P<0.001). And the body mass of the siEZH2 group nude mice was higher than that of control group (all P<0.05). On days 19, 25, and 28, tumor the volume of the siEZH2 group nude mice was smaller than that of control group (all P<0.05). On the 28th day, the mass of tumors dissected in the siEZH2 group of nude mice was lower than that in the control group [(0.30±0.07) g vs. (0.61±0.14) g, t=5.16, P<0.001]。 Conclusions:EZH2 is highly expressed in breast cancer tissues and is significantly associated with poor prognosis. Knockdown of EZH2 can significantly inhibit the proliferation and tumor formation of breast cancer cells.

This study examines the effects of zearalenone(ZEA)on the survival and function of lu-teinized granulosa cells,and studies the role of activating transcription factor 6(ATF6)in regula-ting apoptosis and functional abnormalities of luteinized granulosa cells induced by ZEA.An in vitro model of luteinized granulosa cells was utilized to examine the effects of ZEA treatment on apoptosis,hormone secretion,and the expression of relevant proteins.Furthermore,the expression of ATF6 was manipulated using siRNA to elucidate its regulatory function in the ZEA-induced damage of luteinized granulosa cells in mice.Our findings revealed that ZEA inhibited the activity of luteinized granulosa cells and reduced the secretion of estradiol(E2)and progesterone(P4)in a dose-dependent manner.The expression levels of p-IRE1,ATF6 and StAR in both low(20 pmol/L)and high(40 μmol/L)ZEA groups were significantly increased after 24 h(P＜0.05).GRP78 had no significant change at low concentration treatment(P＞0.05),but significantly increased at high concentration treatment(P＜0.05).Similarly,ATF4 and p-EIF2α had no significant change at low concentration treatment(P＞0.05),but significantly decreased at high concentration treat-ment(P＜0.05).HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).After 48 h of treatment,ATF6 and GRP78 were significantly increased in both low and high concentration treatments(P＜0.05).p-IRE1 was significantly de-creased at low concentration treatment(P＜0.05),but remained unchanged at high concentration treatment(P＞0.05).ATF4,p-EIF2α,HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).St AR was significantly increased in both low and high concentration treatments(P＜0.05).Interference with the expression of ATF6 could sig-nificantly reduce the apoptosis induced by low concentration group(P＜0.05),and enhanced the hormone secretion in both high and low concentration groups(P＜0.05).In conclusion,ZEA can cause damage to luteinized granulosa cells and activate ATF6 signaling pathway.Interference with ATF6 can alleviate apoptosis and hormone secretion disturbance induced by low concentration ZEA,but has limited effect on damage caused by high concentration ZEA.

Objective:To investigate the expression characteristics of Zeste enhancer of Zeste homolog 2 (EZH2) in breast cancer tissue and its influence on tumor progression and prognosis.Methods:Transcriptome data of breast cancer tissue and normal breast tissue adjacent to cancer as well as clinical data of patients were obtained from the cancer genome atlas (TCGA) database, gene expression comprehensive database and European genome phenotype archives database, and the difference of EZH2 expression was analyzed using TIMER 2.0 platform. The survival information of breast cancer patients was obtained from the Kaplan Meier Plotter database, and the overall survival time, relapse free survival time and distant metastasis free survival time of breast cancer patients with low EZH2 expression and high EZH2 expression were compared. Select 14 nude mice were selected and randomly divided into si-EZH2 group and control group, with 7 mice in each group.MCF7 culture suspensions transfected with EZH2 knockdown plasmid and control plasmid were inoculated for corresponding group. The body mass and tumor volume of two groups of nude mice inoculated with MCF7 cells were compared at different times. On the 28th day, the nude mice were euthanized and the tumors were dissected to compare the tumor mass of the two groups of nude mice. The normally distributed quantitative data was represented by xˉ ± s. Two independent sample t-tests were used for comparison between two groups, repeated measures ANOVA was used for comparison of body mass and tumor volume between two groups of nude mice at different times, and Bonferroni test was used for pairwise comparison. The comparison of survival rates was conducted using log rank test. Results:A total of 1085 breast cancer tissues and 291 normal adjacent breast tissues were included in the TCGA database. EZH2 expression in breast cancer tissues was higher than that in normal adjacent breast tissues ( P<0.05). In the Kaplan Meier Plotter database, the total survival time, relapse free survival time, and distant metastasis free survival time of breast cancer patients in the EZH2 overexpression group were shorter than those in the EZH2 low expression group ( P=0.013, <0.001, <0.001). After 7 days of inoculation with MCF7 culture suspension, significant subcutaneous tumors were observed on the left back of both groups of nude mice. On the first day, there were no statistically significant difference in body mass between the two groups of nude mice ( P>0.05); On day 7, 13, 19, 25, and 28, the body mass and tumor volume of both groups of nude mice gradually increased (nude mouse body mass: within group F=29.31, P<0.001, between groups F=234.32, P<0.001, Finteraction=16.83, P<0.001; Tumor volume: within group F=34.00, P<0.001, between groups F=193.17, P<0.001, Finteraction=35.61, P<0.001). And the body mass of the siEZH2 group nude mice was higher than that of control group (all P<0.05). On days 19, 25, and 28, tumor the volume of the siEZH2 group nude mice was smaller than that of control group (all P<0.05). On the 28th day, the mass of tumors dissected in the siEZH2 group of nude mice was lower than that in the control group [(0.30±0.07) g vs. (0.61±0.14) g, t=5.16, P<0.001]。 Conclusions:EZH2 is highly expressed in breast cancer tissues and is significantly associated with poor prognosis. Knockdown of EZH2 can significantly inhibit the proliferation and tumor formation of breast cancer cells.

Objective:To assess the impact of exposure to particulate matter with aerodynamic diameter ≤2.5 μm(PM2.5)on non-accidental mortality under different apparent temperature levels and to further explore the modification effect of apparent temperature.Methods:This study used time-series design.Tianjin and Ningbo from China,Bangkok and Chiang Mai from Thailand were selected as the re-search sites,and the apparent temperature was applied as the exposure index.Through the quantitative estimation of the threshold temperature,the corresponding pollutant concentration was divided into high and low levels,and the generalized Poisson additive model was used to evaluate the association between PM2.5 exposure and non-accidental death of residents at different temperature levels.Results:The ave-rage concentrations of PM2.5 in Tianjin,Ningbo,Bangkok,and Chiang Mai during the study period were(73.6±35.6),(48.0±32.1),(33.5±28.4)and(32.6±28.6)μg/m3,respectively;the average daily non-accidental death counts were 148,57,28,and 8.The analysis of the generalized Poisson addi-tive model showed that the daily non-accidental death counts increased by 0.43％(95％CI:0.33％-0.54％)per 10 μg/m3 increase of PM2.5 in lag 0 day in Tianjin of China;0.27％(95％CI:0.08％-0.46％)per 10 μg/m3 increase of PM2.5 in lag 2 days in Ningbo of China.The effect was magnified in high temperature levels in Tianjin and in low temperatures in Ningbo and Bangkok.The mortality effect of PM2 5 in various temperature levels stayed still in co-pollutant regression models.Conclusion:Exposure to fine particulate matter had an adverse effect on non-accidental mortality,which reminded us to give further attention to the pollution control.The findings also indicated that apparent temperature might modify mortality effects of PM2 .5 and the modification effect varied in different regions.Protective policies due to regional differences should be made and more scientific and social attention on mutual effect of air pollution and climate change needs to be appealed.

Objective:To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma.Methods:A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor.Results:① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group ( P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group ( P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower ( P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group ( P=0.002), whereas the incidence of grade 3 diarrhea was lower ( P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea ( P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group ( P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group ( P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group ( P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups ( P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively ( P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively ( P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively ( P=0.373) . Conclusion:In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

Objective To compare the short-term clinical effects of unilateral dual-channel endoscopic discectomy(UBED)and percutaneous endoscopic intervertebral discectomy(PEID)in the treatment of L5S,Lumbar disc herniation,LDH.Methods From January 2019 to January 2021,a total of 57 cases of L5S,LDH treated by UBED or PEID were analyzed retrospectively,including 30 cases in UBED group and 27 cases in PEID group.The operation time,intraoperative fluoroscopy times,postoperative hospitalization days and surgical complications were compared between the two groups.The visual analogue scale(VAS)and oswestry disability index(ODI)were used to compare the postoperative quality of life of the two groups,and the modified MacNab criteria was used to evaluate the clinical efficacy in the last follow-up.Results The operation time of UBED group and PEID group was(75.30±8.44)minutes and(68.37±4.63)minutes,respectively,and the difference between the two groups was statistically significant(P＜0.05).VAS and ODI of 1 week,3 months,1 year and 1.5 years after surgery in 2 groups were significantly decreased compared with those before surgery,with statistical significance(P＜0.05).The VAS score of low back pain in UBED group was higher than that in PEID group[(3.87±1.14)points vs(2.70±0.67)points]at 1 week after surgery(P＜0.05),and there was no significant difference in VAS and ODI at the other time points(P＞0.05).There was no statistical difference in the results of modified MacNab criteria in the last follow-up(P＞0.05).There were 2 cases of dural tear in PEID group,1 case of dural tear in UBED group and 1 case of temporary nerve root injury in PEID group after operation,all of which were cured after symptomatic treatment.Conclusion Compared with PEID,UBED has a longer operation time,more trauma and more obvious low back pain in the short term after operation.The short-term curative effect of the two operations on L5S1 LDH is similar,the incidence of complications is low,and the times of fluoroscopy are few.Both operations are safe and effective.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Background Epidemiological evidence indicates an association of particulate matter with depression and cognitive performance. From 2013 to 2017, China implemented the Air Pollution Prevention and Control Action Plan to reduce particulate matter concentration. There are few studies on the relationship between the decrease of particulate matter concentration and the improvement of mental health in middle-aged and elderly people. Objective To analyze the relationship between the decrease of city-level particulate matter concentration and the improvement of depression and cognitive function in the middle-aged and elderly population after the implementation of the Air Pollution Prevention and Control Action Plan. Methods Using the China Health and Retirement Longitudinal Study (CHARLS) data in 2011 and 2018, this study applied longitudinal data clustering technology to group cities based on the actual response of each city to the policy (the dynamic change trajectory of PM_2.5 in each city during the study period); the higher the degree of response, the greater the reduction of PM_2.5 concentration in the city. We assigned participants to three groups with different degrees of response to the policy, including low-response group A as the control group, medium-response intervention group B, and high-response intervention group C. A difference-in-differences (DID) model was used to estimate the influence of PM_2.5 decline on the depression and cognitive function among middle-aged and elderly people in China by considering potential individual and city-level time-varying confounders. Depression was measured using the 10-item Center for the Epidemiological Studies of Depression Scale (CES-D10) (10 questions, total score range 0-30) with higher score representing higher severity of depression. Cognitive function was evaluated with reference to the international cognitive function test questionnaire for the middle-aged and the elderly which was further categorized into two dimensions of memory and cognitive status and included 31 questions with a score range of 0-31; the higher the score, the better the cognitive function. Samples with relatively complete outcomes were selected for analysis, including 10729 people in depression analysis and 4510 people in cognitive analysis. Results The longitudinal clustering results indicated that the urban groups with the highest decline of PM_2.5 concentrations (high-response group C) had the highest baseline PM_2.5 concentrations, mainly in Beijing-Tianjin-Hebei region, Chengdu-Chongqing metropolitan area, and Wuhan metropolitan area. In 2011, no significant differences were observed in depression and cognitive function among the three groups of middle-aged and elderly populations (Kruskal Wallis test: P_depression=0.864, P_cognition=0.239). Significant differences were found in depression and cognitive function in both low-response group A and medium-response group B in 2018 compared to 2011 (paired Wilcox test, all P<0.001). However, in the high-response group C, there was no significant difference in depression in 2018 compared to 2011 (P=0.195), while a significant difference was detected in cognitive function (P=0.006). As PM_2.5 concentrations decreased, the DID model showed that the depression of the middle-aged and elderly people in the high-response group C decreased by 7.55% (95%CI: 2.83%-12.03%), and the cognitive function improved by 2.70% (95%CI: 0.25%-5.22%) compared with the low-response group A. However, no intervention effect was observed in group B with moderate response level compared with group A with low response level. Conclusion After the implementation of the Air Pollution Prevention and Control Action Plan policy, the decrease of PM_2.5 concentration has an ameliorative effect on the depression and cognitive function of middle-aged and elderly people in China. Given the aging population and the increasing burden of mental-related diseases in China, the promotion of environmental air pollution control has important public health implications.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.