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.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

Objective To investigate the effects of low background radiation environments in deep underground settings on the biological behavior of NP69 human nasopharyngeal epithelial cells(NP69 cells)and the underlying molecular mechanisms.Methods A parallel control experimental design was adopted and NP69 cells were synchronously cultured in settings of three underground depths at the China in situ Deep-Underground Facility&Life Observatory(DeUFO)—ground level(DeUFO-0 m),1 000 m underground(DeUFO-1 000 m),and 1 500 m underground(DeUFO-1 500 m).Changes in cell proliferation and migration capabilities were assessed using the Cell Counting Kit-8(CCK-8)assay and scratch assay,respectively.High-throughput RNA sequencing(RNA-Seq)was performed to identify differentially expressed genes(DEGs).Functional annotation and pathway enrichment analysis of the DEGs were performed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.Results CCK-8 assay revealed that,after 72 h of culture,the absorbance value of the DeUFO-0 m group was 1.35 times and 1.27 times those of the those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).After 96 h of culture,the absorbance value of the DeUFO-0 m group was 1.52 times and 1.41 times those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).Colony formation assays revealed that the number of cell colonies in the DeUFO-0 m group was 1.59 times and 1.27 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.001).The scratch assay revealed that the 36-hour wound healing rate of the DeUFO-0 m group was 2.22 times and 4.00 times those of the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transwell assays revealed that the number of migrating cells in the DeUFO-0 m group was 2.08 times and 2.56 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transcriptome sequencing analysis revealed consistent upregulation of CELF2,CELF4,CGB8,GRHL2,and DMRTA2 genes in the DeUFO-1 000 m and DeUFO-1 500 m groups.Pathway enrichment analysis indicated significant enrichment of extracellular matrix(ECM)remodeling-associated pathways and gene expression regulation pathways in the experimental groups(false discovery rate[FDR]<0.05).Conclusion The low background radiation environment in deep underground settings suppresses the proliferation and migration activities of NP69 cells by mediating ECM remodeling and post-transcriptional regulatory mechanisms through the regulation of target genes such as the CELF family.This study provides experimental evidence for establishing a dose-response relationship between environmental radiation and cellular effects.

AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.

Objective To analyze the projects of the Management Science Department of the National Natural Science Foundation of China(NSFC)funded to hospital pharmacists from 2013 to 2024,providing references for hospital pharmacists to apply for such projects.Methods Websites such as the National Natural Science Foundation Big Data Knowledge Service Management Portal,MedSci,and LetPub were retrieved,supplemented by manual retrieval.Relevant projects with hospital pharmacists as the project leaders were screened out,and keywords such as the research topic,research theory/model,and research type of the projects were extracted for analysis.Results From 2013 to 2024,40 projects of the Management Science Department of the NSFC were given to hospital pharmacists as project leaders,and both the number of projects and the proportion of funding showed an upward trend.The awarded projects mostly demonstrated the relevance of national macro-pharmaceutical policies and were matched with corresponding management theories/models based on the research content.The research themes and research objects were diverse,and the research types were mainly model construction and pattern construction.Conclusion Pharmacists should closely follow the direction of national policies,seek research inspirations in their daily work,and enhance the learning of management research methods,guiding and regulating research through management theories.

Objective:To investigate the efficacy and safety of hypofractionated radiotherapy combined with temozolomide and bevacizumab in the treatment of primary glioblastoma.Methods:A total of 48 patients who received radiotherapy in Chongqing University Cancer Hospital from Jan. 2020 to Dec. 2023 were enrolled. According to the principle of voluntary participation of patients,research group: hypofractionated radiotherapy+temozolomide+bevacizumab, control group: radiotherapy+temozolomide. The research group received bevacizumab at a dose of 7.5mg/kg, q2w, 1 week before radiotherapy. Hypofractionated radiotherapy (60Gy/20F) was administered with bevacizumab (7.5mg/kg, q2w) combined with temozolomide (75mg/m 2), D1-D42, once a day. Patients would rest for 4 weeks after radiotherapy, and be given bevacizumab (10mg/kg q3w) for 6 cycles until cancer progression and combined with temozolomide (150-200mg/m 2, d1-d5, q28) for 6 cycles. Control group: radiotherapy (60Gy/30F), combined with temozolomide (75mg/m 2) once a day, D1-D42. Patients would rest for 4 weeks after radiotherapy, and be given temozolomide (150-200mg/m 2, d1-d5, q28) for 6 cycles. Both groups were treated until the disease progression or intolerant toxicity. Clinical efficacy evaluation based on neurooncological response evaluation criteria. Results:The total response rate (ORR) in the control group and research group were 37.50% (9 cases/24 cases) and 54.17% (13 cases/24 cases) ; The disease control rate (DCR) ratio was 79.17% (19 cases/24 cases) and 91.67% (22 cases/24 cases) respectively. There were significant differences in ORR and DCR rates between the two groups (all P<0.05). The median OS of patients in the control group and research group were 12.4 months (95% CI: 5.8-9.6) and 18.2 months (95% CI: 8.2-12.4). The median PFS of patients in the control group and research group were 8.9 months (95% CI: 3.8-7.2) and 13.2 months (95% CI: 6.4-10.2). The differences between the two groups were statistically significant ( P<0.05). The incidence of adverse drug reactions in both group was 50.00%, with no statistically difference ( P>0.05) . Conclusion:The newly diagnosed glioblastoma treated with hypofractionated radiotherapy+temozolomide+bevacizumab showed significant advantages compared with conventional radiotherapy in PFS, OS, ORR and DCR.

Objective:To investigate the efficacy and safety of hypofractionated radiotherapy combined with temozolomide and bevacizumab in the treatment of primary glioblastoma.Methods:A total of 48 patients who received radiotherapy in Chongqing University Cancer Hospital from Jan. 2020 to Dec. 2023 were enrolled. According to the principle of voluntary participation of patients,research group: hypofractionated radiotherapy+temozolomide+bevacizumab, control group: radiotherapy+temozolomide. The research group received bevacizumab at a dose of 7.5mg/kg, q2w, 1 week before radiotherapy. Hypofractionated radiotherapy (60Gy/20F) was administered with bevacizumab (7.5mg/kg, q2w) combined with temozolomide (75mg/m 2), D1-D42, once a day. Patients would rest for 4 weeks after radiotherapy, and be given bevacizumab (10mg/kg q3w) for 6 cycles until cancer progression and combined with temozolomide (150-200mg/m 2, d1-d5, q28) for 6 cycles. Control group: radiotherapy (60Gy/30F), combined with temozolomide (75mg/m 2) once a day, D1-D42. Patients would rest for 4 weeks after radiotherapy, and be given temozolomide (150-200mg/m 2, d1-d5, q28) for 6 cycles. Both groups were treated until the disease progression or intolerant toxicity. Clinical efficacy evaluation based on neurooncological response evaluation criteria. Results:The total response rate (ORR) in the control group and research group were 37.50% (9 cases/24 cases) and 54.17% (13 cases/24 cases) ; The disease control rate (DCR) ratio was 79.17% (19 cases/24 cases) and 91.67% (22 cases/24 cases) respectively. There were significant differences in ORR and DCR rates between the two groups (all P<0.05). The median OS of patients in the control group and research group were 12.4 months (95% CI: 5.8-9.6) and 18.2 months (95% CI: 8.2-12.4). The median PFS of patients in the control group and research group were 8.9 months (95% CI: 3.8-7.2) and 13.2 months (95% CI: 6.4-10.2). The differences between the two groups were statistically significant ( P<0.05). The incidence of adverse drug reactions in both group was 50.00%, with no statistically difference ( P>0.05) . Conclusion:The newly diagnosed glioblastoma treated with hypofractionated radiotherapy+temozolomide+bevacizumab showed significant advantages compared with conventional radiotherapy in PFS, OS, ORR and DCR.

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.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.