BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

Objective This study aims to systematically evaluate the evidence-based medicine of traditional Chinese medicine(TCM)in the treatment of dry eye,analyze its efficacy and differences compared with modern Western medicine treatments,and provide a scientific basis for clinical application.Methods By searching Chinese and English databases(including CNKI,Wanfang Data,PubMed,Cochrane Library,etc.),we included meta-analyses and systematic reviews of TCM treatments for dry eye.Literature was screened according to strict inclusion and exclusion criteria,and relevant data were extracted and integrated for analysis.The Mantel-Haenszel fixed-effects model was used to calculate the relative risk(RR)and mean difference(WMD),with the effect size expressed as a 95％confidence interval,to analyze the efficacy in-dicators of TCM treatment for dry eye.Results A total of 21 articles were finally included,involving various TCM inter-ventions for dry eye(such as Chinese herbal medicine,acupuncture,and TCM external therapies).The results showed that TCM treatment was superior to Western medicine alone in improving the overall clinical efficacy[RR=1.63,95％CI(1.46,1.81),P＜0.05],prolonging tear film break-up time[MD=2.23,95％CI(1.85,2.60),P＜0.05],and increasing tear secretion[MD=1.49,95％CI(1.04,1.94),P＜0.05].In addition,acupuncture,the combination of Chinese herbal medicine and Western medicine,and TCM external therapies all demonstrated unique advantages in improving dry eye symptoms and tear function.Conclusion TCM treatment for dry eye shows significant efficacy in key indicators such as overall clinical efficacy,tear film break-up time,and tear secretion,with a high level of safety.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective To investigate the effect of the small molecule inhibitor C42 of kallikrein-related peptidase 7(KLK7)on ovarian cancer with elevated expression of KLK7 and evaluate the feasibility of C42 as a new therapeutic strategy for ovarian cancer.Methods The CCK-8 assay,flow cytometry,cell scratch assay,Transwell assay,and Western blotting were employed to assess the effects of C42 on the proliferation,migration,and invasion of the ovarian cancer cell line SKOV3,which was characterized by high KLK7 expression.Additionally,a subcutaneous xenograft model of ovarian cancer was established with SKOV3 cells in nude mice to evaluate the effects of C42 on the tumor growth and metastasis.The expression levels of proteins associated with tumor metastasis and invasion in the tumor tissue were examined by immunohistochemical techniques.Results The cellular experiment showed that C42 suppressed the proliferation,migration,and invasion(all P<0.001)of SKOV3 cells,compared with the control group.The animal experiment showed that compared with the control group,the 10.2 mg/kg C42 group exhibited a decreased tumor weight(P=0.009) and attenuated liver metastases.Immunohistochemical staining revealed that the 10.2 mg/kg C42 group demonstrated down-regulated expression of the tumor proliferation marker Ki-67(P=0.002)and the tumor metastasis and invasion-associated proteins such as matrix metalloproteinase-9(P=0.027)and Vimentin(P=0.039).Conclusion The small molecule inhibitor C42 of KLK7 effectively suppresses the proliferation,migration,and invasion of ovarian cancer SKOV3 cells.
Female ; Humans ; Ovarian Neoplasms/drug therapy* ; Kallikreins/antagonists & inhibitors* ; Animals ; Mice, Nude ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C

BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective This study aims to systematically evaluate the evidence-based medicine of traditional Chinese medicine(TCM)in the treatment of dry eye,analyze its efficacy and differences compared with modern Western medicine treatments,and provide a scientific basis for clinical application.Methods By searching Chinese and English databases(including CNKI,Wanfang Data,PubMed,Cochrane Library,etc.),we included meta-analyses and systematic reviews of TCM treatments for dry eye.Literature was screened according to strict inclusion and exclusion criteria,and relevant data were extracted and integrated for analysis.The Mantel-Haenszel fixed-effects model was used to calculate the relative risk(RR)and mean difference(WMD),with the effect size expressed as a 95％confidence interval,to analyze the efficacy in-dicators of TCM treatment for dry eye.Results A total of 21 articles were finally included,involving various TCM inter-ventions for dry eye(such as Chinese herbal medicine,acupuncture,and TCM external therapies).The results showed that TCM treatment was superior to Western medicine alone in improving the overall clinical efficacy[RR=1.63,95％CI(1.46,1.81),P＜0.05],prolonging tear film break-up time[MD=2.23,95％CI(1.85,2.60),P＜0.05],and increasing tear secretion[MD=1.49,95％CI(1.04,1.94),P＜0.05].In addition,acupuncture,the combination of Chinese herbal medicine and Western medicine,and TCM external therapies all demonstrated unique advantages in improving dry eye symptoms and tear function.Conclusion TCM treatment for dry eye shows significant efficacy in key indicators such as overall clinical efficacy,tear film break-up time,and tear secretion,with a high level of safety.

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.