Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism. METHODS: Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected. RESULTS: Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group. CONCLUSION Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Myocardial Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology* ; Rats ; Acupuncture Points ; Mitochondrial Dynamics ; Humans ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/genetics* ; Superoxide Dismutase/metabolism*

Rice is the world's largest food crop, and its yield and quality are directly related to food security and human health. Grain size, as one of the important factors determining the rice yield, has been widely concerned by breeders and researchers for a long time. To decipher the regulatory mechanism of rice grain size, we obtained a multi-tiller, dwarf, and small-grain mutant htd1 by ethyl methanesulfonate (EMS) mutation from the Japonica rice cultivar 'Zhonghua 11' ('ZH11'). Genetic analysis indicated that the phenotype of htd1 was controlled by a single recessive gene. Using the mutation site map (Mutmap) method, we identified the candidate gene OsHTD1, which encoded a carotenoid cleavage dioxygenase involved in the biosynthesis of strigolactone (SL). The SL content in htd1 was significantly lower than that in 'ZH11'. Cytological analysis showed that the grain size of the mutant decreased due to the reductions in the length and width of glume cells. The function of htd1 was further verified by the CRISPR/cas9 gene editing technology. The plants with the gene knockout exhibited similar grain size to the mutant. In addition, gene expression analysis showed that the expression levels of multiple grain size-related genes in the mutant changed significantly, suggesting that HTD1 may interact with other genes regulating grain size. This study provides a new theoretical basis for research on the regulatory mechanism of rice grain size and potential genetic resources for breeding the rice cultivars with high yields.
Oryza/growth & development* ; Mutation ; Edible Grain/growth & development* ; Alleles ; Plant Proteins/genetics* ; Dioxygenases/genetics* ; Lactones/metabolism* ; Gene Expression Regulation, Plant ; Genes, Plant ; Gene Editing ; CRISPR-Cas Systems ; Phenotype

Adriamycin is a widely used anti-tumor drug.Targeting mitochondrial fusion proteins/mitofusion 1/2(MFN1/2)and nuclear factor-erythroid 2-related factor 2(NRF2)can up-regulate the expression of mitochondrial fusion protein through PKCε/Stat3/MFN2,SIRT1/MFN2,AMPK/NRF2 and other signaling pathways,promote mitochondrial fusion,maintain kinetic balance and protect mitochondrial function,reduce myocardial cell apoptosis and reduce cardiac toxicity.Understanding the regulatory role and mechanism of mitochondrial fusion in doxorubicin-induced cardio toxicity will provide new strategies for the prevention and treatment of diseases.

Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.

Objective:To explore the mechanism of Honghua Xiaoyao Tablets in the treatment of premature ovarian failure (POF) using network pharmacology and molecular docking technology; To conduct further experimental verification.Methods:The active components and related targets of Honghua Xiaoyao Tablets were obtained using TCMSP and PubChem databases, and the related targets of POF were obtained by using GeneCards database. The Venn online tool was used to screen the intersection genes, and the STRING database was used to construct the PPI network. Then, GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the intersecting genes through the Metescape database, and Cytoscape 3.7.1 software was used to construct the "active component-target" network and "Chinese materia medica-active component-target-key pathway-disease" network. Finally, molecular docking verification was carried out. Mice were divided into blank group, model group, and Honghua Xiaoyao Tablets group using a random number table method, with 8 mice in each group. Except for the blank group, mice in each group were treated with zona pellucida polypeptide 3 (ZP3) and Freund's Complete Adjuvant (FCA) to establish a mouse model of immune POF. Mice in the Honghua Xiaoyao Tablets group received Honghua Xiaoyao Tablets solution 0.56 g/kg for gavage, and the blank control group and the model group received saline for gavage for consecutive 4 weeks. The histopathological changes of the mouse ovary were observed by HE staining. Immunohistochemical staining was used to observe the expression of ESR1, and Western blot was used to detect the expressions of Akt and p-Akt.Results:A total of 80 intersection targets between Honghua Xiaoyao Tablets and POF were obtained, and the PPI network contained 44 core targets. The top 5 compounds in the topological analysis were formononetin, quercetin, Betulinic acid, Hydroxysafflor Yellow A and Baicalin, and the top 5 targets were PPARG, ESR1, AR, AKT1 and IL6. The molecular function of core genes was mainly receptor ligand activity, and its biological process mainly involved the positive regulation of cell migration. The cellular components mainly included membrane rafts, which were involved in signaling pathways such as cancer signaling pathway, proteoglycans in cancer, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. "Chinese materia medica-component-target-pathway-disease" network showed that 8 kinds of Chinese materia medica in the Honghua Xiaoyao Tablets had important core components, among which Glycyrrhizae Radix et Rhizoma and Carthami Flos involved the most important core components. Molecular docking results showed that the active components had a good affinity with the core target. The experimental verification confirmed that Honghua Xiaoyao Tablets promoted follicular development, increased the expression of ESR1 in ovarian tissues and up-regulated the expression level of the key factor of Akt phosphorylation in the PI3K-Akt signaling pathway.Conclusions:The various active components of Honghua Xiaoyao Tablets may act on PPARG, ESR1 and other targets through multiple signaling pathways such as PI3K-Akt and HIF-1 to treat POF. The potential active components are mainly formononetin, quercetin, etc.