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 understand phenotype conversion in patients with first-episode depression over a 7-year period,to explore the longitudinal disease characteristics and functional outcomes of transitions and non-transitions,and to further analyse the relevant factors affecting transitions.Methods A total of 346 patients with Hamilton depression scale-17(HAMD-17)score≥18,aged 18-60 years and a single episode of major depressive disorder were included in the study.They were follow-up for 7 years to assess their natural history including demographic data,disease characteristics,whether transitions to manic occurred,treatment status.At the end of the 7-year follow-up,treatment emergent symptom scale(TESS),medication adherence rating scale(MARS),and global assessment function(GAF)were used to evaluate adverse reactions,compliance to medication,and patient's overall functional level.Patients were divided into two groups based on the occurrence of mania or hypomania episodes during the 7-year period:the conversion group(those who developed episodes)and the non-conversion group(those who did not).Results A total of 138 patients were followed up for 7 years,including 54 patients(39.1%)in the conversion group and 84 patients(60.9%)in the non-conversion group.When the first episode was enrolled at baseline,the age of first episode was earlier in the conversion group than in the non-conversion group[(27.63±9.63)years vs.(41.20±11.92)years],and there were differences in marital status(unmarried 40.7%vs.7.1%,first marriage 53.7%vs.85.7%,remarriage 3.7%vs.2.4%,separated/divorced 0.0%vs.2.4%,widowed 1.9%vs.2.4%).The proportion of patients with precipitating factors was lower in the conversion group(29.6%vs.48.8%)and shorter duration of untreated psychosis(DUP)[60(15,90)d vs.90(30,180)d].The treatment method in the conversion group had lower only used antidepressant drugs(61.1%vs.81.0%)and more antidepressant combined with mood stabilizers(31.5%vs.16.7%)(all P<0.05).In the 7 years,total number of episodes in the conversion group was more than in the non-conversion group(4.33±1.21 vs.2.70±1.25,P<0.05).By the end of 7 years,the GAF score was lower in conversion group than in the non-conversion group(66.57±8.22 vs.69.21±7.20,P<0.05).Dichotomous unconditional logistic regression analyses revealed that age at first episode(OR=1.109,95%CI:1.058-1.161,P<0.001),DUP(d)(OR=1.005,95%CI:1.001-1.009,P=0.017),was an independent influencing factor on conversion over a 7-year period in patients with first-episode depressive disorders.Conclusion The rate of conversion over 7 years in patients with first-episode depressive disorder is 39.1%in the present cohort and converted patients had relatively earlier age of onset,more pre-onset without inducement,shorter DUP(d),more recurrence,higher the rate of combined treatment and worse overall functional outcome.

OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.

OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.

Objective To understand phenotype conversion in patients with first-episode depression over a 7-year period,to explore the longitudinal disease characteristics and functional outcomes of transitions and non-transitions,and to further analyse the relevant factors affecting transitions.Methods A total of 346 patients with Hamilton depression scale-17(HAMD-17)score≥18,aged 18-60 years and a single episode of major depressive disorder were included in the study.They were follow-up for 7 years to assess their natural history including demographic data,disease characteristics,whether transitions to manic occurred,treatment status.At the end of the 7-year follow-up,treatment emergent symptom scale(TESS),medication adherence rating scale(MARS),and global assessment function(GAF)were used to evaluate adverse reactions,compliance to medication,and patient's overall functional level.Patients were divided into two groups based on the occurrence of mania or hypomania episodes during the 7-year period:the conversion group(those who developed episodes)and the non-conversion group(those who did not).Results A total of 138 patients were followed up for 7 years,including 54 patients(39.1%)in the conversion group and 84 patients(60.9%)in the non-conversion group.When the first episode was enrolled at baseline,the age of first episode was earlier in the conversion group than in the non-conversion group[(27.63±9.63)years vs.(41.20±11.92)years],and there were differences in marital status(unmarried 40.7%vs.7.1%,first marriage 53.7%vs.85.7%,remarriage 3.7%vs.2.4%,separated/divorced 0.0%vs.2.4%,widowed 1.9%vs.2.4%).The proportion of patients with precipitating factors was lower in the conversion group(29.6%vs.48.8%)and shorter duration of untreated psychosis(DUP)[60(15,90)d vs.90(30,180)d].The treatment method in the conversion group had lower only used antidepressant drugs(61.1%vs.81.0%)and more antidepressant combined with mood stabilizers(31.5%vs.16.7%)(all P<0.05).In the 7 years,total number of episodes in the conversion group was more than in the non-conversion group(4.33±1.21 vs.2.70±1.25,P<0.05).By the end of 7 years,the GAF score was lower in conversion group than in the non-conversion group(66.57±8.22 vs.69.21±7.20,P<0.05).Dichotomous unconditional logistic regression analyses revealed that age at first episode(OR=1.109,95%CI:1.058-1.161,P<0.001),DUP(d)(OR=1.005,95%CI:1.001-1.009,P=0.017),was an independent influencing factor on conversion over a 7-year period in patients with first-episode depressive disorders.Conclusion The rate of conversion over 7 years in patients with first-episode depressive disorder is 39.1%in the present cohort and converted patients had relatively earlier age of onset,more pre-onset without inducement,shorter DUP(d),more recurrence,higher the rate of combined treatment and worse overall functional outcome.

Objective To establish a new method to measure the elastic modulus of living circulating tumor cells (CTCs) by micropipette aspiration. Methods Living CTCs were enriched by commercial microfluidic chips and identified individually using EpCAM antibody under fluorescence microscope. The elastic modulus of CTCs was measured using micropipette aspiration and compared with cancer cell lines. Results For the elastic modulus of different cancer cell lines, heterogeneity was found not only between the different types of cancer cell lines but also inside the same cell line. The CTCs in breast cancer had a smaller elasticity modulus compared with MCF-7 cancer cell line. Conclusions This method can measure the elastic modulus of living CTCs, which provides cell mechanics data for studying the relationship between physical properties of CTCs and diagnosis of cancers, as well as developing the physical biomarkers of tumor cells.