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.

AIM:To analyze the compliance rate and possible influencing factors for blood concen-tration of meropenem in patients with central ner-vous system(CNS)infections,and to provide basis for optimizing the administration of meropenem in the patients.METHODS:A retrospective analysis was performed in patients who were treated with meropenem and monitored the concentration(Cmin)from January 2021 to December 2022.The basic clinical data of the patients were recorded,and the achievement of meropenem blood concentration was counted.Univariate and binary logistic regres-sion analysis were used to analyze the influencing factors for the e substandard steady-state blood trough concentration of meropenem.The ROC curve was drawn to predict the clinical characteris-tics.RESULTS:Forty-five cases were included.The median Cmin of meropenem was 4.14(0.82,16.29)mg/L,and 51.11％reached the target range with 4 mg/L.Binary logistic regression analysis showed that serum creatinine value and using mannitol were risk factors for the substandard steady-state blood trough concentration of meropenem(P＜0.05).When serum creatinine value was less than 84 μmol/L,the area under the ROC curve was the largest(0.916),the sensitivity was 0.783,the speci-ficity was 0.955,and the Youden index was 0.738.CONCLUSION:The Cmin compliance rate of merope-nem blood concentration in patients with CNS in-fection is low,especially in patients with hyperfunc-tion of kidney and those who using mannitol.It is necessary to conduct drug concentration monitor-ing to optimize the administration of meropenem in patients with CNS infection.

Objective:To investigate the effects of resistance exercise on mitochondrial function, muscle attenuation and muscle fiber morphology in quadriceps femoris of aged rats.Methods:The 18-month-old male rats were randomly divided into five groups( n=8, each): control(not exercise), 0% weight-bearing, 30% weight-bearing, 50% weight-bearing, and 70% weight-bearing exercise.After maximum resistance running, intermittent race table resistance exercise with 0%, 30%, 50%, 70% maximum load were performed.The treadmill placement slope was 35°, the running speed was 15 m/min, and exercise was performed every other day.At the end of the 8 th week, the mitochondrial membrane potential of quadriceps femoris muscle was measured, cytosol contents of cytochrome C(Cyt c), apoptosis-inducing factor(AIF), and apoptotic protein(Smac/DIABLO)were measured, and the morphology and structure of muscle fibers were observed. Results:Compared with the control group, the mitochondrial ΔΨmt was increased in the 0%, 30%, 50% and 70% maximum load groups, with a significant difference in the increment in the 0%, 30% and 50% maximum load groups( t=7.412, 5.611, 6.213, all P<0.01).Compared with the 0% maximum load group, the percentage of cells with mitochondrial ΔΨmt was statistically significantly decreased in the 30% maximum load group(10.6%)( t=9.356, P<0.05), while the percentage of cells with mitochondrial ΔΨmt was statistically significantly increased in the 70% maximum load group(10.03%)( t=8.341, P<0.05).Compared with the control group, the contents of Cyt c, AIF and Smac/DIABLO in the cytoplasm of quadriceps femoris of aged rats with 8-week resistance exercise were decreased, among which the contents of Cyt c and Smac/DIABLO were statistically significantly decreased in the three groups of 0%, 30%, and 50% maximum load( t=8.324, 7.516, and 6.871, all P<0.05), as well as the decrement in AIF of the three groups of 0%, 30%, and 50% maximum load was statistically significant( t =9.434, 8.78, and 7.342, all P<0.05).Compared with the control group, the vacuolar area of muscle fibers was extremely significantly decreased in the 0%, 30%, and 50% maximum load groups( t =5.567, 6.784, and 7.432, P<0.01); the protein content in the quadriceps femoris muscle was very significantly increased in the 30%, 50%, and 70% maximum load groups( t =7.478, 6.765, and 4.564, all P <0.01).Compared with the 0% maximum load group, the protein content in the quadriceps femoris muscle was very significantly increased in the 30%, 50%, and 70% maximum load groups( t=9.236, 8.342, and 6.456, all P<0.01). Conclusions:Low and medium weight-bearing resistance exercise can improve the mitochondrial function of quadriceps femoris, reduce the femoral quadriceps mitochondria-released proapoptotic proteins Cyt c, AIF, and Smac/DIABLO, and reduce the incidence of quadriceps femoris apoptosis.Low and medium weight-bearing resistance exercise can increase the protein content of muscle fibers, reduce the vacuolar area of muscle fibers, maintain muscle mass, and delay the occurrence of sarcopenia.

Objective:To explore effects of different flow rates and temperature settings of high-flow nasal cannula oxygen therapy (HFNC) on patients with mild to moderate community-acquired pneumonia (CAP) accompanied by type I respiratory failure.Methods:Using the convenient sampling method, a total of 92 patients with mild to moderate CAP accompanied by type I respiratory failure who were admitted and received HFNC in the Department of Respiratory and Critical Care Medicine in a Class Ⅲ Grade A hospital in Tianjin were selected as the research objects from December 2019 to December 2020. They were randomly divided into 4 groups, including low temperature and low flow rate group (31 ℃, 30 L/min) , low temperature and high flow rate group (31℃, 50 L/min) , high temperature and low flow rate group (34℃, 30 L/min) , high temperature and high flow rate group (34 ℃, 50 L/min) , with 23 cases in every group. Two-factor factorial analysis of variance was used to compare effects of different flow rates and temperature settings of HFNC on the comfort, oxygenation index, respiratory rate and heart rate of patients with mild to moderate CAP.Results:The comfort level of patients in the low flow rate group (30 L/min) was higher than that of the high flow rate group (50 L/min) , and the comfort level of patients in the low temperature group (31 ℃) was higher than that of the high temperature group (34 ℃) . The differences were statistically significant ( P<0.01) . The oxygenation index of patients in the high flow rate group (50 L/min) was higher than that of the low flow rate group (30 L/min) , and the difference was statistically significant ( P<0.01) . Different flow rates and temperatures of HFNC have no interaction effect on the comfort, oxygenation index and heart rate of patients ( P>0.05) , but they have an interaction effects on respiratory rate ( P<0.01) . Individual effect analysis showed that the respiratory rate of patients in the low temperature and high flow rate group (31 ℃, 50 L/min) was lower than that of the high temperature and high flow rate group (34 ℃, 50 L/min) and the low temperature and low flow rate group (31 ℃, 30 L/min) , and the differences were statistically significant ( P<0.01) . Conclusions:For patients with mild to moderate CAP accompanied by type I respiratory failure, the application of HFNC should start with low temperature and low flow rate parameter settings. Under the condition of ensuring the patient's comfort, the overall effect of flow rate and temperature is integrated and the inhalation flow rate of HFNC is appropriately increased, which can increase the clinical effect of high-flow nasal cannula oxygen therapy.

Objective To establish the animal model of chronic thromboembolic pulmonary hypertension(CTEPH) and to compare the accuracy of dual-energy CT (DECT) pulmonary angiography and histopathology for detecting CTEPH. Methods Eighteen canines were included in the study. All canines underwent paracentesis, embolization, CT scanning, pressure measurement and tranexamic acid feeding. The procedures were repeated every two weeks, until systolic/diastolic pressure in canines was≥30/15 mmHg or mean pulmonary artery pressure ≥ 20 mmHg.And then canines were sacrificed for histopathology examination. For CT pulmonary angiography (CTPA)in DE mode and DECT lung perfused blood volume (Lung PBV) images, the presence or absence of PE or perfusion defects were recorded on a per-canineand aper-lobe basis. With histopathological results as reference standard, the sensitivity, specificity of CTPA and lung PBV to detect PE were computed for two readers. The pairedχ2 test (McNemar test) was used to analyze the difference in diagnostic accuracy between CTPA and Lung PBV. Inter-reader agreement was also calculated with kappa test. Results CTEPH was demonstrated in 13 canines. On a per-canine basis, both readers found uneven and peripheral perfusion defects with DECT in 11 canines (84.6%, 11/13); while 5 canines (38.5%, 5/13) had cutoff or sudden stenosis of pulmonary arteries with CTPA;on a per-lobe basis,
both readers had sensitivities of 14.3%(5/35), 83.3%(30/36), specificities of 100.0%(30/30), 100.0%(29/29), accuracies of 53.8%(35/65), 90.8%(59/65)for CTPA and DECT, respectively. DECT had a higher sensitivity(χ2=-4.690,P<0.01)and accuracy(χ2=8.284,P<0.01) in detecting CTEPH. Excellent and moderate inter-reader agreements were observed with CTPA and DECT (Kappa=0.938, 0.572, both P<0.001). Conclusions It is feasible to make a CTEPH animal model with autologous thrombus. DECT shows a higher accuracy than CTPA to detect CTEPH in this canine model study.

OBJECTIVETo investigate the expression of La protein in cervical cancer tissues and explore its role in the occurrence and progression of cervical cancer.

METHODSThe expression of La protein in cervical cancer and normal cervical tissues was detected by immunohistochemical staining. RNA interference technology was used to silence La protein expression in HeLa cells and the changes in cell proliferation, tumor sphere formation and cell cycles were investigated.

RESULTSThe expression of La protein was significantly higher in cervical cancer tissues than in normal cervical tissues (61% vs 9%, P<0.05). Silencing La protein expression in HeLa cells caused significantly reduced the cell proliferation and lowered the tumor sphere formation rate from the control level of (17.1=1.92)% to (6.3=0.45)% (P<0.05), resulting also in G0/G1 cell cycle arrest and reduced cyclin D1 protein expression.

CONCLUSIONThe RNA binding protein La can promote the development of cervical cancer and may play a critical role in the carcinogenesis and progression of cervical cancer.

Autoantigens ; metabolism ; Cell Cycle Checkpoints ; Cyclin D1 ; metabolism ; Female ; HeLa Cells ; Humans ; RNA Interference ; RNA-Binding Proteins ; metabolism ; Ribonucleoproteins ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology