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.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Objective To establish a high-throughput method that can simultaneously, quickly, and accurately detect main malaria-transmitting Anopheles species and their resistance genes in China, providing a high-throughput monitoring tool for monitoring the main malaria vectors in China after malaria elimination. Methods In different sampling locations, including Tengchong City, Yunnan Province; Wenchang City, Hainan Province; and Donggang City, Liaoning Province, adult specimens of mosquitoes, including Anopheles sinensis, Anopheles minimus, Anopheles dirus, and Anopheles anthropophagus, were collected. Polymerase chain reaction (PCR) technology and Sanger sequencing were employed to detect the ITS2, kdr (L1014), rdl (A296), and ace-1 (G119) genes in individual mosquitoes. For the analysis of mixed samples, an optimized multiplex PCR reaction system, custom-designed dual barcode primers, and next-generation sequencing (NGS) technology were utilized to detect the aforementioned genes. The consistency was assessed using Kappa consistency tests and Chi-square tests for multiple rates. Sensitivity, specificity, and the Youden index were calculated using a four-grid table calculation method. The costs associated with each step of the normal operational process for each method were statistically summarized, and the optimal quantity of mixed samples for detection was determined by a comprehensive approach. Results Conventional PCR amplification of gDNA from 300 mosquitoes resulted in 144 individuals of Anopheles sinensis, 53 individuals of Anopheles dirus, 62 individuals of Anopheles anthropophagus, and 41 individuals of Anopheles minimus, as identified by Sanger sequencing. The mutation frequencies of resistance genes kdr (L1014), rdl (A296), and ace-1 (G119) were found in 73, 27, and 41 specimens, respectively. Using a newly established multiplex PCR reaction system based on custom dual barcode and NGS sequencing technology, samples corresponding to Sanger sequencing were detected under different sample sizes. The two methods showed high consistency in the results (all Kappa>0.900). Multiple comparison tests showed significant differences in the consistencies of the two methods across different sample sizes N (40, 80, 160), N (120, 200, 240, 280), and N (300) (χ2=26.547, P<0.001). The new method demonstrated high sensitivity and specificity across various sample sizes, with the Youden index ranging from highest to lowest as follows: 1 (40, 80, 160)>0.994 (120)>0.990 (280)>0.988 (200)>0.987 (240)>0.985 (300). With an increase in sample size from 40 to 300, the cost per sequencing site for the new method decreased from 20.0 yuan to 8.3 yuan, while the cost per sequencing site for the conventional method decreased from 16.7 yuan to 15.4 yuan. The optimal mixed sample size for the new method was determined to be 280. Conclusion The newly developed multiplex PCR and barcode NGS detection method enables simultaneous screening of four major malaria vector mosquito species and the presence of mutations in the ace-1, kdr, and rdl resistance genes, exhibiting excellent stability, high sensitivity, and specificity. It allows for the efficient analysis of large sample sizes in a single run, offering a cost-effective alternative compared to other types of detection methods.

Objective:To discuss outcomes of emergency repairing for Gustilo III B and III C fractures of forearm with complicated tissue defects and the related influence factors.Methods:From January 2014 to Feburary 2022, data of 98 cases of Gustilo III B and III C fractures with large compound defects of soft tissue, blood vessel, bone, tendon or muscle from elbow to wrist were collected. Primary debridement, bone fixation, wound coverage by free flap, bone transfer(or bone cement filling) or dynamic reconstruction of muscle were completed with emergency surgery in Department of Hand and Foot Microsurgery, Xi'an Fengcheng Hospital. Postoperative follow-ups were conducted through outpatient clinic visits, telephone and WeChat reviews. Video clips, questionnaires and the latest information of patients were also analysed. Rank sum test and Chi-square test were used to examine the relationship between independent variables such as general condition, disease condition and surgical procedures of chimeric tissue transfer group and simple flap transfer group, together with dependent variables such as limb salvage, number of surgery, wound healing, function scores, and complications. P<0.05 were further included in the regression equation to discover the relationship between multiple independent variables and dependent variables. Results:Follow-up lasted for 6-96 months, with an average of 71.1 months. In the chimeric group, the limb salvage rate was at 95.1%, with an infection rate of 8.50% and an average number of surgery was 2.13±0.89. In the simple flap transfer group, the limb salvage rate was at 87.5%, with an infection rate of 15.38% and an average number of surgery was 2.62±0.64. The good rate of Anderson score was 65.3% and the average score of Disability of the Arm, Shoulder and Hand(DASH) was 32.9(0-60) points for all the patients. There were significant differences in dependent variables of limb salvage and infection rate between the 2 groups ( P<0.05). Ischemia time and method of bone fixation led to significant differences in number of surgery ( P<0.05). Methods of bone fixation and the types of flap made significant differences in wound healing ( P<0.05). Underlying disease, bonedefect, Gustilo classification and method of bone fixation all contributed to the significant differences in function score ( P<0.05 or P<0.01) . Conclusion:Emergency surgery for repair of serious injury of forearm has a relatively high limb salvage rate and good functional effects. The limb salvage rate is not correlated with independent variables such as severity of injury, Mangledextremity Severity Score (MESS) and ischemia time, while transfer of a simple flap or a chimeric flap is significantly correlated with the limb salvage rate, infection and wound healing. The severity of injury, ischemia time and bone defect are correlated with functional assessment, number of surgery and bone healing.

OBJECTIVE: To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism. METHODS: A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. RESULTS: Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group. CONCLUSIONS PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Sepsis-Associated Encephalopathy ; Phosphates ; Actins ; Beclin-1 ; Interleukin-6 ; Autophagy ; Ubiquitin-Protein Ligases ; Cognitive Dysfunction ; Sepsis ; Mitochondria ; Protein Kinases

Objective : To detect the changes of autophagic flux at different stages after oxygen⁃glucose deprivationreoxygenation (OGD/R) with several highly sensitive methods. Methods : Primary cortical neurons after oxygen deprivation of sugar after reoxygenation (OGD/R) were divided into the experimental OGD/R group and OGD/R + bafilomycinA1 (BafA1) group , using an RFP⁃GFP series fluorescent tags LC3 gene transfection detection cytolysosome and fusion of lysosomes , transmission electron microscope (TEM) observation the ultrastructure of autophagy , p62/SQSTM1 combining LC3 protein to flip the experimental testing p62 and LC3 protein quantitative , p62 immune staining observing the distribution and content. Results : Under fluorescence microscope , the ratio of autophagy lysosome to autophagosome increased significantly in OGD/R group , and the changes of autophagy structure in different stages could be observed in TEM. The ratio of soluble p62 and LC3 Ⅱ/ Ⅰ reflected the activation of autophagic flux , and p62 was mainly distributed in BafA1 group after fluorescence staining. Conclusion Each method has its own advantages , and different methods and indicators can accurately reflect the specific changes of autophagic flux in different stages after neuronal OGD/R. Mastering and applying these methods can effectively explore central nervous system diseases from the perspective of autophagy.