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 clinical efficacy of acupuncture based on "status-target coherence" theory combined with Kegel exercises for vaginal laxity syndrome (VLS). METHODS: Sixty-six patients with VLS were randomized into an observation group (33 cases, 2 cases dropped out, 1 case was discontinued) and a control group (33 cases, 5 cases dropped out). The observation group was treated with acupuncture combined with Kegel exercises, acupuncture was applied to bilateral Ciliao (BL32), Zhongliao (BL33), Sanyinjiao (SP6), etc. The control group was treated with Kegel exercises. Both acupuncture and Kegel exercises were performed once every other day, three times a week for 12 weeks. Before and after treatment, the vaginal laxity questionnaire (VLQ) score, pelvic floor muscle strength (vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration), degree of vaginal laxity and sexual satisfaction questionnaire (SSQ) grade were observed in both groups. RESULTS: After treatment, the VLQ score, vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration in the observation group were elevated compared with those before treatment (P<0.05), and SSQ grade was improved (P<0.05); and the above indexes in the observation group were better than those in the control group (P<0.05). There were no significant difference before and after treatment in the degree of vaginal laxity in the two groups (P>0.05). CONCLUSION Acupuncture based on "status-target coherence" theory combined with Kegel exercises can effectively enhance the strength of pelvic floor muscles, improve the symptoms of vaginal laxity, and improve the satisfaction of sexual life, and its therapeutic effect is better than Kegel exercises alone.
Humans ; Female ; Adult ; Vagina/physiopathology* ; Acupuncture Therapy ; Exercise Therapy ; Young Adult ; Middle Aged ; Treatment Outcome ; Acupuncture Points ; Combined Modality Therapy ; Vaginal Diseases/therapy*

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective To investigate the changes of serum cardiac-specific troponin I (cTnI) level in patients after lung transplantation. Methods Clinical data of patients undergoing lung transplantation in our hospital from December 2016 to December 2022 were retrospectively analyzed. The relationship between postoperative serum cTnI level and clinical characteristics were explored. Results Finally 20 patients were collected, including 15 males and 5 females with an average age of (51.65±12.79) years. The serum cTnI level was significantly increased after lung transplantation. The serum cTnI reached the highest level on the first day after transplantation, and significantly decreased from the third day after transplantation. The serum cTnI levels in patients with obstructive pulmonary disease and bilateral lung transplantation were significantly higher than those in patients with restrictive pulmonary disease and unilateral lung transplantation on the day after surgery and on the first day after transplantation. Conclusion Transient myocardial injury can occur after lung transplantation, which is characterized by an abnormal increase in serum cTnI level.

Objective To investigate the role of proanthocyanidins (PC) in lipopolysaccharide (LPS)-induced inflammatory response and its possible mechanism in RAW264.7 macrophages. Methods RAW264.7 macrophages were cultured and treated with PBS and different concentrations of PC for 24 hours, followed by 1 μg/mL LPS for 6 hours. Real-time PCR was used to detect the mRNA expression of interleukin1β (IL-1β), IL-6, monocyte chemoattractant protein 1 (MCP-1), tumor necrotic factor α (TNF-α), IL-4 and arginase 1 (Arg1) in RAW264.7 macrophages. Flow cytometry was used to detect the effects of PBS group, LPS group and PC combined with LPS group on M1 and M2 polarization of macrophages. The protein expressions of silenced information regulator 1 (SIRT1), nuclear factor kappa B p65(NF-κB p65) and acetylated NF-κB p65 (Ace-p65) were detected by Western blot analysis after different concentrations of PC treatment. Co-immunoprecipitation assay was used to detect the binding effect of SIRT1 to NF-κB p65 in macrophages treated with PC. Results Compared with PBS group, the mRNA expression of macrophage pro-inflammatory cytokines IL-1β, IL-6, MCP-1 and TNF-α decreased and the mRNA expression of anti-inflammatory factors IL-4 and Arg1 increased in PC group. Compared with LPS group, PC combined with LPS group could significantly inhibit M1 polarization and promote M2 polarization of macrophages. With the increase of PC concentration, the expression of SIRT1 was up-regulated, and NF-κB p65 protein did not change significantly. The expression of Ace-p65 protein decreased significantly when treated with high concentration of PC. Conclusion PC can significantly alleviate the LPS-induced inflammatory response by up-regulating the expression of SIRT1 and inhibiting NF-κB pathway in RAW264.7 macrophages.
Animals ; Mice ; Interleukin-4 ; Interleukin-6 ; Lipopolysaccharides ; Macrophages ; NF-kappa B ; Proanthocyanidins ; RNA, Messenger ; Sirtuin 1/genetics* ; Tumor Necrosis Factor-alpha ; RAW 264.7 Cells

OBJECTIVE To study the tissue distribution and pharmacokinetic characteristics of polyethylene glycol-（polylactic acid-hydroxyacetic acid） -polyethylene glycol triblock copolymer （PELGE） -crebanine nanoparticles （PELGE-Cre-NPS） in rats. METHODS The SD rats were divided into 9 groups （1 group at each time point）， with 6 rats in each group，half male and half female. After PELGE-Cre-NPs（5 mg/kg） was injected into tail vein of rats， appropriate amounts of heart， liver， spleen， lung， kidney and brain tissues were taken at 5， 15， 30， 60， 90， 120， 180， 240 and 300 min， respectively. With verapamil hydrochloride as internal standard， the content of crebanine （Cre） in each tissue was determined by HPLC， and the main pharmacokinetic parameters such as area under the drug-time curve （AUC0－）t and mean retention time （MRT0－）t were calculated.RESULTS At 5-90 min after medication， the content of Cre in each tissue of rats from large to small was lung， kidney， spleen， liver， brain and heart； at 120-300 min after medication， the sequence was lung， spleen， kidney， liver， brain and heart. AUC0－t of Cre in heart， liver， spleen， lung， kidney and brain were （18.86±1.66）， （43.36±4.99）， （51.36±5.34）， （81.86±12.34）， （53.31±3.19） and （27.73±4.76） mg·h/L， respectively. MRT0－t of Cre were （1.94±0.12）， （1.97±1.02）， （1.98±1.23）， （1.89±0.21）， （1.88± 0.06）， （1.85±0.19） h， respectively. CONCLUSIONS PELGE-Cre-NPs mainly distribute in lung tissue， but less in heart tissue， and the elimination of PELGE-Cre-NPs in heart， lung and liver tissue is slow.