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Observational studies have suggested an association between inflammatory markers and low back pain (LBP), but the causal relationship between these factors remains uncertain. We conducted a bidirectional two-sample Mendelian randomization analysis (MR) study to investigate whether there is a causal relationship between inflammatory markers and low back pain. We obtained genetic data for CRP, along with its upstream inflammatory markers IL-6, IL-8, and IL-10, as well as low back pain from publicly available genome-wide association studies (GWAS). We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald Ratio, and MR-PRESSO, to test for causal relationships. Sensitivity analyses were also conducted to assess the robustness of the results. Our analyses utilizing the Inverse Variance Weighted (IVW) method, the MR-Egger method, and the weighted median method indicated that IL-6 may be associated with an increased risk of LBP (Effect Size: -0.009, 95% Confidence Interval: -0.013-0.006, p = 9.16e-08); however, in the reverse direction, there was no significant causal effect of LBP on inflammatory markers. Our study used a Mendelian randomization approach and found that elevated IL-6 levels may reduce the risk of LBP.

[This corrects the article DOI: 10.3389/fimmu.2023.1174656.].

Background: We aimed to investigate whether the polymorphisms of gene heparan sulfate proteoglycan 2 (HSPG2) and chondroitin sulfate proteoglycan 2 (CSPG2) are associated with increased risk of intracranial aneurysms (IAs) susceptibility. Methods: The Cochrane Library, Medline, PubMed, and Embase databases were carefully searched for potential researches before Mar 30, 2018. The title, abstract, and full text were assessed to determine whether the paper was suitable for inclusion. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were presented to assess the associations between CSPG2 and HSPG2 polymorphisms and IAs susceptibility. Results: We enrolled 7 papers, 4 matched single nucleotide polymorphisms (SNPs) of CSPG2 (rs173686, rs251124) or HSPG2 (rs173686, rs251124), and a total of 8651 participations (3674 with IAs and 4977 for control). For the rs251124 polymorphism of CSPG2, the quantitative synthesis from 5 studies showed significant difference in the gene allele comparison of T vs. C (OR, 1.129; 95% CI, 1.029, 1.238; P=0.01). Similar results were found for rs3767137 of HSPG2 (A vs. G, OR, 0.842, 95% CI=0.759-0.935, P=0.001). However, for the rs173686 polymorphism of CSPG2 and rs7556412 polymorphism of HSPG2, no significant difference was found (P=0.259 and P=0.474, respectively) Conclusion: The SNPs rs251124 of CSPG2 and rs3767137 of HSPG2 had statistically significant associations with IAs susceptibility. The minor allele T of rs251124 demonstrated a harmful effect but the minor allele A of rs3767137 demonstrated a protective role with regard to the risk of IAs. However, no such associations were found in the SNPs rs173686 of CSPG2 and rs7556412 of HSPG2.

Intra-operative factors are crucial to early recurrence of hepatocellular carcinoma (HCC) after microwave ablation (MWA), but few models have been developed based on intra-operative data to predict HCC recurrence after MWA. To quantify the intra-operative factors associated with MWA and establish an artificial intelligence (AI) model for predicting early recurrence of HCC after ablation based on contrast-enhanced ultrasound (CEUS) fusion imaging. 79 hCC patients, who underwent MWA with one-year follow-up and intraoperative CEUS fusion imaging assessment were retrospectively included. Three classifiers (support vector machine (SVM), random forest (RF), and multilayer perceptron (MLP)) were developed to predict early HCC recurrence from CEUS fusion images. Thirteen ablation-specific features were defined and screened using minimum redundancy maximum relevance (mRMR), and leave-one-out cross-validation (LOOCV) was adopted for performance evaluation. Comparative analyses were conducted among classifiers and between a senior interventional doctor and the best classifier in terms of the area under the receiver operating characteristic curve (AUC). Of 79 eligible patients who were included, 22 were in the early-recurrence (age 60.18 ± 10.97; 20 males) and 57 were in the non-early recurrence (age 58.81 ± 10.89; 50 males). Six features were selected out by mRMR for early recurrence prediction and AUCs of three models were 0.84 (95% CI: 0.74, 0.94) 0.79 (95% CI: 0.69, 0.89) and 0.77 (95% CI: 0.67, 0.88) (p = 0.20 and 0.23 for SVM and RF, respectively), which was significantly better than that achieved by senior doctor's assessment (AUC, 0.56; 95% CI: 0.44, 0.68; p = 0.002 for MLP). The prediction model based on ablation-specific features using intra-operative ultrasound fusion imaging data was feasible to predict early recurrence of HCC after MWA and showed great potential in guiding the real-time adjustment of the intra-operative ablation strategy so as to achieve precise ablation.

To investigate the efficacy and safety of microwave ablation (MWA) assisted by ultrasound fusion imaging (FI) for primary and secondary liver cancers with a diameter of 3-7 cm.PurposeTo investigate the efficacy and safety of microwave ablation (MWA) assisted by ultrasound fusion imaging (FI) for primary and secondary liver cancers with a diameter of 3-7 cm.A retrospective analysis was conducted on patients with primary and secondary liver cancers (3-7 cm) who underwent MWA with ultrasound FI assistance in our hospital from April 2020 to May 2022. Technical success, technique efficacy, local tumor progression (LTP), major complication, intrahepatic distant recurrence (IDR), and overall survival (OS) were assessed during the follow-up period. In addition, the ablation results of tumors between the medium-sized group (3.1-5.0 cm) and large-sized group (5.1-7.0 cm) were compared.Patients and MethodsA retrospective analysis was conducted on patients with primary and secondary liver cancers (3-7 cm) who underwent MWA with ultrasound FI assistance in our hospital from April 2020 to May 2022. Technical success, technique efficacy, local tumor progression (LTP), major complication, intrahepatic distant recurrence (IDR), and overall survival (OS) were assessed during the follow-up period. In addition, the ablation results of tumors between the medium-sized group (3.1-5.0 cm) and large-sized group (5.1-7.0 cm) were compared.31 patients with 35 primary and secondary liver cancers were treated with MWA assisted by ultrasound FI. Complete ablation was achieved in 34 lesions with a technical success rate of 97.1%. Major complications occurred in 6.5% of patients (2/31), while no ablation-related deaths were reported. The median follow-up time of this study was 24 months (range:10 to 35 months). The technique efficacy rate was 97.1% (34/35), with LTP occurring in three lesions at a rate of 8.8% (3/34). The incidence of IDR was 38.7% (12/31) and the 2-year cumulative OS rate reached 96.7%. Moreover, there were no statistical differences in technique efficacy rate (p=0.286), LTP rate (p=0.328), major complication rate (p=0.503), IDR (p=0.857), and OS (p=0.118) between medium-sized group and large-sized group.Results31 patients with 35 primary and secondary liver cancers were treated with MWA assisted by ultrasound FI. Complete ablation was achieved in 34 lesions with a technical success rate of 97.1%. Major complications occurred in 6.5% of patients (2/31), while no ablation-related deaths were reported. The median follow-up time of this study was 24 months (range:10 to 35 months). The technique efficacy rate was 97.1% (34/35), with LTP occurring in three lesions at a rate of 8.8% (3/34). The incidence of IDR was 38.7% (12/31) and the 2-year cumulative OS rate reached 96.7%. Moreover, there were no statistical differences in technique efficacy rate (p=0.286), LTP rate (p=0.328), major complication rate (p=0.503), IDR (p=0.857), and OS (p=0.118) between medium-sized group and large-sized group.Ultrasound FI-assisted MWA has the potential to be an effective and safe therapeutic strategy for primary and secondary liver cancers ranging from 3-7 cm in size.ConclusionUltrasound FI-assisted MWA has the potential to be an effective and safe therapeutic strategy for primary and secondary liver cancers ranging from 3-7 cm in size.

Purpose To investigate the efficacy of ultrasound fusion imaging-assisted microwave ablation (MWA) for patients with colorectal liver metastases (CRLM) based on stratified analysis of tumor size and location. Methods Patients with CRLM who underwent ultrasound fusion imaging-assisted MWA in our hospital between February 2020 and February 2023 were enrolled into this retrospective study. Ultrasound fusion imaging was used for detection, guidance, monitoring and immediate evaluation throughout the MWA procedures. Technical success, technique efficacy, local tumor progression (LTP), intrahepatic progression and overall survival (OS) were recorded and analyzed. The subgroup analysis of intrahepatic progression of MWA for CRLM was performed according to tumor size and location. Results A total of 51 patients with 122 nodules were enrolled. Both technical success and technique efficacy were acquired in all nodules. In a median follow-up period of 19 months, 2.5% of the nodules (3/122) were observed LTP. The 1-year and 2-year cumulative intrahepatic progression rates were 38.7% and 52.1% respectively. Patients were divided into subgroups according to tumor size (≥ 30 mm, n = 13; < 30 mm, n = 38) and tumor location (perivascular, n = 20; non-perivascular, n = 31 and subcapsular, n = 36; non-subcapsular, n = 15). The cumulative intrahepatic progression rates were similar between the subgroups regarding tumor size and perivascular location, while significantly higher in the subcapsular group than in the non-subcapsular group (p = 0.021). Conclusion Ultrasound fusion imaging-assisted MWA exhibited satisfactory local efficacy for CRLM, especially for non-subcapsular tumors. Graphical Abstract

Purpose This study aimed to explore the reliability and stability of ultrasound-guided attenuation parameter (UGAP) values obtained by two measuring methods and different measuring times. Methods Patients who underwent liver UGAP examinations in our hospital from September 2022 to December 2022 were retrospectively analyzed. The clinical data and UGAP measurements results were collected. Two different measuring methods: static single-frame multi-point measuring and dynamic multi-frame single-point measuring, were performed for each patient, and 10 UGAP values of each measuring method were recorded. The medians of the UGAP values of the 1st–3rd, 1st–5th, 1st–7th and 1st–10th by each measuring method were taken as the final UGAP values of measuring 3, 5, 7 and 10 times. The UGAP values obtained by the two different measuring methods and different measuring times (3, 5, 7 or 10 times) were compared. Results 206 patients were included in this study. There was no statistical difference between UGAP values measured by static single-frame multi-point measuring and dynamic multi-frame single-point measuring ( P  = 0.689, P  = 0.270, P  = 0.298, P  = 0.091), regardless of measuring times (3, 5, 7, 10 times). No significant difference between the UGAP values obtained by 3, 5, 7 and 10 measurements was found ( P  = 0.554, P  = 0.916). Conclusion The UGAP values obtained by the two different measuring methods and different measuring times (3, 5, 7 and 10 times) are stable and reliable. Additionally, 3 times of UGAP measurements might be enough for each patient in clinical practice.

Background: We aimed to investigate whether the polymorphisms of gene heparan sulfate proteoglycan 2 (HSPG2) and chondroitin sulfate proteoglycan 2 (CSPG2) are associated with increased risk of intracranial aneurysms (IAs) susceptibility. Methods: The Cochrane Library, Medline, PubMed, and Embase databases were carefully searched for potential researches before Mar 30, 2018. The title, abstract, and full text were assessed to determine whether the paper was suitable for inclusion. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were presented to assess the associations between CSPG2 and HSPG2 polymorphisms and IAs susceptibility. Results: We enrolled 7 papers, 4 matched single nucleotide polymorphisms (SNPs) of CSPG2 (rs173686, rs251124) or HSPG2 (rs173686, rs251124), and a total of 8651 participations (3674 with IAs and 4977 for control). For the rs251124 polymorphism of CSPG2, the quantitative synthesis from 5 studies showed significant difference in the gene allele comparison of T vs. C (OR, 1.129; 95% CI, 1.029, 1.238; P=0.01). Similar results were found for rs3767137 of HSPG2 (A vs. G, OR, 0.842, 95% CI=0.759-0.935, P=0.001). However, for the rs173686 polymorphism of CSPG2 and rs7556412 polymorphism of HSPG2, no significant difference was found (P=0.259 and P=0.474, respectively) Conclusion: The SNPs rs251124 of CSPG2 and rs3767137 of HSPG2 had statistically significant associations with IAs susceptibility. The minor allele T of rs251124 demonstrated a harmful effect but the minor allele A of rs3767137 demonstrated a protective role with regard to the risk of IAs. However, no such associations were found in the SNPs rs173686 of CSPG2 and rs7556412 of HSPG2.

Rheumatoid arthritis (RA) is a systemic and chronic autoimmune inflammatory disease characterized by severe synovial hyperplasia associated with progressive cartilage degradation. Due to the severe pain and disability caused by RA, effective therapeutic strategies that could simultaneously alleviate the inflammatory response and delay the disease progression are urgently needed. As a major alternative therapy in traditional Chinese medicine, moxibustion has been demonstrated that it could reduce the chronic inflammatory responses of a series of musculoskeletal diseases; however, whether moxibustion has protective effects on RA is still unclear. To investigate the effects of moxibustion on RA, moxibustion was applied to Zusanli (ST36) and Shenshu (BL23) acupoints in a RA rabbit model. HE staining of articular cartilage showed that moxibustion alleviated the cartilage degradation and bone destruction. In addition, moxibustion decreased the osteoclast number in RA rabbits. Real-time PCR revealed that moxibustion decreased the expression of RANKL mRNA while increased the expression of OPG mRNA, indicating a restoration of the balance between osteogenesis and osteoclastogenesis. Taken together, our results indicated that moxibustion had promising antiarthritic effects and could be an useful alternative method in RA therapeutics.

p53 and mouse double minute 2 homolog (MDM2) serve key regulatory roles in the apoptosis of synovial cells. The present study aimed to investigate the effects of electroacupuncture (EA) at the 'Zusanli' (ST36) and 'Xuanzhong' (GB39) acupoints on apoptosis in an adjuvant arthritis (AA) rat model. A total of 40 male Sprague-Dawley rats were randomly divided into Control, AA, AA + EA and AA + sham EA groups (n=10 rats in each group). Rats in all the groups, with the exception of the control group, were injected with Complete™ Freund's adjuvant into the bilateral hindlimb footpad to establish the AA model. Rats in the AA + EA group were treated with EA at the ST36 and GB39 acupoints. Rats in the AA + sham EA group were treated with percutaneous electrical stimulation at a position of 5 mm away from the ST36 and GB39 acupoints. The arthritis index scores and hindlimb paw volumes of the rats in each group were recorded. Subsequently, pathological changes in the synovial tissue were evaluated by hematoxylin and eosin (H&E) staining, and the apoptotic rate of the synovial cells was detected by TUNEL staining. In addition, the expression levels of the apoptosis-associated proteins, Bax, phorbol-12-myristate-13-acetate-induced protein 1 (Noxa) and p53 upregulated modulator of apoptosis (PUMA), were determined by western blot analysis. The expression of both the gene and protein of p53 and MDM2 in synovial tissue was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The results indicated that the arthritis index scores and hindlimb paw volumes upon EA stimulation were significantly decreased compared with those of the AA group (P<0.05). H&E staining revealed that the synovial inflammation of EA stimulation was significantly decreased compared with the AA group (P<0.05). The TUNEL assay results indicated that the apoptotic rate of synovial cells in the AA + EA group was significantly increased compared with that in the AA group (P<0.05). Furthermore, an increased expression of proapoptotic proteins was confirmed by the increased expression levels of Bax, Noxa and PUMA in the AA + EA group. The results of RT-qPCR and western blot analysis demonstrated that, compared with the AA group, EA stimulation led to a marked increase in p53 (P<0.05) and a significant decrease in MDM2 (P<0.05) gene and protein expression. Taken together, these results demonstrated that EA performed on the ST36 and GB39 acupoints led to a significant amelioration in AA injury of model rats, by regulating the p53 signaling pathway and inducing apoptosis.