Objective:To verify the causal relationship between tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-12 (IL-12) and gout using Mendelian randomization (MR) analysis. The findings are expected to provide insights into whether TNF-α, IL-6, IL-12 antagonists and other biological agents can be applied in the treatment of refractory gout (RG) in clinical practice.Methods:This study conducted a two-sample MR using publicly available summary statistics from an independent European ancestry cohort. For the data on TNF-α, IL-6, and IL-12, data were retrieved from the GWAS catalog database. For the gout data, to avoid confounding, the FinnGen database was used. The analysis was performed using R4.3.2 software. The statistical significance threshold was set at P<5×10 -5. Linkage disequilibrium (LDA was set to R2>0.001) was removed, and strongly correlated and independent single nucleotide polymorphism (SNP) loci were selected for analysis. Five methods were used for analysis: inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode. IVW was used as the main analysis method. When pleiotropy was present, MR-Egger estimates were considered more persuasive than IVW estimates, so MR-Egger was taken as the primary analysis method. Cochran′s Q test and MR-Egger intercept test were used to assess heterogeneity and pleiotropy. The leave-one-out method was used to test the stability of MR results by systematically excluding instrumental variables (IVs). Finally, a reverse MR analysis of gout and TNF-α, IL-6, IL-12 was conducted. Results:The IVW-MR, MR Egger, weighted median, simple mode, and weighted mode analyses showed no causal relationship between IL-6, IL-12, and gout (all P>0.05). Cochran′s Q test and MR-Egger intercept test results showed no significant heterogeneity or horizontal pleiotropy affecting causal estimates (all P>0.05). The leave-one-out test indicated stable results. MR-Egger analysis showed a weak causal relationship between TNF-α and gout [ OR(95% CI)=0.892 (0.812, 0.979), b=-0.113, P=0.021], while the other methods (IVW-MR, weighted median, simple mode, weighted mode) showed no causal relationship between TNF-α and gout (all P>0.05). Cochran′s Q test indicated no heterogeneity affecting causal estimates ( P>0.05), but MR-Egger intercept test suggested the presence of horizontal pleiotropy affecting causal estimates ( P<0.05). The reverse MR analysis of gout and TNF-α, IL-6, IL-12 showed no causal relationships (all P>0.05). No significant heterogeneity or horizontal pleiotropy affected causal estimates (all P>0.05), and the leave-one-out test indicated that the results were stable. Conclusion:MR analysis suggests that there is no causal relationship between IL-6, IL-12, and gout, but TNF-α may have a weak causal relationship with gout. More accurate and solid evidence are needed from further prospective randomized controlled trials.

Objective:To investigate children's attention deficit hyperactivity disorder symptoms and their im-pact on parental anxiety and depression,as well as the mediating role of parent-child relationship.Methods:A total of 472 children with ADHD who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Dis-orders,Fourth Edition(DSM-Ⅳ)were selected.The severity of ADHD symptoms was assessed using the Attention Deficit Hyperactivity Disorder Rating Scale(ADHD-RS),parent-child relationships were assessed using the Parent-Child Relationship Test(PCRT),and parental anxiety and depression were assessed using the Generalized Anxiety Disorder 7-item Scale(GAD-7)and the Patient Health Questionnaire-9(PHQ-9),respectively.Mediation analysis was conducted following structural equation modeling construction.Results:There was a positive correlation be-tween ADHD-RS scores and PCRT scores,parental GAD-7 scores,and PHQ-9 scores(r=0.19-0.29,Ps＜0.001).PCRT scores significantly mediated the relationship between ADHD-RS total scores and parental GAD-7 and PHQ-9 scores(β=0.02-0.03,Ps＜0.05).PCRT scores did not significantly mediate the relationship between ADHD-RS inattention scores and parental GAD-7 and PHQ-9 scores(β=0.01-0.02,Ps＞0.05).PCRT scores significantly mediated the relationship between ADHD-RS hyperactivity/impulsivity scores and parental GAD-7 and PHQ-9 scores(β=0.02,Ps＜0.05).Conclusion:The symptoms of ADHD in children are associated with parental anxiety and depression symptoms,with parent-child relationships mediating this relationship.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective:To investigate the efficacy of warm needle acupuncture combined with bone manipulation and Tuina treatment in the treatment of lumbar disc herniation (LDH) and its effects on patients' lumbar function and quality of life. Methods:Fifty patients with LDH admitted to Wenzhou Traditional Chinese Medicine Hospital from December 2022 to December 2023 were included in this study. The patients were randomly divided into an observation group ( n = 25) and a control group ( n = 25) using the random number table method. Patients in the control group received bone manipulation and Tuina treatment, while those in the observation group received warm needle acupuncture combined with bone manipulation and Tuina treatment. Both groups underwent a treatment course of 4 weeks. The therapeutic effects were compared between the two groups. Additionally, the Oswestry Disability Index score, Visual Analog Scale score, Japanese Orthopaedic Association score, and the General Quality of Life Inventory (GQOLI-74) score were compared between the two groups before and after treatment. Results:The total effective rate of treatment in the observation group was significantly higher than that in the control group [96.00% (24/25) vs. 68.00% (17/25), χ2 = 4.88, P < 0.05]. After treatment, the Oswestry Disability Index score and Visual Analog Scale score in the observation group were (9.82 ± 1.76) and (1.72 ± 0.46), respectively, which were significantly lower than those in the control group [(13.97 ± 2.54), (2.89 ± 0.71), t = 6.71, 6.91, both P < 0.001]. In the observation group, the scores for limitations in daily activities, clinical symptoms, subjective symptoms, and the total score were (12.32 ± 2.17), (4.89 ± 0.72), (7.32 ± 1.18), and (24.53 ± 2.94), respectively. These scores were all significantly higher than those in the control group [(9.98 ± 1.64), (3.67 ± 0.58), (5.98 ± 0.76), (19.63 ± 2.87), t = 4.30, 6.60, 4.77, 5.96, all P < 0.001]. Additionally, the scores for social function, psychological function, and physical function in the observation group were (76.82 ± 6.08), (73.42 ± 6.92), and (78.28 ± 6.98), respectively. These scores were significantly higher than those in the control group [(63.32 ± 7.13), (60.09 ± 5.85), (65.21 ± 5.59), t = 7.20, 7.35, 7.31, all P < 0.001]. Conclusions:Warm needle acupuncture combined with bone manipulation and Tuina treatment is highly effective on LDH. The approach can improve patients' lumbar function and quality of life.

Objective:To investigate children's attention deficit hyperactivity disorder symptoms and their im-pact on parental anxiety and depression,as well as the mediating role of parent-child relationship.Methods:A total of 472 children with ADHD who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Dis-orders,Fourth Edition(DSM-Ⅳ)were selected.The severity of ADHD symptoms was assessed using the Attention Deficit Hyperactivity Disorder Rating Scale(ADHD-RS),parent-child relationships were assessed using the Parent-Child Relationship Test(PCRT),and parental anxiety and depression were assessed using the Generalized Anxiety Disorder 7-item Scale(GAD-7)and the Patient Health Questionnaire-9(PHQ-9),respectively.Mediation analysis was conducted following structural equation modeling construction.Results:There was a positive correlation be-tween ADHD-RS scores and PCRT scores,parental GAD-7 scores,and PHQ-9 scores(r=0.19-0.29,Ps＜0.001).PCRT scores significantly mediated the relationship between ADHD-RS total scores and parental GAD-7 and PHQ-9 scores(β=0.02-0.03,Ps＜0.05).PCRT scores did not significantly mediate the relationship between ADHD-RS inattention scores and parental GAD-7 and PHQ-9 scores(β=0.01-0.02,Ps＞0.05).PCRT scores significantly mediated the relationship between ADHD-RS hyperactivity/impulsivity scores and parental GAD-7 and PHQ-9 scores(β=0.02,Ps＜0.05).Conclusion:The symptoms of ADHD in children are associated with parental anxiety and depression symptoms,with parent-child relationships mediating this relationship.

Objective:To study the effects of aluminum exposure on learning and memory and the expression of nerve growth factor(NGF)in the hippocampus of offspring rats,and to investigate the mechanism by which aluminum impairs learning and memory function.Methods:Forty pregnant Wistar rats were randomly assigned to the Control group(Control),low-dose Al group(Al-L),medium-dose Al group(Al-M)and high-dose Al group(Al-H).The off-spring rats were fed with Al through breast milk from birth to weaning,while the rats in the control group were fed with distilled water.The maternal rats Al-L,Al-M and Al-H groups drank distilled water solution containing 2.0,4.0 and 8.0 g/L AlCl3,respectively.After weaning,the offspring rats in the aluminum exposure group drank distilled water so-lution containing 2.0,4.0 and 8.0 g/L AlCl3 by themselves until the 90th day after birth to establish the offspring rat model of subchronic aluminum exposure.After aluminum exposure,the shuttle box test was used to detect the learning and memory ability of offspring rats,and the body weight of offspring rats and hippocampus were weighed to evaluate the effect of aluminum exposure.The expression of nerve growth factor(NGF)protein in hippocampus of offspring rats was detected by Western blot,and the expression of NGF mRNA in hippocampus of offspring rats was detected by real time RT-PCR.Results:The body weight of offspring rats in Al-H group was significantly lower than that in the other three dose groups.In the shuttle box test,compared with the control group,the active avoidance response and passive avoid-ance response of the offspring rats in the aluminum exposure group showed a downward trend with the increase of alumi-num exposure dose,indicating that the learning and memory ability of the offspring rats in the aluminum exposure group was impaired.Compared with the control group,the NGF protein content and NGF mRNA expression in the hippocam-pus of offspring rats in the aluminum exposure group were significantly decreased.Conclusion:Subchronic aluminum exposure down-regulates the expression of NGF in the hippocampus,which may cause learning and memory impairment in offspring rats.

Objective:To investigate the efficacy of warm needle acupuncture combined with bone manipulation and Tuina treatment in the treatment of lumbar disc herniation (LDH) and its effects on patients' lumbar function and quality of life. Methods:Fifty patients with LDH admitted to Wenzhou Traditional Chinese Medicine Hospital from December 2022 to December 2023 were included in this study. The patients were randomly divided into an observation group ( n = 25) and a control group ( n = 25) using the random number table method. Patients in the control group received bone manipulation and Tuina treatment, while those in the observation group received warm needle acupuncture combined with bone manipulation and Tuina treatment. Both groups underwent a treatment course of 4 weeks. The therapeutic effects were compared between the two groups. Additionally, the Oswestry Disability Index score, Visual Analog Scale score, Japanese Orthopaedic Association score, and the General Quality of Life Inventory (GQOLI-74) score were compared between the two groups before and after treatment. Results:The total effective rate of treatment in the observation group was significantly higher than that in the control group [96.00% (24/25) vs. 68.00% (17/25), χ2 = 4.88, P < 0.05]. After treatment, the Oswestry Disability Index score and Visual Analog Scale score in the observation group were (9.82 ± 1.76) and (1.72 ± 0.46), respectively, which were significantly lower than those in the control group [(13.97 ± 2.54), (2.89 ± 0.71), t = 6.71, 6.91, both P < 0.001]. In the observation group, the scores for limitations in daily activities, clinical symptoms, subjective symptoms, and the total score were (12.32 ± 2.17), (4.89 ± 0.72), (7.32 ± 1.18), and (24.53 ± 2.94), respectively. These scores were all significantly higher than those in the control group [(9.98 ± 1.64), (3.67 ± 0.58), (5.98 ± 0.76), (19.63 ± 2.87), t = 4.30, 6.60, 4.77, 5.96, all P < 0.001]. Additionally, the scores for social function, psychological function, and physical function in the observation group were (76.82 ± 6.08), (73.42 ± 6.92), and (78.28 ± 6.98), respectively. These scores were significantly higher than those in the control group [(63.32 ± 7.13), (60.09 ± 5.85), (65.21 ± 5.59), t = 7.20, 7.35, 7.31, all P < 0.001]. Conclusions:Warm needle acupuncture combined with bone manipulation and Tuina treatment is highly effective on LDH. The approach can improve patients' lumbar function and quality of life.

Objective:To verify the causal relationship between tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-12 (IL-12) and gout using Mendelian randomization (MR) analysis. The findings are expected to provide insights into whether TNF-α, IL-6, IL-12 antagonists and other biological agents can be applied in the treatment of refractory gout (RG) in clinical practice.Methods:This study conducted a two-sample MR using publicly available summary statistics from an independent European ancestry cohort. For the data on TNF-α, IL-6, and IL-12, data were retrieved from the GWAS catalog database. For the gout data, to avoid confounding, the FinnGen database was used. The analysis was performed using R4.3.2 software. The statistical significance threshold was set at P<5×10 -5. Linkage disequilibrium (LDA was set to R2>0.001) was removed, and strongly correlated and independent single nucleotide polymorphism (SNP) loci were selected for analysis. Five methods were used for analysis: inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode. IVW was used as the main analysis method. When pleiotropy was present, MR-Egger estimates were considered more persuasive than IVW estimates, so MR-Egger was taken as the primary analysis method. Cochran′s Q test and MR-Egger intercept test were used to assess heterogeneity and pleiotropy. The leave-one-out method was used to test the stability of MR results by systematically excluding instrumental variables (IVs). Finally, a reverse MR analysis of gout and TNF-α, IL-6, IL-12 was conducted. Results:The IVW-MR, MR Egger, weighted median, simple mode, and weighted mode analyses showed no causal relationship between IL-6, IL-12, and gout (all P>0.05). Cochran′s Q test and MR-Egger intercept test results showed no significant heterogeneity or horizontal pleiotropy affecting causal estimates (all P>0.05). The leave-one-out test indicated stable results. MR-Egger analysis showed a weak causal relationship between TNF-α and gout [ OR(95% CI)=0.892 (0.812, 0.979), b=-0.113, P=0.021], while the other methods (IVW-MR, weighted median, simple mode, weighted mode) showed no causal relationship between TNF-α and gout (all P>0.05). Cochran′s Q test indicated no heterogeneity affecting causal estimates ( P>0.05), but MR-Egger intercept test suggested the presence of horizontal pleiotropy affecting causal estimates ( P<0.05). The reverse MR analysis of gout and TNF-α, IL-6, IL-12 showed no causal relationships (all P>0.05). No significant heterogeneity or horizontal pleiotropy affected causal estimates (all P>0.05), and the leave-one-out test indicated that the results were stable. Conclusion:MR analysis suggests that there is no causal relationship between IL-6, IL-12, and gout, but TNF-α may have a weak causal relationship with gout. More accurate and solid evidence are needed from further prospective randomized controlled trials.

Objective A precise microinvasive robot system coupled with a cooperative robot matrix and an end effector of a wire-controlled microvariable path robot was proposed.A puncture needle structure,including the rigid body of the outer needle,non-uniform flexible body of the inner needle,force control wire,internal imaging of the image fiber,and other components,was designed to verify the feasibility of this system.Methods By constructing the puncture structure of the puncture robot,the structural optimization design of the key components affecting the variable-path precision puncture needle was analyzed by constructing the puncture structure of a puncture robot.Based on the orthogonal experimental design method,a three-factor and three-level experiment that primarily affected the accuracy of the puncture needle was designed,namely,the starting distance of the hole center from the edge,the diameter of the hole,and the distance between the two holes.The experiment was verified and simulated using a real object.Results The displacement of the titanium-nickel needle tip had a significant relationship with the starting distance of the hole center from the edge,and the main and secondary influencing factors were as follows:starting distance of the hole center from the edge>hole diameter>hole distance.When the starting distance of the hole center from the edge was 1 mm,the diameter of the hole was 0.2 mm,and the distance between the two holes was 2.6 mm,the displacement of the titanium-nickel needle tip was the maximum value.Conclusions The experiment verified the functional applicability of the designed system and the linear elastic hysteresis characteristics of variable path puncture,providing a reference for further in vivo experiments and system optimization.

Objective:To investigate the effects of stellate ganglion block(SGB)on serum inflammatory cytokines and the expression of toll-like receptor 4(TLR4),cysteine aspartate protease 3(caspase-3),and NF-κB(p65)pro-teins in rats with acute peritonitis(AP),with the goal of elucidating the mechanisms through which SGB modulates inflammatory responses.Methods:40 SPF grade male rats were randomly assigned to 4 groups:control group(Con-trol),acute peritonitis group(AP),acute peritonitis+right stellate ganglion block group(AP+SGB),and acute peri-tonitis+right stellate ganglion block+TLR4 inhibitor resatorvid group(AP+SGB+TAK-242),with 10 rats in each group.Acute peritonitis was induced in the AP,AP+SGB,and AP+SGB+TAK-242 groups via intraperitoneal injec-tion of 1 ml/100 g of 2％acetic acid solution.After establishing the model,blood samples were collected from the tail vein at 1 h,6 h,12 h,and 24 h respectively.Serum levels of interleukin-10(IL-10),tumor necrosis factor-alpha(TNF-α),interleukin-1 β(IL-1 β),and high mobility group protein B1(HMGB1)were measured using ELISA.After 24 hours,the peritoneal tissues were collected for analysis.Protein levels of TLR4,caspase-3,and NF-κB(p65)were quantified via Western Blot,while simultaneously,their mRNA expression levels were assessed using RT-qPCR.His-topathological alterations were evaluated by hematoxylin and eosin(HE)staining and then observed under optical microscopy.Results:At all time points,the AP,AP+SGB,and AP+SGB+TAK-242 groups showed significantly higher levels of IL-10,TNF-α,IL-1 β,and HMGB1 compared to the S group(P＜0.05).The AP+SGB group exhibi-ted significantly lower TNF-α,IL-1 β,and HMGB1 levels and higher IL-10 levels than the AP group at corresponding time points(P＜0.05).The AP+SGB+TLR4 group demonstrated further reductions in TNF-α,IL-1 β,and HMGB1 levels and additional increases in IL-10 levels relative to the AP+SGB group(P＜0.05).Both the AP+SGB and AP+SGB+TAK-242 groups showed significant decreases in TLR4,caspase-3,and NF-κB(p65)protein expression(P＜0.05).Similarly,TLR4 and NF-κB(p65)mRNA expression levels were markedly downregulated in these groups(P＜0.05).Conclusion:SGB can mitigate the inflammatory response in acute peritonitis rats by inhibiting the TLR4/NF-κB signaling pathway through the downregulation of TLR4 and NF-κB(p65).