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 compare the changes in the concentration of relevant growth factors released from platelet-rich plasma (PRP) stored at -80℃ by cryopreservation and at 4℃ by refrigerated lyophilization over 2 years, aiming to provide a theoretical basis for prolonging PRP storage duration. Methods: PRP (n=15) was separated using a blood cell separator and stored under -80℃ cryopreservation (F-PRP group) and 4℃ refrigerated freeze-drying conditions (FD-PRP group). The contents of growth factors (PDGF-AA, PDGF-BB, EGF, TGF-β1, and VEGF) in both groups were measured by ELISA at 1, 3, 6, 9, 12 and 24 months. Results: PDGF-AA and VEGF maintained good stability in both groups for up to 24 months. PDGF-BB and TGF-β1 showed high stability in the first 12 months but their stability decreased gradually from 12th to 24th months. EGF demonstrated good stability in the first 6 months, and its stability gradually decreased from the 9th to 24th months. Comparing the F-PRP and FD-PRP groups, the concentrations of the five growth factors in the FD-PRP group were either not statistically different or higher than those in the F-PRP group at all time points. Specifically, the concentrations of EGF were significantly higher in the FD-PRP group at all time points. Conclusion: Both -80℃ freezing and 4℃ freeze-drying enable long-term preservation of PRP. Freeze-drying imposes less stringent storage requirements and facilitates growth factor compared to frozen storage.

OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective: To investigate the expressions of GPR15 and FOXP3 in colorectal carcinoma(CRC) tissues and their clinical prognostic values. Methods : A total of 132 patients with CRC underwent radical surgery were collected. The control group selected the normal mucosal tissues more than 5 cm away from the edge of the cancer focus. Immunohistochemistry(Envision two-step method) was used to detect the expression levels of GPR15 and FOXP3 in CRC and adjacent tissues, and analyze their relationships with clinicopathological factors of colorectal cancer. Kaplan-Meier method was used to draw the survival curve to analyze the correlation between the expressions of GPR15 and FOXP3 and the survival prognosis of patients with CRC. The factors influencing prognosis of patients with colorectal cancer were analyzed by Cox regression. Results : The immunohistochemistry showed that the expression levels of GPR15 and FOXP3 in CRC were significantly higher than those in normal colorectal mucosal tissues(P<0.05). The expression of GPR15 in CRC tissues was correlated with location, nerve invasion and TNM stage; FOXP3 expression was correlated with sex(P<0.05).Both expressions were not significantly correlated with the clinicopathologic features of age, tumor size, differentiation degree, tissue type, depth of invasion, tumor budding, vascular invasion and lymph node metastasis. Correlation analysis showed that there was no significant correlation between GPR15 and FOXP3 expression(Kappa=-0.019,P>0.05). The survival prognosis of GPR15 positive group was significantly worse than that of negative group(log-rank: χ2=4.3,P=0.039);while the survival prognosis of FOXP3 positive group was significantly better than that of negative group(log-rank: χ2=7.3,P=0.007).Age ≤55 years, positive GPR15 and negative FOXP3 were independent risk factors for poor prognosis in patients with CRC(P<0.05). Conclusion The expression levels of GPR15 and FOXP3 in CRC are significantly higher than those in paracancer tissues, GPR15 and FOXP3 are expected to become new tumor markers for early screening, accurate treatment and prognosis assessment of CRC.

Objective To investigate the levels and clinical significance of microRNA(miR)-17-5p and miR-141-3p in the serum of children with bacterial meningitis(BM).Methods A total of 111 children with BM ad-mitted to the First Affiliated Hospital of Xinjiang Medical University from May 2019 to May 2022 were in-cluded as the study group,and another 111 healthy children who underwent physical examinations were in-cluded as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the ex-pression levels of serum miR-17-5p and miR-141-3p.Pearson correlation was used to analyze the correlation between serum miR-17-5p,miR-141-3p levels and inflammatory factors in children with BM.Multivariate Lo-gistic regression was applied to analyze the influencing factors of BM occurrence.Receiver operating character-istic(ROC)curve was applied to analyze the diagnostic value of miR-17-5p and miR-141-3p levels for BM.Re-sults The serum levels of miR-17-5p and miR-141-3p in the study group were obviously lower than those in the control group(P＜0.05),while the serum levels of C-reactive protein(CRP),procalcitonin(PCT),inter-feron-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in the study group were high-er than those in the control group(P＜0.05).According to Pearson correlation analysis,miR-17-5p and miR-141-3p were negatively correlated with CRP,PCT,IFN-γ,TNF-α,IL-1β,and IL-6(P＜0.05).According to multivariate Logistic analysis,CRP,PCT,IFN-γ,TNF-α,IL-1β,and IL-6 were risk factors affecting the occur-rence of BM(P＜0.05),while miR-17-5p and miR-141-3p were protective factors affecting the occurrence of BM(P＜0.05).According to the ROC curve,the area under the curve(AUC)of serum level of miR-17-5p for diagnosing BM was 0.756,and the AUC of serum level of miR-141-3p for diagnosing BM was 0.720.The AUC of the combination of the two for diagnosing BM was 0.819,which was larger than that of single detec-tion(Zcombination vs.miR-17-5p=2.278,Zcombination vs.miR-141-3p=2.425,P＜0.05).Conclusion The expression levels of miR-17-5p and miR-141-3p in the serum of children with BM are reduced.The two are related to the levels of inflammatory factors,and their combined detection has a high diagnostic value for BM.

Objective:To evaluate the efficacy of Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulse in the treatment of neurogenic bladder (NB) caused by spinal cord injury (SCI); To explore its effects on urodynamics.Methods:A randomized controlled trial study was conducted. A total of 116 patients with NB caused by SCI in the First Affiliated Hospital of Hunan University of Chinese Medicine from January 2022 to June 2024 were selected as the observation objects and divided into 2 groups with random number table method, with 58 cases in each group. On the basis of conventional bladder function training, the control group was given low-frequency electronic pulse therapy, while the observation group was treated with the Tongdu Tiaoshen method on the basis of the control group. Both groups were treated continuously for 3 months. The urination conditions of the patients were observed before and after the treatment respectively, and the residual urine volume, single urine volume within 24 hours, the number of urine leaks within 24 hours, and the number of urinations within 24 hours were recorded; urodynamic parameters such as bladder volume, urine flow rate, detrusor pressure, bladder compliance, and detrusor contractility were measured using a urodynamic analyzer; the severity of NB symptoms was evaluated using the Chinese version of the Neurogenic Bladder Symptom Scale (NBSS), and the quality of life was evaluated using the Chinese version of the Short Form Health Assessment Scale (SF-Qualiveen). The levels of IL-1β, IL-6 and TNF-α were detected by ELISA. Adverse reactions were recorded during the treatment period and the clinical efficacy was evaluated.Results:The total effective rate was 91.38% (53/58) in the observation group and 75.86% (44/58) in the control group. There was a statistically significant difference between the two groups ( χ2=5.10, P=0.024). After treatment, the residual urine volume, single urine volume within 24 hours, frequency of urine leakage within 24 hours, and frequency of urination within 24 hours in the observation group were lower than those in the control group ( t values were -15.68, 3.75, -3.81, and -7.54 respectively, P<0.01). The bladder capacity, urine flow rate, detrusor pressure, bladder compliance and detrusor contractility were higher than those of the control group ( t values were 11.04, 7.49, 9.76, 5.65 and 4.36 respectively, P<0.01), while the NBSS score and SF-Qualiveen score were lower than those of the control group ( t values were -10.82 and -9.83 respectively, P<0.01). No obvious adverse reactions occurred in either group during the treatment period. Conclusion:Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulses can improve the bladder function of NB caused by SCI, restore urodynamics, and improve the quality of life. Its mechanism may be related to the inhibition of inflammatory responses.

Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

Objective To investigate the effects of short-term and long-term high-fructose diets on hippocampal neurometabolites and anxiety and depression-like behaviors in mice,revealing the potential mechanisms of high-fructose diets in mood disorders and providing a experimental basis for the prevention and treatment of related diseases.Methods C57BL/6J male mice were randomly divided into two groups,control group(standard diet,n=10)and experimental group(high-fructose diet,n=10).Four weeks(short-term)and eight weeks(long-term)later,each group of mice was examined for body weight and fasting blood glucose,and neurometabolites levels in the hippocampus were detected by hydrogen proton magnetic resonance spectroscopy(1H-MRS),followed by the open-field test,the forced-swimming test,and the tail-suspension test to evaluate anxiety-like and depression-like behaviors.Results High fructose diet for 4 weeks elevated glutamate levels and reduced glutathione and myo-inositol levels in mice,accompanied by shortened immobility time in the forced swim test.High fructose diet for 8 weeks not only led to abnormalities in body weight and glucose metabolism but also caused a reversal decrease in hippocampal glutamate levels and induced significant anxiety-like behaviors,and the decrease in hippocampal glutamate levels showed a significant negative correlation with the enhancement of anxiety-like behaviors.Conclusion Altered hippocampal glutamate levels may be a key contributing factor to the anxiety-like behaviors induced by long-term high-fructose diet.