Objective:To investigate the influence of serum C-X-C motif chemokine ligand 9 (CXCL9) and C-X3-C motif chemokine ligand 1 (CX3CL1) on the development of preeclampsia in patients with gestational diabetes mellitus (GDM).Methods:A retrospective analysis was conducted on the clinical data of 398 GDM patients admitted to Huangshi Aikang Hospital from January 2021 to August 2024. Based on the occurrence of preeclampsia, patients were divided into the GDM-preeclampsia group (51 cases) and the simple GDM group (347 cases). The baseline data, blood glucose indicators, four lipid items, platelet count (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, serum creatinine, and 24-hour urinary protein quantification were compared between the two groups. The influencing factors for GDM complicated by preeclampsia were analyzed, and the predictive value of serum CXCL9 and CX3CL1 for the onset of preeclampsia in GDM patients was assessed. Measurement data with a normal distribution were expressed as Mean ± SD, and the t'-test was used for intergroup comparisons when variances were unequal; measurement data with a skewed distribution were expressed as M ( Q1, Q3), and the Wilcoxon rank-sum test was used for intergroup comparisons; counting data were expressed as case (%), and the χ2 test was used for intergroup comparisons. Unconditional logistic regression models were used to analyze the risk factors for preeclampsia in GDM patients. The predictive value of serum CXCL9 and CX3CL1 levels for preeclampsia in GDM patients was analyzed using the receiver operator characteristic (ROC) curve. Results:Pre-pregnancy body mass index, glycated hemoglobin, and 24-hour urinary protein quantification in the GDM-preeclampsia group [(24.50±3.74) kg/m 2, (5.68±0.52)%, 0.42 (0.17, 0.69) g] were all higher than those in the simple GDM group [(22.70±2.97) kg/m 2, (5.42±0.44)%, 0.30 (0.10, 0.44) g], with statistically significant differences between groups (statistic values: t'=3.90, t'=3.85, U=2.70; P values: <0.001, <0.001, 0.007, respectively). Serum CXCL9 levels in the GDM-preeclampsia group [(111.69±36.65) ng/L] were lower than those in the simple GDM group [(200.16±85.57) ng/L], while CX3CL1 levels [(2.22±0.29) μg/L] were higher than those in the simple GDM group [(1.83±0.35) μg/L], with statistically significant differences ( t' values: 7.28 and 7.58, respectively; both P<0.001). Multivariate logistic regression analysis showed that increased CX3CL1 ( OR=1.562, 95% CI: 1.237-1.972), decreased CXCL9 ( OR=0.979, 95% CI: 0.970-0.989), increased pre-pregnancy body mass index ( OR=1.226, 95% CI: 1.060-1.417), and increased glycated hemoglobin ( OR=3.474, 95% CI: 1.192-10.122) were associated with an increased risk of developing preeclampsia in GDM patients ( P values: <0.001, <0.001, 0.006, 0.023, respectively). The ROC curve showed that the area under the curve for serum CXCL9 (sensitivity: 88.24%, specificity: 70.89%) and CX3CL1 (sensitivity: 78.43%, specificity: 69.16%) in predicting preeclampsia in GDM patients were both >0.50 ( P values: 0.015, 0.034, respectively), indicating that both have high predictive efficacy, with CXCL9 being slightly superior to CX3CL1. Conclusion:Decreased serum CXCL9 and increased CX3CL1 are associated with an increased risk of preeclampsia in GDM patients. Both can serve as auxiliary predictive indicators for preeclampsia in GDM patients.

Objective To investigate the effects of parecoxib sodium on pain and Toll-like receptor 4(TLR4)/p38 mitogen activated protein kinase(p38MAPK)pathway in rats with femoral fracture.Methods Sixty rats were randomly separated into sham operation group,model group,TLR4 inhibitor(TAK-242)group(3 mg/kg),parecoxib sodium group(10 mg/kg),and parecoxib sodium+TLR4 activator lipopolysaccharide group(10 mg/kg parecoxib sodium+15 mg/kg LPS),with 12 rats in each group.Except for the sham operation group,rats in all other groups were used to establish a femoral fracture model by transverse cutting of the mid femur.After 28 days of treatment in each group,X-rays were used to detect the degree of fracture healing in rats.The mechanical pain threshold(PWMT)and thermal pain threshold(PWTL)of rats were measured.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in serum.Micro-CT method was applied to detect changes in femoral bone density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular quantity(Tb.N)in rats.HE staining was applied to observe the pathological changes of bone tissue at the fracture site in rats.Western blot was applied to detect the expression of TLR4/p38MAPK pathway related proteins in bone tissue at the fracture site.Results Compared with the sham operation group,the fracture lines of rats in the model group were obvious,with a small amount of callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N decreased,while the levels of serum IL-6,TNF-α,and IL-10,and the levels of TLR4 and p-p38MAPK/p38MAPK proteins in the bone tissue at the fracture site increased(P＜0.05).Compared with the model group,the fracture lines in the TAK-242 group and the parecoxib sodium group were blurred,and there was an increase in callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N,the serum IL-10 level increased,while the serum IL-6,TNF-αlevels,the TLR4 and p-p38MAPK/p38MAPK protein levels in bone tissue at the fracture site decreased(P＜0.05).LPS could upregulate the phosphorylation levels of TLR4 and p38MAPK,and weaken the relieving effects on anti-inflammatory and pain of parecoxib sodium on fracture rats.Conclusion Paracoxib sodium may alleviate pain and accelerate fracture healing in rats with femoral fractures by inhibiting the TLR4/p38MAPK pathway and suppressing inflammatory responses.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

Objective To investigate the effects of parecoxib sodium on pain and Toll-like receptor 4(TLR4)/p38 mitogen activated protein kinase(p38MAPK)pathway in rats with femoral fracture.Methods Sixty rats were randomly separated into sham operation group,model group,TLR4 inhibitor(TAK-242)group(3 mg/kg),parecoxib sodium group(10 mg/kg),and parecoxib sodium+TLR4 activator lipopolysaccharide group(10 mg/kg parecoxib sodium+15 mg/kg LPS),with 12 rats in each group.Except for the sham operation group,rats in all other groups were used to establish a femoral fracture model by transverse cutting of the mid femur.After 28 days of treatment in each group,X-rays were used to detect the degree of fracture healing in rats.The mechanical pain threshold(PWMT)and thermal pain threshold(PWTL)of rats were measured.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in serum.Micro-CT method was applied to detect changes in femoral bone density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular quantity(Tb.N)in rats.HE staining was applied to observe the pathological changes of bone tissue at the fracture site in rats.Western blot was applied to detect the expression of TLR4/p38MAPK pathway related proteins in bone tissue at the fracture site.Results Compared with the sham operation group,the fracture lines of rats in the model group were obvious,with a small amount of callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N decreased,while the levels of serum IL-6,TNF-α,and IL-10,and the levels of TLR4 and p-p38MAPK/p38MAPK proteins in the bone tissue at the fracture site increased(P＜0.05).Compared with the model group,the fracture lines in the TAK-242 group and the parecoxib sodium group were blurred,and there was an increase in callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N,the serum IL-10 level increased,while the serum IL-6,TNF-αlevels,the TLR4 and p-p38MAPK/p38MAPK protein levels in bone tissue at the fracture site decreased(P＜0.05).LPS could upregulate the phosphorylation levels of TLR4 and p38MAPK,and weaken the relieving effects on anti-inflammatory and pain of parecoxib sodium on fracture rats.Conclusion Paracoxib sodium may alleviate pain and accelerate fracture healing in rats with femoral fractures by inhibiting the TLR4/p38MAPK pathway and suppressing inflammatory responses.

Objective:To investigate the influence of serum C-X-C motif chemokine ligand 9 (CXCL9) and C-X3-C motif chemokine ligand 1 (CX3CL1) on the development of preeclampsia in patients with gestational diabetes mellitus (GDM).Methods:A retrospective analysis was conducted on the clinical data of 398 GDM patients admitted to Huangshi Aikang Hospital from January 2021 to August 2024. Based on the occurrence of preeclampsia, patients were divided into the GDM-preeclampsia group (51 cases) and the simple GDM group (347 cases). The baseline data, blood glucose indicators, four lipid items, platelet count (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, serum creatinine, and 24-hour urinary protein quantification were compared between the two groups. The influencing factors for GDM complicated by preeclampsia were analyzed, and the predictive value of serum CXCL9 and CX3CL1 for the onset of preeclampsia in GDM patients was assessed. Measurement data with a normal distribution were expressed as Mean ± SD, and the t'-test was used for intergroup comparisons when variances were unequal; measurement data with a skewed distribution were expressed as M ( Q1, Q3), and the Wilcoxon rank-sum test was used for intergroup comparisons; counting data were expressed as case (%), and the χ2 test was used for intergroup comparisons. Unconditional logistic regression models were used to analyze the risk factors for preeclampsia in GDM patients. The predictive value of serum CXCL9 and CX3CL1 levels for preeclampsia in GDM patients was analyzed using the receiver operator characteristic (ROC) curve. Results:Pre-pregnancy body mass index, glycated hemoglobin, and 24-hour urinary protein quantification in the GDM-preeclampsia group [(24.50±3.74) kg/m 2, (5.68±0.52)%, 0.42 (0.17, 0.69) g] were all higher than those in the simple GDM group [(22.70±2.97) kg/m 2, (5.42±0.44)%, 0.30 (0.10, 0.44) g], with statistically significant differences between groups (statistic values: t'=3.90, t'=3.85, U=2.70; P values: <0.001, <0.001, 0.007, respectively). Serum CXCL9 levels in the GDM-preeclampsia group [(111.69±36.65) ng/L] were lower than those in the simple GDM group [(200.16±85.57) ng/L], while CX3CL1 levels [(2.22±0.29) μg/L] were higher than those in the simple GDM group [(1.83±0.35) μg/L], with statistically significant differences ( t' values: 7.28 and 7.58, respectively; both P<0.001). Multivariate logistic regression analysis showed that increased CX3CL1 ( OR=1.562, 95% CI: 1.237-1.972), decreased CXCL9 ( OR=0.979, 95% CI: 0.970-0.989), increased pre-pregnancy body mass index ( OR=1.226, 95% CI: 1.060-1.417), and increased glycated hemoglobin ( OR=3.474, 95% CI: 1.192-10.122) were associated with an increased risk of developing preeclampsia in GDM patients ( P values: <0.001, <0.001, 0.006, 0.023, respectively). The ROC curve showed that the area under the curve for serum CXCL9 (sensitivity: 88.24%, specificity: 70.89%) and CX3CL1 (sensitivity: 78.43%, specificity: 69.16%) in predicting preeclampsia in GDM patients were both >0.50 ( P values: 0.015, 0.034, respectively), indicating that both have high predictive efficacy, with CXCL9 being slightly superior to CX3CL1. Conclusion:Decreased serum CXCL9 and increased CX3CL1 are associated with an increased risk of preeclampsia in GDM patients. Both can serve as auxiliary predictive indicators for preeclampsia in GDM patients.

Objective:To explore the clinical efficacy of posterior femoral muscle flaps combined with posterior femoral cutaneous nerve nutrient vessel flap and closed lavage in the treatment of stage Ⅳ ischial tuberosity pressure ulcers.Methods:This study was a retrospective observational study. From March 2021 to March 2022, 15 patients with stage Ⅳ ischial tuberosity pressure ulcers who met the inclusion criteria were admitted to Dezhou Dongcheng Hospital, including 11 males and 4 females, aged 31 to 72 years. The pressure ulcer wound size ranged from 6.0 cm×4.5 cm to 10.0 cm×6.0 cm, with cavity diameters of 10-14 cm. Five cases were complicated with ischial tuberosity bone infection. After clearing the lesion, the biceps femoris long head muscle flap with an area of 10.0 cm×4.0 cm-18.0 cm×5.0 cm and the semitendinosus muscle flap with an area of 8.0 cm×4.0 cm-15.0 cm×5.0 cm combined with the posterior femoral cutaneous nerve nutrient vessel flap with an area of 6.5 cm×5.5 cm-10.5 cm×6.5 cm was transplanted to repair the pressure ulcer wound. The flap donor area was directly sutured, and the closed lavage with tubes inserted into the wound cavity was performed for 2-3 weeks. The postoperative survival of the muscle flaps and skin flaps, the wound healing of the donor and recipient areas were observed. The recurrence of pressure ulcers, the appearance and texture of flaps, and scar conditions of the donor and recipient areas were followed up.Results:All the muscle flaps and skin flaps in the 15 patients successfully survived after surgery. Two patients experienced incisional dehiscence at one week after surgery due to improper turning over, during which the incision in the recipient area was pressed on, and the wounds healed after dressing changes of 3 to 4 weeks; the wounds in the donor and recipient areas healed well in the other patients. All patients received follow-up after surgery. During the follow-up period of 6 to 12 months, none of the patients experienced pressure ulcer recurrence, and the texture, color, and thickness of the skin flaps closely resembled those of the surrounding skin at the recipient site, with only linear scar left in the donor and recipient areas.Conclusions:When using the posterior femoral muscle flaps combined with the posterior femoral cutaneous nerve nutrient vessel flap and closed lavage to treat stage Ⅳ ischial tuberosity pressure ulcers, the tissue flap can be used to fully fill in the dead space of the pressure ulcers. After treatment, the wound heals well, the appearance of the donor and recipient areas is better, and the pressure ulcers are less prone to reoccur.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

This article elaborates on the bidirectional relationship between sleep disorders and cerebral small vessel disease (CSVD), and explores the specific associations and possible mechanisms between sleep disorders such as obstructive sleep apnea, periodic limb movements during sleep, restless leg syndrome, insomnia and other sleep disorders, and CSVD.

Objective To understand the epidemiological and etiological characteristics of hand-foot-mouth disease (HFMD) in Shijiazhuang City from 2009 to 2021, and to provide scientific evidence for the prevention and control of HFMD. Methods The epidemic data and etiological data of HFMD in Shijiazhuang City from 2009 to 2021 were collected, and descriptive epidemiological methods were used for data analysis. Results The reported incidence of HFMD in Shijiazhuang showed a fluctuating downward trend from 2009 to 2021, with a high incidence every other year in most years. The proportion of severe cases and the mortality rate showed a decreasing trend (χ²_{severe cases}=282.09, P<0.001; χ²_mortality=51.33, P<0.001). There were two peaks of HFMD incidence throughout the year: the main peak occurring in spring and summer and the secondary peak occurring in autumn and winter. The peak month of incidence showed a backward trend after 2015. Cases were mainly children aged 5 years and below. The ratio of male to female was 1.53:1, and the gender incidence rate was significantly different (χ²=4 507.84，P<0.001). The deaths were mainly children aged 2 years old and below, accounting for 88.89%. The incidence of HFMD decreased with age (t_r=-2.85，P<0.05). The highest incidence was in urban areas (114.50/100 000). The pathogenic composition of different cases was different and the difference was statistically significant (χ²2 =521.86，P<0.001). The dominant pathogens in mild cases presented diverse characteristics. EV71 was dominant in severe cases and death cases, accounting for 82.77% and 96.67%, respectively. The proportion of other enteroviruses in severe cases showed an increasing trend. A total of 630 745 doses of EV71 inactivated vaccine were administered in Shijiazhuang from 2017 to 2021, with an average annual vaccination rate of 8.53%. After the implementation of EV71 vaccination, the proportion of severe cases, the mortality rate and the proportion of EV71 all decreased compared to those before, and the differences were statistically significant (χ²_{proportion of severe cases}=93.71，P=0.000，χ²_{mortality rate}=26.62，P=0.000，χ²_{proportion of EV71}=1060.86，P=0.000). Conclusion The incidence of HFMD in Shijiazhuang presented a declining trend, and the dominant etiological changes of different cases were different. It is necessary to continue to strengthen the etiological monitoring, health education and EV71 vaccination for the prevention and control of HFMD.