BACKGROUND:This study provided insight into the molecular mechanisms by which exogenous basic fibroblast growth factor(bFGF)promotes wound healing. OBJECTIVE:To investigate the effect of exogenous bFGF on macrophage phenotype transition and granulation regeneration during wound repair in rats. METHODS:(1)In vitro experiment:Cells were divided into normal control group,low-dose bFGF group,high-dose bFGF group,and bFGF+valproic acid group.100 and 200 μg/L bFGF was added into the cell culture medium of low-dose bFGF group and high-dose bFGF group,respectively,while 200 μg/L bFGF and 20 mmol/L valproic acid were added into the cell culture medium of valproic acid group.EdU test,scratch test and tubule formation test were used to detect the effects of bFGF on proliferation,migration and angiogenesis of human umbilical vein endothelial cells.(2)In vivo experiment:Sprague-Dawley rats were randomly divided into model group,low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.The open wound model of full-thickness skin defect was established in low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.Rats in the low-and high-dose bFGF groups were given 100 and 200 μg/L bFGF through subcutaneous injection,while those in the bFGF+valproic acid group received subcutaneous injection of 200 μg/L bFGF and intraperitoneal injection of 10 mg/kg valproic acid.The wound healing rate of rats was detected at 7 and 14 days of administration.TUNEL was used to detect the apoptosis of cells in wound tissue.Enzyme linked immunosorbent assay was used to detect the serum levels of malondialdehyde,superoxide dismutase,tumor necrosis factor-α and interleukin-10.Immunofluorescence detection was conducted to detect the phenotypic transformation of macrophages in wound tissue.Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen,platelet endothelial cell adhesion molecule-1(CD31)and vascular endothelial growth factor in wound tissue.Western blot was used to detect the expression of Notch1 and Jagged1 in wound tissue. RESULTS AND CONCLUSION:(1)Compared with the normal control group,bFGF could significantly promote the proliferation,migration and angiogenesis of human umbilical vein endothelial cells in a dose-dependent manner.(2)Compared with the model group,bFGF could significantly promote wound healing,downregulate the rate of apoptosis in wound tissue,decrease the levels of malondialdehyde and tumor necrosis factor-α in serum,increase the levels of superoxide dismutase and interleukin-10,promote the conversion of macrophages to type M2 in wound tissue,upregulate the expression of proliferating cell nuclear antigen,CD31 and vascular endothelial growth factor in wound tissue,and inhibit the expression of Notch1 and Jagged1 in a dose-dependent manner.Valproic acid could partially reverse the promoting effect of bFGF on wound healing.To conclude,bFGF can significantly promote wound healing and granulation regeneration and induce the conversion of macrophages to M2,which may be related to the regulation of Notch1/Jagged1 signaling pathway.

Objective:To investigate the clinical-epidemiological characteristics of connective tissue diseases (CTD) complicated with pulmonary hypertension in Shanxi province from 2018 to 2021.Methods:This was a cross-sectional study. Data of CTD patients with pulmonary hypertension from 2018 to 2021 were collected from the Shanxi Provincial Health Statistics Direct Reporting System based on inpatient medical records. The demographic and clinical data of patients with different CTD types were analyzed.Results:A total of 1 697 CTD patients with pulmonary hypertension were included, among whom there were 451 cases (26.58%) of Sj?gren′s syndrome, 392 cases (23.10%) of systemic lupus erythematosus, 289 cases(17.03%) of systemic sclerosis, 109 cases (6.42%) of mixed CTD, 69 cases (4.07%) of Takayasu arteritis, and 387 cases (22.80%) of other CTD. The majority of patients were female (1 410 (83.09%)), and 783 cases (46.14%) were aged between 41 and 65 years, and 6 cases (0.35%) were performed right heart catheterization. The prevalence of CTD with pulmonary hypertension increased from 0.06/10 4 in 2018 to 0.20/10 4 in 2021. There were significant differences in the severity of pulmonary hypertension, New York Heart Association (NYHA) functional class, length of hospital stay, medical costs, and clinical outcomes among patients with different CTD subtypes (all P<0.001). Patients with systemic sclerosis had the highest proportion of NYHA functional class Ⅲ/Ⅳ(65.1%(188/289)), the longest length of hospital stays (13 (9, 18) days), the highest average medical costs (13 622.67 (8 636.38, 20 597.75) ￥(RMB)), and the lowest rate of improvement and discharge (51.90%(150/289)). Conclusions:Between 2018 and 2021, Shanxi province, where CTD is more common in Sj?gren′s syndrome, has a high proportion of women, a high proportion of people aged 41-65 years, and a low prevalence of right ventricular catheterization in patients with CTD complicated with pulmonary hypertension. The prevalence of CTD complicated with pulmonary hypertension shows a rising trend in Shanxi province from 2018 to 2021, while patients with systemic sclerosis exhibit the most severe cardiac impairment and poorer clinical outcomes compared to other subtypes.

Spinal muscular atrophy (SMA), a hereditary neuromuscular disease, may lead to progressive muscle weakness and atrophy in the proximal limbs resulting from decreased survival motor neuron (SMN) protein expression caused by SMN1 gene mutation. Currently, drugs clinically used for SMA gene therapy include nusinersen, sofosbuvir, and risdiplam, whic have limited scopes of application. Some drugs need to be used for a long time, and none of them can achieve a complete cure. Intrathecal injection of supplemented SMN1 gene has entered clinical trials, showing good curative effect. At the same time, basic researches indicate that CRISPR/Cas9 gene editing technology shows good prospect in correcting the mutant genes in SMA. This article reviews the clinical characteristics of SMA and research progress of gene therapy, aiming to provide a new perspective for diagnosis and treatment of SMA.

In order to establish a simple,sensitive and specific diagnostic method for the simultane-ous detection of Mycoplasma hyorhinis(Mhr)and Mycoplasma hyopneumoniae(Mhp)in swine,specific primers and probes were designed using the Mhr p37 and Mhp p36 gene sequences as the target genes,and the dual LFD-RPA rapid test was established by screening the primers and probes,optimizing primer ratios and evaluating its effectiveness through the sensitivity,reproduc-ibility and clinical sample testing.The sensitivity,specificity,reproducibility and clinical samples were evaluated.The results showed that the established dual LFD-RPA assay could complete the amplification in 15 min at 39 ℃,and its optimal primer ratio was 1.6∶0.8,and the lowest detection limits were up to 3.63 and 3.60 copies/μL,respectively;the reproducibility was stable;and there was no cross-reactivity with Pasteurella multocida,Bordetella bronchiseptica,Haemophilus pa-rasuis,Actinobacillus pleuropneumoniae,Escherichia coli.The test successfully established a dual LFD-RPA assay,which can detect Mhr and Mhp simultaneously,and is simple,sensitive and spe-cific without relying on specialized equipment,and is suitable for carrying out on-site rapid diagno-sis of Mhr and Mhp.

Objective To analyze the effect of Roflumilast combined with Budesonide in the treatment of chronic bronchitis complicated with chronic obstructive pulmonary disease(COPD).Methods A total of 98 patients with chronic bronchitis complicated with COPD admitted from February 2023 to February 2025 were selected and divided into group A(n=49)and group B(n=49)by random number table method.Group A was given Budesonide,and group B was given Roflumilast combined with Budesonide.The clinical efficacy,symptom scores[Chronic Obstructive Pulmonary Disease Assessment Test(CAT),modified British medical research council(mMRC)],pulmonary function[forced vital capacity(FVC),peak exploratory flow(PEF),forced exploratory volume in one second(FEV1)],respiratory mechanics indexes[airway resistance(Raw),dynamic compliance(Cdyn),peak inspiratory pressure(PIP)],inflammatory factors[interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP)],oxidative stress markers[8-iso-prostaglandin F2α(8-iso-PGF2α),malondialdehyde(MDA),super oxide dismutase(SOD),glutathione peroxidase(GSH-Px)],adverse reactions and prognosis were compared between the two groups.Results The total effective rate of group B[95.92%(47/49)]was higher than that of group A[83.67%(41/49)](P<0.05).After treatment,CAT,mMRC score,PIP,Raw,8-iso-PGF2α,MDA,hs-CRP,TNF-α and IL-8 in group B were lower than those in group A,while FVC,PEF,FEV1,Cdyn,SOD and GSH-Px were higher than those in group A(P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).The number of acute exacerbation in group B was less than that in group A at 3 and 6 months after treatment(P<0.01).Conclusion The combination therapy of Roflumilast and Budesonide is significantly effective in the treatment of chronic bronchitis complicated with COPD.It can alleviate clinical symptoms,improve patients'pulmonary function and respiratory mechanics,inhibit inflammation and oxidative stress response,and has a favorable safety profile and good prognosis.

Objective To analyze the effect of Roflumilast combined with Budesonide in the treatment of chronic bronchitis complicated with chronic obstructive pulmonary disease(COPD).Methods A total of 98 patients with chronic bronchitis complicated with COPD admitted from February 2023 to February 2025 were selected and divided into group A(n=49)and group B(n=49)by random number table method.Group A was given Budesonide,and group B was given Roflumilast combined with Budesonide.The clinical efficacy,symptom scores[Chronic Obstructive Pulmonary Disease Assessment Test(CAT),modified British medical research council(mMRC)],pulmonary function[forced vital capacity(FVC),peak exploratory flow(PEF),forced exploratory volume in one second(FEV1)],respiratory mechanics indexes[airway resistance(Raw),dynamic compliance(Cdyn),peak inspiratory pressure(PIP)],inflammatory factors[interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP)],oxidative stress markers[8-iso-prostaglandin F2α(8-iso-PGF2α),malondialdehyde(MDA),super oxide dismutase(SOD),glutathione peroxidase(GSH-Px)],adverse reactions and prognosis were compared between the two groups.Results The total effective rate of group B[95.92%(47/49)]was higher than that of group A[83.67%(41/49)](P<0.05).After treatment,CAT,mMRC score,PIP,Raw,8-iso-PGF2α,MDA,hs-CRP,TNF-α and IL-8 in group B were lower than those in group A,while FVC,PEF,FEV1,Cdyn,SOD and GSH-Px were higher than those in group A(P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).The number of acute exacerbation in group B was less than that in group A at 3 and 6 months after treatment(P<0.01).Conclusion The combination therapy of Roflumilast and Budesonide is significantly effective in the treatment of chronic bronchitis complicated with COPD.It can alleviate clinical symptoms,improve patients'pulmonary function and respiratory mechanics,inhibit inflammation and oxidative stress response,and has a favorable safety profile and good prognosis.

In order to establish a simple,sensitive and specific diagnostic method for the simultane-ous detection of Mycoplasma hyorhinis(Mhr)and Mycoplasma hyopneumoniae(Mhp)in swine,specific primers and probes were designed using the Mhr p37 and Mhp p36 gene sequences as the target genes,and the dual LFD-RPA rapid test was established by screening the primers and probes,optimizing primer ratios and evaluating its effectiveness through the sensitivity,reproduc-ibility and clinical sample testing.The sensitivity,specificity,reproducibility and clinical samples were evaluated.The results showed that the established dual LFD-RPA assay could complete the amplification in 15 min at 39 ℃,and its optimal primer ratio was 1.6∶0.8,and the lowest detection limits were up to 3.63 and 3.60 copies/μL,respectively;the reproducibility was stable;and there was no cross-reactivity with Pasteurella multocida,Bordetella bronchiseptica,Haemophilus pa-rasuis,Actinobacillus pleuropneumoniae,Escherichia coli.The test successfully established a dual LFD-RPA assay,which can detect Mhr and Mhp simultaneously,and is simple,sensitive and spe-cific without relying on specialized equipment,and is suitable for carrying out on-site rapid diagno-sis of Mhr and Mhp.

Objective:To investigate the clinical-epidemiological characteristics of connective tissue diseases (CTD) complicated with pulmonary hypertension in Shanxi province from 2018 to 2021.Methods:This was a cross-sectional study. Data of CTD patients with pulmonary hypertension from 2018 to 2021 were collected from the Shanxi Provincial Health Statistics Direct Reporting System based on inpatient medical records. The demographic and clinical data of patients with different CTD types were analyzed.Results:A total of 1 697 CTD patients with pulmonary hypertension were included, among whom there were 451 cases (26.58%) of Sj?gren′s syndrome, 392 cases (23.10%) of systemic lupus erythematosus, 289 cases(17.03%) of systemic sclerosis, 109 cases (6.42%) of mixed CTD, 69 cases (4.07%) of Takayasu arteritis, and 387 cases (22.80%) of other CTD. The majority of patients were female (1 410 (83.09%)), and 783 cases (46.14%) were aged between 41 and 65 years, and 6 cases (0.35%) were performed right heart catheterization. The prevalence of CTD with pulmonary hypertension increased from 0.06/10 4 in 2018 to 0.20/10 4 in 2021. There were significant differences in the severity of pulmonary hypertension, New York Heart Association (NYHA) functional class, length of hospital stay, medical costs, and clinical outcomes among patients with different CTD subtypes (all P<0.001). Patients with systemic sclerosis had the highest proportion of NYHA functional class Ⅲ/Ⅳ(65.1%(188/289)), the longest length of hospital stays (13 (9, 18) days), the highest average medical costs (13 622.67 (8 636.38, 20 597.75) ￥(RMB)), and the lowest rate of improvement and discharge (51.90%(150/289)). Conclusions:Between 2018 and 2021, Shanxi province, where CTD is more common in Sj?gren′s syndrome, has a high proportion of women, a high proportion of people aged 41-65 years, and a low prevalence of right ventricular catheterization in patients with CTD complicated with pulmonary hypertension. The prevalence of CTD complicated with pulmonary hypertension shows a rising trend in Shanxi province from 2018 to 2021, while patients with systemic sclerosis exhibit the most severe cardiac impairment and poorer clinical outcomes compared to other subtypes.

Spinal muscular atrophy (SMA), a hereditary neuromuscular disease, may lead to progressive muscle weakness and atrophy in the proximal limbs resulting from decreased survival motor neuron (SMN) protein expression caused by SMN1 gene mutation. Currently, drugs clinically used for SMA gene therapy include nusinersen, sofosbuvir, and risdiplam, whic have limited scopes of application. Some drugs need to be used for a long time, and none of them can achieve a complete cure. Intrathecal injection of supplemented SMN1 gene has entered clinical trials, showing good curative effect. At the same time, basic researches indicate that CRISPR/Cas9 gene editing technology shows good prospect in correcting the mutant genes in SMA. This article reviews the clinical characteristics of SMA and research progress of gene therapy, aiming to provide a new perspective for diagnosis and treatment of SMA.

Objective By using high-resolution magnetic resonance angiography to display the vascular wall imaging so as to evaluate the relationship between plaque characteristics and postoperative in-stent restenosis(ISR)in patients with middle cerebral artery stenosis.Methods A total of 66 patients with symptomatic atherosclerotic middle cerebral artery stenosis,who were admitted to the Affiliated Hospital of Chengde Medical College of China from January 2019 to March 2023,were enrolled in this study.Before stent implantation,all the 66 patients completed high-resolution magnetic resonance angiography.According to the postoperative imaging follow-up results,the patients were divided into ISR group and non-ISR group.The preoperative plaque characteristics,which were assessed by high-resolution magnetic resonance imaging,were compared between the two groups.Results ISR group had 14 patients and non-ISR group had 52 patients.Most of the plaques were located in the inferior lateral wall(37.8％)and the ventral lateral wall(28.7％),in which no statistically significant difference existed between the two groups(P＞0.05).Compared with non-ISR group,in ISR group the negative remodeling degree was obviously higher and the difference between the two groups was statistically significant(x2=6.026,P=0.049).The plaque load in ISR group and non-ISR group was 79.09±8.82 and 69.46±10.49 respectively,and the difference between the two groups was statistically significant(t=3.143,P=0.003).The homocysteine level in ISR group and non-ISR group was(16.02±4.24)mol/L and(12.05±3.34)mol/L respectively,and the difference between the two groups was statistically significant(t=3.717,P＜0.001).In ISR group,there were more significantly contrast-enhanced plaques(78.5％vs.42.3％),with statistically significant difference(x2=6.311,P=0.043).Multivariate logistic regression analysis showed that plaque load(OR=1.225,95％CI:1.040-1.443,P=0.015)and homocysteine level(OR=1.676,95％CI:1.150-2.442,P=0.007)were the independent risk factors for ISR.ROC curve analysis showed that in predicting ISR,the AUC,specificity and sensitivity of the plaque load were 0.765(95％CI:0.622-0.908,P=0.002),0.731 and 0.714 respectively,which of the homocysteine level were 0.767(95％CI:0.623-0.911,P=0.002),0.942 and 0.500 respectively.The combination use of plaque load and homocysteine level could achieve the best predictive effect,its AUC,specificity and sensitivity were 0.887(95％CI:0.794-0.981,P＜0.001),0.904 and 0.714 respectively.Conclusion The plaque load assessed by high-resolution magnetic resonance imaging and the homocysteine level have higher specificity and sensitivity in predicting ISR in patients with middle cerebral artery stenosis.