ObjectiveTo evaluate the therapeutic effect of Shenji Guben prescription （SJGB） on chronic obstructive pulmonary disease （COPD） in mice and to explore its potential therapeutic mechanism via transcriptomics. MethodsA mouse model of COPD was established by combined exposure to lipopolysaccharide （LPS） and cigarette smoke. C57BL/6J mice were randomly allocated into a control group， a model group， an acetylcysteine （78 mg·kg^-1·d^-1） group， and low- （7.5 g·kg^-1·d^-1）， medium- （15 g·kg^-1·d^-1）， and high-dose （30 g·kg^-1·d^-1） SJGB groups. After 13 weeks of modeling， oral administration was initiated and continued for 28 days. The therapeutic effects of SJGB were assessed based on body weight， lung function， lung tissue pathology， and inflammatory factors in bronchoalveolar lavage fluid （BALF）. Ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） was employed to identify the active ingredients in SJGB. Transcriptomic profiling of lung tissue was performed by RNA-seq to identify differentially expressed genes （DEGs）， followed by gene ontology （GO） enrichment analysis， Kyotoencyclopedia of Genes and Genomes （KEGG） enrichment analysis， Gene Set Enrichment Analysis （GSEA）， and protein-protein interaction （PPI） network construction. Key genes were further validated by Western blot and Real‑time polymerase chain reaction （Real-time PCR）. ResultsAfter drug intervention， the final body weights of mice in medium- and high-dose SJGB groups were higher than those in the model group （P<0.05）. Compared with the model group， SJGB groups demonstrated a significant decrease in expiratory time （Te）， along with increases in peak expiratory flow （PEF）， 50% expiratory flow （EF50）， tidal volume （TV）， and expiratory volume （EV） （P<0.05）. High-dose SJGB ameliorated pathological changes in the lung tissue， reduced peribronchial inflammation scores， and decreased mean linear intercept （MLI） （P<0.01）. Compared with the model group， medium- and high-dose SJGB groups showed reductions in interleukin-6 （IL-6） and interleukin-1β （IL-1β） levels （P<0.01）. UHPLC-MS/MS revealed that the five most abundant components in SJGB were （S）-actinidine， ephedrine， pyroglutamic acid， methylephedrine， and coumarin. Transcriptomic analysis revealed 219 DEGs regulated by SJGB， suggesting that the anti-COPD effects of SJGB may be mediated through key genes such as cluster of differentiation 68 （CD68）， integrin subunit alpha X （ITGAX）， and cathepsin S （CTSS）， primarily involved in the lysosomal pathway. Western blot and Real-time PCR results confirmed that SJGB inhibited the expression of CD68， ITGAX， and CTSS compared with the model group （P<0.05）. ConclusionSJGB effectively improved the lung function and attenuated lung tissue inflammation in the mouse model of COPD by modulating the lysosomal pathway and related genes including CD68， ITGAX， and CTSS.

Objective To investigate the potential beneficial predictors for endovascular treatment(EVT)in case of acute anterior circulation large vessel occlusion with large-core infarction.Methods We made a retrospective inclusion of 92 patients with anterior circulation large vessel occlusion and core infarct volume ranging from 50 to 100 mL,who underwent EVT at Zhangzhou Municipal Hospital of Fujian Province from March 2018 to February 2021.All the patients were confirmed as anterior circulation large infarction and large infarct volume using computed tomography(CT),computed tomography angiography(CTA),and computed tomography perfusion(CTP)before EVT.All clinical and imaging data were collected to observe the postoperative recurrence rate,incidence of symptomatic intracranial hemorrhage(sICH),and functional prognosis 90 days.Then the patients were divided into favorable outcomes group(mRS≤3)and unfavorable outcomes group(mRS＞3)based on Rankin scores 90 days post-stroke.Univariate and multivariate Logistic analysis were conducted to analyze factors influencing the patients'prognosis.By combining the results of multivariate analysis,we constructed receiver operating characteristic(ROC)curves and identified the cut-off value to evaluate the predictive value of age for post-vascular treatment prognosis.Results Among the included patients,the postoperative revascularization rate(mTIICI≥2b)was 95％(88 cases),the rate of favorable outcomes at 90 days postoperatively(mRS≤3)was 32.61％(30 cases),the incidence of sICH was 13％,and the mortality rate was 31.5％.Compared with the unfavorable outcomes group,the favorable outcomes group had a younger age and a higher proportion of males.Multivariate analysis indicated that older age was an independent risk factor for adverse outcomes following endovascular treatment(OR=4.97,95％CI:1.78-13.90,P=0.002).The ROC curve indicated that the area under the curve was maximized at the age of 72.5 years(AUC=0.763,95％CI:0.661-0.864,P＜0.001).Its sensitivity and specificity was 0.565 and 0.833,respectively.Conclusion Age is an independent predictor of the prognosis of acute procirculatory large core stroke.Patients with large core infarction older than 72.5 years may not benefit from endovascular therapy,which needs to be confirmed by a multicenter large sample prospective randomized controlled trial.

Objective To investigate the potential beneficial predictors for endovascular treatment(EVT)in case of acute anterior circulation large vessel occlusion with large-core infarction.Methods We made a retrospective inclusion of 92 patients with anterior circulation large vessel occlusion and core infarct volume ranging from 50 to 100 mL,who underwent EVT at Zhangzhou Municipal Hospital of Fujian Province from March 2018 to February 2021.All the patients were confirmed as anterior circulation large infarction and large infarct volume using computed tomography(CT),computed tomography angiography(CTA),and computed tomography perfusion(CTP)before EVT.All clinical and imaging data were collected to observe the postoperative recurrence rate,incidence of symptomatic intracranial hemorrhage(sICH),and functional prognosis 90 days.Then the patients were divided into favorable outcomes group(mRS≤3)and unfavorable outcomes group(mRS＞3)based on Rankin scores 90 days post-stroke.Univariate and multivariate Logistic analysis were conducted to analyze factors influencing the patients'prognosis.By combining the results of multivariate analysis,we constructed receiver operating characteristic(ROC)curves and identified the cut-off value to evaluate the predictive value of age for post-vascular treatment prognosis.Results Among the included patients,the postoperative revascularization rate(mTIICI≥2b)was 95％(88 cases),the rate of favorable outcomes at 90 days postoperatively(mRS≤3)was 32.61％(30 cases),the incidence of sICH was 13％,and the mortality rate was 31.5％.Compared with the unfavorable outcomes group,the favorable outcomes group had a younger age and a higher proportion of males.Multivariate analysis indicated that older age was an independent risk factor for adverse outcomes following endovascular treatment(OR=4.97,95％CI:1.78-13.90,P=0.002).The ROC curve indicated that the area under the curve was maximized at the age of 72.5 years(AUC=0.763,95％CI:0.661-0.864,P＜0.001).Its sensitivity and specificity was 0.565 and 0.833,respectively.Conclusion Age is an independent predictor of the prognosis of acute procirculatory large core stroke.Patients with large core infarction older than 72.5 years may not benefit from endovascular therapy,which needs to be confirmed by a multicenter large sample prospective randomized controlled trial.

OBJECTIVE To explore the therapeutic effect and safety of Maiwei Yangfei Decoction(MWYF)in the treatment of idiopathic pulmonary fibrosis of qi-yin deficiency type.METHODS A total of 58 patients with idiopathic pulmonary fibrosis of qi-yin deficiency type were randomly divided into an experimental group and a control group with 29 cases in each group according to a 1:1 ratio.Two cases dropped out of the experimental group and three cases dropped out of the control group.The control group received standardized treatment of Western medicine,and the experimental group received MWYF on the basis of the treatment of the control group.The treatment course of both groups was 3 months.The TCM syndrome score,lung function,6-minute walking distance(6MWD),transcutaneous blood oxygen saturation(SpO2),high-resolution computed tomography(HRCT)score,St.George's respir-atory questionnaire(SGRQ)score and serum sialoglycoprotein antigen(KL-6)level of the two groups were compared before and after treatment.Blood routine and liver and kidney function of the two groups were detected before and after treatment,and the occurrence of adverse reactions during treatment was recorded.RESULTS After treatment,the total score of TCM syndrome of the two groups was significantly improved(P<0.01),and the experimental group was better than the control group(P<0.01);the DLCO%of the experi-mental group increased(P<0.05),and the experimental group was higher than the control group(P<0.05).The experimental group showed significant improvement in 6MWD,HRCT grid shadow,SGRQ symptom score and total score,and serum KL-6 level(P<0.05,P<0.01),which was better than the control group(P<0.05,P<0.01).No serious adverse events occurred in either group dur-ing the treatment.CONCLUSION MWYF combined with standardized Western medicine treatment can effectively improve the clini-cal symptoms of patients with idiopathic pulmonary fibrosis of qi-yin deficiency type,reduce the expression level of serum KL-6,and has a definite effect and good safety.

Objective To investigate the changes of dorsal root ganglia(DRG)neurons in rats with voltage-gated sodium channel 1.7 loss-of-function(Nav1.7 LOF)and its involvement in congenital insensitivity to pain.Methods Immunofluorescence,Western blot,and alternative splicing analysis were used to verify the expression deletion of DRG neurons and Nav1.7 in spinal cord of Nav1.7 LOF rats.Using antibodies for peripherin,calcitonin gene-related peptide(CGRP),isolectin B4(IB4),and neuronal nuclear antigen(NeuN)in the DRG and spinal cord tissues,immunofluorescence staining was performed to observe the differences in DRG neuronal sub-populations and central terminal projections between Nav1.7 LOF rats and wild-type rats.Bulk RNA-Seq and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the difference of gene expression in the DRG neurons between Nav1.7 LOF and WT rats.Following 55℃ thermal stimulation of the hind paw in Nav1.7 LOF rats,c-Fos and phospho-extracellular signal-regulated kinase(p-ERK)antibody staining was used to observe the activation of DRG neurons and spinal dorsal horn neurons.Results Nav1.7 was absent in the DRG neurons and spinal cord of Nav1.7 LOF rats.Compared with wild-type rats,Nav1.7 LOF rats exhibited a decreased proportion of IB4+non-peptidergic neurons in DRG tissues.Additionally,there was a significant loss of central projections of IB4+neurons in the spinal dorsal horn.The RNA-Seq and RT-qPCR results demonstrate that in Nav1.7 LOF rats,the gene expression of Mas-related G protein-coupled receptor(MRGPR),markers for 1B4+non-peptidergic neurons,was downregulat-ed.Compared with WT rats,there was no difference in c-Fos and p-ERK staining in DRG neurons of Nav1.7 LOF rats following ther-mal stimulation of the hindpaw.However,there was no c-Fos or p-ERK staining in spinal dorsal horn neurons,suggesting that the neu-rons were not activated.Conclusion Nav1.7 LOF rats exhibit a decreased proportion of IB4+non-peptideric neurons in DRG tissue and their central terminal projections.Noxious stimuli could activate DRG neurons,but could not activate dorsal horn neurons,suggesting the pain signal is interrupted between the central terminals of DRG neurons and the spinal dorsal horn.

Objective To compare the effects of intratracheal instillation by lumbar spinal needle and intratracheal atomization on bleomycin-induced pulmonary fibrosis modeling in mice,to determine the optimal modeling method.Methods Seventy-two C57BL/6J mice were divided randomly into control,lumbar spinal needle and aerosolization groups,according to body weight(n=24 mice per group).Mice in the control and lumbar spinal needle groups received intratracheal instillation of saline or bleomycin,respectively,and mice in the aerosolization group received aerosolized bleomycin intracheally by microsprayer aerosolizer.Micro-computed tomography(CT),histopathological changes,hydroxyproline(HYP)levels,Collagen Ⅰ(COL Ⅰ)and α-smooth muscle actin(α-SMA)protein expression were examined on days 14 and 21 to evaluate the degree of pulmonary fibrosis in each group.Results Mice in the two model groups showed listlessness,slow responses,and decreased body weights on days 14 and 21,compared with the control group(P＜0.001).Micro-CT showed white shadows surrounding the trachea in the lumbar spinal needle group,while the shadows were more diffuse in the aerosol group.The degrees of alveolitis and pulmonary fibrosis were highest in the aerosolization group,with a time-dependent trend.The hydroxyproline contents were significantly increased in the two model groups on days 14 and 21 after modeling(P＜0.05),with the increase on day 21 being more significant and stable(P＜0.001).COL Ⅰ expression was significantly increased in both the lumbar spinal needle group and aerosolization group on days 21 after modeling,especially in the aerosolization group(P＜0.001).Expression levels of α-SMA were significantly higher in the lumbar spinal needle group and aerosolization group compared with the control group on days 21(P＜0.001);however,there was no significant difference between the two model groups.Conclusions intratracheal atomization of bleomycin is the optimal method for establishing a mouse model of pulmonary fibrosis.

Objective To investigate the changes of dorsal root ganglia(DRG)neurons in rats with voltage-gated sodium channel 1.7 loss-of-function(Nav1.7 LOF)and its involvement in congenital insensitivity to pain.Methods Immunofluorescence,Western blot,and alternative splicing analysis were used to verify the expression deletion of DRG neurons and Nav1.7 in spinal cord of Nav1.7 LOF rats.Using antibodies for peripherin,calcitonin gene-related peptide(CGRP),isolectin B4(IB4),and neuronal nuclear antigen(NeuN)in the DRG and spinal cord tissues,immunofluorescence staining was performed to observe the differences in DRG neuronal sub-populations and central terminal projections between Nav1.7 LOF rats and wild-type rats.Bulk RNA-Seq and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the difference of gene expression in the DRG neurons between Nav1.7 LOF and WT rats.Following 55℃ thermal stimulation of the hind paw in Nav1.7 LOF rats,c-Fos and phospho-extracellular signal-regulated kinase(p-ERK)antibody staining was used to observe the activation of DRG neurons and spinal dorsal horn neurons.Results Nav1.7 was absent in the DRG neurons and spinal cord of Nav1.7 LOF rats.Compared with wild-type rats,Nav1.7 LOF rats exhibited a decreased proportion of IB4+non-peptidergic neurons in DRG tissues.Additionally,there was a significant loss of central projections of IB4+neurons in the spinal dorsal horn.The RNA-Seq and RT-qPCR results demonstrate that in Nav1.7 LOF rats,the gene expression of Mas-related G protein-coupled receptor(MRGPR),markers for 1B4+non-peptidergic neurons,was downregulat-ed.Compared with WT rats,there was no difference in c-Fos and p-ERK staining in DRG neurons of Nav1.7 LOF rats following ther-mal stimulation of the hindpaw.However,there was no c-Fos or p-ERK staining in spinal dorsal horn neurons,suggesting that the neu-rons were not activated.Conclusion Nav1.7 LOF rats exhibit a decreased proportion of IB4+non-peptideric neurons in DRG tissue and their central terminal projections.Noxious stimuli could activate DRG neurons,but could not activate dorsal horn neurons,suggesting the pain signal is interrupted between the central terminals of DRG neurons and the spinal dorsal horn.

Objective To compare the effects of intratracheal instillation by lumbar spinal needle and intratracheal atomization on bleomycin-induced pulmonary fibrosis modeling in mice,to determine the optimal modeling method.Methods Seventy-two C57BL/6J mice were divided randomly into control,lumbar spinal needle and aerosolization groups,according to body weight(n=24 mice per group).Mice in the control and lumbar spinal needle groups received intratracheal instillation of saline or bleomycin,respectively,and mice in the aerosolization group received aerosolized bleomycin intracheally by microsprayer aerosolizer.Micro-computed tomography(CT),histopathological changes,hydroxyproline(HYP)levels,Collagen Ⅰ(COL Ⅰ)and α-smooth muscle actin(α-SMA)protein expression were examined on days 14 and 21 to evaluate the degree of pulmonary fibrosis in each group.Results Mice in the two model groups showed listlessness,slow responses,and decreased body weights on days 14 and 21,compared with the control group(P＜0.001).Micro-CT showed white shadows surrounding the trachea in the lumbar spinal needle group,while the shadows were more diffuse in the aerosol group.The degrees of alveolitis and pulmonary fibrosis were highest in the aerosolization group,with a time-dependent trend.The hydroxyproline contents were significantly increased in the two model groups on days 14 and 21 after modeling(P＜0.05),with the increase on day 21 being more significant and stable(P＜0.001).COL Ⅰ expression was significantly increased in both the lumbar spinal needle group and aerosolization group on days 21 after modeling,especially in the aerosolization group(P＜0.001).Expression levels of α-SMA were significantly higher in the lumbar spinal needle group and aerosolization group compared with the control group on days 21(P＜0.001);however,there was no significant difference between the two model groups.Conclusions intratracheal atomization of bleomycin is the optimal method for establishing a mouse model of pulmonary fibrosis.

ObjectiveTo investigate the association of nonalcoholic fatty liver disease (NAFLD) with insulin resistance and dyslipidemia in patients with type 2 diabetes mellitus,and to analyze the risk factors.Methods A total of 200 patients with type 2 diabetes mellitus including 99 with NAFLD and 101 without NAFLD were recruited.Height,weight,waist circumference,hip circumference,liver enzymes,blood lipids,fasting and postprandial blood glucose,insulin,C-peptide,and HbA1C levels were detected.Body mass index ( BMI),waist-hip ratio( WHR),and improved insulin and C-peptide index(HOMA-C-peptide) were calculated and compared between two groups.ResultsCompared with non-NAFLD group,weight,BMI,waist circumference,hip circumference,alanine aminotransferase ( ALT),aspartate aminotransferase,triglyceride ( TG ),total cholesterol ( TC ),low density lipoprotein-cholesterol(LDL-C) were significantly higher in NAFLD group( all P＜0.01 ),while age,duration,and high density lipoprotein-cholesterol were lower( all P＜0.05 ).The incidence of combined hyperlipidemia,especially hypertriglyceridemia,was significantly higher in NAFLD group( P＜0.01 ).Fasting and postprandial 1 h blood glucose [ ( 2.07 ±0.36 vs 1.83 ±0.43 ) mmol/L,( 14.04 ± 3.96 vs 12.59 ± 3.90 ) mmol/L ],fasting and postprandial 1 h Cpeptide [ (2.79± 1.15 vs 2.08±1.29 ) ng/ml,( 1.33 ±0.45 vs 1.12±0.54) ng/ml ],HbA1C [ (2.09±0.33 vs 1.96±0.28) ％ ],and HOMA-C-peptide index were significantly increased in NAFLD group ( P ＜ 0.05 or P ＜ 0.01 ).Logistic analysis showed that TG,BMI,and ALT were the major risk factors of NAFLD in type 2 diabetes mellitus( P＜0.05 or P＜0.01 ).ConclusionTriglyceridemia,obesity,and raised ALT level were significantly associated with an increased risk of NAFLD in patients with type 2 diabetes mellitus.