BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

Objective: To investigate the influencing factors for delay in healthcare-seeking, definitive diagnosis and identification in patients with pulmonary tuberculosis (PTB) in Minhang District, Shanghai Municipality, so as to provide the basis for effectively reducing delay in PTB patients. Methods: Data of PTB patients in Minhang District from 2017 to 2022 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were analyzed, and factors affecting delay in healthcare-seeking, definitive diagnosis and identification were identified using multivariable logistic regression models. Results: A total of 4 214 PTB patients were reported in Minhang District from 2017 to 2022, including 2 802 males and 1 412 females, with a male-to-female ratio of 1.98∶1. The majority of patients were aged 25 to <45 years (1 664 cases, 39.49%). The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were 36.81%, 30.21% and 38.09%, respectively. Delay in healthcare-seeking was associated with the year (2018, OR=0.708; 2019, OR=0.549; 2020, OR=0.670; 2021, OR=0.682), gender (female, OR=1.199), occupation (worker, OR=1.379; housekeeping service/housework/unemployed, OR=1.481), case identification route (symptom-based consultation, OR=11.159), and level of the first-diagnosed hospital (city-level, OR=1.528). Delay in definitive diagnosis was associated with age (45 to <65 years, OR=1.476), occupation (commercial service, OR=0.687; housekeeping service/housework/unemployed, OR=0.672), household registration (non-local, OR=0.820), case identification route (symptom-based consultation, OR=0.616), pathogen test result (negative/not tested, OR=1.903), and the level of the first-diagnosed hospital (city-level, OR=0.311). Delay in identification was associated with the year (2018, OR=0.785; 2019, OR=0.647; 2020, OR=0.790; 2021, OR=0.710), occupation (commercial service, OR=0.687), household registration (non-local, OR=0.848) and level of the first-diagnosed hospital (city-level, OR=0.560) Conclusions Year, gender, occupation, case identification route and level of the first-diagnosed hospital are influencing factors for delay in healthcare-seeking in PTB patients. Age, occupation, household registration, case identification route, pathogen test result and level of the first-diagnosed hospital are influencing factors for delay in definitive diagnosis. Year, occupation, household registration and level of the first-diagnosed hospital are influencing factors for delay in identification.

Objective:To assess the optimal timing and short-term clinical efficacy of sinus drug-eluting stent placement in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:The minimum sample size was calculated using G-power 3.1.9.7 software. From March 2021 and May 2023, a total of 114 eligible patients with CRSwNP were recruited in this study at the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University. The patients were randomly assigned to three groups: the control group, the intraoperative stent group, and the postoperative stent group. In the intraoperative stent group, drug-eluting stents were implanted during endoscopic sinus surgery (ESS), while patients in the postoperative stent group received drug-eluting stent 2 weeks after ESS, following routine debridement of the surgical cavity. Bilateral ethmoid sinus stenting was performed for both stent groups, while the control group only underwent ESS with standard postoperative cavity debridement. All subjects were followed up at 2, 4, 8, and 12 weeks postoperatively. Nasal symptom Visual Analog Scale (VAS) scores and endoscopic evaluations of the ethmoid cavity-assessing obstruction, crusting, polypoid mucosal changes, epithelialization of ethmoid cavity, need for intervention, and complications such as middle turbinate lateralization and adhesions-were collected to evaluate the treatment efficacy of three groups. Statistical analyses were performed using GraphPad Prism 9. Analysis of variance (ANOVA) was applied to analyze continuous variables among the three groups, and chi-square tests were used for categorical variables.Results:Among 114 CRSwNP patients, 21 lost follow-up patients and 7 postoperative oral corticosteroid intervention patients were excluded. Finally, 86 patients were included in the analysis, including 45 males and 41 females, aged 18-65 years. The cohort comprised 29 in the control group, 29 in the intraoperative stent group, and 28 in the postoperative stent group. Successful bilateral ethmoid sinus stent implantation was achieved in both stent groups. At 4 weeks postoperatively, compared with the control group, both stent groups showed significant improvements in nasal congestion and rhinorrhea scores ( P<0.05). At 8 weeks, the postoperative group continued to demonstrate superior outcomes in these two symptoms (both P<0.05), while the intraoperative group only showed significant improvement in nasal congestion ( P<0.05). No significant differences were observed in facial pressure, olfactory loss, or nasal dryness scores among the three groups (all P>0.05). Endoscopic evaluation revealed that both stent groups had significant improvements in ethmoid sinus obstruction scores at 4 weeks compared with the control group, with the postoperative group maintaining this advantage at 8 weeks ( P<0.05). At 2 weeks, the intraoperative stent group had higher crusting scores than other groups ( P<0.05). At 2 weeks after stent implantation, the postoperative stent group had significantly lower crusting scores than the intraoperative stent group ( P<0.001). The intraoperative group had a significantly lower incidence of ethmoid sinus edema and polypoid changes at 4 weeks compared with the control group ( P<0.05), while the postoperative group showed reduced rates of these pathological changes at 4, 8, and 12 weeks (all P<0.05). The postoperative stent group had significantly higher rates of ethmoid sinus mucosal epithelialization at 8 and 12 weeks postoperatively compared with the control group. The intraoperative stent group required fewer interventions than the control group at both 8 and 12 weeks, while the postoperative stent group maintained lower interventions rates at all follow-up points after implantation (all P<0.05). Additionally, the incidence of complications was significantly lower in both stent groups compared with the control group ( P<0.05). Overall, stent implantation at different time points showed similar efficacy, with the postoperative group demonstrating more stable outcomes and less crusting/coagulation formation compared with the intraoperative group. Conclusions:The implantation of corticosteroid sinus stents in the ethmoid sinuses effectively controls postoperative inflammation, promotes mucosal epithelialization, and reduces postoperative intervention rates. Stent implantation two weeks after surgery is feasible. Adjusting the timing of stent placement can minimize crust formation and maximize the corticosteroid effect, thereby facilitating a benign course of the surgical site.

Home rehabilitation is the main rehabilitation model for elderly patients with hip fractures in China, and the application of digital health technology shows great potential in improving the quality of home rehabilitation for this population. This paper describes the concept of digital health technology, the current application status of different types of digital health technology in home rehabilitation for elderly patients with hip fractures, and discusses existing issues and future prospects, aiming to provide a reference for digital home rehabilitation nursing for elderly hip fracture patients.

Objective:To explore the correlation among SMAD4 gene polymorphisms, early life traumatic experience and their interactions with clinical feature of obsessive-compulsive disorder (OCD). Methods:Totally 484 OCD patients who met the DSM-Ⅳ diagnostic criteria and 368 health controls who met the enrollment criteria were recruited from September 2013 to September 2018. The Yale-Brown obsessive-compulsive scale (Y-BOCS) was used to assess the severity of obsessive-compulsive symptoms, the Beck depression inventory Ⅱ (BDI-Ⅱ) was used to assess the severity of depressive symptoms, the Beck anxiety inventory (BAI) was used to assess the severity of anxiety symptoms, and early trauma inventory-short form (ETI-SF) was used to assess early traumatic experience. SMAD4: rs12452684, rs2276163, rs17663887 and rs3819122 were genotyped using the Taqman genotyping technique. Data were analyzed using SPSS 20.0 software, and comparisons among groups were performed using chi-square test, t-test, Mann-Whitney U non-parametric test and analysis of covariance. Correlation was analyzed using Spearman correlation analysis, and interactions were analyzed using general linear model. Results:All sites except rs17663887 met the Hardy-Weinberg equilibrium (rs12452684: χ2=0.29, P=0.59; rs2276163: χ2=2.58, P=0.11; rs3819122: χ2=0.22, P=0.64).Allele, genotype frequencies of SMAD4: rs12452684, rs2276163 and rs3819122 were not statistically significant between the OCD and the health control groups ( χ2=0.02, 1.20, 0.04, all P>0.05; χ2=1.85, 3.98, 1.45, all P>0.05). The results of covariance analysis (corrected for age and gender) showed that there were significantly differences in compulsion (CC: 12.47±4.23, CT: 12.53±4.15, TT: 13.97±3.11; AA: 12.63±4.08, AC: 12.49±4.19, CC: 13.87±2.93) and total Y-BOCS scores(CC: 25.31±6.42, CT: 25.68±5.90, TT: 27.75±6.01; AA: 25.54±6.52, AC: 25.56±5.98, CC: 27.63±5.75) among the three genotypes of the SMAD4: rs2276163 and rs3819122 between the two groups ( F=3.58, 3.87, 3.48, 3.73, all P<0.05). Emotional abuse in the ETI-SF was positively correlated with obsession and total Y-BOCS scores( r=0.14, 0.14, both P<0.05). The interactions of rs2276163, rs3819122 and emotional abuse were associated with obsession scores ( F=4.65, 3.63, 2.93, all P<0.01). Conclusions:The more emotional abuse experienced in early life, the more severe obsessive-compulsive symptoms, and the interaction between the SMAD4 gene and early traumatic experience is involved in the development of OCD.

Home rehabilitation is the main rehabilitation model for elderly patients with hip fractures in China, and the application of digital health technology shows great potential in improving the quality of home rehabilitation for this population. This paper describes the concept of digital health technology, the current application status of different types of digital health technology in home rehabilitation for elderly patients with hip fractures, and discusses existing issues and future prospects, aiming to provide a reference for digital home rehabilitation nursing for elderly hip fracture patients.

Objective:To explore the correlation among SMAD4 gene polymorphisms, early life traumatic experience and their interactions with clinical feature of obsessive-compulsive disorder (OCD). Methods:Totally 484 OCD patients who met the DSM-Ⅳ diagnostic criteria and 368 health controls who met the enrollment criteria were recruited from September 2013 to September 2018. The Yale-Brown obsessive-compulsive scale (Y-BOCS) was used to assess the severity of obsessive-compulsive symptoms, the Beck depression inventory Ⅱ (BDI-Ⅱ) was used to assess the severity of depressive symptoms, the Beck anxiety inventory (BAI) was used to assess the severity of anxiety symptoms, and early trauma inventory-short form (ETI-SF) was used to assess early traumatic experience. SMAD4: rs12452684, rs2276163, rs17663887 and rs3819122 were genotyped using the Taqman genotyping technique. Data were analyzed using SPSS 20.0 software, and comparisons among groups were performed using chi-square test, t-test, Mann-Whitney U non-parametric test and analysis of covariance. Correlation was analyzed using Spearman correlation analysis, and interactions were analyzed using general linear model. Results:All sites except rs17663887 met the Hardy-Weinberg equilibrium (rs12452684: χ2=0.29, P=0.59; rs2276163: χ2=2.58, P=0.11; rs3819122: χ2=0.22, P=0.64).Allele, genotype frequencies of SMAD4: rs12452684, rs2276163 and rs3819122 were not statistically significant between the OCD and the health control groups ( χ2=0.02, 1.20, 0.04, all P>0.05; χ2=1.85, 3.98, 1.45, all P>0.05). The results of covariance analysis (corrected for age and gender) showed that there were significantly differences in compulsion (CC: 12.47±4.23, CT: 12.53±4.15, TT: 13.97±3.11; AA: 12.63±4.08, AC: 12.49±4.19, CC: 13.87±2.93) and total Y-BOCS scores(CC: 25.31±6.42, CT: 25.68±5.90, TT: 27.75±6.01; AA: 25.54±6.52, AC: 25.56±5.98, CC: 27.63±5.75) among the three genotypes of the SMAD4: rs2276163 and rs3819122 between the two groups ( F=3.58, 3.87, 3.48, 3.73, all P<0.05). Emotional abuse in the ETI-SF was positively correlated with obsession and total Y-BOCS scores( r=0.14, 0.14, both P<0.05). The interactions of rs2276163, rs3819122 and emotional abuse were associated with obsession scores ( F=4.65, 3.63, 2.93, all P<0.01). Conclusions:The more emotional abuse experienced in early life, the more severe obsessive-compulsive symptoms, and the interaction between the SMAD4 gene and early traumatic experience is involved in the development of OCD.

Objective:To assess the optimal timing and short-term clinical efficacy of sinus drug-eluting stent placement in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:The minimum sample size was calculated using G-power 3.1.9.7 software. From March 2021 and May 2023, a total of 114 eligible patients with CRSwNP were recruited in this study at the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University. The patients were randomly assigned to three groups: the control group, the intraoperative stent group, and the postoperative stent group. In the intraoperative stent group, drug-eluting stents were implanted during endoscopic sinus surgery (ESS), while patients in the postoperative stent group received drug-eluting stent 2 weeks after ESS, following routine debridement of the surgical cavity. Bilateral ethmoid sinus stenting was performed for both stent groups, while the control group only underwent ESS with standard postoperative cavity debridement. All subjects were followed up at 2, 4, 8, and 12 weeks postoperatively. Nasal symptom Visual Analog Scale (VAS) scores and endoscopic evaluations of the ethmoid cavity-assessing obstruction, crusting, polypoid mucosal changes, epithelialization of ethmoid cavity, need for intervention, and complications such as middle turbinate lateralization and adhesions-were collected to evaluate the treatment efficacy of three groups. Statistical analyses were performed using GraphPad Prism 9. Analysis of variance (ANOVA) was applied to analyze continuous variables among the three groups, and chi-square tests were used for categorical variables.Results:Among 114 CRSwNP patients, 21 lost follow-up patients and 7 postoperative oral corticosteroid intervention patients were excluded. Finally, 86 patients were included in the analysis, including 45 males and 41 females, aged 18-65 years. The cohort comprised 29 in the control group, 29 in the intraoperative stent group, and 28 in the postoperative stent group. Successful bilateral ethmoid sinus stent implantation was achieved in both stent groups. At 4 weeks postoperatively, compared with the control group, both stent groups showed significant improvements in nasal congestion and rhinorrhea scores ( P<0.05). At 8 weeks, the postoperative group continued to demonstrate superior outcomes in these two symptoms (both P<0.05), while the intraoperative group only showed significant improvement in nasal congestion ( P<0.05). No significant differences were observed in facial pressure, olfactory loss, or nasal dryness scores among the three groups (all P>0.05). Endoscopic evaluation revealed that both stent groups had significant improvements in ethmoid sinus obstruction scores at 4 weeks compared with the control group, with the postoperative group maintaining this advantage at 8 weeks ( P<0.05). At 2 weeks, the intraoperative stent group had higher crusting scores than other groups ( P<0.05). At 2 weeks after stent implantation, the postoperative stent group had significantly lower crusting scores than the intraoperative stent group ( P<0.001). The intraoperative group had a significantly lower incidence of ethmoid sinus edema and polypoid changes at 4 weeks compared with the control group ( P<0.05), while the postoperative group showed reduced rates of these pathological changes at 4, 8, and 12 weeks (all P<0.05). The postoperative stent group had significantly higher rates of ethmoid sinus mucosal epithelialization at 8 and 12 weeks postoperatively compared with the control group. The intraoperative stent group required fewer interventions than the control group at both 8 and 12 weeks, while the postoperative stent group maintained lower interventions rates at all follow-up points after implantation (all P<0.05). Additionally, the incidence of complications was significantly lower in both stent groups compared with the control group ( P<0.05). Overall, stent implantation at different time points showed similar efficacy, with the postoperative group demonstrating more stable outcomes and less crusting/coagulation formation compared with the intraoperative group. Conclusions:The implantation of corticosteroid sinus stents in the ethmoid sinuses effectively controls postoperative inflammation, promotes mucosal epithelialization, and reduces postoperative intervention rates. Stent implantation two weeks after surgery is feasible. Adjusting the timing of stent placement can minimize crust formation and maximize the corticosteroid effect, thereby facilitating a benign course of the surgical site.

Objective:To explore the value of the imaging nomogram model based on preoperative CT features of patients with small intestinal stromal tumor (SIST) in predicting pathological risk classification.Methods:This was a cohort study. The patients who were diagnosed as primary SIST by postoperative pathology in Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to October 2023 were retrospectively included. According to the modified 2008 National Institutes of Health classification criteria, the patients were divided into a pathological intermediate/high-risk group (86 cases) and a very low/low-risk group (56 cases). The features of preoperative enhanced CT images of SIST were analyzed, including tumor boundary, necrosis, intra-tumoral hemorrhage, intra-tumoral calcification, growth pattern, enhancement pattern, enhancement degree, enlarged vessels feeding or draining the mass (EVFDM), and tumor location. Patients were followed up to determine the recurrence-free survival (RFS). Univariate and multivariate logistic regression were used to screen the independent predictors of SIST with pathological medium/high-risk group. The independent predictors were combined to construct an imaging prediction model, and a nomogram was drawn. The receiver operating characteristic curve was used to evaluate the predictive efficacy of the model. The Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the differences in RFS.Results:Univariate logistic regression results showed that tumor shape, necrosis, intra-tumoral hemorrhage, EVFDM, and tumor location were potentially related to medium/high-risk SIST. Multivariate logistic regression results showed that tumor shape ( OR=3.92, 95% CI 1.58-9.71, P=0.003), necrosis ( OR=4.60, 95% CI 1.91-11.09, P<0.001), and EVFDM ( OR=6.25,95% CI 1.74-22.47, P=0.005) were independent predictors of pathological intermediate/high-risk SIST. The area under the curve of the imaging predictive model combining the three predictors to predict the intermediate/high-risk SIST was 0.835 (95% CI 0.769-0.901), the sensitivity was 0.810, the specificity was 0.839, and the accuracy was 0.789. Taking the cut-off value (0.810) as the boundary value, the patients were divided into the high-risk group (74 cases) and the low-risk group (68 cases) according to the prediction results. The median RFS of the predicted high-risk group was poorer than that of the predicted low-risk group, and the difference was statistically significant ( χ2=5.20, P=0.023). Conclusions:The imaging nomogram model based on preoperative CT image features shape, necrosis, and EVFDM can effectively predict the pathological intermediate/high-risk SIST before surgery and has important predictive value for postoperative recurrence.