ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Objective:To investigate the dynamic changes of cytokine levels in patients with sepsis and to identify potential biomarkers for evaluating the prognosis of the disease.Methods:A total of 195 patients with sepsis hospitalized at the Department of Infectious Diseases and the Department of Critical Care Medicine of the First Affiliated Hospital of Soochow University from August 2022 to October 2024 were recruited, and 70 healthy individuals undergoing physical examinations were recruited as the healthy control group. The levels of 11 cytokines, including interferon γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were compared between the sepsis patients and the healthy controls. Spearman correlation analysis was used to assess the correlation between cytokine levels and sequential organ failure assessment (SOFA) scores in sepsis patients. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic value of cytokines for sepsis. Delong test was used to compare AUC. Based on the 28-day survival outcomes, the sepsis patients were categorized into non-survival group and survival group. The levels of the 11 cytokines in patients on the 1st, 3rd, 7th, 14th, 21st and 28th days after confirmed sepsis were dynamically monitored, and their change characteristics were analyzed. Mann-Whitney U test was used for statistical comparison. Results:The age of the 195 patients with sepsis was 68.0 (55.0, 76.0) years old, including 124 males (63.6%), 64 died and 131 survived.The levels of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, TNF-α, CRP in the sepsis group were all higher than those in the healthy control group ( Z=-2.99, -5.42, -4.95, -4.09, -5.05, -11.30, -8.66, -8.23, -5.64, -4.75, -2.12 and -10.75, respectively, all P<0.05). The differences were statistical significance. The levels of IL-2 ( r=0.149, P=0.037), IL-6 ( r=0.223, P=0.002), IL-8 ( r=0.159, P=0.026), and IL-10 ( r=0.188, P=0.009) in patients with sepsis were positively correlated with SOFA scores. The AUC of CRP in diagnosing sepsis was 0.989 with the sensitivity of 97.4% and the specificity of 100.0%. The AUC of IL-6 in diagnosing sepsis was 0.953, with the sensitivity of 93.3% and the specificity of 97.1%, and the AUC of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12P70, IL-17A, and TNF-α were 0.620, 0.718, 0.699, 0.665, 0.703, 0.850, 0.836, 0.727, 0.691, and 0.574, respectively.The AUC of the 11 cytokines were all lower than that of CRP, and the differences were all statistically significant ( Z=2.34, 10.24, 8.03, 8.08, 10.64, 8.70, 5.91, 5.17, 8.91, 9.25 and 4.10, respectively, all P<0.05).During the dynamic monitoring, the IFN-γ and IL-1β levels in the non-survival group increased gradually. The IFN-γ levels on the 14th and 21st day in the non-survival group were higher than those in the survival group ( Z=0.53 and 0.08, respectively, both P<0.05), and IL-1β levels on the 14th, 21st, and 28th days were also higher than those in the survival group ( Z=0.03, 0.26 and 0.31, respectively, all P<0.05). IL-6 and IL-8 levels reached their peaks on the 14th day, which were significantly higher than those in the survival group ( Z=0.01 and 0.02, respectively, both P<0.05), and then decreased, and the differences were all statistically significant. Conclusions:The levels of IFN-γ and IL-1β in the non-survival sepsis patients show a gradually increasing trend. The dynamic changes of IL-6 have certain significance for the prediction of disease severity and prognosis evaluation in sepsis.

OBJECTIVE: To explore the mechanism of BNIP3-mediated mitophagy in m.3635G>A related Leber's hereditary optic neuropathy (LHON). METHODS: A trans-mitochondrial cybrid cell line derived from a Chinese LHON patient carrying the m.3635G>A, diagnosed at the Eye Hospital of Wenzhou Medical University in September 2013, was selected as the study subject. A trans-mitochondrial cybrid cell line from a healthy control with an identical mitochondrial background was included as a control. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and Western blotting were employed to assess the expression of autophagy-related proteins, aiming to explore the role of BNIP3-mediated mitophagy in m.3635G>A related LHON. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2023-J-096). RESULTS: Compared with the control group, the protein expression levels of autophagy-related markers LC3 (LC3-II/LC3-I) and LAMP1 were significantly reduced in the variant group (P < 0.05). Additionally, the protein levels of macroautophagy-related proteins ATG12, ATG7, and ATG5 were also significantly decreased (P < 0.05). Compared with the control cells, the mRNA and protein expression levels of mitophagy-associated protein BNIP3 were significantly reduced in the cells of the variant group (P < 0.05). Compared with the control group, both mRNA and protein expression levels of the mitophagy-related protein BNIP3 were significantly reduced in the variant group (P < 0.05). CONCLUSION The m.3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.
Humans ; Proto-Oncogene Proteins/metabolism* ; Mitophagy/genetics* ; Membrane Proteins/metabolism* ; Optic Atrophy, Hereditary, Leber/metabolism* ; Mitochondria/metabolism* ; Cell Line ; Male

Objective To analyze the characteristics of TCM symptoms of aging in female insomnia patients;To provide syndrome differentiation evidence for clinical prevention and treatment of female aging.Methods A cross-sectional study method was used to include female insomnia patients who attended outpatient clinics at Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing Changping District Hospital of Traditional Chinese Medicine,and the Third Affiliated Hospital of Beijing University of Chinese Medicine from August 2021 to July 2024.The patients'clinical information was collected,and frequency analysis,factor analysis,and clustering analysis of the relevant clinical information of the 107 female insomnia patients were conducted,which,together with the experts'opinions,resulted in characteristics of TCM syndrome elements and syndrome distribution of aging in female insomnia patients.Results Totally 20 core items were screened and 7 common factors were obtained from the factor analysis.There were 5 types of syndrome elements of disease location associated with aging symptoms in female patients with insomnia,including heart,liver,spleen,kidney and lung;and there were 7 types of syndrome elements of disease property,including qi deficiency,yin deficiency,qi stagnation,blood deficiency,heat,phlegm,and dampness.There were 4 types of syndromes were obtained from the systematic clustering,including heart-kidney disharmony syndrome,heart-liver stagnation syndrome,spleen deficiency and qi stagnation syndrome,lung-spleen qi deficiency syndrome.Conclusion By analyzing the TCM syndrome characteristics of aging symptoms in female patients with insomnia,four types of syndromes are obtained.The heart-kidney disharmony syndrome is the common syndrome.The internal relationship between insomnia and aging process in female patients with insomnia is revealed from the perspective of pathogenesis,which can provide a research basis for the clinical practice of TCM anti-aging guided by syndrome differentiation and treatment in the future.

Objective:To explore the factors influencing the recovery of swallowing function after a brainstem hemorrhage and to construct a prediction model.Methods:Clinical data on 134 persons with dysphagia after a brainstem hemorrhage were collected retrospectively. According to their swallowing ability at discharge, the patients were divided into a swallowing recovery group and a non-recovery group. Univariate correlation analysis and multivariate logistic regression analysis were used to explore the independent factors influencing the recovery of swallowing function and to construct a prediction nomogram. The receiver operating characteristics (ROC) curves were evaluated to analyze the nomogram′s predictive value and those of the relevant influencing factors.Results:Sixty-two of the patients (46%) had recovered their swallowing function at discharge, while 72 (54%) had not. Univariate correlation analysis showed that there had been significant differences in tracheal intubation, NIHSS score, FOIS score, Barthel index and Glasgow coma scale (GCS )score between the two groups, on average. The multivariate logistic regressions showed that a low NIHSS score, a high FOIS score and a high GCS score were independent predictors of swallowing function recovery, so they were used in the prediction model. ROC curve analysis showed that the area under the curve (AUC) of the prediction model was 0.953 (95% CI: 0.902~0.982) with a sensitivity of 87% and a specificity of 93%. The model′s predictions were thus better than using an NIHSS score, GCS score or FOIS score alone. Conclusions:NIHSS score, GCS score and FOIS score can independently predict the recovery of swallowing function after a brainstem hemorrhage. A prediction model constructed using all three has good predictive power.

Objective:To explore the mechanism of BNIP3-mediated mitophagy in m. 3635G>A related Leber′s hereditary optic neuropathy (LHON).Methods:A transmitochondrial cybrid cell line derived from a Chinese LHON patient carrying the m. 3635G>A, diagnosed at the Eye Hospital of Wenzhou Medical University in September 2013, was selected as the study subject. A transmitochondrial cybrid cell line from a healthy control with an identical mitochondrial background was included as a control. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and Western blotting were employed to assess the expression of autophagy-related proteins, aiming to explore the role of BNIP3-mediated mitophagy in m. 3635G>A related LHON. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2023-J-096).Results:① Compared with the control group, the protein expression levels of autophagy-related markers LC3 (LC3-Ⅱ/LC3-Ⅰ) and LAMP1 were significantly reduced in the variant group ( P<0.05). Additionally, the protein levels of macroautophagy-related proteins ATG12, ATG7, and ATG5 were also significantly decreased ( P<0.05). ② Compared with the control cells, the mRNA and protein expression levels of mitophagy-associated protein BNIP3 were significantly reduced in the cells of the variant group ( P<0.05). Compared with the control group, both mRNA and protein expression levels of the mitophagy-related protein BNIP3 were significantly reduced in the variant group ( P<0.05). Conclusion:The m. 3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.

Objective:To explore the dual mediating effects of health belief and depression among health knowledge, social support, and health behaviors based on the capacity, opportunity, motivation-behavior (COM-B) model, and analyze the influencing factors of health behaviors in patients with ischemic stroke.Methods:This multi-center cluster sampling research recruited ischemic stroke patients ( n=1 696) who were hospitalized in neurology departments of five tertiary hospitals in Henan Province from October 2023 to October 2024. A cross-sectional investigation was conducted using the general information questionnaire, social support rating scale (SSRS), stroke prevention knowledge questionnaire(SPKQ), short form health belief model scale(SF-HBMS), health promoting lifestyle profile-Ⅱ (HPLP-Ⅱ), and patient health questionnaire-9(PHQ-9) to ultimately reveal the pathways and effect sizes among variables. Partial correlation analysis and multiple linear stepwise regression analysis were conducted to examine the relationships among social support, health knowledge, health belief, health behaviors, and depression in stroke patients by SPSS 26.0 software. Structural equation modeling was constructed using AMOS 28.0 software, and the mediating effect was tested using the Bootstrap method. Results:The scores of social support, health knowledge, health belief, and health behaviors among ischemic stroke patients were (37.46±9.94), (26.56±6.84), (75.62±12.62) and (130.79±26.27), respectively. The score of depression was 5.00 (2.00, 8.00). Health behaviors were positively correlated with health knowledge, social support, and health belief( r=0.333, 0.246, 0.267, all P<0.05), while negatively correlated with depression ( r=-0.146, P<0.05). Multiple linear stepwise regression analysis showed that health knowledge, social support, health belief, and depression were all influencing factors of health behaviors in ischemic stroke patients (all P<0.05). Health belief (effect value=0.068, 95% CI=0.048-0.093) and depression (effect value=0.009, 95% CI=0.003-0.018) both played partial mediating roles between health knowledge and health behaviors, accounting for 17.3%(0.077/0.446) of the total effect. Meanwhile, health belief (effect value=0.045, 95% CI=0.029-0.063) and depression (effect value=0.016, 95% CI=0.008-0.027) both played partial mediating roles between social support and health behaviors, accounting for 26.5%(0.061/0.230) of the total effect. Conclusion:Health knowledge and social support can not only directly influence health behaviors but also indirectly affect them through health belief and depression in patients with ischemic stroke.

Objective To investigate the effect of the Shenghua Sanjia decoction on endometrial damage after induced abortion in rats by regulating the Fas/Fas ligand(FasL)signaling pathway.Methods Fifty pregnant rats were randomly assigned to five groups:normal con-trol,model,low-and high-dose Shenghua Sanjia decoction(12.6 g/kg and 25.2 g/kg,respectively),and dydrogesterone(3 mg/kg)groups,with 10 rats in each group.In all groups except the normal control group,rats were administered 16.6 mg/kg mifepristone combined with 100 μg/kg misoprostol to establish an artificial abortion model,and the endometrial injury model was established by a mechanical injury method.After administering the respective drug intervention,enzyme-linked immunosorbent assay(ELISA)was used to measure serum levels of estrogen(E2),progesterone(P),and prolactin(PRL).Histopathological changes of the endometrium were evaluated using HE staining.Masson staining was employed to assess endometrial fibrosis,whereas TdT-mediated dUTP nick-end labeling(TUNEL)was uti-lized to detect apoptosis in the endometrial tissue.Additionally,the mRNA expression levels of the estrogen receptor(ER),progesterone receptor(PR),prolactin receptor(PR LR),vascular endothelial growth factor(VEGF),Fas,and FasL in the endometrial tissue were measu-red using real-time quantitative PCR.Finally,Western blotting was performed to analyze the protein expression levels of transforming growth factor-β(TGF-β),matrix metalloproteinase-9(MMP-9),Fas,and FasL in the endometrial tissue.Results Compared to the normal control group,the model group showed a decreased E2,P,and PRL serum levels,a reduction in the mRNA expressions of ER,PR,PRLR,and VEGF as well as decreased protein expression of MMP-9 in the endometrial tissue.However,the apoptosis rate,mRNA expression of Fas and FasL,and protein expression of TGF-β,Fas,and FasL in the endometrial tissue were all increased(P＜0.05).Lastly,the endo-metrial tissue was found to be severely damaged with the collagen fibers increased.Compared to the model group,the low-and high-dose Shenghua Sanjia decoction and dydrogesterone groups showed an increase in the serum levels of E2,P,and PRL,as well as an elevation in the mRNA expression of ER,PR,PRLR,and VEGF;similarly the protein expression of MMP-9 in the endometrial tissue was increased.However,the apoptosis rate,mRNA expression of Fas and FasL,and protein expression of TGF-β,Fas,and FasL in the endometrial tissue were all decreased(P＜0.05).Conversely,the histopathological damage of the endometrium was found to be alleviated with the collagen fibers decreased.Conclusion The Shenghua Sanjia decoction can reduce endometrial fibrosis and apoptosis,while promoting endome-trial repair after the induction of abortion in rats.The underlying mechanism may be associated with the inhibition of the Fas/FasL signa-ling pathway activity.

Objective To explore the definition and connotation of kinesiophobia in patients with heart failure,hence to provide a reference for clinical practice.Methods A systematic search was conducted on databases including CNKI,Wanfang Data,Web of Science,PubMed and Embase.Walker and Avant's concept analysis was applied to analyse the literature related to kinesiophobia in patients with heart failure.Results A total of 30 articles were included.The defining attributes of kinesiophobia in patients with heart failure were identified as emotional responses,cognitive biases,physical perceptions and avoidance behaviours.Antecedents included general demographic factors,disease-related factors,exercise self-efficacy,psychological factors and social support.Consequences included reduction in exercise adherence,decrease in physical function and increase in psychological burden.Conclusion The concept analysis of kinesiophobia in patients with heart failure can help healthcare providers with a better understanding and prevention of the kinesiophobia,and provides a reference for the researches in kinesiophobia in patients with heart failure.

BACKGROUND:The definitive cause of adolescent idiopathic scoliosis is not yet known.The search for a clinical approach to address adolescent idiopathic scoliosis is imminent.OBJECTIVE:To investigate the effect of Schroth therapy combined with core strength training on mild adolescent idiopathic scoliosis and to provide more bases for the clinical treatment of mild adolescent idiopathic scoliosis.METHODS:110 patients with mild adolescent idiopathic scoliosis attending the Department of Rehabilitation Medicine and Department of Spine Surgery of Affiliated Hospital of Nantong University from July 2022 to January 2024 were selected as the study subjects.They were divided into the trial group and the control group according to the wishes of the patients and their parents,with 55 cases in each group.The control group was observed and followed up,and the trial group underwent Schroth therapy combined with core strength training for 45 minutes a day for 24 weeks.The differences in imaging parameters,body surface indexes,three-dimensional ultrasound imaging angle,and quality of life were compared between the two groups before and after treatment.RESULTS AND CONCLUSION:(1)At 24 weeks after treatment,major curve Cobb,apical vertebral translation,and cervical lordosis were significantly improved in the trial group(P＜0.05),while there was no significant difference in the control group(P＞0.05).Major curve Cobb and apical vertebral translation in the trial group were significantly better than those in the control group(P＜0.05).(2)At 24 weeks after treatment,angle of trunk rotation in the trial group was significantly lower than that before treatment(P＜0.05),while there was no significant difference between before and after treatment in the control group(P＞0.05),and angle of trunk rotation in the trial group was significantly lower than that of the control group(P＜0.05).(3)At 24 weeks after treatment,the center of laminae angle of three-dimensional ultrasound imaging was significantly reduced in the trial group(P＜0.05),while there was no significant difference in the control group before and after treatment(P＞0.05).The center of laminae angle of three-dimensional ultrasound imaging was smaller in the trial group than that in the control group(P＜0.05).(4)At 24 weeks after treatment,in terms of the quality of life,pain dimension score in the trial group was significantly increased(P＜0.05).Both trial and control groups showed significantly higher scores in the self-image dimension compared with that before treatment(P＜0.05).Both groups had significantly lower scores in the mental health dimension compared with that before treatment(P＜0.05).In the dimensions of pain,self-image,mental health,and satisfaction,the trial group was significantly higher than the control group(P＜0.05).(5)It is indicated that Schroth therapy combined with core strength training can improve the major curve Cobb,apical vertebral translation,and cervical lordosis angle,reduce the angle of trunk rotation,decrease the center of laminae angle of three-dimensional ultrasound imaging,and improve the quality of life,and it is effective in the treatment of mild adolescent idiopathic scoliosis.