Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*

OBJECTIVE: To compare the clinical efficacy and complication rates of staged open reduction internal fixation (ORIF) and external fixation combined with limited internal fixation (EFLIF) in the treatment of high-energy Pilon fractures. METHODS: A retrospective selection was conducted on 78 patients diagnosed with high-energy tibial Pilon fractures who received treatment between January 2021 and October 2023. These patients were categorized into the staged ORIF group and the EFLIF group according to their respective treatment protocols. The staged ORIF group comprised 48 patients, including 29 males and 19 females, aged from 33 to 53 years old with a mean age of (43.25±4.67) years old. The time from injury to treatment averaged (6.54±2.21) hours. All patients received staged ORIF treatment. The EFLIF Group consisted of 30 patients, including 18 males and 12 females, aged from 36 to 54 years old with a mean age of (43.37±3.24) years old. The time from injury to treatment averaged (6.87±1.96) hours. All patients received EFLIF treatment. The recovery of ankle joint function, fracture reduction quality, fracture healing time, and surgical-related indicators between two groups were observed and compared six months after surgery. Additionally, the postoperative complications of the two groups were recorded. RESULTS: Both groups of patients were followed up and the duration ranged from 6 to 12 months, with an average of (8.97±1.26) months. At 6-month postoperative follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) score in the ORIF group was (83.15±20.93), which did not show a statistically significant difference compared to the EFLIF group (81.88±20.67), P>0.05. The excellent and good rate of fracture reduction in the staged ORIF group was 33.33% (16/48), which did not show a statistically significant difference compared to the EFLIF group (30.00%, 9/30), P>0.05. The hospitalization duration and fracture healing time in the staged ORIF group were (16.57±1.25) days and (12.14±1.15) weeks, respectively. When compared to the EFLIF group, which demonstrated a hospitalization duration of (15.97±2.16 ) days and a fracture healing time of (12.36±1.17) weeks, no statistically significant differences were observed (P>0.05). The intraoperative blood loss in the staged ORIF group was (76.54±11.65) ml, which was significantly higher than that in the EFLIF group (70.15±10.29) ml, and the difference was statistically significant (P<0.05). The incidence of superficial tissue infection was 2.08%(1/48), which was significantly lower than that observed in the EFLIF group at 16.67% (5/30), and this difference was statistically significant (P<0.05). CONCLUSION Both staged ORIF and EFLIF were effective treatment options for high-energy closed Pilon fractures of the tibia. However, regarding the prevention of superficial tissue infection, staged ORIF demonstrates superior risk control compared to EFLIF.
Humans ; Male ; Female ; Middle Aged ; Adult ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; External Fixators ; Open Fracture Reduction/methods* ; Treatment Outcome

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-

Aim To investigate the regulatory effects of 3-bromopyruvate (3-BrPA) on apoptosis and autophagy of fibroblast-like synoviocytes (FLS) in rats based on AMPK/mTOR signaling pathway and the underlying mechanism. Methods FLS of rats in vitro were cultured and induced by tumor necrosis factor-α (TNF-α) to construct a model of rheumatoid arthritis (R A). MTT assay was used to explore the optimal concentration of TNF-α and 3 -BrPA for induction and treatment of FLS. The effects of 3-BrPA on the migration and invasion of FLS were detected by Wound healing assay and Transwell assay. The apoptosis of FLS was tested by flow cytometry and mitochondrial membrane potential assay kit (JC-1). Moreover, FLS autophagic flux was detected by mCherry-EGFP-LC3B-overexpressed plasmids, and the expression of apoptosis/autophagy-related proteins as well as AMPK/mTOR pathway-related proteins were detected by Western blot. Results 3-BrPA (15 μmol • L) significantly inhibited the proliferation, migration, and invasion of FLS stimulated by TNF-a (25 μg • L

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

ObjectiveTo investigate the dynamic change of monocyte-derived macrophages （MDMs） in chronic hepatitis B （CHB） during the treatment by ETV or TDF， and the association between the polarization of monocyte-derived macrophages （MDMs） and HBV DNA， HBeAg in CHB. MethodsPeripheral blood of 101 patients with chronic hepatitis B and 20 healthy donors were enrolled. MDMs were purified from 86 patients with CHB and 12 healthy donors by peripheral blood mononuclear cell （PBMC）. Flow cytometry was use to analyze the expression of specific markers on polarized macrophages to further evaluate the polarization of MDMs （M1/M2 MDMs）， including CD80， HLA-DR， CD163 and CD206. Additionally， qPCR was used to evaluate the mRNA expression of inflammatory factors of MDMs in 15 patients with chronic hepatitis B and 8 healthy controls. ResultsThe proportion of CD163⁺CD206⁺MDMs （M2 MDMs） were reduced in patients with CHB （P = 0.030）， compared with healthy controls. Correspondingly， the mRNA expression of anti-inflammatory factor， IL-10， decreased significantly （P = 0.040）. With the progress of nucleos（t）ide analogs （NAs） therapy， the proportion of CD163⁺CD206⁺MDMs （M2 MDMs） increased gradually （P < 0.001）， while the proportion of CD80⁺HLA-DR⁺MDMs （M1 MDMs） decreased gradually （P = 0.005）. In addition， M2 MDMs were negatively associated with both HBeAg （P = 0.019）， HBV DNA （P = 0.002）， AST （P = 0.048） and ALT （P = 0.030） in patients with CHB. ROC curve analysis showed that CD163⁺CD206⁺MDMs （M2 MDMs） had high predicting value for the virologic response of CHB during NA therapy， and could be used to predict undetectable HBV DNA ［ROC 95％CI： 0.705 （0.594，0.815）］ and HBeAg seroconversion ［ROC 95％CI： 0.740 （0.634，0.847）］. ConclusionsThere are dynamic changes of MDMs polarization in patients with CHB during NA therapy， and the negative correlation between the proportion of M2 MDMs and HBV DNA， HBeAg indicates that M2 MDMs could have a high predicting value in the virologic response of CHB during NA therapy.

Objective:To investigate the protective effect of quercetin （Qu） on articular cartilage of knee osteoarthritis and its mechanism by inhibiting p38 mitogen activated protein kinase （MAPK） signaling pathway. Method:Through the network pharmacology technology，we scientifically predicted and analyzed the target factors and signal pathways of Qu in the protection of articular cartilage in patients with osteoarthritis. We selected a prediction pathway closely related to osteoarthritis and validated it by cell experiment in vitro. The best intervention concentration of the drug was selected by cell counting kit-8 （CCK-8） method. The osteoarthritis and its closely related inflammatory factors interleukin（IL）-1β and tumor necrosis factor（TNF）-α were detected by enzyme linked immunosorbent assay（ELISA）. The expression of related mRNA and protein in p38 signal pathway after Qu intervention were detected by quantitative real time polymerase chain reaction（Real-time PCR） and Western blot. Result:It was predicted that MAPK signal pathway was closely related to osteoarthritis by network pharmacology，and p38 MAPK pathway，which was most closely related to osteoarthritis，was selected for study. The results showed that 100 μmol·L^-1 Qu had the most obvious effect in decreasing the expression of related inflammatory factors，inhibited the expression of p38，phosphorylated（p）-p38，matrix metalloproteinase-13（MMP-13），A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-4（ADAMTS-4） in the pathway，and promoted the expression of CollagenⅡ. Conclusion:Qu could decrease the expression of cartilage inflammatory factors in the prevention and treatment of osteoarthritis，and the effect can be well developed by intervening and inhibiting p38 MAPK pathway related factor expression level. All the results show that Qu can decrease osteoarthritis inflammatory factors and protect articular cartilage in patients with osteoarthritis.

Objective To systematically analyze the framework and core content of physical activity inclusive school health policies. Methods This study conducted systematic content analysis of key messages of WHO key documents related to physical activity and school health services, and constructed policy and research framework. WHO's key policy documents in the field of school health included: Making Every School a Health-Promoting School Implementation Guidelines, WHO Guidelines on School Health Services, and the Global Criteria and Indicators for Making Every School a Health-Promoting School, and the key documents in the field of physical activity mainly include Global Action Plan for Physical Activity Promotion 2018-2030: Strengthening Physical Activity for a Healthy World, and WHO Guidelines on Physical Activity and Sedentary Behavior (Children and adolescents). Results Physical activity, as a health strategy and development strategy, is one of the most important tools for achieving health-promoting schools. In the area of health and education, the key to building health-promoting schools is to focus on child functioning and development, with the goal of promoting healthy inclusion and equity in schools. In the school setting, physical activity for children and adolescents is integrated into the school health service continuum with a focus on health promotion. At the macro level, the state and relevant authorities should establish a strategic structure and strategic planning for the integration of physical activity into the school health service system. At the meso level, educational institutions should develop and improve school health service policies and programs, and improve school health service tools based on the requirements of WHO school health service guidelines. Child health services are achieved through the provision of high-quality physical education programs and after-school physical activities. At the micro level, guided by global standards for building health-promoting schools, physical activity is promoted in the form of lessons and activities for healthy child development. Integrating physical activity into the school health service system can be done in six areas: school health leadership and governance, school infrastructure funding, school health service delivery that supports physical activity, human resources for school health, school health-related medicine and technology, and school health information system. We need to implement health-promoting school policies, strengthen multi-level school leadership and governance, raise the necessary funds to develop human resources adapted to the construction of health-promoting schools and build programs to support physical activity. Conclusion School health service is an important area for promoting children's health and achieving the UN 2030 Sustainable Development Goals, and physical activity is an important strategy of school health services. Policy documents issued by WHO construct the integration of physical activity into the policy framework of the school health service system, of which the core component is to integrate physical activity into the health-promoting school with educational and physical activity approaches. According to the WHO six building blocks of health service system, the integration of physical activity into the school health requires strengthening school health leadership and governance, improving school infrastructure financing, developing school health human resources, developing school-based health-related medical technologies, and establishing a health information system for sharing student health data.

Objective To explore the theories, content and approaches of integrating physical activity in children's eye health service system in the context of health services. Methods From the perspectives of six building blocks of WHO health system, namely, leadership and governance, financing, human resources for health, service delivery, medical technology, and health information system, we analyzed the policy framework and key contents related to school-based eye health and physical activity, and explored how to promote the implementation of physical activity into the school-based eye health service system, and the integration of physical activity into the eye health continuum: prevention, intervention, rehabilitation, and health promotion. Results In perspective of health system, the integration of physical activity into school-based eye health services should be in accordance with the five principles of cross-cutting health services, namely, universal accessibility and equity, human rights, evidence-based, life-span, and empowerment. According to the World Vision Report, WHO advocates to build a person-centered eye health service system, and person-centeredness is the core concept of the new model of school-based eye health services and physical activity integration. WHO advocates a school-based approach to education and physical activity in health-promoting schools to promote student health, physical activity as a preventive, interventional, rehabilitation and health promotive measure related to children's eye health, and vigorously train professionals within schools who have knowledge and skills related to physical activity and eye health, build an information system on physical activity and children's eye health, and promote the integration of physical activity into the school-based eye health service system. Conclusion Physical activity is an important measure to promote children's eye health and an important component to achieve a person-centered eye health service system. Based on the six building blocks of the WHO health service system, a school-based eye health service that integrates a theoretical and methodological system of physical activity is constructed, requiring the provision of health promotion methods such as education and physical activity in the school setting, to enhance leadership and governance of eye health services based on educational and physical activity approaches in the school setting, establish new funding mechanisms, provide financial security, develop human resources related to physical activity for eye health, improve related service delivery systems, develop high-quality physical activity intervention eye health techniques and equipment, and integrate information on children's physical activity and eye health into school health information systems to achieve children's eye health and promote their physical and mental development.

OBJECTIVE: Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19. METHODS: A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored. RESULTS: COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3 CONCLUSION Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3
Adult ; Antiviral Agents/therapeutic use* ; COVID-19/pathology* ; Capsules ; DNA, Viral/analysis* ; Drugs, Chinese Herbal/therapeutic use* ; Feces/virology* ; Female ; Humans ; Length of Stay ; Lymphocyte Count ; Male ; Medicine, Chinese Traditional/methods* ; Middle Aged ; Retrospective Studies ; SARS-CoV-2/genetics* ; Severity of Illness Index ; Treatment Outcome ; Young Adult