BACKGROUND:In recent years,improving the health of skeletal muscles through exercise has become an important research concern for scholars.Appropriate exercise has a positive effect on skeletal muscles.Among them,how to activate the sphingosine kinase1(SphK1)/sphingosine-1-phase(S1P)/sphingosine-1-phase receptor2(S1PR2)signaling pathway during exercise so as to improve the health of skeletal muscles is receiving attention from researchers. OBJECTIVE:To investigate how exercise improves the health of skeletal muscles through the SphK1/S1P/S1PR2 signaling pathway,and to explore new methods for treating related muscle diseases in order to improve human skeletal muscle health. METHODS:The first author searched for relevant literature from the establishment of the database to the present in the Web of Science,PubMed,CNKI,WanFang,and VIP databases.The search terms were"signaling pathway,SphK1,S1P,S1PR2,skeletal muscle,satellite cell,myogenesis,exercise"in Chinese and English.Finally,69 articles were included for review and analysis. RESULTS AND CONCLUSION:The SphK1/S1P/S1PR2 signaling pathway is a complex regulatory network that triggers downstream signal transduction processes by SphK1 to catalyze the interaction between S1P and receptors such as S1PR2,thereby regulating multiple biological functions of cells,tissues,organs,and systems.The SphK1/S1P/S1PR2 signaling pathway can regulate satellite cell proliferation and myoblast differentiation,improving myogenesis.The physiological basis of the SphK1/S1P/S1PR2 signaling pathway and the potential impact of exercise on it were analyzed through literature research.Acute aerobic exercise can increase the expression of SphK1 in skeletal muscle.Both human and animal studies have confirmed that acute and long-term exercise can increase the expression of S1P in skeletal muscle.In addition,studies have shown that long-term resistance exercise can increase the expression of S1PR2 in skeletal muscle.Some experimental results indicate that acute and long-term exercise have no significant effect on muscle or blood S1P levels,and the reason for different results may be due to different research subjects,methods,intensities,and frequencies selected,while the specific mechanism is not yet clear.Research suggests that exercise can promote the expression of the SphK1/S1P/S1PR2 signaling pathway in skeletal muscle and regulate downstream related signaling pathways.Research on this signaling pathway may provide new strategies and methods for the treatment of skeletal muscle diseases,thereby improving skeletal muscle health.In the future,we should deepen the research on the association between SphK1/S1P/S1PR2 signaling pathway and skeletal muscle health,further reveal its regulatory relationship with satellite cells and myoblasts as well as its interactions with the upstream and downstream pathways,explore its clinical application value,take into account the changes of this pathway when formulating the rehabilitation program,explore the specific mechanisms by which different types of exercise affect the SphK1/S1P/S1PR2 signaling pathway in skeletal muscles,and use the SphK1/S1P/S1PR2 signaling pathway as a potential therapeutic target for diseases.Further development and application of human muscle models should be developed to improve research depth and accuracy.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

BACKGROUND:Exercise is an effective method for preventing and treating osteoporosis,but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE:To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats,and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS:A rat model of postmenopausal osteoporosis was established,and a 24-week moderate-intensity exercise was used for intervention.After the experiment,serum estradiol levels were measured by ELISA,and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT.The biomechanical indicators of the tibia were tested by a three-point bending test.Autophagosomes were observed by transmission electron microscopy.The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION:The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group(P＜0.01).The body mass of rats in each group increased,and the order was the ovariectomized group＞the ovariectomized+exercise group＞the sham-operation group＞the sham-operation+exercise group.The bone mineral density and bone mass of rats in all groups significantly increased(P＜0.01),but the increase in the ovariectomized group was significantly lower than that of the other groups,and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group.Compared with the sham-operation group,the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased(P＜0.01),while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased(P＜0.01).Compared with the ovariectomized+exercise group,the ovariectomized group showed significantly lower bone volume fraction,number of trabeculae,and bone mineral density of cancellous bone(P＜0.05),extremely significantly lower trabecular thickness(P＜0.01),and significantly higher mean trabecular pattern factor,trabecular separation,and structural model index(P＜0.01).Compared with the ovariectomized group,the LC3-Ⅱ/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group(P＜0.05).Compared with the sham-operation and ovariectomized groups,the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups,respectively.To conclude,moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels.

Objective:To compare the effects of high-power and conventional power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation, postoperative troponin levels, and atrial fibrillation recurrence.Methods:A retrospective selection was conducted on 105 patients with paroxysmal atrial fibrillation admitted to the Baoding NO.1 Central Hospital from January 2017 to December 2020. According to different treatment methods, they were divided into a high-power ablation group of 52 cases and a conventional power ablation group of 53 cases. The intraoperative rate of single circle acute pulmonary vein isolation, the recovery of electrical conduction after acute pulmonary vein isolation, and the location and number of points that need to be added were compared between the two groups; At the same time, two groups were compared in terms of surgical time, ablation time, surgical radiation exposure time and radiation dose, intraoperative complications postoperative cardiac troponin levels at 12 hours, and recurrence of atrial fibrillation within 1 year after ablation.Results:The intraoperative single loop pulmonary vein isolation rate and postoperative troponin levels in the high-power atrial fibrillation ablation group were higher than those in the conventional atrial fibrillation ablation group (all P<0.05). The surgical time, ablation time, and the number of sites and points that need to be added during surgery were less than those in the conventional atrial fibrillation ablation group (all P<0.05). There was no statistically significant difference in the incidence of intraoperative complications and postoperative atrial fibrillation recurrence between the two groups (all P>0.05). Conclusions:High power atrial fibrillation ablation has a higher single loop acute pulmonary vein isolation rate, fewer patch sites and points, shorter surgical time, and greater ablation damage compared to conventional ablation, and the clinical efficacy of the two groups is similar after surgery.

Taking chronic atrophic gastritis （CAG） as an example， the frontier technologies in data science have been introduced into the inheritance， innovation and development of traditional Chinese medicine （TCM）， providing reference for conducting real-world clinical research on specialized diseases of TCM. This paper put forward the construction of CAG data science system by elaborating the connotation of data science and its application value in TCM， and discussed the path to build CAG data science system， namely through "data acquisition-knowledge expression-knowledge reasoning" to establish CAG database， knowledge base and develop diagnosis platform differentiating diseases and syndromes. Besides， this paper analyzed the prospects of CAG data science in improving data governance ability and knowledge discovery efficiency， deepening the level of knowledge sharing， promoting interdisciplinary integration， and strengthening the integration process of industry， academia and research.

Objective:To investigate the effect and molecular mechanism of miR-15a-5p regulation Wnt signaling pathway in PQ-induced pulmonary fibrosis.Methods:The PQ-induced 16HBE cell model was constructed, high-throughput miRNA chip and RT-qPCR were used to screen for miR-15a-5p with significant differences. The experimental groups were as follows: NC group (normal control);no special treatment; PQ group: 50 μmol/L PQ treated cells for 72 h; miR-15a-5p group: 16HBE stable cell lines transfected with miR-15a-5p overexpressing lentivirus; miR-15a-5p+PQ group: Stable cell lines were treated with 50 μmol/L PQ for 72 h. The expression of Wnt pathway-related genes Wnt3α and β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA, epithelial marker genes Occludin and CK18 were detected by RT-qPCR and Western blot. The mice model of PQ-induced pulmonary fibrosis was constructed, and the protein expression and lung tissue injury were detected by Western blot, HE staining and immunohistochemistry. Data were expressed as mean ± standard deviation, and independent sample t-test was used to analyze the data between the two groups. Results:The expressions of Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly up-regulated in cell injury models ( P<0.05), the epithelial cell marker genes Occludin and CK18 significantly down-regulated ( P<0.05), overexpression of miR-15a-5p could inhibit the expression of Wnt3α and alleviated the EMT induced by PQ. In animal models, Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly increased ( P<0.01), the structure of lung tissue was disordered and fibrosis occurred, overexpression of miR-15a-5p inhibited the expression of Wnt3α protein ( P<0.05) and ameliorated lung tissue injury. Conclusions:miR-15a-5p ameliorates PQ-induced lung injury by modulating the Wnt3α/β-catenin signaling pathway, thereby inhibiting the development of pulmonary fibrosis.

Objective:To explore the protective mechanism of Xuebijing injection (referred to as Xuebijing) on sepsis-associated acute respiratory distress syndrome (ARDS).Methods:① Animal experiments: 100 mice were randomly(random number) divided into 4 groups, including sham operation (Sham) group, cecal ligation and puncture (CLP) group, CLP+low-dose Xuebijing (L-XBJ) group, and CLP+high-dose Xuebijing (H-XBJ) group. The survival rate, lung histological changes, lung wet/dry (W/D) ratio, cell count and protein concentration in bronchoalveolar lavage fluids (BALF), inflammatory factors levels in serum, oxidative stress indicators, cell apoptosis, and key proteins of HIF-1α/p38 MAPK/NF-κB signaling pathway were measured. ② Cell experiments: Mouse alveolar macrophages (MH-S) were cultured in vitro and divided into 6 groups, including control (Con) group, lipopolysaccharide (LPS) group, LPS+L-XBJ group, and LPS+H-XBJ group, LPS+H-XBJ+ dimethyloxallyl glycine (DMOG, HIF-1α activator) group, LPS+H-XBJ+ 2-methoxyestradiol (2ME2, HIF-1α inhibitor) group. The effects of Xuebijing on inflammatory factors, oxidative stress, and cell apoptosis and their relationship with HIF-1α/p38 MAPK/NF-κB signaling pathway were detected.Results:Xuebijing increased the survival rate of mice with sepsis-associated ARDS, relieved lung tissue damage [lung injury score: CLP group (8.778±0.588), CLP+L-XBJ group (5.833±0.310), and CLP+H-XBJ group (4.750±0.246)], alleviated lung W/D ratio, and decreased pneumonia cell infiltration and protein exudation (all P<0.05). Additionally, Xuebijing treatment also diminished the expression of inflammatory factors (TNF-α, IL-1β, and IL-6), intracellular reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) formation, superoxide dismutase (SOD) depletion, and cell apoptosis in LPS-induced MH-S cells and CLP-induced sepsis-associated ARDS mice (all P<0.05). Furthermore, mechanistic investigation further clarified the effects of Xuebijing on inflammation, oxidative stress, and cell apoptosis through the HIF-1α/p38 MAPK/NF-κB signaling pathway. Conclusions:Xuebijing can exert anti-inflammatory, anti-oxidative, and anti-apoptotic effects by suppressing the HIF-1α/p38 MAPK/NF-κB signaling pathway, thereby conferring protection against sepsis-associated ARDS.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.