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.

OBJECTIVE To construct and evaluate nomogram prediction model for refractory chemotherapy-induced nausea and vomiting （CINV）. METHODS The data of malignant tumor patients who received chemotherapy at the Third People’s Hospital of Zhengzhou from January 2017 to December 2023 were collected. These patients were categorized into the occurrence group and the non-occurrence group according to the occurrence of refractory CINV. Multivariate Logistic regression analysis was employed to screen predictive factors for refractory CINV and constructing a nomogram prediction model. Model performance was assessed via receiver operating characteristic curve analysis. Model calibration was evaluated using Bootstrap resampling. Decision curve analysis （DCA） was used to determine the clinical net benefit of three strategies under different risk thresholds. Clinical impact curves were utilized to assess the clinical value of the model at different risk thresholds. Shapley additive explanations （SHAP） analysis was performed to evaluate individual factor contributions to the predictive model. RESULTS A total of 388 patients were included， with 219 experiencing refractory CINV. Multivariate Logistic regression identified 11 predictive factors for refractory CINV， including gastrointestinal disease history， anticipated nausea and vomiting， chemotherapy-induced emetic risk classification， and electrolyte levels， etc. The model’s area under the curve was 0.80 [95% confidence interval （0.76， 0.84）]， with a mean error of 0.036. DCA demonstrated the prediction model had higher clinical net benefit when the risk threshold was between 0.05 and 0.85. SHAP analysis revealed the top three predictive factors as gastrointestinal disease history （0.924）， chemotherapy- induced emetic risk classification （0.866）， and electrolyte levels （0.581）. CONCLUSIONS Eleven factors， including gastrointestinal disease history， anticipated nausea and vomiting， chemotherapy-induced emetic risk classification， and electrolyte levels， are identified as predictors of refractory CINV. The model based on these factors has good predictive ability， which can be used to predict the risk of refractory CINV.

ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.

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 study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

Objective To compare seminal carnitine levels between normal males and asthenozoospermic patients,evaluate its correla-tion with progressive motility(PR)of sperm,and observe the effects of exogenous carnitine supplementation on asthenozoospermic pa-tients.Methods Semen samples were collected from 511 normal fertile males and asthenozoospermic patients.Seminal was measured using a fixed-time assay kit and the levels of carnitine were compared between the two groups.The consistency between seminal carni-tine and PR was assessed.Additionally,77 asthenozoospermic patients received L-carnitine(1 g/time,3 times/day,30 days/course).The levels of seminal carnitine and PR alteration pre-and post-treatment were monitored.Results The seminal L-carnitine level in the patients with asthenospermia([194.34±65.41]μmol/L)was significantly lower than that in normal fertile males([405.43±72.12]μmol/L)(P＜0.01).When the seminal L-carnitine level ≥325 μmol/L was set as the threshold,the statistical results showed that Kappa value was 0.81,with a diagnostic coincidence rate of 93.74％.After one course of administration of L-carnitine,the concentra-tion of seminal L-carnitine([356.03±84.87]μmol/L)and PR([32.69±8.35]％)were significantly higher those that before treat-ment([183.61±79.54]μmol/L and[16.56±7.74]％,P＜0.01).Conclusion The seminal carnitine assay kit could be used for ac-curate and high-throughput quantification of clinical samples,facilitating asthenozoospermia diagnosis and therapeutic efficacy evalua-tion.Exogenous carnitine supplementation may elevate seminal carnitine levels and sperm motility in asthenozoospermic patients and po-tentially improve their fertility.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.