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.

Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

Objective To investigate the effect of pneumoperitoneum pressure during robotic-assisted kidney transplantation (RAKT) on the function of the transplant kidney. Methods The data of 243 kidney transplant recipients were retrospectively analyzed and divided into open kidney transplantation (OKT) group (n=105) and RAKT group (n=138). The RAKT group was further divided into 13 mmHg group (n=67) and 7 mmHg group (n=71) based on pneumoperitoneum pressure. The donor information, recipient's preoperative general data, intraoperative data, and postoperative recovery of the three groups were compared. In the RAKT group, the renal artery, segmental artery, interlobar artery, and venous flow velocity of the transplant kidney were measured using laparoscopic ultrasound. Results There was a statistically significant difference in donor types among the groups (P<0.05), while other donor information and recipient's preoperative general data showed no statistically significant differences (all P>0.05). There were no statistically significant differences in serum creatinine and complications at 30 days and 1 year postoperatively among the groups (all P>0.05). The OKT group and 7 mmHg group had more intraoperative urine output than the 13 mmHg group. Both RAKT groups had less intraoperative blood loss and shorter hospital stays than the OKT group, and longer operation times than the OKT group (all P<0.05). There were no statistically significant differences in operation time, intraoperative blood loss, and hospital stay between the two RAKT groups (all P>0.05). The vascular flow velocity of the transplant kidney decreased at 13 mmHg compared to 7 mmHg pneumoperitoneum pressure, but the differences were not statistically significant (all P>0.05). Conclusions Controllable pneumoperitoneum pressure has a limited impact on the vascular flow velocity of the transplanted kidney. RAKT is a safe and effective surgical method under appropriate pneumoperitoneum pressure, and choosing a lower pneumoperitoneum pressure is more conducive to the early recovery of renal function postoperatively.

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.

ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index （DFI） and sperm mitochondrial membrane potential （MMP） in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group （64 cases） and a control group （64 cases）. The experimental group received Yishen Tongluo prescription， while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate， sperm progressive motility （PR）， total sperm motility （PR+NP）， sperm function （sperm tail hypotonic swelling rate， sperm acrosin activity）， sperm DFI， and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study， and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study， including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% （9/61）， higher than that in the control group at 6.67% （4/60）， though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group （P<0.05）. Compared with the results before treatment， sperm PR， PR + NP， sperm tail hypotonic swelling rate， sperm acrosin activity， sperm DFI， and sperm MMP were significantly improved in both groups after treatment （P<0.05）， with greater improvements in the experimental group （P<0.05）. However， there was no significant change in sperm concentration in either group after treatment. During the study， no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility， increase spouse pregnancy rate， enhance sperm function， and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Background::Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies. However, comprehensive reports on the burden of digestive system diseases in China are lacking. Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces.Methods::This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence, mortality rate, disability-adjusted life years (DALYs), years of life disability, years of life lost, and changes in the burden of digestive diseases across Chinese provinces from 1990 to 2019. The analysis of disease burden primarily examines the characteristics of sub-disease distribution, time trends, age distribution, and sex distribution. Additionally, we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index (SDI).Results::In 2019, there were 499.2 million cases of digestive system diseases in China, resulting in 1,557,310 deaths. Stomach cancer, colon and rectal cancer, and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases. Meanwhile, cirrhosis and other chronic liver diseases, gastroesophageal reflux disease, and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases. The risk of gastric cancer sharply increases among men after the age of 40 years, leading to a significant disparity in burden between men and women. As the SDI increased, the DALYs associated with digestive system diseases in China and its provinces showed a downward trend.Conclusion::Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI.