OBJECTIVE To investigate ameliorative effects and mechanisms of two probiotics （Bacillus subtilis， Lactobacillus acidophilus） combined with Aurantii Fructus Immaturus （AFI） on functional dyspepsia （FD） in rats. METHODS Rats were randomly divided into blank group， model group， positive control group （domperidone group， 2.7 mg/kg）， AFI group （9 g/kg）， L. acidophilus group （5×107 cfu/kg）， B. subtilis group （5×107 cfu/kg）， L. acidophilus+ AFI group （L. acidophilus 5×107 cfu/kg+ AFI 9 g/kg）， and B. subtilis+AFI group （B. subtilis 5×107 cfu/kg+AFI 9 g/kg）， with 8 rats in each group. Except for the blank group， FD model was established by tail-clamping stimulation+hunger and satiety disorder+swimming exhaustion in other groups. After modeling， each group was given the corresponding drug/probiotic suspensions/physiological saline intragastrically， once a day， for 14 consecutive days. After the last medication， gastric emptying rate and the rate of propulsion of the small intestine in rats were measured； the levels of brain-gut peptide-related indicators [gastrin （GAS）， substance P （SP）， vasoactive intestinal peptide （VIP）， somatostatin （SS） and cholecystokinin （CCK）] in the serum of rats were measured. The pathological morphology of the gastric antrum tissue and duodenal tissue was observed. Cecal contents from the rats were collected for gut microbiota sequencing analysis. The protein expression levels of tyrosine kinase receptor c-Kit and stem cell factor （SCF） in the gastric antrum tissue， as well as Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor κB （NF-κB） in the duodenal tissue of the rats were detected. RESULTS Compared with the blank group， model group showed significantly lower gastric emptying rate， small intestinal propulsion rate， serum levels of GAS and SP， relative abundance of Firmicutes， Ace， Chao and Sobs indexes of the gut microbiota， and protein levels of SCF and c-Kit in gastric antrum （P＜0.05）， while serum levels of VIP， SS and CCK， relative abundance of Bacteroidetes， as well as protein expressions of TLR4， MyD88， and NF-κB， were significantly higher （P＜0.05）. The histological structure JZYC23S53） of the gastric antrum tissue appeared basically normal； however， abnormalities were observed in the duodenal structure， with a significant infiltration of inflammatory cells visible. Compared with the model group， all treatment groups significantly modulated most of the above indexes （P＜0.05）. The histological structure of the gastric antrum tissue was normal. Except for the B. subtilis group and the B. subtilis+AFI group， the pathological states of the duodenum in the remaining rats gradually recovered. Compared with each single drug group， most of above indexes in rats from each combination group showed further improvement （P＜0.05）. CONCLUSIONS The combination of AFI with two probiotics can improve gastrointestinal motility in FD rats， and the effect is superior to that of using the drugs alone. The specific underlying mechanisms may be related to the activation of the SCF/c-Kit signaling pathway and the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

AIM:To investigate the effects of skeletal muscle mass on cardiac structure and function in rats subjected to abdominal aortic constriction(AAC),and to explore its potential mechanisms.METHODS:(1)Thirty male SD rats were randomly divided into 3 groups:control(CON)group(n=10),muscular atrophy(MA)group(n=10),and muscular hypertrophy(MH)group(n=10).The rats in MA group underwent bilateral tibial nerve removal to induce MA,while those in MH group engaged in weight-bearing running to promote MH.Four weeks later,skeletal muscle sam-ples were collected,and indicators of MA and MH were assessed.(2)Another rats after modeling above were divided into 4 groups:CON group(n=10),cardiac pathological remodeling group(AAC group;n=10),MA+AAC group(n=10),and MH+AAC group(n=10).All rats,except those in CON group which underwent a sham operation,received AAC sur-gery.Four weeks after surgery,cardiac structure and function were assessed by echocardiography,while morphological changes of the soleus and gastrocnemius muscles and myocardium were evaluated by pathological staining.Serum myo-statin(MSTN)level was measured using ELISA.The mRNA expression levels of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)in the myocardium,and MSTN in the skeletal muscle and myocardium were detected by real-time PCR.RESULTS:After 4 weeks of either denervation or weight-bearing running,significant atrophy and hyper-trophy of the gastrocnemius and soleus muscles were observed in MA and MH groups,respectively,compared with CON group.However,no significant differences were noted in heart weight/body weight ratio,left ventricular end-diastolic wall thickness,ejection fraction,or other related indexes among these groups(P>0.05).In comparison to AAC group,the rats in MA+AAC group showed a significant increase in heart weight/body weight ratio and left ventricular end-diastolic an-terior wall thickness,a decrease in end-diastolic internal diameter,an increase in ejection fraction(P<0.05 or P<0.01),and exacerbated myocardial fibrosis.Conversely,in MH+AAC group,there was a significant decrease in heart weight/body weight ratio and left ventricular end-diastolic wall thickness,an increase in end-diastolic internal diameter,and a lower ejection fraction(P<0.05 or P<0.01),with reduced myocardial fibrosis.Compared with AAC group,myocardial ANP and BNP mRNA expression significantly increased in MA+AAC group and decreased in MH+AAC group(P<0.01).Additionally,soleus and gastrocnemius muscle MSTN mRNA expression,myocardial MSTN mRNA expression,and se-rum MSTN level significantly increased in MA+AAC group(P<0.01)and significantly decreased in MH+AAC group(P<0.05).CONCLUSION:Atrophic skeletal muscle exacerbated the pathological remodeling induced by AAC surgery,whereas hypertrophic skeletal muscle mitigated this remodeling.Skeletal muscle mass plays a critical role in cardiac patho-logical remodeling,with MSTN potentially regulating this process.

Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis（sJIA）.Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected，and the clinical manifestations，efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score（sJADAS）was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children（4 males and 6 females）with refractory sJIA，the average age of onset was（7.5±3.3）years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was（4.4±1.7）years，and the longest course of disease was 8.3 years. Before the application of thalidomide，all the 10 children experienced relapses（ranging from 2 to 10 times）. The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes［（10.19±3.67）×10 9/L，（8.53±2.83）×10 9/L vs.（16.11±7.81）×10 9/L， F=7.918，11.084， P=0.020，0.009］，C-reactive protein［19.13（0.38，35.21）mg/L，8.05（0.10，18.00）mg/L vs. 59.34（24.20，131.90）mg/L， F=7.030，12.731， P=0.026，0.006］，sJADAS scores［6.00（1.50，12.50）scores，3.00（0，12.50）scores vs. 20.00（11.50，28.00）scores， F=14.710，17.870， P=0.004，0.002］were decreased significantly. The doses of prednisone［0.13（0，0.45）mg/（kg·d），0.02（0，0.06）mg/（kg·d）vs. 0.42（0.16，1.47）mg/（kg·d）， F=5.890，7.623， P=0.041，0.022］were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases，and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA，and can reduce the required dose of prednisone and prolong the tocilizumab free remission.

AIM:To rapidly evaluate the effective-ness,safety and economy of dienogest in the treat-ment of endometriosis so as to provide evidence-based reference for clinical drug selection and deci-sion.METHODS:Retrieved from PubMed,Embase,Cochrane Library,CNKI,SinoMed,Wanfang and health technology assessment(HTA)organization websites,HTA report,systematic review/Meta-anal-ysis and pharmacoeconomic study were included during the inception to Sep 2023.Data extraction and quality evaluation were carried out for the lit-erature that met the inclusion and exclusion crite-ria,and the research results were summarized and analyzed qualitatively.RESULTS:Nine systematic re-view/Meta-analyses,and 2 pharmacoeconomic studies were included.The quality of Meta-analysis literatures was low,and the quality of economic re-search was good.In terms of effectiveness,com-pared with no treatment,dienogest can significant-ly reduce postoperative recurrence rate,VAS score,and improve pregnancy rate and effective rate;Di-enogest has similar therapeutic effects in terms of recurrence rate as GnRHa and COC;With regard to recurrence rate and pregnancy rate,dienogest is superior to danazol,gestrinone,and mifepristone.In terms of safety,compared with placebo,the inci-dence of vaginal bleeding and headache was signifi-cantly increased with dienogest,and there was no difference in bone loss;The incidence of vaginal bleeding caused by dienogest was significantly high-er than that of GnRHa,but the incidence of hot flashes and bone loss was lower.In terms of econo-my,dienogest has a more cost-effective advantage comparing with GnRHa,but does not have econom-ic benefits comparing with COC.CONCLUSION:Di-enogest has good effectiveness and safety in the treatment of endometriosis,and economically su-perior to GnRHa,but inferior to COC.

Objective To investigate the value of serum cell cycle protein-dependent kinase 1(CDK1)and aurora kinase A(AURKA)in the diagnosis of patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Methods A total of 50 HBV-HCC patients,50 patients with hepatitis B virus-related liver cirrhosis(HBV-LC),and 50 chronic hepatitis B(CHB)patients who were hospitalized in Department of Gastroenterology,Gansu Provincial Hospital,from June 2022 to December 2023 were enrolled,and 50 healthy individuals,matched for age and sex,who received physical examination at Physical Examination Center during the same period of time were enrolled as control group.Related data were recorded for all patients,including age,sex,complications,and the results of routine blood test,liver function,and coagulation for the first time after admission.ELISA was used to measure the serum levels of CDK1 and AURKA.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and the least significant difference Bonferroni test was used for further comparison between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.The Spearman correlation analysis was used to investigate the correlation between CDK1 and AURKA,and the receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to investigate the value of CDK1 and AURKA in the diagnosis of HBV-HCC.Results There were significant differences in liver function parameters between the HBV-HCC patients and the control group(all P<0.05);there were significant differences between the CHB group and the HBV-HCC group in albumin,Glb,direct bilirubin,aspartate aminotransferase(AST),gamma-glutamyl transpeptidase(GGT),and alkaline phosphatase(all P<0.05);there were significant differences between the HBV-LC group and the HBV-HCC group in Glb,AST,and GGT(all P<0.05).The HBV-HCC group had significantly higher serum levels of CDK1 and AURKA than the HBV-LC group,the CHB group,and the control group(all P<0.05).There was a significant positive correlation between CDK1 and AURKA in the overall study population and the HBV-HCC patients(r=0.526 6 and 0.815 2,P<0.001).With the control group as reference,CDK1 had an AUC of 0.832 3 in the diagnosis of HBV-HCC,with a sensitivity of 92.86%and a specificity of 75%,and AURKA had an AUC of 0.886 6 in the diagnosis of HCC,with a sensitivity of 95.80%and a specificity of 74%.With the CHB group as reference,CDK1 had an AUC of 0.833 3 in the diagnosis of HBV-HCC,with a sensitivity of 93.75%and a specificity of 75%,and AURKA had an AUC of 0.972 7 in the diagnosis of HBV-HCC,with a sensitivity of 95.83%and a specificity of 91.67%.With the HBV-LC group as reference,CDK1 had an AUC of 0.608 5 in the diagnosis of HBV-HCC,with a sensitivity of 66.67%and a specificity of 54.17%,and AURKA had an AUC of 0.762 2 in the diagnosis of HBV-HCC,with a sensitivity of 95.83%and a specificity of 47.92%.Conclusion The serum levels of CDK1 and AURKA increase with the progression of hepatitis B-associated chronic liver disease,and significant increases in serum CDK1 and AURKA have a certain value in the diagnosis of HBV-HCC.

Objective:To compare the similarities and differences of macrophage activation syndrome（MAS）combined with systemic juvenile idiopathic arthritis（sJIA）versus with juvenile onset systemic lupus erythematosus（JSLE）.Methods:The clinical data of 48 children with MAS admitted to the Department of Nephrology and Immunology in Children's Hospital of Hebei Province from May 2015 to January 2023 were retrospectively analyzed. The patients were divided into sJIA-MAS and JSLE-MAS group，and the clinical manifestations，laboratory indicators and treatment of the two groups were compared.Results:Among the 48 children（14 males and 34 females）with MAS，the average age of onset was 9.5（3.0，11.8）years. There were 28 cases（11males and 17 females）of sJIA-MAS and 20 cases（3 males and 17 females）of JSLE- MAS. All the 48 children with MAS had fever and hyperferinemia，and the fever with sJIA-MAS was mostly continued fever or remittent fever. Respiratory tract infection was the most common trigger in sJIA-MAS［15 cases（53.6%）］，and disease activity was the most common trigger in JSLE-MAS［13 cases（65.0%）］.Additionally，viral infections（EB virus and cytomegalovirus）were also one of the triggers in MAS［sJIA：7 cases（25%），JSLE：4 cases（20%）］.Compared with JSLE-MAS，the number of days with fever［15.0（12.0，21.0）days vs. 6.0（4.0，9.5）days， Z=-3.812， P=0.001］and the length of hospital stay［29.0（26.3，39.8）days vs.26.0（19.3，30.8）days， Z=-1.958， P=0.049］were longer in sJIA. Compared with JSLE-MAS，ALT［（685.32±561.67）U/L vs.（139.61±124.44）U/L， t=4.973， P=0.001］，AST［784.00（235.25，1 251.25）U/L vs.189.50（53.25，374.08）U/L， Z=-3.283， P=0.001］，CRP［11.48（3.56，28.89）mg/L vs.1.91（0.53，8.98）mg/L， Z=-3.200， P=0.001］，ferritin［32 167.0（12 384.8，65 963.8）μg/L vs.2 003.5（922.5，11 430.0）μg/L， Z=-4.130， P=0.001］，ferritin max/ESR min［1 353.35（355.75，4 342.53）vs.91.92（34.94，291.53）， Z=-4.120， P=0.001］were higher in sJIA.The decrease of CRP was greater in sJIA［80.04（45.64，143.71）mg/L vs.10.20（6.27，25.64）mg/L， Z=-4.433， P=0.001］.Compared with sJIA-MAS，peripheral white blood cell counting［4.05（2.90，7.73）×10 9/L vs.1.56（1.15，3.47）×10 9/L， Z=-3.577， P=0.001］and platelet counting［（162.68±92.19）×10 9/L vs.（110.10±72.99）×10 9/L， t=2.118， P=0.040］were lower in JSLE-MAS. Kidney involvement was more common in JSLE-MAS［10 cases（50%）vs.0 cases（0%）， χ 2=17.684， P=0.001］.There was no significant difference in the incidence of sJIA-MAS and JSLE-MAS meeting the criteria of hemophagocytic lymphohistiocytosis［6 cases（21.4%）vs.5 cases（25.0%）， χ 2=0.084， P=0.772］. Conclusion:Compared with JSLE-MAS，sJIA-MAS is more dangerous and difficult to control，while JSLE-MAS involves more organs，among which the blood system and kidney are more common.

Hepatic fibrosis characterized by various chronic liver injuries can lead to abnormal activation of hepatic stellate cells， unbalanced production and degradation of extracellular matrix proteins， and excessive deposition that destroys the normal structure of the liver. The aggravated liver fibrosis can cause irreversible cirrhosis and hepatocellular carcinoma， becoming a great challenge to the global health. Ferroptosis is a new form of iron-dependent cell death discovered in recent years， which mainly involves abnormal iron metabolism， lipid peroxide accumulation， and weakening of the antioxidant defense system. A number of studies have reported that inducing ferroptosis in hepatic stellate cells or alleviating ferroptosis in the liver can ameliorate liver fibrosis and reduce liver injury. Chinese medicine widely applied in the treatment of chronic liver diseases has demonstrated good safety， wide therapeutic effects， and easy access compared with Western medicine. Therefore， The intervention of hepatic stellate cells or hepatic ferroptosis by Chinese medicine may be a new direction for the prevention and treatment of liver fibrosis in the future. This paper summarized the various regulatory mechanisms of ferroptosis and expounded how ferroptosis affected the progression of liver fibrosis， providing theoretical support for the prevention and treatment of liver fibrosis with Chinese medicine in the future.

Objective To observe the effect of transcutaneous electrical acupoint stimulation(TEAS)on circulation depression in patients underwent thoracoscopic radical resection of lung cancer under general anesthesia combined with thoracic paravertebral block(TPVB).Methods A total of 150 patients from Octomber 2021 to May 2022,58 males and 92 females,aged 19-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,underwent thoracoscopic radical resection of lung cancer under general anesthesia combined with TPVB were enrolled.According to random number table method,the patients were divided into two groups:the TEAS group and the control group,75 patients in each group.In the TEAS group,transcutaneous electrical acupoint stimulation was performed at Hegu,Neiguan,and Zusanli 30 minutes be-fore induction until the end of operation.In the control group,the electrodes were only connected at the same time point without electrical stimulation.HR,SBP,DBP,MAP,and BIS were recorded before stimu-lation(T0),10 minutes after TPVB(T1),the time of skin incision(T2),30 minutes after operation star-ted(T3),60 minutes after operation started(T4),the end of operation(T5),and 30 minutes after opera-tion(T6).The incidences of bradycardia,tachycardia,hypotension,and hypertension,and the usages of vasoactive drugs during operation were recorded.The dosages of propofol,sufentanil,and remifentanil in the operation were recorded.The VAS pain score 1,2,and 7 days after operation,the usages of analgesics used within 7 days after operation,postoperative adverse effects such as nausea and vomiting,dizziness,chest tightness,and shortness of breath,and the length of hospital stay were recorded.Results Compared with the control group,intraoperative infusion volume,incidence of hypotension,hypertension,and circulation depression,the usages of deoxyepinephrine,ephedrine,norepinephrine,and urapidil intraoperation,VAS pain scores 1 and 2 days after operation,and the usage of analgesics within 7 days after operation were sig-nificantly decreased(P＜0.05),length of hospital stay was significantly shortened(P＜0.05),SBP,DBP,and MAP were significantly increased at T1(P＜0.05),the dosagesof propofol,sufentanil,and remifentanil were significantly decreased in the TEAS group(P＜0.05).There were no significantly differ-ences of nausea and vomiting,dizziness,and shortness of breath between the two groups.Conclusion TEAS can improve the circulation depression,and reduce the incidences of intraoperative hypotension and hypertension,decrease the dosages of anesthetics and the rate of using vasoactive drugs during operation,improve early postoperative acute pain and shorten the length of hospital stay in patients undergoing thoraco-scopic radical resection of lung cancer under general anesthesia combined with TPVB.

Objective To observe the effect of neuromuscular electrical stimulation on bone angiogene-sis and osteoporosis induced by denervation in sarcopenia osteoporosis rats,and explore the correlation of the miRNA expression level in circulating extracellular vesicles to bone angiogenesis and osteoporo-sis.Methods Ten-week-old male Sprague-Dawley rats were randomly divided into a sham operation control group(con,n=8),a double leg tibial nerve loss group(DD,n=8)and a double leg tibial nerve loss + right leg electrical stimulation group(D+ES,n=8).The tibial nerve of both legs was re-moved in DD and D+ES groups,and one week later the D+ES group received 8-week neuromuscular electrical stimulation.Samples were taken 24 hours after the last stimulation.Trabecular bone parame-ters were detected using micro-CT and its morphology was observed using hematoxylin and eosin(HE)staining.Immunohistochemical staining was used to identify the vascular markers platelet endothe-lial cell adhesion molecule-1(PECAM-1/CD31)and vascular endothelial growth factor A(VEGFA).Moreover,plasma exosomes were extracted and purified,and the vesicles were identified by electron microscopy,nanoparticle tracking analysis(NTA)and Western blotting.Meanwhile,the real time PCR was used to determine the expression of myogenic miR-1,miR-133a,miR-133b and miR-206 in exo-somes.Results(1)Compared with the CON group,the volume and weight of gastrocnemius and sole-us muscles in the DD group reduced significantly(P＜0.001),and the tibial trabecular bone parameters changed pathologically.After 8-week stimulation,compared with the DD group,the volume and weight of gastrocnemius and soleus muscles in D+ES group increased significantly(P＜0.05),and tibial trabecular bone parameters improved significantly.(2)The immunohistochemical staining results indicat-ed that,compared with CON group,the expression of CD31 and VEGFA in the tibia of DD group re-duced significantly,while that of the D+ES group increased significantly compared with DD group.(3)The results of NTA showed that,compared with CON group,the concentration of circulating extra-cellular vesicles in the DD group decreased significantly(P＜0.001),and the expression of miR-1,miR-133a,miR-133b and miR-206 in exosomes increased significantly(P＜0.05,P＜0.01,P＜0.05,P＜0.05 respectively).Compared with the DD group,the concentration of circulating exosomes in D+ES group increased significantly(P＜0.05),and the expression of the above four miRNAs decreased signifi-cantly(P＜0.05 for all).Conclusion Tibial nerve denervation can successfully establish the model of sar-copenia osteoporosis and neuromuscular electrical stimulation significantly relieves such denervation in-duced changes.Moreover,electrical stimulation also significantly increases the concentration of circulat-ing exosomes,and the expression of myogenic miRNAs carried by them,which suggests that the latter may be related to bone angiogenesis and the progression of osteoporosis.