ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS） coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema. MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene （DNCB）， and it was randomly divided into the normal group， the model group， the medium- and high-dose groups of Ermiao Situ decoction （3.40 g·kg^-1 and 6.80 g·kg^-1）， and the prednisone acetate group （2.51 mg·kg^-1）， with eight rats in each group， totalling 46 rats， of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS， combined with network pharmacology for the prediction of key components， core targets， and signaling pathways， and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin （GAS）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured by enzyme-linked immunosorbent assay （ELISA）. Interleukin-6 （IL-6）， Janus kinase 1 （JAK1）， phosphorylated （p）-JAK1， signal transduction and activation of transcription factor 3 （STAT3）， and p-STAT3 protein expression level was determined by Western bolt. ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats， which were predicted to act on 198 targets for the treatment of damp-heat eczema， among which the key ingredients included rhodopsin， huangpai alkaloids， and quercetin， and the main core targets included STAT3， tumor necrosis factor （TNF）， and IL-6， which were mainly involved in the cancer signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase （Akt） signaling pathway， T helper 17 （Th17） cell differentiation signaling pathway， and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6， JAK1， and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group， rats in the model group were depressed. They had loose hair， loose stools， epidermal oozing， vesiculation， and generation of thick scabs in the form of scales， decreased body weight， increased anus temperature and water intake， and increased indexes of the spleen， thymus gland， and stomach （P<0.05， P<0.01）， and the lesion tissue could be seen to be hyperkeratotic， with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned， deficient， and structurally disorganized， and obvious inflammatory cell aggregation was seen. The levels of GAS， IL-4， and IL-13 in serum were significantly reduced （P<0.05， P<0.01）， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the lesion tissue were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， rats in each administration group had stable mental states， formed feces， a clean perianal area， and basically normal epidermis. Only a small amount of scaly scabs existed， and the rats had body weight increased， with decreased anal temperature and water intake， as well as decreased spleen， thymus， and gastric indexes （P<0.05， P<0.01）. Epidermal thickness was decreased， and epidermal and dermal separation boundaries were obvious， but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased， and the structure was restored to varying degrees. The levels of GAS， IL-4， and IL-13 content in the serum of rats were increased to varying degrees， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the dermal lesion tissue were significantly decreased （P<0.05， P<0.01）. ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

OBJECTIVE To evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system. METHODS Based on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS The results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%. CONCLUSIONS When using 3 times China’s 2022 GDP per capita （257 094 yuan/ QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost- effective.

BACKGROUND:As a routine method after lumbar spine surgery,a drainage tube is convenient for postoperative bleeding drainage and management,and there is still no consensus on the choice of postoperative removal time for short-segment lumbar spine surgery with less risk. OBJECTIVE:To explore the effect of different drainage times on early clinical efficacy after short-segment lumbar fusion. METHODS:A prospective randomized controlled study was performed on 220 patients in the Affiliated Hospital of Southwest Medical University who underwent posterior lumbar interbody fusion for lumbar degenerative diseases from March 2017 to April 2021.According to the different drainage times,the patients were randomly divided into removal on the second day after operation(group A),removal on the third day after operation(group B),and removal after the observation method 24-hour drainage volume<30 mL(group C).The perioperative indicators and follow-up results of the three groups of patients were observed and compared. RESULTS AND CONCLUSION:(1)Because 7 patients were lost to follow-up,2 patients were excluded,and 211 patients were finally included(72 patients in group A,71 patients in group B,and 68 patients in group C).(2)The average drainage time of group C was 2.91 days.The postoperative drainage volume in group A was significantly less than that in groups B and C,and the difference was statistically significant(P<0.05).On day 3 after operation,the hematocrit value of group C was lower than that of group A and group B,and the difference was statistically significant(P<0.05).Postoperative activity time and hospital stay in group A were shorter than those in groups B and C,and the difference was statistically significant(P<0.05).(3)Four patients in group A,two patients in group B and three patients in group C received an allogeneic blood transfusion.There was no significant difference among the groups(P>0.05).(4)In terms of postoperative complications,there were no statistical differences in postoperative wound leakage and surgical site infection in all three groups(P>0.05).(5)All patients were followed up for more than 12 months.Visual analog scale score and Oswestry dysfunction index of the three groups of patients before discharge and at the last follow-up were significantly improved compared with those before surgery(P<0.05).There was no statistical significance among the groups(P>0.05).(6)It is indicated that the removal of the drainage tube on the second day after a posterior lumbar fusion can effectively reduce the time to get out of bed and hospital stay,without increasing the postoperative blood loss and the risk of complications.

BackgroundPatients after percutaneous coronary intervention （PCI） are prone to experience depression， which has been shown to significantly affect patients' quality of recovery in postoperative period. Resourcefulness plays an important role between stress and depression， yet there is insufficient research evidence on the predictive effect of intellectual resourcefulness levels on depressive symptoms among patients undergoing PCI. ObjectiveTo investigate the cross-lagged effect between level of resourcefulness and depressive symptoms among patients after PCI， so as to provide references for alleviating depressive symptoms in patients after PCI. MethodsA total of 363 patients who had undergone PCI in Tangshan Gongren Hospital from September to December 2019 were selected using random sampling technique. All participants were subjected to complete Chinese Resourcefulness Scale （CRS） and Chinese version of Cardiac Depression Scale （C-CDS） at both baseline and two years after PCI. A structural equation model was constructed to determine the cross-lagged effect between the level of resourcefulness and depressive symptoms in patients. ResultsMale patients scored higher on CRS （t=-19.871， P<0.01） and lower on C-CDS （t=25.557， P<0.01） after two years of PCI compared with female patients after PCI. Correlation analysis indicated that the baseline CRS score was positively correlated with two years after PCI CRS score （r=0.550， P<0.01）， C-CDS score of baseline was positively correlated with two years after PCI C-CDS score （r=0.524， P<0.01）， baseline CRS score was negatively correlated with C-CDS scores at both baseline （r=-0.717， P<0.01） and two years after PCI （r=-0.472， P<0.01）， and two years after PCI， CRS score was negatively correlation with C-CDS score （r=-0.618， P<0.01）. The cross-lagged analysis revealed that baseline CRS score significantly predicted CRS score of two years after PCI （β=0.382， P<0.01） and C-CDS score of two years after PCI （β=-0.200， P<0.01）. Baseline C-CDS score significantly predicted C-CDS score of two years after PCI （β=0.381， P<0.01） and CRS score of two years after PCI （β=-0.235， P<0.01）. There was a reciprocal relationship between baseline CRS score and baseline C-CDS score （β=-0.717， P<0.01）. ConclusionThe established cross-lagged model yields the presence of a reciprocal prediction of level of resourcefulness and depressive symptoms measured in patients at two time points. The higher the baseline level of resourcefulness， the lighter the depressive symptoms experienced by patients two years after PCI surgery.The more severe the baseline depressive symptoms， the lower the patients' level of resourcefulness two years after PCI surgery.［Funded by Project of Hebei Provincial Department of Science and Technology （number， 182777154）］

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Objective:To establish the HPLC fingerprint of Bolbostemmatis Rhizoma standard decoction; To determine the three effective components with similar structure by quantitative analysis of multi-components by single marker (QAMS); To evaluate the quality of Bolbostemmatis Rhizoma standard decoction.Methods:HPLC was adopted to establish the fingerprints of 15 batches of Bolbostemmatis Rhizoma standard decoction. The Chromatographic column was Waters XBridge Phenyl (4.6 mm×250 mm, 5 μm). The mobile phase was acetonitrile-0.1% phosphoric acid solution with gradient elution. Cluster analysis (HCA) and principal component analysis (PCA) were conducted based on the relative peak area of common peaks. The same method as the fingerprint was used to establish QAMS of tubeimoside A, B, C on Bolbostemmatis Rhizoma standard decoction.Results:There were 14 common peaks in the fingerprint of Bolbostemmatis Rhizoma standard decoction. It was confirmed that the peak 3 was L-tryptophan, the peak 11 was tubeimoside B, the peak 12 was tubeimoside C, and the peak 13 was tubeimoside A. 15 batches of Bolbostemmatis Rhizoma standard decoction from different origins were divided into 3 categories by HCA and PCA. There was no significant difference between QAMS and the external standard method (ESM) through the system suitability inspection. Conclusion:This method is accurate, reliable and has good specificity, which can effectively evaluate the quality of Bolbostemmatis Rhizoma standard decoction.

Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus(HBV)infection and an age of≤30 years by establishing a noninvasive model,and to investigate the diagnostic value of this model.Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People's Hospital from January 2017 to January 2023 and met the inclusion criteria,and according to the results of liver biopsy,they were divided into treatment group with 41 patients(with indications for antiviral therapy)and observation group with 134 patients(without indications for antiviral therapy).The two groups were analyzed in terms of the indicators including clinical data,imaging examinations,and serum biochemical parameters.The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy,and different models for predicting the need for antiviral therapy were constructed based on related parameters.The receiver operating characteristic(ROC)curve was used to compare the diagnostic value of different models.The independent-samples t test was used for comparison of normally distributed continuous variables between groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results There were significant differences between the treatment group and the observation group in alanine aminotransferase,ferritin,total cholesterol(CHOL),triglyceride,platelet count,liver stiffness measured by sound touch elastography(STE),and procollagen Ⅲ N-terminal propeptide(PIIIP)(all P<0.05).The multivariate Logistic regression analysis showed that CHOL(odds ratio[OR]=0.4,95％confidence interval[CI]:0.2—1.0),STE(OR=1.5,95％CI:1.0—2.1),and PIIIP(OR=1.1,95％CI:1.0—1.1)were independent predictive factors for the indications for antiviral therapy.Model 1(STE+PIIIP+CHOL),model 2(STE+PIIIP),model 3(STE+CHOL),model 4(PIIIP+CHOL)had an area under the ROC curve of 0.908,0.848,0.725,and 0.725,respectively,while STE,PIIIP,and CHOL used alone had an AUC of 0.836,0.725,and 0.634,respectively,suggesting that model 1 had the largest AUC,with a specificity of 77.34％and a sensitivity of 96.36％,and had a significant difference compared with STE,PIIIP,CHOL,and the models 2,3,and 4(Z=0.21,3.08,3.06,3.23,0.89,and 0.88,all P<0.05).Conclusion The noninvasive model established based on CHOL,STE,and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of≤30 years.