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.

Objective To explore the feasibility of quantitative EEG parameters for prognostic prediction of patients with severe aneurysmal subarachnoid hemorrhage(SaSAH)90 d after the onset of the disease.Methods Patients with SaSAH admitted to the Neurosurgical Intensive Care Unit(NSICU)of Henan Provincial People's Hospital from September 2022 to September 2023 were prospectively consecutively enrolled,and baseline data were collected,including age,gender,medical history(hypertension,diabetes mellitus,coronary artery disease,and stroke),history of smoking,history of drinking,location of aneurysm(anterior circulation,posterior circulation),surgical modality(craniotomy,interventional surgery,hybrid surgery),Hunt-Hess classification,Glasgow coma scale(GCS)score,acute physiology and chronic health status scoring system Ⅱ(APACHE Ⅱ)score,subarachnoid hemorrhage early brain edema score(SEBES),first randomized blood glucose level after admission to NSICU,lactate level,and duration of NSICU stay.Quantitative EEG monitoring was performed in all patients within 48 h after admission to the NSICU,and amplitude-integrated electroencephalogram(aEEG)upper and lower boundaries,95％spectral edge frequency(SEF95),α change,(δ+θ)to(α+β)power ratio(DTABR),brain symmetry index(BSI),and spectral entropy were collected.Based on modified Rankin scale(mRS)scores 90 d after onset,patients were categorized into good prognosis(mRS score 2 points)and poor prognosis(mRS score 3-6 points)groups.Spearman rank correlation was used to analyze the correlation between quantitative EEG parameters and mRS scores in SaSAH patients.Multifactorial Logistic regression analysis was used to screen for correlates of poor prognosis,and receiver operating characteristic(ROC)curves were plotted to evaluate the efficacy of each index in predicting patients'poor prognosis.Results(1)A total of 72 patients with SaSAH were included,with 47 in the poor prognosis group and 25 in the good prognosis group,and the poor prognosis rate at 90 d after the onset was 65.3％.There was no statistically significant difference between the two groups in terms of gender,age,hypertension,diabetes mellitus,coronary artery disease,history of stroke,history of smoking,history of drinking,location of aneurysm,surgical modality,lactate level,and length of hospitalization in the NSICU(all P＞0.05);the differences between the Hunt-Hess grading,SEBES,and random blood glucose were statistically significant upon comparison(all P＜0.05).Compared with the good prognosis group,the changes of aEEG upper and lower boundary,SEF95,α change and spectral entropy were lower in the poor prognosis group,but DTABR and BSI were higher(all P＜0.05).(2)Spearman rank correlation analysis showed that the upper border of aEEG(r=-0.41,P＜0.01),lower border of aEEG(r=-0.54,P＜0.01),SEF95(r=-0.46,P＜0.01),α change(r=-0.53,P＜0.01)and spectral entropy(r=-0.39,P＜0.01)were negatively correlated with the mRS scores of SaSAH patients,and DTABR(r=0.52,P＜0.01)and BSI(r=0.33,P＜0.01)were positively correlated with poor prognosis of SaSAH patients.(3)The results of multifactorial Logistic regression analysis showed that Hunt-Hess grading(level Ⅳ vs.Ⅲ:OR,1.203,95％CI 1.005-1.441,P=0.044;level V vs.Ⅲ:OR,1.661,95％CI 1.109-2.487,P=0.014),SEBES(OR,1.647,95％CI 1.050-2.586;P=0.030),aEEG lower border(OR,0.687,95％CI 0.496-0.953l;P=0.024),SEF95(OR,0.436,95％CI0.202-0.937;P=0.034),α change(OR,0.368,95％CI0.189-0.717;P=0.003),DTABR(OR,1.324,95％CI 1.064-1.649;P=0.012),and BSI(OR,1.513,95％CI 1.026-2.231;P=0.036)were influencing factors of poor prognosis in SaSAH patients.ROC curve analysis showed that all of the above seven indicators had a certain predictive value for poor prognosis in SaSAH patients,among which the area under the curve of DTABR was the highest as 0.862(95％CI 0.761-0.932),with sensitivity 85.11％and specificity 80.00％.Conclusion Quantitative EEG parameters aEEG lower border,SEF95,α change,DTABR,and BSI may have certain predictive value for the short-term prognosis of SaSAH patients,which needs to be further confirmed in future multi-center large-sample studies.

Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age. Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively. Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk. Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.

Gualou Niubangtang is a classic formula for eliminating swelling and dispersing lumps， commonly used in the clinical treatment of breast diseases in traditional Chinese medicine （TCM）. This paper employed bibliometric methods to collect and organize 12 pieces of data from ancient texts related to Gualou Niubangtang， ultimately screening 10 valid references from 10 ancient Chinese medical books. Information regarding the prescription origin， main indications， formulation principles， drug composition， dosages， preparation methods， and decoction techniques was systematically verified. The results indicate that Gualou Niubangtang originates from the Orthodox Manual of External Medicine （Wai Ke Zheng Zong） by Chen Shigong in the Ming Dynasty. The formula consists of 12 Chinese medicines， including Citri Reticulatae Pericarpium， Arctii Fructus， Gardeniae Fructus， Lonicerae Japonicae Flos， Glycyrrhizae Radix et Rhizoma， Trichosanthis Semen， Scutellariae Radix， Trichosanthis Radix， Forsythiae Fructus， Gleditsiae Spina， Bupleuri Radix， and Citri Reticulatae Pericarpium Viridm. In terms of drug origins， the dominant radical for Trichosanthis Semen and Trichosanthis Radix is Trichosanthes kirilowii， and the historical dominant radical for Glycyrrhizae Radix et Rhizoma is Glycyrrhiza uralensis. The nine medicines， Citri Reticulatae Pericarpium， Arctii Fructus， Gardeniae Fructus， Lonicerae Japonicae Flos， Scutellariae Radix， Forsythiae Fructus， Gleditsiae Spina， Bupleuri Radix， and Citri Reticulatae Pericarpium Viridm， are consistent with the 2020 edition of the Chinese Pharmacopoeia. The preparation methods involve frying Arctii Fructus， removing the heart from Forsythiae Fructus， while the remaining 10 medicines are used raw. The efficacy includes clearing heat， removing toxins， reducing swelling， and dispersing lumps. Clinically， it is used to treat conditions such as breast carbuncles， breast gangrene， and knot-like swellings and pain. The dosage， converted to modern standards， includes 3.73 g of Trichosanthis Semen， 3.73 g of Trichosanthis Radix， 3.73 g of Arctii Fructus， 3.73 g of Scutellariae Radix， 3.73 g of Gardeniae Fructus， 3.73 g of Forsythiae Fructus， 3.73 g of Gleditsiae Spina， 3.73 g of Lonicerae Japonicae Flos， 3.73 g of Glycyrrhizae Radix et Rhizoma， 3.73 g of Citri Reticulatae Pericarpium， 1.85 g of Citri Reticulatae Pericarpium Viridm， and 1.85 g of Bupleuri Radix. The preparation is in the form of a decoction， with the 12 medicines added to 400 mL of water and decocted until 160 mL. The liquid is then mixed with 200 mL of yellow wine and taken before meals three times a day. Through the excavation and organization of ancient literature regarding Gualou Niubangtang， key information has been identified to provide a scientific basis for its clinical application and further development.

Objective:To construct a prognostic predictive model for patients with moderate to severe traumatic brain injury (msTBI) based on regional cerebral oxygen saturation (rScO 2) and transcranial Doppler ultrasound (TCD) monitoring parameters and validate its effectiveness. Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 patients with msTBI who were treated at Henan Provincial People′s Hospital from January 2021 to December 2022, including 104 males and 57 females, aged 19-76 years [(53.1±12.8)years]. Glasgow coma scale (GCS) score was 3-12 points [(7.0±1.9)points]. Both rScO 2 and TCD monitoring were performed. Based on the results of prognostic evaluation of patients with the modified Rankin scale (mRS) score at 90 days after discharge, the patients were divided into good prognosis group (mRS score≤3 points, n=88) and poor prognosis group (mRS score of 4-6 points, n=73). The following data of the two groups were collected: the general data, clinical data, rScO 2 monitoring parameters and TCD monitoring parameters. Univariate analysis was employed to compare the differences in the relevant prognostic indicators. Multivariate Logistic stepwise regression analysis was conducted to determine the predictors of poor prognostic outcomes in msTBI patients and regression equations were constructed. A nomogram predictive model based on regression equations was drawn with R language. The discriminability of the model was evaluated by drawing the receiver operating characteristic (ROC) curve, to calculate the area under the curve (AUC), sensitivity, specificity, and Jordan index of the model, and measuring the consistency index (C index). Hosmer-Lemeshow (H-L) goodness of fit test was conducted to evaluate the fit of the model, and the calibration curve was used to evaluate the calibration degree of the model. Decision curve analysis (DCA) was employed to evaluate the clinical benefit and applicability of the model. Results:There were significant differences between the two groups in the clinical data (cerebral hernia formation, GCS on admission, acute physiology and chronic health evaluation II (APACHE II) score on admission, Rotterdam CT score on admission, oxygenation index on admission, mean arterial pressure on admission), rScO 2 monitoring parameters (mean rScO 2, maximum rScO 2, rScO 2 variability), TCD monitoring parameters [peak systolic blood flow velocity (Vs), average blood flow velocity (Vm), pulse index (PI)] ( P<0.05 or 0.01). The results of multivariate Logistic stepwise regression analysis showed that cerebral hernia formation ( OR=9.28, 95% CI 3.40, 25.33, P<0.01), Rotterdam CT score on admission ( OR=1.92, 95% CI 1.32, 2.78, P<0.01), rScO 2 variability ( OR=4.66, 95% CI 1.74, 12.43, P<0.01), Vs ( OR=0.66, 95% CI 0.61, 0.75, P<0.01) and PI ( OR=20.07, 95% CI 4.17, 16.50, P<0.01) were predictive factors for poor prognosis in patients with msTBI. The regression equation was constructed with the forementioned 5 variables: Logit [ P/(1- P)]=2.23×"brain hernia formation"+0.65×"Rotterdam CT score on admission"+1.54×"rScO 2 variability"-0.42×"Vs"+3.00×"PI"-6.75. The AUC of prognostic predictive model of msTBI patients was 0.90 (95% CI 0.85, 0.95), with the sensitivity and specificity of 86.3% and 78.4%, Youden index of 0.65 and C index of 0.90. H-L goodness of fit test showed that the calibration degree of the predictive model was accurate ( χ2 =12.58, P>0.05). The average absolute error of the calibration curve was 0.025, showing that the calibration of the model was good. DCA results showed that this model had higher net return rate than the reference model within the probability range of risk threshold (20%-100%), with good clinical application value in evaluating the risk of poor prognosis of msTBI patients. Conclusion:The model constructed based on the combination of rScO 2 and TCD monitoring parameters (rScO 2 variability, Vs and PI) with multiple clinical indicators (cerebral hernia formation and Rotterdam CT score on admission) has good predictive performance for the prognosis of msTBI.

Objective To compare the curative efficacy of conventional transcatheter arterial chemoembolization(C-TACE)and drug-eluting bead transcatheter arterial chemoembolization(D-TACE)combined with local thermal ablation in the treatment of massive hepatocellular carcinoma(HCC).Methods A total of 72 patients with massive HCC,who were admitted to the Nanyang Municipal First People's Hospital of China from April 2018 to June 2021,were enrolled in this study.By using random number table method,the patients were divided into study group(n=36)and control group(n=36).The patients of the control group were treated with local thermal ablation combined with C-TACE,while the patients of study group were treated with local thermal ablation combined with D-TACE.The clinical efficacy,tumor markers,liver function,serological indicators,blood perfusion indexes,and adverse reactions were compared between the two groups.All patients were followed up for two years.The progression-free survival(PFS)were compared between the two groups.Results The disease control rate(DCR)and objective response rate(ORR)in the study group were higher than those in the control group(P＜0.05).At 3 months after operation,the levels of alpha-fetoprotein(AFP)and prothrombin induced by Vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)were decreased in both groups(P＜0.05),which in the study group were obviously lower than those in the control group(P＜0.05);the alanine aminotransferase(ALT)level was increased in both groups,which in study group was lower than that in the control group(P＜0.05);the albumin(ALB)level was decreased in both groups(P＜0.05),which in the study group was higher than that in the control group(P＜0.05);the epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF)and thymokinase 1(TK1)levels were decreased in both groups(P＜0.05),which in the study group were lower than those in the control group;the blood volume(BV)and blood flow(BF)were decreased in both groups(P＜0.05),which in the study group was lower than those in the control group;the mean transit time(MTT)of contrast agent was increased in both groups(P＜0.05),which in the study group was higher than that in the control group.During the follow-up of two years,one patient in each group was lost in touch,the follow-up success rate was 97.22％.The median PFS in the study group and the control group was 15.41 months(95％CI:7.02-23.19)and 12.34 months(95％CI:6.16-22.30)respectively.The PFS curve of the study group was better than that of the control group(P＜0.05).Conclusion Local thermal ablation combined with D-TACE can improve liver function and blood perfusion in patients with massive HCC,with a remarkable clinical efficacy.This therapy can reduce tumor markers levels,regulate serum EGFR,VEGF and TK1 expressions,and prolong the median PFS,besides,it is clinically safe and reliable.

Objective:To investigate the effects of Apelin-13 regulatory peptide on neuronal cell pyroptosis in mice modeled with cerebral ischemia-reperfusion(I/R).Methods:We prepared a mouse cerebral I/R model using middle cerebral artery embolization and Reperfusion(MCAO/R).The HT22 cell injury model was prepared by the oxygen glu-cose deprivation/reoxygenation(OGD/R),and Apelin-13 treatment was also given.Neurological function was assessed by neurological deficit score;hematoxylin-eosin(HE)staining and Nissl staining were used to observe the morphologic changes of the infarcted area of the mice;and 2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;The expression of NOD-like receptor thermoprotein structural domain-related protein 3(NLRP3),gasdermin D(GSDMD),caspase-1,apoptosis-associated speck-like protein(ASC),interleukin 1β(IL-1β),and interleukin 18(IL-18)in brain tissues from infarcted areas or HT22 cells was detected by Western Blot,and IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA)in serum of mice and culture supema-tants;The cell viability and cell damage of HT22 were detected by CCK-8 kit and lactate dehydrogenase(LDH)assay kit,respectively;caspase-1 activity was measured by caspase-1 activity kit in HT22 cells;and the expression of caspase-1 and GSDMD was observed by immunofluorescence staining in HT22 cells.Results:Apelin-13 significantly improved neurological function and cerebral infarct volume in I/R mice,and attenuated pathological damage in the in-farcted area.It also reduced the serum levels of IL-1β and IL-18.In addition,Apelin-13 reduced the expression of mol-ecules such as NLRP3,GSDMD,caspase-1,IL-1β,and IL-18 in the cerebral infarct area of mice.In vitro experiments showed that Apelin-13 significantly increased the viability of OGD/R-treated HT22 cells,decreased caspase-1 activity,and reduced the LDH content,as well as decreased the expression of molecules such as NLRP3,GSDMD,caspase-1,IL-1β,IL-18,and so on,in OGD/R-treated HT22 cells.Conclusion:Apelin-13 inhibits pyroptosis through the NL-RP3/caspase-1/GSDMD pathway in cerebral ischemia/reperfusion mice and thus exerts neuroprotective effects.

Sarcoidosis is a systemic disease of unknown etiology characterized by the formation of noncaseating granulomas.Its clinical manifestations are heterogeneous,and the determinants of clinical course(such as active vs inac-tive,remission vs chronic progression,and fibrosis vs non-fibrosis)are poorly understood.Despite considerable effort over many years,the exact pathogenesis of sarcoidosis has not been fully elucidated.Animal models have made significant con-tributions to understanding the etiology and the development of this disease.In this review,we presented the clinical rele-vance of animal models in sarcoidosis,summarized the methods for constructing the models,and discussed how they have strengthened our understanding of sarcoidosis.

Chronic myeloid leukemia (CML) is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells. With the improvement of disease awareness and the introduction of new drugs, more than 90% of CML patients can achieve long-term survival. However, a few patients still show drug resistance. This article reviews the mechanism of drug resistance in CML patients treated with tyrosine kinase inhibitor (TKI) and the characteristics of ABL kinase region mutation.