ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

Background: This study was performed to characterize the incidence, costs, and risk factors associated with renal and cardiovascular adverse outcomes following primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Patients with STEMI who underwent pPCI using iso-osmolar contrast were enrolled at 39 centers. The incidence of acute kidney injury (AKI) and major adverse renal and cardiovascular events (MARCE) was analyzed, as well as inpatient costs. Logistic regression analysis was performed to identify risk factors. Results: Among 2,293 patients, the incidence of AKI and MARCE within 72 hours post-pPCI was 4.14% (n = 95) and 4.40% (n = 101), respectively. AKI and/or MARCE were associated with systolic blood pressure (AKI: odds ratio [OR], 1.009; 95% confidence interval [CI], 1.000–1.018), hypertension (AKI: OR, 1.815; 95% CI, 1.133–2.906; MARCE: OR, 1.760;95% CI, 1.118–2.769), anterior wall infarction (AKI: OR, 1.895; 95% CI, 1.196–3.004; MARCE:OR, 1.939; 95% CI, 1.240–3.032), Killip class (AKI: OR, 1.465; 95% CI, 1.117–1.922; MARCE:OR, 1.467; 95% CI, 1.131–1.903), and serum creatinine (SCr; MARCE: OR, 1.006; 95% CI, 1.000–1.012). Hospitalization costs for patients with STEMI who developed AKI or MARCE were significantly higher than for those without AKI (9,595 ± 5,795 vs. 8,279 ± 3,872 USD, P = 0.003) or without MARCE (9,890 ± 5,616 vs. 8,255 ± 3,859 USD, P < 0.001). Conclusions In patients with STEMI undergoing pPCI with iso-osmolar contrast, the incidence of AKI and MARCE was associated with higher hospitalization costs. Systolic blood pressure, hypertension, anterior wall infarction, Killip class, and SCr were identified as risk factors for these outcomes.

Objective To systematically evaluate the risk prediction models for anastomotic leakage (AL) in patients with esophageal cancer after surgery. Methods A computer-based search of PubMed, EMbase, Web of Science, Cochrane Library, Chinese Medical Journal Full-text Database, VIP, Wanfang, SinoMed and CNKI was conducted to collect studies on postoperative AL risk prediction model for esophageal cancer from their inception to October 1st, 2023. PROBAST tool was employed to evaluate the bias risk and applicability of the model, and Stata 15 software was utilized for meta-analysis. Results A total of 19 literatures were included covering 25 AL risk prediction models and 7373 patients. The area under the receiver operating characteristic curve (AUC) was 0.670-0.960. Among them, 23 prediction models had a good prediction performance (AUC>0.7); 13 models were tested for calibration of the model; 1 model was externally validated, and 10 models were internally validated. Meta-analysis showed that hypoproteinemia (OR=9.362), postoperative pulmonary complications (OR=7.427), poor incision healing (OR=5.330), anastomosis type (OR=2.965), preoperative history of thoracoabdominal surgery (OR=3.181), preoperative diabetes mellitus (OR=2.445), preoperative cardiovascular disease (OR=3.260), preoperative neoadjuvant therapy (OR=2.977), preoperative respiratory disease (OR=4.744), surgery method (OR=4.312), American Society of Anesthesiologists score (OR=2.424) were predictors for AL after esophageal cancer surgery. Conclusion At present, the prediction model of AL risk in patients with esophageal cancer after surgery is in the development stage, and the overall research quality needs to be improved.

ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective To explore the predictive value of serum interleukin-17A(IL-17A),pentraxin-3(PTX3)and serum amyloid A(SAA)expression in Kawasaki disease(KD)children for non-response to in-travenous immunoglobulin(IVIG).Methods A total of 120 KD children who received IVIG treatment in the hospital from January 2022 to December 2024 were selected as the research objects.According to the response to IVIG treatment,they were divided into the sensitive group(n=90)and the non-response group(n=30).The clinical data of all children were collected.The predictive value of serum IL-17A,PTX3 and SAA expres-sion alone and in combination for non-response to IVIG treatment were explored by receiver operating charac-teristic(ROC)curve.The influencing factors of non-response to IVIG treatment in KD children were explored by multivariate Logistic regression.Results The levels of serum IL-17A,PTX3 and SAA in the non-response group were higher than those in the sensitive group(P＜0.05).The area under the curve(AUC)of serum IL-17A,PTX3 and SAA levels and their combined detection for predicting non-response to IVIG treatment were 0.704(95％CI:0.659-0.749),0.769(95％CI:0.719-0.819),0.813(95％CI:0.768-0.863),and 0.922(95％CI:0.877-0.967),respectively.The AUC of the combined detection of the three was larger than those of the individual detection of serum IL-17A,PTX3 and SAA(Zcombination-IL-17A=8.465,P＜0.001,Zcombination-PTX3=12.791,P＜0.001,Zcombination-SAA=9.984,P＜0.001).There were no statistically significant differences in age,body mass index(BMI),gender,KD type,fever duration before initial IVIG treatment,time from onset to ini-tial treatment,conjunctival congestion,changes in fingers and toes,rash,lymph node enlargement,platelet(PLT)count,hemoglobin(Hb)between the two groups(P＞0.05).The white blood cell(WBC)count,neu-trophil count(NEU),alanine aminotransferase(ALT),aspartate aminotransferase(AST)in the non-re-sponse group were higher than those in the sensitive group(P＜0.05).Multivariate Logistic regression analy-sis showed that serum IL-17A(OR=2.555,95％CI:1.529-4.270),serum PTX3(OR=3.473,95％CI:1.940-6.216),and serum SAA(OR=3.022,95％CI:1.823-5.011)were the risk factors of non-response to IVIG treatment(P＜0.05).Conclusion The combined detection of serum IL-17A,PTX3 and SAA levels can be used as important biological markers for predicting non-response to IVIG in KD children,providing a theoretical basis for early identification of high-risk children.

Objective To explore the efficacy of Yishen Yangyin Gujing Prescription[derived from Zuogui Wan(Bolus for Replenishing Kidney-Yin)]for the treatment of diabetic nephropathy in type 2 diabetes mellitus(T2DM)with qi and yin deficiency syndrome,and to observe its effects on inflammatory responses,pancreatic β-cell function and renal function.Methods A total of 162 T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome who admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2020 to July 2023 were randomly divided into an observation group and a control group according to the random number table method,with 81 cases in each group.The control group was given conventional western medicine treatment for lowering blood pressure and renal protection,while the observation group was treated with Yishen Yangyin Gujing Prescription on the basis of treatment for the control group.The course of treatment for the two groups covered 12 weeks.Before and after the treatment,the changes in the outcomes of the two groups were observed,and the outcomes included the total scores of traditional Chinese medicine(TCM)syndrome,insulin sensitivity index,insulin secretion index,24-h urine total protein quantification(24hUTP),and serum levels of glycosylated hemoglobin(HbA1c),fasting insulin(FINS),fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),transforming growth factor β1(TGF-β1),NLRP3 inflammasome,interleukin 6(IL-6),superoxide dismutase(SOD)and sphingosine-1-phosphate(S1P).After treatment,the clinical efficacy of the two groups of patients was compared.Results(1)After 12-week treatment,the total effective rate of the observation group was 93.83%(76/81),and that of the control group was 83.95%(68/81).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group(χ2=9.163,P<0.05).(2)After treatment,the insulin sensitivity index and insulin secretion index in the two groups of patients were increased(P<0.05)and the total scores of TCM syndromes were decreased(P<0.05)when compared with those before treatment,and the increase of insulin sensitivity index and insulin secretion index as well as the decrease of the total scores of TCM syndrome in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,the serum levels of HbA1c,FINS,FBG,SCr,BUN and 24hUTP in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of the above indicators in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the serum TGF-β1,IL-6,and NLRP3 inflammasome levels in the two groups of patients were decreased(P<0.05)and the serum S1P and SOD levels were increased(P<0.05)when compared with those before treatment,and the decrease of serum TGF-β1,IL-6,and NLRP3 inflammasome levels as well as the increase of serum S1P and SOD levels in the observation group was significantly superior to that in the control group(P<0.05).Conclusion For T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome,the combined use of western medicine and Yishen Yangyin Gujing Prescription treatment is helpful to alleviate inflammatory response,improve the function of pancreatic β-cells,regulate the blood glucose level,improve renal function,and enhance the clinical efficacy.

Objective:To observe the effect of point injection at Zusanli(ST36)plus abdominal point application on gastrointestinal dysfunction after laparoscopic surgery.Methods:A total of 204 patients with gastrointestinal dysfunction after laparoscopic surgery were recruited and divided into four groups using the random number table method,with 51 cases in each group.The control group received conventional postoperative intervention.In addition to the treatment in the control group,the point injection group was given point injection at Zusanli(ST36),the application group was offered abdominal point application,and the integrated group received point injection at Zusanli(ST36)and abdominal point application.The treatment lasted 3 consecutive days in all four groups.The recovery time of gastrointestinal function indicators and the incidence rate of postoperative nausea and vomiting(PONV)were observed and recorded.Before and after treatment,the visual analog scale(VAS)was used to assess abdominal pain intensity,the venous blood type 1 helper T cells/type 2 helper T cells(Th1/Th2)was determined,the serum levels of interleukin(IL)-6 and interferon(IFN)-γ were detected using the enzyme-linked immunosorbent assay,and the plasma levels of motilin and gastrin were measured using radioimmunoassay.Results:Compared to the control group,the first exhaust time,the first defecation time,and the time of restoring fluid diet came earlier in the other three groups(P<0.05)and were earlier in the integrated group than in the point injection and application groups(P<0.05).The point injection,application,and integrated groups had a lower PONV incidence rate than the control group,and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons showed that the VAS score and the levels of IL-6 and INF-γ decreased after treatment in all four groups(P<0.05);the point injection,application,and integrated groups were lower than the control group(P<0.05),and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons also demonstrated that the levels of Th1/Th2,motilin,and gastrin increased after the intervention in the four groups(P<0.05);the point injection,application,and integrated groups were higher than the control group(P<0.05),and the integrated group was higher than the point injection and application groups(P<0.05).Conclusion:Point injection at Zusanli(ST36)plus abdominal point application can encourage postoperative exhaust,defecation,and the recovery of diet fluid,alleviate postoperative abdominal pain,reduce PONV,balance Th1/Th2,and regulate the secretion of motilin and gastrin in patients with gastrointestinal dysfunction after laparoscopic surgery.

The thermal sensitivity of enzymes is a key bottleneck that restricts their practical application,and the development of efficient enzyme stability enhancement technology has important application value.Based on the principle of metal-polyphenol coordination chemistry,this study used tannic acid-ferric ion(TA-FeⅢ)coordination polymer to nano-encapsulate catalase(CAT)and systematically explored its stability enhancement effect.The catalytic activity retention rate of the immobilized enzyme in extreme environments(High temperature,organic solvents,denaturants and pH 3-11)was significantly improved compared with that of the free enzyme,proving that the TA-FeⅢ nanoshell had a significant environmental barrier effect.In the long-term stability test,the immobilized enzyme retained 20％activity after a 30-d storage at room temperature,and its effective activity was prolonged to 8 times that of the free enzyme in the accelerated inactivation test at 37 ℃.In addition,several cyclic catalytic experiments demonstrated that the immobilized enzyme exhibited good reusability,thus broadening its practical application.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.