ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease （CMD）. MethodsPubMed， Cochrane Library， CNKI， Wanfang Data， and VIP were searched for the randomized controlled trials （RCTs） on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31， 2023. The primary outcome indicators included the index of microcirculatory resistance （IMR）， coronary flow reserve （CFR）， and corrected TIMI flow frame count （cTFC）. The secondary outcome indicators included symptomatic efficacy， left ventricular ejection fraction （LVEF）， hypersensitive C-reactive protein （hs-CRP）， nitric oxide （NO）， and adverse events. Cochrane risk-of-bias assessment tool 2.0 （RoB 2.0） and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations， Assessment， Development and Evaluation （GRADE） was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study， involving 3 029 patients. Compared with conventional Western medicine alone， the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR ［mean difference （MD）=-5.93， 95% confidence interval （95%CI） ［-8.73，-3.14］， n=382， P<0.01］， cTFC （MD=-9.35， 95%CI ［-13.94，-4.76］， n=618， P<0.01）， and hs-CRP ［standard mean difference （SMD）=-1.50， 95%CI ［-1.90，-1.11］， n=1 483， P<0.01］， improved the CFR （SMD=1.14， 95%CI ［0.08，2.19］， n=304， P=0.03）， symptomatic efficacy ［relative risk （RR）=1.36， 95%CI ［1.21，1.53］， n=756， P<0.01］， LVEF （MD=4.39， 95%CI ［2.31，6.47］， n=533， P<0.01）， and NO （SMD=3.16， 95%CI ［2.07，4.25］， n=946， P<0.01） of CMD patients. In terms of safety， the combined therapy reduced the occurrence of adverse events in CMD patients （RR=0.49， 95%CI ［0.29，0.82］， n=591， P=0.01）. GRADE showed moderate quality evidence for adverse events， low quality evidence for cTFC， symptomatic efficacy， LVEF， and NO， and very low quality evidence for IMR， CFR， and hs-CRP. ConclusionBased on microcirculatory function indicators， the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.

It is believed that "deficiency qi retention and stagnation" is the fundamental pathogenesis of coronary microvascular dysfunction （CMD） after percutaneous coronary intervention （PCI）. Patients often have severe coronary vessel congestion before PCI， leading to emptiness in the heart's collaterals， which results in deficiency of healthy qi， poor movement of blood and body fluids， so the heart collaterals are susceptible to stagnation and stasis，then phlegm and stasis generate； after PCI， it is easy to damage the healthy qi then lead to qi deficiency， causing qi， blood， and body fluids fail to transport， thereby leading to blood stasis and phlegm turbidity retention， generating heat and wind to damage the heart and body. It is proposed that the prevention before PCI should replenish qi and collaterals， expel blood stasis and resolve phlegm， to support "deficient qi" in heart collaterals and prevent "stagnation" after PCI. Postoperative management should focus on replenishing qi and protecting the collaterals， eliminating pathogen and controlling development， so as to avoid exacerbating deficiency and stagnation by damaging healthy qi， and eliminate pathogen and unblock the collaterals to interrupt the pathogenesis， which prevent "retention and stagnation" from changes.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

Objective:To explore the effective components and potential mechanisms of Xiefei Lishui Prescription in the treatment of heart failure.Methods:Ultra high-performance liquid chromatography tandem four stage rod time of flight mass spectrometry (UPLC-Q-TOF-MS) technology was used to analyze and identify the active components of Xiefei Lishui Prescription. Drug targets were predicted through the Swiss Target Prediction database, and disease targets were collected from Gene Cards, Dis GENET, and TTD databases. The intersection of drug targets and disease targets was screened using a STRING database for protein interaction to identify core targets. The core targets were included in the DAVID database for GO enrichment and KEGG analysis. Finally, molecular docking validation was performed between the drug components and the corresponding core targets.Results:The results identified 10 active components of Xiefei Lishui Prescription, and 8 potential active components were screened using network pharmacology for the treatment of heart failure with Xiefei Lishui Prescription, corresponding to 160 related action targets. A total of 1 305 disease-related targets were collected, and a total of 51 targets ad 17 core targets were included in the string database for protein interaction analysis. GO functional enrichment and KEGG analysis indicated that the mechanism of Xiefei Lishui Prescription in treating heart failure may be related to pathways such as protein binding, ATP binding, and negative regulation of the VEGF signaling pathway and T cell receptor pathway during apoptosis. The molecular docking results showed that baicalin exhibited good binding activity with ESR1, sorghum isoflavones with ESR1, and quercetin with AKT1, EGFR, IL2, and ABCB1.Conclusion:Xiefei Lishui Prescription may exert therapeutic effects on heart failure through multiple pathways by targeting ESR1, AKT1, EGFR, and other targets.

ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg^-1） and trimetazidine group （5.4 mg·kg^-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.

Based on network pharmacology and in vitro assays,we conducted a collaborative investi-gation into the protective effects of ginsenosides Rg1 and Re on LPS-induced damage of porcine je-junal epithelial cells IPEC-J2.Network pharmacology was used to obtain and screen the intersec-ting targets of Rg1 and Re to alleviate intestinal barrier damage,and molecular docking technique was used to verify the predicted results of network pharmacology.The experiment included the Control group,LPS group,Rg1 group,and Re group.The effects of different concentrations of Rg1 and Re on cell survival rate,apoptosis rate,TEER value,FD4 permeability,and inflammatory fac-tors of IPEC-J2 were observed,and the effects of different concentrations of Rg1 and Re on the mRNA expression levels of apoptosis-related genes were also detected by fluorescence quantitative PCR.The results of network pharmacology showed that the prevention of intestinal barrier damage by Rg1,Re mainly involved the processes of PI3K-Akt and MAPK signaling pathways.The molec-ular docking results showed that the binding energy of Rg1 to all intersecting targets was less than 0,while that of ginsenoside Re to SRC targets only was less than 0.In vitro experiments showed that pretreatment with different concentrations of Rg1 and Re increased the survival rate and TEER value of LPS-treated IPEC-J2 to varying degrees,and reduced the apoptosis,the decrease of FD4 permeability,and the secretion of inflammatory factor TNF-α,suggesting that Re and Rg1 prevented the intestinal barrier from damage.It was shown that Re and Rg1 could effectively re-duce the effects of LPS treatment on IPEC-J2 cells.Rg1 significantly upregulated the mRNA ex-pression levels of MAPK8,MAPK10,HRAS,and significantly down-regulated the mRNA expres-sion levels of MAP2K1,PIK3CG,IL-2 and SRC;and Re significantly upregulated the mRNA ex-pression levels of MAPK8,MAPK10,HRAS,and PIK3R1,BCL2 gene mRNA expression levels.These results suggest that ginsenosides Rg1,Re and ginsenoside products containing Rg1 and Re deserve further investigation in preventing intestinal barrier damage in piglets.

Objective To explore the potential mechanism of Shuangshen Ningxin Capsules in the treatment of coronary microvascular disease(CMVD)using transcriptomics;To verify it.Methods Totally 30 male SD rats were randomly divided into sham-operation group,model group and Shuangshen Ningxin Capsules group,with 10 rats in each group.Shuangshen Ningxin Capsules group was given Shuangshen Ningxin Capsules solution(90 mg/kg)in advance for 7 days by gavage,while the sham-operation group and model group were given normal saline.CMVD rat model was established through left ventricular injection of embolic microspheres 2 hours after the last administration.The sham-operation group underwent open chest surgery and injected normal saline.24 hours after modeling,ultrasound was used to detect cardiac function[left ventricular systolic anterior wall thickness(LVAWs),left ventricular diastolic anterior wall thickness,left ventricular systolic posterior wall thickness,left ventricular diastolic posterior wall thickness,left ventricular end systolic diameter(LVIDs),left ventricular end diastolic diameter,left ventricular end diastolic volume,left ventricular end systolic volume(LVVs),stroke volume(SV),cardiac output(CO),ejection fraction(EF),fractional shortening(FS)];the reagent kit was used to detect the contents of serum CK,CK-MB and LDH;TTC staining was used to detect myocardial infarction area;HE staining was used to observe myocardial tissue morphology;transcriptome sequencing was used to detect common differentially expressed genes among the sham-operation group,model group and Shuangshen Ningxin Capsules group,GO and KEGG pathway enrichment analysis was performed on differentially expressed genes,and mRNA expression of differentially expressed genes were validated through RT-PCR.Results Compared with the sham-operation group,LVAWs,SV,CO,EF and FS of the model group significantly decreased,LVIDs and LVVs significantly increased(P<0.05,P<0.01),serum CK,CK-MB and LDH contents significantly increased(P<0.05,P<0.01),the area of myocardial infarction increased,the arrangement of myocardial cells was disorderly,and there was obvious infiltration of inflammatory cells.Compared with the model group,the rats in Shuangshen Ningxin Capsules group showed a significant decrease in LVIDs and LVVs,a significant increase in LVAWd,LVPWs,EF and FS(P<0.01),a significant decrease in serum CK,CK-MB and LDH contents(P<0.05,P<0.01),and a significant reduction in myocardial infarction area(P<0.01),the arrangement of myocardial cells was relatively neat,and the infiltration of inflammatory cells was reduced.The transcriptome sequencing results showed that there were 287 common differentially expressed genes among the sham-operation group,model group and Shuangshen Ningxin Capsules group,mainly enriched in chemokine signaling pathway,JAK-STAT signaling pathway,regulation of actin cytoskeleton,adrenergic signaling in cardiomyocytes,PPAR signaling pathway,NOD-like receptor signaling pathway,etc.RT-PCR validation results showed that Shuangshen Ningxin Capsules could significantly down-regulate the mRNA expressions of JAK2,STAT1,CXCL10,CXCL13 and CCR1 in myocardial tissue of model rats(P<0.05,P<0.01).Conclusion Shuangshen Ningxin Capsules can significantly improve cardiac function and reduce myocardial infarction area in CMVD rats,possibly by inhibiting the expressions of JAK-STAT signaling pathway JAK2 and STAT1,reducing the expressions of chemokines and their receptors(CXCL10,CXCL13,CCR1),reducing the recruitment of inflammatory cells,and exerting anti-inflammatory effects.

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

Myocardial fibrosis is characterized by pathological remodeling of extracellular matrix,which is a common pathological change during the development of various cardiovascular diseases.Qi transformation dysfunction in the zang-fu organs,subtle substance accumulation,and endogenous turbid evil production lead to the occurrence of diseases.The theory of turbid blood is widely used to elucidate the pathological changes of diseases and guide the prevention and treatment.Turbid blood,as a special pathogenic factor and pathological product,plays a crucial role in the oxidative stress process of myocardial fibrosis.Qi deficiency of the heart and spleen,stagnation of turbid blood,impaired blood circulation in the heart,and the inability to maintain the oxidative-reductive system balance of myocardial cells are the root causes of disease onset.Accumulation of turbid blood,intermingled phlegm and blood stasis,blockage of heart vessels,and accumulation of metabolic waste products contribute to disease progression.Prolonged turbidity accumulation leads to cardiac enlargement,scattered mental state,and pathological remodeling of the extracellular matrix,indicating a severe disease stage.Early treatment focuses on strengthening the vital qi and spleen,reducing turbidity and recovering clarity.In the middle stage,the key is to resolve phlegm,eliminate stasis,and promote clarity while removing turbidity.In the late stage,detoxification,turbidity elimination,and restoring clarity are emphasized.By adhering to the characteristics of the pathological mechanism and using traditional Chinese medicine intervention,it is possible to suppress oxidative stress,prevent pathological remodeling of the extracellular matrix,and improve myocardial fibrosis.