ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

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 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*

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.

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.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective:To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats.Methods:The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β 1 (TGF-β 1) were detected by Western blotting ( n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results:At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β 1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group ( t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group ( t=7.21, P<0.05). Conclusions:The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

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.

This paper explained the etiology and mechanism of atrial fibrillation based on the theory of "deficiency qi stagnation" for directing the treatment. It is believed that “deficiency qi” is the root of atrial fibrillation， which can be divided into deficiency of pectoral qi in heart and lungs of the upper jiao， deficiency of center qi in spleen and stomach of the middle jiao， and deficiency of original qi in kidney of the lower jiao， and stagnation of stasis， phlegm dampness， cold dampness and other pathogenic qi as the pathological basis of atrial fibrillation， which lead to the development of atrial fibrillation by constraint to heat， or stagnation of cold and dampness， or pathogens stagnation in heart and lung. The therapeutic principles is to supplement deficiency and remove stagnation， and Qingliang Buqi Tiaomai Decoction （清凉补气调脉汤） is often used to supplement the center and boost qi， rectify qi and unblock vessels； Qingliang Huashi Tiaomai Decoction （清凉化湿调脉汤） is often used to strengthen the middle and remove phlegm， dry dampness and unblock vessels； Ziyang Wenhua Tiaomai Decoction （滋养温化调脉汤） is often used to bank up original qi， supplement yin and tonify yang， dissipate cold and unblock vessels.