ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

Malignant tumor metastasis is the key factor leading to poor prognosis of patients， and it is a difficult problem to be overcome in the field of tumor therapy. Metabolic reprogramming， as a key link in the regulation of tumor metastasis activity， affects the growth， invasion， and metastasis of tumor cells by changing the metabolic pathways of intracellular substances （such as glucose， amino acids， lipids， and nucleotides）. In particular， metabolic reprogramming plays a key role in the multistage linked steps related to tumor metastasis and can play a crucial role in several key stages of tumor tissue dissociation in situ， hematogenous metastasis， and remote colonization. Malignant tumor cells can selectively adjust their own metabolic state to adapt to the growth conditions of different metastatic microenvironments and colonization sites and then choose the most favorable growth and metabolism strategy. According to the holistic concept of traditional Chinese medicine （TCM）， the metastasis of malignant tumors is generally closely related to the metabolic state of the whole body. One of the advantages of TCM in the treatment of malignant tumors is systemic regulation. With its multi-pathway， multi-target， and multi-component therapeutic characteristics， TCM can effectively control the metastasis of malignant tumors by regulating the degradation of tumor epithelial mesenchymal transformation （EMT） and extracellular matrix （ECM）， anchoring the independent growth of tumor cells and the tumor microenvironment. In this paper， the potential regulatory effects of metabolic reprogramming on the metastasis of malignant tumors were discussed， and the latest research progress of the regulation of metabolic reprogramming by TCM on tumor metastasis was reviewed. At the same time， the key targets of TCM and its bioactive components in the process of tumor metastasis intervention were reviewed. This study aims to provide a more valuable basis and clearer idea for the treatment of malignant tumor metastasis by regulating metabolic reprogramming with TCM.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However， there are many toxic side effects in clinical application， which seriously hinder the treatment process. Therefore， it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine （TCM） has a long history of treating colorectal cancer and offers advantages such as safety， effectiveness， multiple targets， multiple pathways and minimal toxic side effects， which have made it increasingly popular worldwide. According to TCM， the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer， such as Jianpi compound， Jianpi Xiaoai decoction， and Bushen Jiedu Sanjie decoction. TCM monomers， such as emodin， berberine， and tanshinone， mainly focus on clearing heat and removing toxin， circulating blood and transforming stasis， and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis， and research has shown that pathways such as Wnt/β-catenin， phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt）， Janus kinase 2/signal transduction and transcription activating factor 3 （JAK2/STAT3）， nuclear factors-κB （NF-κB）， vascular endothelial growth factor （VEGF） play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review， we searched various literature databases， such as PubMed， China National Knowledge Infrastructure （CNKI）， and VIP， using keywords such as "colorectal cancer"， "signaling pathway"， "invasion and metastasis"， and "traditional Chinese medicine"， to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

Staphylococcus aureus is a Gram-positive bacterium with strong pathogenicity. With the widespread use of antibiotics， its multi-drug resistance has gradually increased. Among them， methicillin-resistant S. aureus （MRSA） is one of the main pathogens of hospital and community infections. Antimicrobial peptides are short-chain peptides with good antibacterial effects and low drug resistance， which have been widely studied in recent years. This study summarizes the mechanism of action of antimicrobial peptides and related study on antimicrobial peptides against MRSA from different sources. It is found that the mechanisms of action of antimicrobial peptides include targeting bacterial cell membranes， bacterial cells， and bacterial cell walls， etc. Besides isolating antimicrobial peptides with anti-MRSA activity from animals， plants， and microorganisms， antimicrobial peptides can also be obtained through synthetic methods. Among them， GHa-derived peptides from animal sources， Ib-AMP4 from plant sources， Ph-SA from microbial sources， the synthetic peptide LLKLLLKLL-NH2， and so on， due to their effective antibacterial activity， rapid bactericidal speed， and low toxicity， are promising candidates for anti-MRSA drugs.

[Objective] To analyze the clinicopathological characteristics of treatment-naive patients with highly suspected prostate cancer (PCa) with prostate-specific antigen (PSA) level ≥20 ng/mL, to provide reference for promoting early screening of PCa. [Methods] A retrospective analysis was conducted on the clinical data of treatment-naive patients with PSA level ≥20 ng/mL, undergoing prostate biopsy for highly suspected PCa at the Department of Urology, Tianjin Medical University Second Hospital during Jan.2013 and Jun.2023. The correlation between patients' age, body mass index (BMI), PSA, prostate volume (PV), prostate cancer-specific antigen density (PSAD), prostate imaging reporting and data system (PI-RADS) score, and International Society of Urological Pathology (ISUP) grade with highly suspected PCa metastasis and PSA stratification were analyzed. [Results] A total of 1778 suspected patients were enrolled. Pathological findings confirmed PCa in 1465 cases (82.4%), with 487(33.2%) diagnosed as metastatic PCa. Over the past decade, the number of patients undergoing prostate biopsy for highly suspected PCa and being confirmed has been increasing annually, with the proportion of metastatic cases remaining at around 30%. Compared with those with PSA level being 20-50 ng/mL, patients with PSA level >50 ng/mL had older age, lower BMI, higher PSAD, higher PI-RADS, higher ISUP, more diverse pathological types, and a higher incidence of metastasis (P<0.05) with lower proportion of urban residents. Additionally, analysis of metastatic PCa cases showed that 46.8%(228/487) had oligometastasis (≤5 metastatic lesions), including 99.0% bone metastasis, 4.1% extraregional lymph node metastasis, and 4.3% other organ metastasis. [Conclusion] Over the past 10 years, there has been a continuous increase in the number of treatment-naive biopsied cases and newly diagnosed cases of highly suspicious PCa with PSA level ≥20 ng/mL, while the proportion of metastatic cases remains high. Therefore, proactive efforts should be made to promote early screening of high-risk suspected cases.

OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.

OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.