BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl₄)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl₄-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7's interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl₄-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.

Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Hepatectomy is the most important curative treatment for liver neoplasms, and its deve-lopment has experienced such concepts as local resection, irregular resection, regular resection and anatomic resection. With the enhanced understanding of hepatic anatomy, the progression of hepatic parenchymal dissection devices and the implementation of controlled low central venous pressure strategies, both open and minimally invasive hepatectomy have gained great popularity and development. Under the guidance of the concept of precision surgery, anatomic resection has garnered increasing attention, yet a contentious debate persists regarding the selection between anatomic and non-anatomic liver resection. In clinical practice, it is imperative to conduct a comprehensive evaluation of the tumor's location, size, biological characteristics, and hepatic function. This evaluation should consider the safety and thoroughness of the surgical procedure, as well as the potential for tumor recurrence and the subsequent follow-up treatment. Ultimately, the selection of surgical methods should be based on maximizing the patient's benefits. This paper reviews and discusses the published literatures, both domestic and abroad, on the norms and research progress of anatomic liver resection for hepatocellular carcinoma.

Objective:To establish HPLC chromatogram for Aspongopus; To determine 8 nucleoside components of uracil, adenine, uridine, uric acid, hypoxanthine, adenosine, xanthine and canine quinolinic acid; To provide reference for quality control and evaluation.Methods:The Agilent ZORBAX SB-Aq chromatographic column (4.6 mm×250 mm, 5 μm) was used for gradient elution with mobile phases consisting of a methanol (A) and 0.05% phosphoric acid (B). The column temperature was 25 ℃, the flow rate was 0.8 ml/min, and the detection wavelength was 254 nm. HPLC chromatograms for Aspongopus were established and the contents of 8 components were determined.Results:The characteristic chromatogram of 15 batches aspongopus herbs was established. A total of 10 common characteristic peaks were identified and 8 were identified. The similarity between the characteristic chromatogram of samples and the control chromatogram was 0.969-0.997. The content determination showed that the linear range of uracil, adenine, urin, uric acid, hypoxanthine, adenosine, xanthine and xanuric acid was among 0.002 0-0.644 0, 0.001 4-0.448 0, 0.001 0-1.257 0, 0.005 4-6.221 0, 0.001 0-0.724 0, 0.001 0-0.644 0, 0.002 0-1.113 0, 0.003 8-2.059 0 μg, respectively, with a good linear relationship ( r≥0.999); the repeatability and stability of RSD were <2.0%, and the average sampling recovery rate was between 99.36% and 103.40%. Conclusion:The characteristic chromatogram and content determination method established in this study are simple, reliable, reproducible and accurate, and can be used for the qualitative and quantitative analysis of Aspongopus and can provide a reference for the quality evaluation method of the Aspongopus.

Objective To establish an ultra-high liquid chromatography(UPLC)characteristic spectrum of Rheum tanguticum Maxim.ex Balf.water decoction and conduct chemical pattern recognition analysis,and to identify the medicinal materials of different origins and different processed products.Methods:UPLC was adopted to establish the characteristic spectra of 15 batches of Rheum tanguticum Maxim.ex Balf.Cluster analysis combined with principal component analysis was used to analyze their quality.Rhei Radix et Rhizoma from different origins and different processed products of Rheum tanguticum Maxim.ex Balf.were identified.Results:The characteristic spectrum of Rheum tanguticum Maxim.ex Balf.water decoction was established,18 common peaks were identi-fied,and 15 batches of Rheum tanguticum Maxim.ex Balf.were divided into 2 categories according to their origins by cluster analysis.The similarity between 15 batches of samples from different origins and the control spectrum was greater than 0.900.According to OPLS-DA analysis,a total of 6 markers(rhein-8-O-β-D-glu-cosid,resveratrol-4'-O-β-D-(6''-O-D-gallyl)glucopyranside,isolindleyin,rhein,epicatechin-3-O-D-gallate,and catechin)affecting the quality of Rheum tanguticum Maxim.ex Balf.water decoction samples were found.Rhei Radix et Rhizoma from different origins and different processed products of Rheum tanguticum Maxim.ex Balf.can be effectively distinguished.Conclusion:The established characteristic spectrum method is easy to operate and has good repeatability.It can be used for the quality control of Rheum tanguticum Maxim.ex Balf.water decoction,and can provide reference for the formulation of quality standard of formula granules of Rhei Radix et Rhizoma.

Objective:Ventricular septal defect(VSD)is a prevalent congenital cardiac anomaly.By enhancing the occluder design and optimizing procedural approaches,the indications for VSD closure can be broadened while minimizing associated complications.The utilization of fully biodegradable occluder holds promising potential in resolving conduction block issues encountered during VSD closure.This study aims to compare the results of the fully biodegradable occluder with the metal occluder in transoesophageal echocardiography-guided VSD closure via lower sternal level minor incision at the interim follow-up,and to find risk factors for the occurrence of electrocardiographic and valvular abnormalities postoperatively. Methods:We reviewed the postoperative and 3-year follow-up data of all patients who underwent the randomized controlled study of VSD closure from January 1 to November 7,2019 in the Second Xiangya Hospital of Central South University.The safety and efficacy of the procedure were assessed and compared between the 2 groups by electrocardiogram and echocardiography results,and the risk factors for the occurrence of postoperative electrocardiogram and valve abnormalities were studied with Logistic regression analysis. Results:Twelve and fifteen patients underwent VSD closure with the metallic occluder and the fully biodegradable occluder,respectively.All patients survived during the follow-up period without major complications such as atrioventricular block,significant residual shunt,too rapid absorption of the occluder,and significant valvular regurgitation.There were no significant differences in the results of electrocardiograph and color Doppler ultrasonography the metal occluder group and the fully biodegradable occluder group 1,2,and 3 years after operation(all P>0.05).The size of the occluder were risk factors for tricuspid regurgitation at 2 and 3 years postoperatively,and the difference between the occluder size and the VSD defect size were risk factors for tricuspid regurgitation at 2 years postoperatively(P<0.05). Conclusion:This study adequately demonstrates the safety and efficacy of fully biodegradable occluders in small VSD closure and shows the same postoperative effects as conventional nitinol occluders.

Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.