ObjectiveTo compare the contents and relative molecular weight distributions of proteins and polypeptides in Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules of Hirudo single medicinal preparations， to evaluate the in vitro anticoagulant， antiplatelet and fibrinolytic activities of the three preparations， and to investigate the effects of temperature， pH and digestive enzymes on the anticoagulant activities of the three preparations. MethodsThe contents of soluble proteins and polypeptides in the three preparations were determined by bicinchoninic acid assay（BCA） and Bradford method， and the relative molecular weight distributions of the three preparations were determined by electrophoresis combined with gel chromatography. The antithrombin activity of the three preparations was evaluated by fibrinogen-thrombin time（Fibg-TT） method， and their anticoagulant activities were further assessed by the elongations of activated partial thromboplastin time（APTT）， prothrombin time（PT） and thrombin time（TT）. The antiplatelet aggregation activities of the three preparations were measured by turbidimetry and the fibrinolytic activities were measured by fibrin plate method. Relative TT was used as index to investigate the effects of temperature， pH and digestive enzyme buffer on anticoagulant activities of the three preparations. ResultsAt the lowest single dosage， the contents of proteins and polypeptides were in the order of Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. Both Huoxue Tongmai capsules and Maixuekang capsules had 11 electrophoretic bands between 4.0 kDa and 90 kDa， the bands of Maixuekang capsules were more clear in the range of >25 kDa， and there was 1 obvious band at 14 kDa for the two capsules. Huoxue Tongmai capsules had one specific band at 9.0 kDa and Maixuekang capsules had one specific band at 48.0 kDa. Naoxuekang dropping pills only had 2 electrophoretic bands at 6.5 kDa and 8.5 kDa， primarily containing peptides below 2 kDa， most of which were oligopeptides. The anticoagulant activity concentrations of the three preparations exhibited a certain dose-dependent effect. At the lowest single dosage， The anticoagulant activity concentrations were ranked as Naoxuekang dropping pills>Huoxue Tongmai capsules>Maixuekang capsules. The prolongation effect of the three preparations on coagulation time was dose-dependent. At the same concentration， the prolongation effect of Naoxuekang dropping pills and Huoxue Tongmai capsules was APTT prolongation rate>TT prolongation rate>PT prolongation rate， whereas for Maixuekang capsules， the sequence was TT prolongation rate>APTT prolongation rate>PT lengthening rate. At the single minimum dosage， the order of APTT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules≈Naoxuekang dropping pills， the order of PT prolongation rate was Naoxuekang dropping pills≈Maixuekang capsules>Huoxue Tongmai capsules， and the order of TT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. The three preparations showed dose-dependent effects on platelet aggregation induced by adenosine diphosphate（ADP） and arachidonic acid（AA）， and the effect induced by ADP was stronger than that induced by AA. The anti-platelet aggregation effect of Naoxuekang dropping pills was significantly stronger than that of Maixuekang capsules（P<0.01）， whereas Huoxue Tongmai capsules had the effect of promoting platelet aggregation. None of the three preparations had the ability to dissolve fibrin. The anticoagulant activity of Naoxuekang dropping pills was least affected by heating， while the activities of the two capsules decreased significantly within 5 min above 80 ℃， and continued to decrease within 2 h. Compared with pure water， the anticoagulant activities of the three preparations could be increased by 1-3 times under strong acidity（pH 1-3）. In the pepsin buffer， the anticoagulant activity of Naoxuekang dropping pills could be increased by 1-3 times， while the anticoagulant activities of Huoxue Tongmai capsules and Maxuekang capsules were significantly decreased， the lowest levels were about 60% and 20%， respectively. In trypsin buffer， the anticoagulant activities of Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules decreased significantly， and the lowest levels decreased to about 41%， 41% and 35%， respectively. ConclusionThe contents of proteins and polypeptides and relative molecular weights of the preparations derived from lyophilized fresh Hirudo powder， dried Hirudo powder and reflux extract of Hirudo decrease sequentially， and the anticoagulant activity decrease gradually， but the anticoagulant pathway is different. And the anti-platelet aggregation activity of the reflux extract is significantly enhanced. The heat resistance and gastrointestinal stability of the three preparations increase successively， and the first two are suitable for enteric-soluble preparations， while the latter is suitable for routine oral administration. The above results can provide data reference for the rationality of different preparation methods， active substances， pharmacodynamics and mechanism of Hirudo preparations.

Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Aim Excessive cerebral inflammation caused by chronic alcohol intake is an important risk factor for central nervous system injury. The purpose of this study was to explore the protective effect of konjac mannan oligosaccharide (KMOS) on central nervous system inflammation in alcohol-fed mice and its mechanism. Methods The chronic alcohol fed model of C57BL/6J mice was established using Gao-binge method. And the different doses of KMOS were gavaged every day for 6 weeks. The neuronal damage and microglia activation were evaluated in cerebral cortex and hippocampus. The damage of colon tissue was assessed and serum LPS concentrations were measured. In vitro, Caco-2 cells were stimulated with LPS to establish intestinal mucosal injury model. Results Chronic alcohol intake can cause brain neuron damage in mice, and different doses of KMOS effectively reduced the activation state of microglia, decreased the expression of inflammatory factors caused by the activation of the NLRP3 inflammasome and alleviated neuronal damage in the brain tissue of alcohol-fed mice. The results of colon tissue analysis showed that the use of KMOS effectively reduced the concentration of endotoxin LPS in serum of alcohol-fed mice, alleviated the pathological injury and inflammatory response of colon tissue, and enhanced the expression of Occludin in intestinal tissue. In vitro experiments also showed that KMOS significantly inhibited the inflammatory reaction of Caco-2 cells exposed to alcohol and increased the expression of Occludin protein. Conclusions KMOS treatment effectively inhibited intestinal inflammation caused by alcohol intake, repaired intestinal barrier to prevent the entry of intestinal LPS into brain tissue, decreased the activation of microglia, and then improved brain neuron damage. KMOS had the potential to prevent alcoholic nerve injury.

OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of cinacalcet and etelcalcetide， to provide a reference for safe drug use in the clinic. METHODS ADE reports related to cinacalcet and etelcalcetide were extracted from the FDA Adverse Event Reporting System from January 1st， 2004 to June 30th， 2023 using the OpenVigil online tool. The Bayesian confidence propagation neural network method was adopted to detect the signals of ADE from the key organ systems. The signals were encoded according to the preferred term in the ADE terminology set of the Medical Dictionary for Regulatory Activities （26.0 edition）. RESULTS A total 41 709 and 1 710 ADE reports were extracted， and 29 and 45 safety signals were detected in key systems for cinacalcet and etelcalcetide， respectively； 20 and 36 positive signals were not included in the drug instructions. Hypocalcemia/decreased serum calcium， abnormal blood parathyroid hormone （PTH）/increased or decreased serum PTH were common ADEs of the two drugs， which were detected in the study. Among the signals not included in the drug instructions， new moderate and strong signals were detected， such as cinacalcet-induced calcification defense （metabolic and nutritional diseases）， bone starvation syndrome and high conversion bone diseases （musculoskeletal and connective tissue diseases） as well as etelcalcetide-induced sudden death， necrosis and treatment of non-responders （general disorders， administration site）， unstable angina pectoris， myocardial ischemia （cardiac diseases）， intestinal perforation， gastric antrum vasodilation and gastric ulcer （gastrointestinal diseases）. CONCLUSIONS In the clinical application of the two drugs， apart from the common ADEs such as hypocalcemia and abnormal blood PTH， the surveillance of some new potential ADEs should also be carried out， such as bone starvation syndrome， calcification defense， ventricular disease and other cinacalcet-induced ADEs， sudden death， myocardial ischemia， unstable angina pectoris， intestinal perforation， gastric ulcer and other etecalcetide-induced ADEs. If new ADEs appear， clinic should promptly assess the benefits and risks， and update the treatment plan and pharmacological monitoring plan to ensure the safety of patient medication.

Transarterial chemoembolization （TACE） is currently the primary treatment method for advanced liver cancer. This article elaborates on the current status of application of TACE in hepatocellular carcinoma from the aspects of existing techniques， patient selection， and efficacy assessment and summarizes the research advances and prospects of TACE combined with local treatment and systemic therapy， so as to provide new ideas for clinical practice and experimental studies.

OBJECTIVE To study the antifungal activity of Huangqin decoction （HQD） against Trichophyton mentagrophytes and explore its mechanism. METHODS Minimal inhibitory concentration （MIC）， minimal fungicidal concentration （MFC）， mycelial length， spore germination rate， biomass and mycelium ultrastructure observation were performed to evaluate the antifungal activity of HQD against T. mentagrophytes. The effects of HQD on the cell wall of T. mentagrophytes were detected through sorbitol protection experiment. By measuring the content of ergosterol and the activities of squalene epoxide （SE） and lanosterol 14α-demethylase （CYP51）， the activity of HQD on the cell membrane of T. mentagrophytes was investigated. The effects of HQD on T. mentagrophytes mitochondria were investigated by determining the activities of malate dehydrogenase （MDH）， succinate dehydrogenase （SDH）， and ATPases （including sodium potassium ATPase， calcium magnesium ATPase， and total ATPase）. RESULTS HQD exhibited significant antifungal activity against T. mentagrophytes with MIC of 3.13 mg/mL and MFC of 25 mg/mL. After intervention with HQD， the mycelial length of T. mentagrophytes was significantly shortened （P＜0.05）； spore germination rate， biomass， the content of ergosterol in the cell membrane， the activities of SE and CYP51 in the cell membrane and MDH， SDH and ATPase in mitochondria were all decreased significantly （P＜0.05）； cell structure had been ；damaged to a certain extent， but the integrity of the cell wall had not been affected. CONCLUSIONS HQD shows significant antifungal activity against T. mentagrophytes， the mechanism of which may be associated with reducing the 0791- content of ergosterol in the cell membrane and the activities of SE， CYP51， and mitochondria-related enzymes.

Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

Objective:To analyze the effect of different vascular access on the outcome in peripheral blood stem cells collection by a network Meta-analysis, and to provide a reference for clinical medical staff to select the best vascular access.Methods:A systematic search was carried out in Chinese Knowledge Infrastructure database (CNKI), Wanfang Database, VIP Database, Chinese Biomedical Literature Database, Cochrane Library, Web of Science, PubMed, Embase, from inception until April 15, 2023. Two researchers independently screened literature and extracted data. Bayesian network meta-analysis was performed using R4.2.2 and Addis-1.16.6 softwares.Results:A total 7 pieces of research were included, 5 vascular access methods were peripheral artery, peripheral vein, artery-vein, femoral vein-central venous catheter (FV-CVC), and internal jugular vein-CVC (IJV-CVC). The results showed that compared with the peripheral veins, there was no significant difference on CD34 cells between other vascular accesses in the primary outcome measure when collected peripheral blood stem cell collection. On the single blood volume treatment time, peripheral vein and IJV-CVC were statistically significant ( MD = 14.80, 95% CI 2.70-22.38, P<0.05) . The SUCRA ranking probability chart showed that on CD34 cells, FV- CVC>IJV-CVC>artery-vein>peripheral artery>peripheral vein access; for a single blood volume treatment time and monocyte number, peripheral artery was superior and the next was peripheral vein. Conclusions:Current evidence suggested that Peripheral artery may be the best vascular access in peripheral blood stem cells collection, which opens a new way to establish the vascular access for peripheral blood stem cells collection, but it needs to be confirmed by large clinic trials.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To investigate the clinical efficacy of bilateral V-Y advancement island flaps on buttocks in repairing postoperative defects in patients with perianal Paget′s disease.Methods:From January 2009 to January 2021, a retrospective analysis was performed on clinical data collected from 13 patients with perianal Paget′s disease, whose perianal defects resulting from the tumor resection were reconstructed with bilateral V-Y advancement island flaps on the buttocks in the Department of Dermatology, Hangzhou Third People′s Hospital. The postoperative recovery of the buttocks and the effects on the defecation function were evaluated.Results:The areas of perianal defects in 13 cases ranged from 4.8 cm × 5.6 cm to 12.2 cm × 6.4 cm. All defects were successfully repaired by using the bilateral V-Y advancement island flaps, and all surgical wounds healed primarily. One case first received temporary ileostomy, and then received ileostomy closure 3 months later, resulting in the recovery of defecation function; in another 1 case of perianal Paget′s disease comorbid with rectal cancer, the permanent sigmoid colostomy was performed to divert feces, and the defecation function was lost. After the follow-up for 1 - 6 years, the buttocks were symmetrical in shape in all the 13 patients, and 12 with preserved anus had normal defecation function. No tumor recurrence was observed in 12 patients without other malignant tumors after the operation, while 3 patients experienced mild anal stenosis without anal mucosa eversion or wound dehiscence; 1 patient with perianal Paget′s disease complicated by anal canal adenocarcinoma developed bilateral inguinal lymph node and internal iliac lymph node metastasis 1 year after the operation, and died 6 months later.Conclusion:The bilateral V-Y advancement island flaps on the buttocks have the advantages of reliable blood supply and sufficient advancement mobility, and can be used to repair large skin defects around the anus.