Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (I_Na.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC₅₀) values of Mel on transient sodium current (I_Na.T) and specific I_Na.L opener 2 nmol·L^-1 sea anemone toxins II (ATX II) increased I_Na.L were 686.615 and 7.37 μmol·L^-1, respectively. Mel did not affect L-type calcium current (I_Ca.L), transient outward current (I_to), and AP. In addition, 16 μmol·L^-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking I_Na.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

As a new transdermal drug delivery system, microneedles can significantly improve skin permeability, enhance drug transdermal delivery, and demonstrate unique advantages in breaking stratum corneum barrier of skin. This feature enables microneedles to demonstrate enormous potential in delivering biotechnology drugs. The traditional delivery method for biotechnology drugs is mainly injection, which brings problems such as pain and skin redness to patients, leading to poor patient compliance. In addition, the production, transportation, and storage of biotechnology drugs require strict low-temperature conditions to maintain their activity and increase cost output. Microneedles, by contrast, have many benefits, providing new avenues and solutions for biomolecular delivery. Accordingly, this review introduced the microneedle drug delivery system for delivery biotechnology drugs, and summarized the research progress of microneedle systems in biotechnology drugs.

Objective To observe the regulating effect and mechanism of Yichang Sanjie Granules on intestinal flora and immune function in mice with colon cancer.Methods Sixty mice were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Yichang Sanjie Granules,and the overexpression of melanoma absent gene 2(AIM2)plasmid(pcDNA-AIM2)intervention group,with 10 mice in each group.Colorectal cancer model was prepared by oxidized azomethine(AOM)/dextran sulfate sodium(DSS)induction method in all groups except normal group.After drug administration,the survival curves of mice in each group were plotted and the tumor volume was calculated;serum levels of immunoglobulin(Ig)G,IgM,interleukin(IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA);peripheral blood levels of CD3+,CD4+,CD8+ T cells were detected by flow cytometry;the splenic index was determined;Hematoxylin-eosin(HE)staining was used to observe the pathological changes in colon tissues;16S-rDNA intestinal flora sequencing was used to detect the α-diversity of intestinal flora and the structure of intestinal flora communities;and protein immunoblotting(Wetsern Blot)was used to detect the protein expressions of AIM2,apoptosis-associated speckled-like protein containing a CARD(ASC),and cystatinase-1(caspase-1)in colon tissues.Results Compared with the normal group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the model group were significantly decreased,and the tumor volume,serum levels of IL-1β and IL-18,peripheral blood level of CD8+,and splenic index were significantly increased(all P＜0.05),and the HE staining results showed the characteristic manifestations of colon cancer;compared with the model group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group were significantly increased,and the tumor volume,serum levels of IL-1β and IL-18,level of peripheral blood CD8+,and splenic index were significantly decreased(all P＜0.05),and the HE staining results showed the manifestations of colon cancer were improved.Compared with the normal group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group,and Ruminiclostridium in the model group were significantly decreased,while the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was increased in the model group(P＜0.05);compared with the model group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group and Ruminiclostridium were significantly increased,and the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was decreased in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group(all P＜0.05).Conclusion Yichang Sanjie Granules can increase autoimmunity and improve intestinal flora structure in mice with colon cancer,and its mechanism is related to the activation of AIM2 inflammatory vesicles.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective To investigate the protective effect and mechanism of propofol on the blood-brain barrier in rats with cerebral ischemia.Methods A total of 48 10-week-old male SD rats were randomly divided into the sham group,the cerebral ischemia group,the propofol group and the propofol+LY294002 group.Twenty-four hours before the induction of the model,the rats in the propofol+LY294002 group were intracerebroventricularly injected with PI3K inhibitor LY294002(0.3 mg·kg-1),and the rats in the other groups were administrated with saline(10 μL).Rats in the cerebral ischemia group,the propofol group and the propofol+LY294002 group established cerebral ischemia models by carotid artery occlusion.Rats in the sham group only isolated the common carotid artery and ligated the external carotid artery without other treatment.During the modeling period,the rats in the propofol group and the propofol+LY294002 group were given propofol(10 mg·kg-1)via the tail vein,and the sham group and the propofol group were treated with saline.After 24 hours,the neurological function of rats was evaluated by Zea Longa method;the area of cerebral infarction was detected by TTC staining;the degree of cerebral edema was detected by the dry-wet weight method.EB tracer method was used to evaluate the integrity of the blood-brain barrier;ELISA was used to detect inflammatory cytokines in cerebrospinal fluid;Western blot was used to detect the expression of PI3K/AKT signaling pathway proteins and blood-brain barrier tight junction proteins Claudin-5 and Occludin.Results Cerebral ischemia led to the increase of neurological function scores and local infarction of brain tissues in rats.Compared with the sham group,the EB content in the brain tissue of rats in the cerebral ischemia group increased,the degree of brain edema increased,and the content of inflammatory cytokines in the cerebrospinal fluid increased.And the use of propofol could significantly decrease the neurological function scores,reduce the area of cerebral infarction,inhibit EB penetrating blood-brain barrier,reduce the degree of brain edema,reduce the release of inflammatory cytokines,and up-regulate the expression of PI3K/AKT signaling pathway proteins and tight junction proteins Claudin-5 and Occludin.LY294002 significantly reversed the above effects of propofol.Conclusion Propofol can maintain the expression of tight junction proteins Claudin-5 and Occludin through the PI3K/AKT signaling pathway,protect the structural and functional integrity of blood-brain barrier,reduce the degree of brain edema,prevent other inflammatory cytokines into the brain tissue,reduce cerebral infarction,and alleviate the neurological functional damage caused by cerebral ischemia.

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

The research status of the actuation technology of wearable exoskeletons was introduced.Kinds of actuation technologies and actuators were analyzed in terms of advantage,disadvantage and applicable scenario.It's pointed out the actuation technology of wearable exoskeletons should be oriented to high-performance micro-motors,new actuators,actuation modularity and intellectualization.[Chinese Medical Equipment Journal,2024,45(4):104-110]

The current research status of different structures,driving modes and training modes of hand rehabilitation robots at home and abroad was introduced.The disadvantages of the existing hand rehabilitation robots were analyzed.It's pointed out hand rehabilitation robots in the future would involve in the combination of rigid and flexible wearing,new intelligent driving mode and multi-mode rehabilitation training.[Chinese Medical Equipment Journal,2024,45(11):88-96]

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.
Humans ; Potassium Channels ; Medicine, Chinese Traditional ; Anti-Arrhythmia Agents/therapeutic use* ; Arrhythmias, Cardiac/drug therapy* ; Heart Diseases/drug therapy* ; Ions

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Facial Paralysis/etiology* ; Diagnosis, Differential ; Jugular Foramina ; Retrospective Studies ; Cough ; Hoarseness ; Neoplasm Recurrence, Local ; Chondrosarcoma/surgery*