AIM:To measure preoperative corneal curvature in elderly cataract patients using five different systems, including Keratograph 5M, Pentacam, KR.800 autorefractor, IOL Master, and KR-1W wavefront aberrometer, analyze its discrepancy and consistency, and provide a reference for accurate intraocular lens(IOL)power calculation in elderly patients before cataract surgery.METHODS:This prospective study included 53 elderly cataract in-patients(90 eyes)who were admitted to our ophthalmology department between October 2022 and November 2024. The corneal curvature values(K1, K2)of postoperative eyes were measured using Keratograph 5M, Pentacam, KR.800, IOL Master, and KR-1W, and the mean keratometry(Km)was calculated.RESULTS:Statistically significant differences were observed in K1, K2, and Km values between Keratograph 5M and Pentacam, as well as between Keratograph 5M and IOL Master(all P<0.05), whereas no significant differences were found in K1, K2 and Km between Keratograph 5M and KR.800 or KR-1W(all P>0.05). Pearson correlation analysis showed a certain correlation of K1, K2 and Km obtained from Keratograph 5M with those from KR.800, Pentacam, IOL Master, and KR-1W(r=0.913-0.987, all P<0.001). Bland-Altman scatter plots demonstrated good consistency between Keratograph 5M and KR.800 or KR-1W, while its consistency with Pentacam and IOL Master was relatively poor.CONCLUSION:As an ocular surface analyzer, Keratograph 5M offers advantages such as simplicity, rapid measurement, strong repeatability, and low patient cooperation requirements. In elderly patients, corneal curvature measurements obtained by Keratograph 5M demonstrated good consistency with those from KR.800 and KR-1W, making them interchangeable based on individual conditions and cooperation levels of patients. However, its consistency with Pentacam and IOL Master was relatively poor; therefore, clinical practical situation should be considered when selecting such measurement devices.

Clathrin-mediated endocytosis (CME) is a critical process by which cells internalize macromolecular substances and initiate vesicle trafficking, serving as the foundation for many cellular activities. Central to this process are clathrin-coated structures (CCSs), which consist of clathrin-coated pits (CCPs) and clathrin plaques. While clathrin-coated pits are well-established in the study of endocytosis, clathrin plaques represent a more recently discovered but equally important component of this system. These plaques are large, flat, and extended clathrin-coated assemblies found on the cytoplasmic membrane. They are distinct from the more typical clathrin-coated pits in terms of their morphology, larger surface area, and longer lifespan. Recent research has revealed that clathrin plaques play roles that go far beyond endocytosis, contributing to diverse cellular processes such as cellular adhesion, mechanosensing, migration, and pathogen invasion. Unlike traditional clathrin-coated pits, which are transient and dynamic structures involved primarily in the internalization of molecules, clathrin plaques are more stable and extensive, often persisting for extended periods. Their extended lifespan suggests that they serve functions beyond the typical endocytic role, making them integral to various cellular processes. For instance, clathrin plaques are involved in the regulation of intercellular adhesion, allowing cells to better adhere to one another or to the extracellular matrix, which is crucial for tissue formation and maintenance. Furthermore, clathrin plaques act as mechanosensitive hubs, enabling the cell to sense and respond to mechanical stress, a feature that is essential for processes like migration, tissue remodeling, and even cancer progression. Recent discoveries have also highlighted the role of clathrin plaques in cellular signaling. These plaques can serve as scaffolds for signaling molecules, orchestrating the activation of various pathways that govern cellular behavior. For example, the recruitment of actin-binding proteins such as F-actin and vinculin to clathrin plaques can influence cytoskeletal dynamics, helping cells adapt to mechanical changes in their environment. This recruitment also plays a pivotal role in regulating cellular migration, which is crucial for developmental processes. Additionally, clathrin plaques influence receptor-mediated signal transduction by acting as platforms for the assembly of signaling complexes, thereby affecting processes such as growth factor signaling and cellular responses to extracellular stimuli. Despite the growing body of evidence that supports the involvement of clathrin plaques in a wide array of cellular functions, much remains unknown about the precise molecular mechanisms that govern their formation, maintenance, and turnover. For example, the factors that regulate the recruitment of clathrin and other coat proteins to form plaques, as well as the signaling molecules that coordinate plaque dynamics, remain areas of active research. Furthermore, the complex interplay between clathrin plaques and other cellular systems, such as the actin cytoskeleton and integrin-based adhesion complexes, needs further exploration. Studies have shown that clathrin plaques can respond to mechanical forces, with recent findings indicating that they act as mechanosensitive structures that help the cell adapt to changing mechanical environments. This ability underscores the multifunctional nature of clathrin plaques, which, in addition to their role in endocytosis, are involved in cellular processes such as mechanotransduction and adhesion signaling. In summary, clathrin plaques represent a dynamic and versatile component of clathrin-mediated endocytosis. They play an integral role not only in the internalization of macromolecular cargo but also in regulating cellular adhesion, migration, and signal transduction. While much has been learned about their structural and functional properties, significant questions remain regarding the molecular mechanisms that regulate their formation and their broader role in cellular physiology. This review highlights the evolving understanding of clathrin plaques, emphasizing their importance in both endocytosis and a wide range of other cellular functions. Future research is needed to fully elucidate the mechanisms by which clathrin plaques contribute to cellular processes and to better understand their implications for diseases, including cancer and tissue remodeling. Ultimately, clathrin plaques are emerging as crucial hubs that integrate mechanical, biochemical, and signaling inputs, providing new insights into cellular function and the regulation of complex cellular behaviors.

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To study the pharmacokinetic characteristics of lamotrigine tablets in Chinese healthy subjects under fasting and fed conditions,and to evaluate the bioequivalence and safety profiles between the domestic test preparation and the original reference preparation.Methods Twenty-four Chinese healthy male and female subjects were enrolled under fasting and fed conditions,18 male and 6 female subjects under fasting conditions,17 male and 7 female subjects under fed conditions.A random,open,single-dose,two preparations,two sequences and double-crossover design was used.Plasma samples were collected over a 72-hour period after give the test or reference preparations 50 mg under fasting and fed conditions.The concentration of lamotrigine in plasma was detected by liquid chromatography-tandem mass spectrometry,and the main pharmacokinetic parameters were calculated to evaluate the bioequivalence by WinNonLin 8.1 program.Results The main pharmacokinetic parameters of single-dose the tested and reference preparations were as follows:The fasting condition Cmax were(910.93±248.02)and(855.87±214.36)ng·mL-1;tmax were 0.50(0.25,4.00)and 1.00(0.25,3.50)h;t1/2 were(36.1±9.2)and(36.0±8.2)h;AUC0_72h were(27 402.40±4 752.00)and(26 933.90±4 085.80)h·ng·mL-1.The fed condition Cmax were(701.62±120.67)and(718.95±94.81)ng·mL-1;tmax were 4.00(1.00,5.00)and 4.00(0.50,5.00)h;t1/2 were(44.2±12.4)and(44.0±12.0)h;AUC0-72h were(30 253.20±7 018.00)and(30 324.60±6 147.70)h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax and AUC0-72 hfor the test preparation and reference preparation were all between 80.00％and 125.00％under fasting and fed conditions.Conclusion Two kinds of lamotrigine tablets are bioequivalent,and have similar safety in Chinese healthy male and female subjects under fasting and fed conditions.

Objective To observe clinical outcomes of propofol and remazolam in patients undergoing elective painless fiberoptic bronchoscopic biopsy.Methods Patients who underwent painless fibreoptic bronchoscopic biopsy in our hospital from March 2022 to April 2023 were selected for the study and divided into 2 groups using simple randomisation method.In the control group,anaesthesia was induced with 1 mg·kg-1 propofol,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 4-6 mg·kg-1·h-1 propofol.In the treatment group,anaesthesia was induced with 0.2 mg·kg-1 remazolam,3 μg·kg-1 fentanyl,0.1 mg·kg-1 cis-atracurium,and anaesthesia was maintained with 0.2-0.4 mg·kg-1·h-1 remazolam.We compared the awakening time,laryngeal mask removal time,microscopy time,and the proportion of additional anaesthetics in the 2 groups,and detected the levels of S100β,neuron-specific enolase(NSE),interleukin-6(IL-6),tumour necrosis factor-alpha(TNF-α)in the 2 groups preoperatively and at 24 h postoperatively,and statistically counted the occurrences of adverse reactions in the 2 groups.Results The time for pulling out the laryngeal mask in the treatment group was significantly lower than that in the control group,while the time for microscopy,time for awakening,and proportion of additional anaesthesia drugs were not statistically significant when compared with that in the control group(all P＞0.05).The overall anaesthesia effect grading of the test group was not statistically significant when compared with the control group(P＞0.05).S100β were(0.66±0.17)and(0.78±0.21)μg·L-1;NSE were(8.47±1.78)and(11.47±2.06)μg·L-1;IL-6 were(8.64±1.21)and(12.89±1.47)pg·mL-1;TNF-α were(6.27±1.07)and(9.13±1.41)pg·mL-1,respectively,which were higher than that of preoperative period,and the treatment group was lower than that of the control group at 24 h postoperatively,and the difference was statistically significant(all P＜0.05).The incidence of adverse drug reactions in the treatment group and the control group were 13.75％and 22.50％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The use of remazolam in painless fiberoptic bronchoscopic biopsy is less neurologically damaging,stabilizes hemodynamics.

The dynamin superfamily protein (DSP) encompasses a group of large GTPases that are involved in various membrane remodeling processes within the cell. These proteins are characterized by their ability to hydrolyze GTP, which provides the energy necessary for their function in membrane fission, fusion, and tubulation activities. Dynamin superfamily proteins play critical roles in cellular processes such as endocytosis, organelle division, and vesicle trafficking. It is typically classified into classical dynamins and dynamin-related proteins (Drp), which have distinct roles and structural features. Understanding these proteins is crucial for comprehending their functions in cellular processes, particularly in membrane dynamics and organelle maintenance. Classical dynamins are primarily involved in clathrin-mediated endocytosis (CME), a process crucial for the internalization of receptors and other membrane components from the cell surface into the cell. These proteins are best known for their role in pinching off vesicles from the plasma membrane. Structually, classical dynamins are composed of a GTPase domain, a middle domain, a pleckstrin homology (PH) domain that binds phosphoinositides, a GTPase effector domain (GED), and a proline-rich domain (PRD) that interacts with SH3 domain-containing proteins. Functionally, the classical dynamins wrap around the neck of budding vesicles, using GTP hydrolysis to constrict and eventually acting as a “membrane scissor” to cut the vesicle from the membrane. In mammals, there are three major isoforms: dynamin 1 (predominantly expressed in neurons), dynamin 2 (ubiquitously expressed), and dynamin 3 (expressed in testes, lungs, and neurons). Recent studies have also revealed some non-classical functions of classical dynamins, such as regulating the initiation and stabilization of clathrin-coated pits (CCPs) at the early stages of CME, influencing the formation of the actin cytoskeleton and cell division. Drps share structural similarities with classical dynamins but are involved in a variety of different cellular processes, primarily related to the maintenance and remodeling of organelles, and can be mainly categorized into “mediating membrane fission”, “mediating membrane fusion” and “non-membrane-dependent functions”. Proteins like Drp1 are crucial for mitochondrial division, while others like Fis1, Mfn1, and Mfn2 are involved in mitochondrial and peroxisomal fission and fusion processes, which are essential for the maintenance of mitochondrial and peroxisomal integrity and affect energy production and apoptosis. Proteins like the Mx protein family exhibit antiviral properties by interfering with viral replication or assembly, which is critical for the innate immune response to viral infections. Some other proteins are involved in the formation of tubular structures from membranes, which is crucial for the maintenance of organelle morphology, particularly in the endoplasmic reticulum and Golgi apparatus. Studies on dynamin superfamily proteins have been extensive and have significantly advanced our understanding of cellular biology, disease mechanisms, and therapeutic potential. These studies encompass a broad range of disciplines, including molecular biology, biochemistry, cell biology, genetics, and pharmacology. By comprehensively summarizing and organizing the structural features and functions of various members of the dynamin superfamily protein, this review not only deepens the understanding of its molecular mechanisms, but also provides valuable insights for clinical drug research related to human diseases, potentially driving further advancements in the field.

This paper applied gas chromatography-mass spectrometry (GC-MS), network pharmacology and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) metabolomics techniques to study the material basis and mechanism of action of Ning Shen Essential Oil in anti-insomnia. The main volatile components of Ning Shen Essential Oil were analyzed by gas chromatography-mass spectrometry (GC-MS), and the insomnia-related targets were predicted using the Traditional Chinese Medicine Systematic Pharmacology Database and Analytical Platform (TCMSP) and the databases of GeneCards, OMIM and Drugbank. The insomnia model of rats was replicated by intraperitoneal injection of 4-chloro-DL-phenylalanine (PCPA). Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDUTCM20221025010). The modulating effect of Compound Ning Shen Essential Oil on anxiety behavior of rats was evaluated by behavioral related indexes. The serum levels of corticotropin-releasing hormone (CRH), adrenotropic corticotropic hormone (ACTH) and melatonin (MT) were measured by enzyme-linked immunoassay (ELISA). Rat serum and hippocampus were taken for nuclear magnetic resonance (¹H NMR) metabolomics to detect the changes of endogenous metabolites in rat serum hippocampus, to designate the differential metabolites and to construct metabolic pathways. The results showed that the exercise distance in the open field experiment and the number of times and time to enter the open arm in the elevated cross maze experiment of the rats in the model group were significantly reduced (P < 0.05, P < 0.01). The behavioral indexes of rats improved to different degrees after the administration of Ning Shen Essential Oil. The serum CRH and ACTH levels of rats in the model group increased significantly (P < 0.05, P < 0.01), and the MT level decreased significantly (P < 0.01); After the intervention, serum CRH and ACTH levels were reduced to different degrees, and MT levels could be regressed. ¹H NMR metabolomics screened 10 potential biomarkers related to insomnia, which involved in 6 potential metabolic pathways. A total of 35 components of Ning Shen Essential Oil were detected by GC-MS, the main component targets of Ning Shen Essential Oil and insomnia disease targets were intersected, a total of 172 intersecting genes were screened, and 26 core targets were identified. The study demonstrated that Ning Shen Essential Oil had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of the hypothalamic-pituitary-adrenal axis (HPA) related hormones and metabolism of amino acids, lipids and choline.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

OBJECTIVE To establish a ultra-high-performance liquid chromatography-mass spectrum/mass spectrum(UPLC-MS/MS) method for the determination of anlotinib in human plasma and assessment of clinical application. METHODS Zanubrutinib was used as internal standard and the extraction process was performed through protein precipitation method using acetonitrile, followed by separation on an Ultimate XB-C18(100 mm×2.1 mm, 3.0 μm) column using acetonitrile and 10 mmol·L−1 ammonium acetate-0.1% formic acid step-elution gradient. The flow rate was 0.6 mL·min−1 and injection volume was 5 μL. The mass analysis was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, and the mass spectrometer was set at m/z 408.1→339.1 for anlotinib and m/z 472.2→290.1 for internal standard, respectively. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability of the method and clinical application were investigated. RESULTS The method was validated over the concentration range of 1.0−100.0 ng·mL−1, with R2=0.998 4. The precision RSD was<9%, the recovery and matrix effect were 104.81%−107.32% and 102.54%−105.26%, respectively, and this method had good stability and was not affected by matrix effect. The method had been used for determined 52 advanced non-small cell lung cancer patients treated with anlotinib. The trough plasma concentration (Ctrough) was measured on day 43 after initiation of anlotinib treatment. Anlotinib Ctrough were higher than lower limit of quantitation (1.0 ng·mL−1) from 52 patients. The plasma concentration of anlotinib Ctrough was (11.38±4.29)ng·mL−1 with 37.66% coefficients of variation, which were shown large inter-patient variability. CONCLUSION This method is high sensitivity, specificity and accurate, and suitable for determination of anlotinib in human plasma.