Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

The study of active substances in traditional Chinese medicine(TCM) is the foundation of TCM pharmacology, TCM quality control, and new drug development, and it is also one of the most popular directions in TCM modernization research in recent years. Due to their diverse chemical compositions and complex component-effect relationships, Chinese medicines often require the comprehensive use of multidisciplinary technologies such as chemistry, biology, and information science to reveal their active substances and targets. In this paper, we review the innovative breakthroughs made in the past 30 years in the discovery strategies and technological means for the research of active substances in traditional Chinese medicine from the perspective of technological changes, and focus on the new direction of the research of active substances in traditional Chinese medicine under the paradigm shift of scientific research brought about by artificial intelligence, with the aim of promoting research in related fields to move in the direction of more accurate, efficient, and intelligent, and providing innovative ideas for the research of active substances in traditional Chinese medicine under the new situation.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Artificial Intelligence ; Drug Discovery/methods* ; Animals

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective:To analyse the distribution and antimicrobial resistance profile of clinical bacterial isolates in Anhui province.Methods:Surveillance data was collected from 83 members of the Anhui Antimicrobial Resistance Surveillance Network（HuiNet）during October 2022 to September 2023，to analyze the resistance of major bacteria to commonly used antibiotics and the detection of clinically common drug-resistant bacteria. The data was analyzed using WHONET 5.6 and SPSS 25.0 software.Results:A total of 201 647 clinical bacteria isolates were collected，with Gram-negative bacteria accounting for 74.8%（150 847/201 647）. The most prevalent Gram-positive bacterial strains were Staphylococus aureus（32.8%，16 648/50 800），followed by Staphylococcus epidermidis（14.0%，7 098/50 800）， Enterococcus faecalis（10.7%，5 458/50 800）， Enterococcus faecium（9.1%，4 613/50 800）and Staphylococcus hominis（7.4%，3 778/50 800）；the most prevalent Gram-negative bacterial strains were Escherichia coli（28.9%，43 577/150 847），followed by Klebsiella pneumoniae（22.5%，34 006/150 847）， Pseudomonas aeruginosa（14.7%，22 171/150 847）， Acinetobacter baumannii complex（9.4%，14 194/150 847）and Enterobacter cloacae（3.5%，5 235/150 847）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococcus aureus（MRCNS）were 39.5%（6 442/16 325）and 75.7%（12 343/16 312），respectively. No vancomycin- and teicolanin-resistant Staphylococcus were detected. The prevalence of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis were 0.5% and 0.6%，respectively. The prevalence of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae（CR-KPN）were 1.9%（805/42 956）and 11.7%（3 950/33 761），respectively. The resistance rate of CR-KPN to tigecycline was 3.9%. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CR-PAE）and Acinetobacter baumannii（CR-ABA）complex were 18.4%（3 936/21 447）and 62.9%（8 649/13 744），respectively，with low resistance rate to polycolistin B（6.9% and 1.7%，respectively）. The detection rates of MRSA，CR-ABA complex，third-generation cephalosporin-resistant Escherichia coli（CTX/CRO-R-ECO）and quinolone-resistant Escherichia coli（QNR-ECO）in northern Anhui were the highest（50.3%，72.9%，59.2% and 55.6%，respectively），which were higher than those in central and southern Anhui（ χ2=112.734 and 575.069，132.747 and 233.885，93.986 and 471.209，60.062 and 230.669，all P<0.001），and the detection rate in central Anhui was higher than that in southern Anhui（ χ2=278.671，29.219，207.395 and 80.267，all P<0.001）. The detection rates of CR-KPN and thirdgeneration cephalosporinresistant Klebsiella pneumoniae（CTX/CRO-R-KPN）in central Anhui were the highest（15.5% and 33.3%，respectively），which were higher than those in northern and southern Anhui（ χ2=156.237 and 325.533，76.928 and 180.686，all P<0.001），and the detection rate in northern Anhui was higher than that in southern Anhui（ χ2=32.202 and 25.539， P<0.001）. The detection rates of CTX/CRO-R-ECO and QNR-ECO were the highest in the elderly（55.2% and 55.8%，respectively），which were higher than those in children，and young and middle aged adults（ χ2=23.906 and 120.575，376.404 and 196.612， P<0.001）. The detection rate of CTX/CRO-R-KPN in neonates was the highest（57.1%），which was significantly higher than that in children，adults and the elderly（ χ2=46.141，38.843 and 32.093， P<0.001），and the detection rate in the elderly was higher than that in children and adults（ χ2=13.604 and 13.471， P<0.001）. The detection rates of MRSA and MRCNS were the highest in children（42.8% and 77.8%，respectively），which were higher than those in adults（ χ2=21.766 and 10.704， P<0.001）. Except MRSA and vancomycin-resistant Enterococcus faecium and faecalis，the detection rates of major drug-resistant bacteria in tertiary hospitals were higher than those in secondary hospitals（ P<0.05 or <0.01）. Conclusion:In 2023，the situation of antimicrobial resistance in Anhui province was serious，especially in northern and central Anhui，and targeted drug resistance control measures should be taken according to the monitoring results. At the same time，it is necessary to pay attention to the bacterial resistance in the elderly，newborns and children，and strengthen the rational use of antibiotics by clinicians to curb the spread of drug-resistant bacteria.

Objective:This study aims to develop a validated instrument for assessing the degree of integration perceived by patients in the services provided by general practitioner(GP)teams,and to evaluate the current state of integrated medical-prevention services.Methods:The survey tool was initially created through a review of existing literature and semi-structured interviews.It was subsequently refined and enhanced following consultations with experts.The utility of the instrument was confirmed through empirical research,which also facilitated an analysis of the status quo regarding the integration of medical and prevention services.Results:The devised instrument encompasses 18 items distributed across six dimensions:service comprehensiveness,service continuity,depth of service,continuity of relationship,patient-centricity,and service coordination.The cumulative score reflecting patients'perception of the integration level in GP teams'medical-prevention services was 54.30±12.45.Conclusion:The survey instrument developed in this research is characterized by its rationality,novelty,and practical relevance.It offers a patient-centered perspective for assessing the quality of integrated medical and prevention services for primary chronic diseases.While the overall perception of integration among patients is positive,there is a notable deficiency in the depth of services provided.There is a need for optimization of the service process,clarification of the service path,refinement of service management,and development of an integrated incentive mechanism for medical and preventive care,aiming for a deeper integration between medical services and preventive care.

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*

AIM: To explore the pathogenesis and surgical outcomes of different types of myopic traction maculopathy(MTM)using optical coherence tomography(OCT).METHODS: A total of 193 patients(210 eyes)with MTM were retrospectively included, of which 74 eyes(35.2%)underwent vitrectomy combined with internal limiting membrane(ILM)peeling. The patients were categorized into three groups: foveal detachment(FD), foveoschisis(FS)and lamellar macular hole(LMH). Based on the central foveal thickness(CFT)at baseline(M0), eyes with FD were classified into two subgroups: extensive FD and limited FD. Outcomes included best-corrected visual acuity(BCVA), CFT, posterior staphyloma height(PSH), the presence of epiretinal membrane(ERM)and ILM detachment. Risk factors for BCVA at 6mo after vitrectomy(M6)were analyzed using linear regression.RESULTS: At M0, ERM was highly present in eyes with LMH(rs=0.28, P<0.001). Eyes with FD and FS were characterized by higher incidence of ILM detachment(rs=-0.25, P<0.001). After vitrectomy, CFT and BCVA significantly improved in all eyes(P<0.001). Eyes with extensive FD were characterized by a thicker CFT(rs=0.56, P<0.001), a lower incidence of ILM detachment(rs=-0.25, P=0.034)and a thicker nasal PSH(rs=0.27, P=0.024)than eyes with limited FD. Eyes with extensive FD were associated with a worse BCVA at M0(P=0.013)and M6(P=0.030)than eyes with limited FD. Extensive FD(β=-0.295, P=0.042)and BCVA at M0(β=0.669, P<0.001)were risk factors for a worse BCVA at M6.CONCLUSION: There are several pathogenetic mechanisms in MTM. ILM detachment may exert a dominant role in the development of FD and FS, while ERM may have a role in LMH. Vitrectomy combined with ILM peeling improved functional and anatomical outcomes in MTM patients. Eyes with extensive FD may carry a poor prognosis.

Non-puerperal mastitis(NPM)is a group of chronic inflammatory diseases with breast pain,lumps,abscesses and sinus tracts/fistulas as the main clinical manifestations,which is easily confused with breast cancer or other benign breast diseases.NPM always leads to a long treatment cycle and high recurrence rate,which may cause a large economic and psychological burden to patients.At present,the etiology and pathogenesis of NPM are still unclear,but it has a certain correlation with immune abnormality,bacterial infection,hormone disorder and other factors.Although several diagnostic methods available,the diagnosis of NPM relies on histopathological examination mainly.The treatment methods of the disease include observation and follow-up,pharmacotherapy,surgical treatment,etc.,but there is still no unified standard for specific treatment timing and treatment selection.In view of the controversy over etiology and treatment selection of NPM,this paper comprehensively summarizes the latest research progress in disease characteristics,clinical diagnosis and treatment of NPM based on domestic and foreign literature,aiming to provide reference and inspiration for the selection of reasonable clinical diagnosis and treatment.

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.
Humans ; Animals ; Mice ; Photothermal Therapy ; Triple Negative Breast Neoplasms/pathology* ; Antimicrobial Cationic Peptides ; Immunotherapy/methods* ; Cell Line, Tumor ; Phototherapy/methods* ; Nanoparticles/chemistry*