ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Diabetes mellitus （DM） is a metabolic disease caused by absolute or relative insulin deficiency and reduced insulin sensitivity in peripheral cells， posing a serious threat to global health. Chronic complications arising in the later stages of DM can lead to the decline or even loss of function in multiple organs， including the eyes， heart， liver， kidneys， nerves， and feet， making them the primary cause of mortality in DM patients. Although modern medicine has made some progress in the treatment of these complications， challenges such as high costs and adverse drug reactions remain. Thus， identifying highly effective drugs with minimal adverse effects has become a top priority. Astragalus membranaceus is a shining gem in the treasure trove of Chinese medicine. Numerous studies have shown that its primary active component， astragaloside Ⅳ， possesses various biological activities， including anti-inflammatory， antioxidant， and antiviral effects， as well as benefits for cardiac and cerebral function， nerve conduction， and myocardial protection. Meanwhile， the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a crucial role in regulating oxidative stress， inflammatory responses， apoptosis， and autophagy. Extensive research has highlighted the significant role of this pathway in various DM complications， leading to widespread studies on its interaction with astragaloside Ⅳ. This review summarizes research findings on how astragaloside Ⅳ alleviates pancreatic cytotoxicity in DM patients by modulating the PI3K/Akt pathway. Additionally， it highlights its protective effects on basic cardiac function， inhibition of retinal cell damage， improvement of cerebral nerve dysfunction， reduction of chronic kidney and liver damage， and mitigation of neurovascular toxicity in the lower limbs. These insights provide a valuable reference for the clinical application of A. membranaceus and its active monomer， astragaloside Ⅳ， in the treatment of DM and its complications.

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

Pre-admission is a critical initiative to optimize medical service processes and alleviate the challenge of "difficult access to healthcare. "However, there is currently a lack of standardized protocols for pre-admission procedures. This study aims to systematically analyze key nodes and risk factors in pre-admission process design and propose optimization strategies, providing a foundation for policy formulation and hospital practices. By constructing a "forward-reverse" dual-process model of pre-admission and identifying risk points based on stakeholder theory (patients, hospitals, healthcare administration, and insurance), the study reveals that while pre-admission can reduce the average length of stay, improve bed turnover rates, and enhance patient satisfaction, it also presents risks such as cross-period financial settlement, challenges in insurance policy adaptability, demands for information system integration, and the need for defining medical safety boundaries. To optimize the pre-admission process and mitigate these risks, this study explores framework improvements in areas including eligibility criteria, mode selection, cost settlement, transition between pre-admission and inpatient status, and cancellation of pre-admission, offering practical guidance for public hospitals. The authors argue that pre-admission requires tripartite collaboration among hospitals, insurers, and healthcare administrations: hospitals should establish top-level design, continuously refine processes, and implement dynamic risk assessment mechanisms; insurance providers should support cross-period settlement policies; and healthcare administrations should issue guiding policies or standardized protocols. Through multi-department coordination and collaborative efforts, the optimization and innovation of pre-admission processes can be advanced, ultimately delivering more efficient and convenient healthcare experiences for patients.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

ObjectiveTo screen the differential markers by analyzing volatile components in Dalbergia odorifera and its counterfeits， in order to provide reference for authentication of D. odorifera. MethodThe volatile components in D. odorifera and its counterfeits were detected by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the GC conditions were heated by procedure（the initial temperature of the column was 50 ℃， the retention time was 1 min， and then the temperature was raised to 300 ℃ at 10 ℃ for 10 min）， the carrier gas was helium， and the flow rate was 1.0 mL·min^-1， the split ratio was 10∶1， and the injection volume was 1 mL. The MS conditions used electron bombardment ionization（EI） with the scanning range of m/z 35-550. The compound species were identified by database matching， the relative content of each component was calculated by the peak area normalization method， and principal component analysis（PCA）， orthogonal partial least squares-discrimination analysis（OPLS-DA） and cluster analysis were performed on the detection results by SIMCA 14.1 software， and the differential components of D. odorifera and its counterfeits were screened out according to the variable importance in the projection（VIP） value>2 and P<0.05. ResultA total of 26， 17， 8， 22， 24 and 7 volatile components were identified from D. odorifera， D. bariensis， D. latifolia， D. benthamii， D. pinnata and D. cochinchinensis， respectively. Among them， there were 11 unique volatile components of D. odorifera， 6 unique volatile components of D. bariensis， 3 unique volatile components of D. latifolia， 6 unique volatile components of D. benthamii， 8 unique volatile components of D. pinnata， 4 unique volatile components of D. cochinchinensis. The PCA results showed that， except for D. latifolia and D. cochinchinensis， which could not be clearly distinguished， D. odorifera and other counterfeits could be distributed in a certain area， respectively. The OPLS-DA results showed that D. odorifera and its five counterfeits were clustered into one group each， indicating significant differences in volatile components between D. odorifera and its counterfeits. Finally， a total of 31 differential markers of volatile components between D. odoriferae and its counterfeits were screened. ConclusionHS-GC-MS combined with SIMCA 14.1 software can systematically elucidate the volatile differential components between D. odorifera and its counterfeits， which is suitable for rapid identification of them.

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.