ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions， as well as to review the payment methods of drugs （including in-hospital and external drug dispensing）. METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally， an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 （before the system upgrade） and May to August 2025 （after the system upgrade）. RESULTS After the upgrade of the pre-prescription review system， the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval （CI）＝0.3%-6.7%， P ＝0.037 ] ； the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level （95%CI＝31.6%-88.5%， P ＝0.026）， and the average monthly sequential decrease was 29.5% （95%CI＝12.2%-43.4%， P ＝0.012）. Moreover， the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade， a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs， and strengthens the supervision of off-label drug use， achieving dual guarantees of clinical rationality and medical insurance compliance.

OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

Acute hypoxic exposure can induce functional brain impairment, driven by molecular mechanisms including mitochondrial dysfunction, intracellular calcium overload, glial cell activation and inflammatory responses, blood-brain barrier disruption, and alterated cerebral blood flow. Acetazolamide, a broad-spectrum carbonic anhydrase inhibitor, is a standard clinical treatment and remains the only medication approved by the Food and Drug Administration for the prevention and treatment of acute mountain sickness. Substantial evidence confirms that under acute hypoxic exposure, acetazolamide exerts multi-level neuroprotective effects on brain tissue by inhibiting carbonic anhydrase VB and other isoforms. These protective mechanisms involve preserving mitochondrial integrity, regulating calcium homeostasis and pH balance, modulating glial cell activity to mitigate neuroinflammation, maintaining blood-brain barrier structure integrity, and improving cerebral perfusion through cerebrovascular regulation. This article reviewed the molecular pathological mechanisms of hypoxia-induced nervous system damage, summarized the pharmacological properties and neuroprotective effects of acetazolamide, and provided a theoretical basis for therapeutic interventions against high-altitude hypoxic neural injury.

Acute hypoxic exposure can induce functional brain impairment, driven by molecular mechanisms including mitochondrial dysfunction, intracellular calcium overload, glial cell activation and inflammatory responses, blood-brain barrier disruption, and alterated cerebral blood flow. Acetazolamide, a broad-spectrum carbonic anhydrase inhibitor, is a standard clinical treatment and remains the only medication approved by the Food and Drug Administration for the prevention and treatment of acute mountain sickness. Substantial evidence confirms that under acute hypoxic exposure, acetazolamide exerts multi-level neuroprotective effects on brain tissue by inhibiting carbonic anhydrase VB and other isoforms. These protective mechanisms involve preserving mitochondrial integrity, regulating calcium homeostasis and pH balance, modulating glial cell activity to mitigate neuroinflammation, maintaining blood-brain barrier structure integrity, and improving cerebral perfusion through cerebrovascular regulation. This article reviewed the molecular pathological mechanisms of hypoxia-induced nervous system damage, summarized the pharmacological properties and neuroprotective effects of acetazolamide, and provided a theoretical basis for therapeutic interventions against high-altitude hypoxic neural injury.

ObjectiveTo address the shortage of high-caliber multidisciplinary professionals in China's rehabilitation engineering field and the prominent issue of "separation between medicine and engineering" in existing curricula, this study introduces the World Health Organization rehabilitation competency framework (RCF) to construct a systematic curriculum system for rehabilitation engineering. MethodsGuided by the four core competency domains of RCF (practice, professionalism, learning and development, management and leadership) and their associated supporting knowledge, the rehabilitation engineering curriculum was restructured into a modular framework, piloted and validated within the Biomedical Engineering (Intelligent Robotics) program at University of Health and Rehabilitation Sciences. ResultsA four-tiered curriculum system comprising General Education-Disciplinary Platform-Professional Core-Diverse Electives with a total of 160 credits was established, achieving precise mapping between competency objectives and course content. The students in the pilot cohort demonstrated outstanding academic performance (50% ranked in the top ten of their major), they also gained a deeper understanding and mastery of interdisciplinary knowledge integrating medicine and engineering. ConclusionThe RCF-based curriculum system effectively promotes the organic integration of medical and engineering knowledge, providing an internationally aligned competency-oriented paradigm for rehabilitation engineering talent cultivation, which holds significant value for broader application.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

Background and aims Hepatocellular carcinoma (HCC) cells are metabolically reprogrammed for excessive uptake and metabolism of many nutrients. The tumor suppressive microRNA-148a-3p (miR-148a-3p) is downregulated in HCC, whereas its function in regulating HCC cell metabolism remains obscure. Herein we aimed to delineate the role of miR-148a-3p in HCC cell metabolism by using novel bioengineered miR-148a-3p (BioRNALeu/miR-148a-3p) agent produced in vivo. Methods BioRNALeu/miR-148a-3p was designed by using human leucyl transfer RNA fused hsa-pre-miR-34a carrier, overexpressed in Escherichia coli (E. coli), and purified to high homogeneity. After transfection into HCC cells, the released miR-148a-3p levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by CellTiter-Glo assays. Targets were validated by dual-luciferase reporter assays, immunoblotting, and immunofluorescence confocal imaging. Glycolysis capacity was evaluated by Seahorse XF assays, and glucose, lactate, and amino acid levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results BioRNALeu/miR-148a-3p was efficiently processed into target miR-148a-3p in HCC cells to effectively inhibit cell proliferation in a dose- and time-dependent manner. Mechanistically, miR-148a-3p suppressed the protein levels of glucose transporter GLUT1/SLC2A1 and L-type amino acid transporter LAT1/SLC7A5 via acting on their 3′-untranslated regions, as well as amino acid transporter ASCT2/SLC1A5. These, in turn, led to a reduction of glucose uptake, lactate production, and glycolytic flux in HCC cells, and alteration of intracellular amino acid metabolome including glutamine, leucine, phenylalanine, tyrosine, and methionine. Conclusions Reintroduction of miR-148a-3p into HCC cells modulates glucose and amino acid metabolism via regulating multiple SLC transporters, thereby suppressing HCC cell viability. These findings highlight the role of miR-148a-3p in HCC cell metabolism and potential of bioengineered miRNA molecules for functional studies and therapeutic development.

BACKGROUND: Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs have been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients. METHODS: The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI ( n = 40), H2RA ( n = 31), or control group ( n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group. CONCLUSIONS: PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs. REGISTRATION www.chictr.org.cn (ChiCTR2000029552).
Humans ; Proton Pump Inhibitors/therapeutic use* ; Acute Coronary Syndrome/microbiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Male ; Middle Aged ; Histamine H2 Antagonists/therapeutic use* ; Aged ; Single-Blind Method

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*