OBJECTIVE To analyze the influencing factors for achieving target plasma drug concentration （trough） （abbreviated as “PDC”） of vancomycin in patients from high-altitude regions and establish a predictive model for PDC using single- center data， providing references for rational clinical drug use. METHODS Inpatients with vancomycin （1 g， q12 h） administered intravenously in our hospital from January 2021 to June 2024 were retrospectively included. Demographic data， liver and kidney function and hematological indexes were collected. Spearman correlation analysis was used to evaluate the correlation between vancomycin PDC and each detection index. Univariate analysis was used to evaluate the differences of each index in patients with different PDC， and the effects of different gender， body mass index， age and underlying diseases （hypertension/diabetes） on vancomycin PDC. Based on the results of correlation analysis and univariate analysis， multiple linear stepwise regression analysis was used to obtain the independent predictors of vancomycin PDC and construct the prediction model. RESULTS A total of 141 patients were included， with an overall attainment rate of 46.81% for the target PDC of vancomycin. Correlation analysis showed that the vancomycin PDC was positively correlated with age， blood urea nitrogen， uric acid （UA）， serum creatinine （CRE） and β2- microglobulin （β2-MG）， and negatively correlated with height， weight， creatinine clearance rate （CCR）， glomerular filtration rate （GFR）， alanine transaminase （ALT）， hemoglobin （HGB）， white blood cell count and neutrophils （P＜0.05）. There were significant differences in age， CRE and other 14 indexes among different PDC groups （P＜0.05 or P＜0.01）. Age and underlying diseases had significant effects on vancomycin PDC （P＜0.05 or P＜0.01）. CCR， direct bilirubin （DBil）， β2-MG， UA， HGB and height （standardized coefficients were －0.371， 0.367， 0.169， 0.232， －0.140， －0.132； P＜0.05） were independent predictors of vancomycin PDC. The F value of the regression equation was 34.858 （P＜0.05）， the R2 was 0.610， and the adjusted R2 was 0.592. CONCLUSIONS The vancomycin PDC of patients in high-altitude regions is affected by multiple factors such as renal function， liver function and hematological indexes. CCR， HGB and height could be used to predict vancomycin PDC negatively， while DBil， β2-MG and UA could be used to predict vancomycin PDC positively. The variables of the established prediction model could explain 59.2% of the variation of vancomycin PDC.

Objective To investigate the outcome of endovascular aortic repair under digital subtraction angiography (DSA) in the treatment of Stanford type B aortic dissection (TBAD). Methods A total of 104 TBAD patients admitted to our hospital from October 2019 to October 2022 were selected,of which 52 patients treated with best medication treat (BMT) were included into the BMT group,and 52 patients who underwent endovascular aortic repair under DSA on the basis of BMT were included into the combination group. The acute physiological and chronic health evaluation Ⅱ (APACHE Ⅱ) score,serum inflammatory indicators,liver and kidney function indicators,and coagulation function indicators before and after treatment,and hospital stay were compared between the two groups. Results The APACHE Ⅱ score,liver and kidney function indicators and inflammatory factors after treatment in the combination group were lower than those before treatment and in the BMT group (P<0.05). The combination group had more significant changes of coagulation function indicators after treatment than those before treatment and in the BMT group (P<0.05). The hospital stay of the combination group was shorter than that of the BMT group (P<0.05). Conclusion Endovascular aortic repair under DSA for TBAD can reduce inflammatory response,improve liver and kidney functions and coagulation function,and shorten the hospital stay,which has a better therapeutic effect than conservative drug treatment.

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Meropenem （MEM） is one of the important drugs for the treatment of severe infections， but the standard dose is often difficult to achieve an effective therapeutic concentration target. This article reviews the related studies on the population pharmacokinetics of MEM in patients with severe infection. It is found that the apparent volume of distribution （Vd） and clearance rate are the most important factors affecting the dose adjustment， and the factors affecting Vd include serum albumin， age， overall weight， shock status， and chest/abdomen/cerebrospinal fluid drainage. The main factors affecting the clearance rate were renal function， renal replacement therapy treatment mode and combination therapy. For adult patients with severe infections in China， MEM is recommended to be administered in an individualized manner based on glomerular filtration rate， with a dosage range of 500 to 1 500 mg given every 4 to 6 hours， and prolonged infusion is preferred. When the minimum inhibitory concentration （MIC） of the pathogenic bacteria reaches 64 mg/L， therapeutic drug monitoring is required. For therapeutic efficacy， it is essential to ensure that the trough concentration remains above the MIC； to prevent drug resistance， it should be maintained above 4×MIC. Regarding safety， it is recommended that the upper limit of the trough concentration be 32 mg/L， and blood sampling for monitoring can be conducted as early as after 1 to 2 doses of administration.

A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for the simultaneous determination of 498 farm chemical residues in Atractylodis Macrocephalae Rhizoma. Furthermore, the established method was used to determine the residues in 30 batches of Atractylodis Macrocephalae Rhizoma samples from different habitats. The samples were extracted with acetonitrile containing 1% glacial acetic acid, and the extract was purified by dispersive solid-phase extraction with sorbents of magnesium sulfate, primary secondary amine(PSA), C_(18), silica gel, and graphitized carbon black(GCB). The prepared samples were then analyzed by HPLC-MS/MS, and the internal standard method was used to quantify the residues. The experimental results showed that the 498 farm chemicals presented good linear relationship within the range of 5-400 ng·mL~(-1), with correction coefficients greater than 0.990. Within the linear ranges, the recovery of 495 farm chemicals(except daimuron, chinomethionat, and emamectin benzoate) at three spiked levels(0.05, 0.10, and 0.20 mg·kg~(-1)) was in the range of 61.18%-132.1%, with the RSD of 0.24%-15%. A total of 16 farm chemicals were detected in 30 batches of samples. Among them, difenoconazole and tebuconazole showed higher detection rates, and the detection rate of difenoconazole was 76.7%. The residues of 4 batches of samples exceeded the limits of quantitation of 33 banned farm chemicals stipulated in the Chinese Pharmacopoeia. The theoretical maximum residue limits of the farm chemicals except banned farm cheimicals were used as the judgment standard of safety risks, under which the detected residues of clothianidin, difenoconazole, and pirimiphos-methyl exceeded the theoretical maximum residue limits. The new method established in this paper is simple and reliable, and it can thus be used for qualitative and quantitative analyses of farm chemical residues in Atractylodis Macrocephalae Rhizoma.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Atractylodes/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/analysis* ; Pesticide Residues/analysis* ; Liquid Chromatography-Mass Spectrometry

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Objective:This study aims to initially establish a scoring system for comprehensively reflecting the severity of intracranial atherosclerotic lesions and to explore the correlation between this score and atherosclerotic risk factors as well as stroke events.Methods:This study retrospectively analyzed patients who underwent head and neck computer tomography angiography(CTA)examinations and had head MRI examinations within one month before or after the CTA examination from January 2021 to August 2024 in Beijing Hospital.An intracranial atherosclerosis disease score(ICADS)system was constructed based on the degree and number of vascular stenosis.The relationship between ICADS and atherosclerotic risk factors was explored by grouping patients according to the quartile of ICADS.Patients were divided into acute stroke group and non-acute stroke group to compare differences in ICADS and cerebrovascular disease risk factors between the two groups, and to investigate the correlation between stroke events and ICADS.Results:There were statistically significant differences in the proportions of patients with hypertension and diabetes among different ICADS groups.Multiple linear regression analysis showed that hypertension( B=1.17, 95% CI: 0.20-2.14, P<0.05)and diabetes( B=2.75, 95% CI: 1.85-3.64, P<0.001)were risk factors for higher ICADS.The ICADS was higher in the acute stroke group than in the non-acute stroke group(9 vs.6, P<0.001), and a higher ICADS was identified as a risk factor for stroke( OR=1.10, 95% CI: 1.07-1.14, P<0.001). Conclusions:ICADS can comprehensively reflect the severity of intracranial atherosclerotic lesions and is correlated with stroke events, making it useful for clinical screening of high-risk patients for stroke.

Objective:This study aims to analyze the weight management policy practices in Japan,South Korea,and Singapore to provide international references for improving China's weight health management and metabolic disease prevention system.Methods:Based on the Innovative Care for Chronic Conditions Framework(ICCC),we conducted a literature review and policy analysis methods of domestic and international policies and publications on weight management,systematically analyzing and summarizing relevant strategies and practices to extract key insights in Japan,South Korea,and Singapore.Results:All three countries have established a multi-level collaborative governance system:at the macro level,they built institutional foundations through legislation,cross-sectoral collaboration,and diversified financing;at the meso level,they enhanced management efficiency via comprehensive medical services,multidisciplinary coordination,and smart information systems,while community-level initiatives fostered supportive environments through health education and environmental modifications;at the micro level,they emphasized personalized interventions and family involvement to strengthen self-management capabilities.Conclusion:China can learn from these neighboring countries'experiences to develop a multi-tiered prevention system,strengthen primary care capacity,improve medical security mechanisms,and facilitate a shift from disease treatment to health management,ultimately constructing a weight management solution with Chinese characteristics.