ObjectiveHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） and GC-triple quadrupole MS（GC-QqQ-MS） in combination with non-targeted and targeted metabolomics were employed to systematically analyze the chemical composition differences of Xihuangwan prepared with natural musk and artificial musk， and establish an identification system for them. MethodsThe volatile components of 9 batches of Xihuangwan samples from 8 manufacturers were analyzed by HS-SPME-GC-MS non-targeted metabolomics， and identified by comparing their MS data with the National Institute of Standards and Technology（NIST） spectral library. Orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to identify differential volatile components of Xihuangwan prepared with natural musk and artificial musk. Additionally， GC-QqQ-MS targeted metabolomics was applied to quantify the levels of α-pinene， β-elemene， muscone， dehydroepiandrosterone， bornyl acetate， and octyl acetate in 27 batches of samples from 9 manufacturers. Cluster analysis， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA） were conducted to further explore the differences in volatile components between Xihuangwan samples prepared with natural musk and artificial musk. ResultsNon-targeted metabolomics identified 291 volatile compounds in Xihuangwan， including alkanes， esters， alkanes， alcohols， ketones， naphthalenes and others. OPLS-DA analysis revealed distinct separation between Xihuangwan samples containing artificial musk（A1， C1， D1， E1， F1， G1， I1） and those containing natural musk（H1， H3）. A total of 30 differential metabolites were identified. The relative contents of these 30 differential metabolites were visualized using a radar chart， revealing significant differences in the levels of octanol， borneol acetate and muscone. Cluster analysis and PCA results from targeted metabolomics indicated that Xihuangwan could be classified into two distinct groups：one composed of natural musk（H1， H3） and the other of artificial musk， sample H2. PLS-DA identified muscone， octyl acetate， and dehydroepiandrosterone as key differential volatile components. Although no significant difference was observed in the content of octyl acetate between the two groups， statistically significant differences were found for muscone and dehydroepiandrosterone（P<0.05）. ConclusionMuscone and dehydroepiandrosterone can be used for the differentiation of Xihuangwan samples containing natural musk from those containing artificial musk. This study systematically and comprehensively analyzed the differences in the types and contents of major volatile components in Xihuangwan prepared with natural musk and artificial musk， providing a scientific basis for quality evaluation and control of Xihuangwan.

ObjectiveHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） and GC-triple quadrupole MS（GC-QqQ-MS） in combination with non-targeted and targeted metabolomics were employed to systematically analyze the chemical composition differences of Xihuangwan prepared with natural musk and artificial musk， and establish an identification system for them. MethodsThe volatile components of 9 batches of Xihuangwan samples from 8 manufacturers were analyzed by HS-SPME-GC-MS non-targeted metabolomics， and identified by comparing their MS data with the National Institute of Standards and Technology（NIST） spectral library. Orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to identify differential volatile components of Xihuangwan prepared with natural musk and artificial musk. Additionally， GC-QqQ-MS targeted metabolomics was applied to quantify the levels of α-pinene， β-elemene， muscone， dehydroepiandrosterone， bornyl acetate， and octyl acetate in 27 batches of samples from 9 manufacturers. Cluster analysis， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA） were conducted to further explore the differences in volatile components between Xihuangwan samples prepared with natural musk and artificial musk. ResultsNon-targeted metabolomics identified 291 volatile compounds in Xihuangwan， including alkanes， esters， alkanes， alcohols， ketones， naphthalenes and others. OPLS-DA analysis revealed distinct separation between Xihuangwan samples containing artificial musk（A1， C1， D1， E1， F1， G1， I1） and those containing natural musk（H1， H3）. A total of 30 differential metabolites were identified. The relative contents of these 30 differential metabolites were visualized using a radar chart， revealing significant differences in the levels of octanol， borneol acetate and muscone. Cluster analysis and PCA results from targeted metabolomics indicated that Xihuangwan could be classified into two distinct groups：one composed of natural musk（H1， H3） and the other of artificial musk， sample H2. PLS-DA identified muscone， octyl acetate， and dehydroepiandrosterone as key differential volatile components. Although no significant difference was observed in the content of octyl acetate between the two groups， statistically significant differences were found for muscone and dehydroepiandrosterone（P<0.05）. ConclusionMuscone and dehydroepiandrosterone can be used for the differentiation of Xihuangwan samples containing natural musk from those containing artificial musk. This study systematically and comprehensively analyzed the differences in the types and contents of major volatile components in Xihuangwan prepared with natural musk and artificial musk， providing a scientific basis for quality evaluation and control of Xihuangwan.

Objective To investigate the cranial magnetic resonance imaging （MRI） features of patients with hepatolenticular degeneration （also known as Wilson disease，WD） and epilepsy， and to identify the neuroimaging risk factors for seizures in WD patients. Methods A total of 69 WD patients with epilepsy who were hospitalized in Affiliated Hospital of Neurology Institute， Anhui University of Chinese Medicine， from January 2018 to November 2025 were enrolled as study group， while 80 WD patients without seizures， matched for sex and age， during the same period of time were randomly selected as control group. Cranial MRI findings were compared between the two groups. Results There were 69 WD patients （43 male patients and 26 female patients） in the study group， with a mean age of （29.46±8.58） years at the time of attending the hospital， and all these patients had abnormal electroencephalogram （EEG） findings. There were no significant differences between the two groups in age of onset，disease duration， WD subtype， and serum copper. Cranial MRI showed that the putamen was the most common site of brain injury （47 patients， 68.1%）， followed by the frontal lobe （40 patients，58.0%） and the parietal lobe （31 patients，44.9%）， and there was a significantly higher probability of epilepsy in patients with abnormal lesions in the frontal， temporal， or parietal lobes （P<0.05）. Conclusion While the putamen is the most common site of brain injury in WD patients with epilepsy， frontal or temporal lobe injuries are neuroimaging risk factors for seizures in such patients.
Epilepsy, Frontal Lobe ; Putamen

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective To assess the survival vulnerability of Oncomelania hupensis in Jiangxi Province under future climate scenarios, and to identify low-vulnerability areas for its survival in this province. Methods Village-level O. hupensis snail survey and O. hupensis snail control with chemical treatments in Jiangxi Province from 2016 to 2024 were captured from the Parasitic Disease Prevention and Control Information Management System of China Disease Prevention and Control Information System. Climatic data were primarily sourced from the Resource and Environmental Science Data Platform, Chinese Academy of Sciences (http://www.resdc.cn/), including annual average temperature, annual average precipitation, annual accumulated temperature above 10 °C, annual accumulated temperature above 0 °C, annual maximum temperature, annual minimum temperature, and annual average relative humidity, and nineteen bioclimatic variables were downloaded from the WorldClim website (https://www.worldclim.org/), including mean diurnal range, isothermality, temperature seasonality, and so on. Elevation and normalized difference vegetation index were catprued from the Resource and Environmental Science Data Platform, Chinese Academy of Sciences (http://www.resdc.cn/), and distance to rivers was downloaded from the WorldPop website (http://www.worldpop.org), and land use and land cover (LULC) data were downloaded from the Big Earth Data Center, Chinese Academy of Sciences (https://data.casearth.cn/), and nature reserve data were obtained from the China Nature Reserve Specimen Resource Sharing Platform (http://www.papc.cn/). Three Shared Socioeconomic Pathways (SSPs) from the Beijing Climate Center-Climate System Model version 2-Medium Resolution (BCC-CSM2-MR) global climate model were employed as future climate scenarios, including SSP126, SSP245, SSP585, and the biomod2 ensemble model in R package was used to simulate suitable habitats for O. hupensis snails in Jiangxi Province in 2050 and 2070 under these scenarios. A snail survival vulnerability index was constructed based on the area of suitable snail habitats, area covered by snail control through chemical treatment, area covered by nature reserves, and changes in snail habitat fragmentation, and a map of snail survival vulnerability distribution was plotted. Results The real area of snail habitats ranged from 78 486.76 to 85 309.47 hm², and the area of snail control with chemical treatment ranged from 10 138.98 to 13 240.16 hm² in Jiangxi Province from 2016 to 2024. There were 429 to 531 villages detected with snails during the nine-year period, and the number of actually snail-infested villages ranged from 645 to 686. A total of 818 snail-present points and 1 996 snail-absent points were obtained from snail survey records. The best performance of the biomod2 ensemble model was achieved if a weighted mean approach was used as the ensemble strategy, with a true skill statistic value of 0.799 and an area under the receiver operating characteristic curve of 0.957, and modeling identified annual average relative humidity and annual average precipitation as two most influencing climatic variables for snail distribution. Relative to the current areas of suitable snail habitats under present climate conditions, the area of suitable snail habitats was projected to expand by 24.49% to 46.28% in Jiangxi Province under future climate scenarios, and the proportion of nature reserves areas in the areas of suitable snail habitats was projected to decrease slightly from the current 2.77% to approximately 2.52%, while the proportion of areas of snail control through chemical treatment in areas of suitable snail habitats varied from 0.64% to 19.57%, and the percentage of changes in snail habitat fragmentation ranged from 3.86% to 12.23%. Based on these four indicators, the snail survival vulnerability index was estimated to range from –1.96 to 0.62 in Jiangxi Province. The arithmetic mean of the snail survival vulnerability index differed under three SSP scenarios (SSP126, SSP245 and SSP585), with the highest mean value (–0.69) in 2070 under SSP126, and the lowest mean value (–0.78) in 2070 under SSP585. Conclusions The snail survival vulnerability index ranges from –1.96 to 0.62 in Jiangxi Province under future climate scenarios, and the suitable habitats for O. hupensis snails appear an overall tendency towards expansion. Low-vulnerability snail habitats are mainly distributed along the shores of Poyang Lake and the Yangtze River in Jiangxi Province, partially overlapping with nature reserves. Intensified surveillance of O. hupensis snails is recommended in these areas in the future.

Objective To evaluate the characteristics, related therapeutic regimens, risk factors of cardiovascular adverse events (CVAEs) and prognosis in the current therapy of newly diagnosed multiple myeloma (NDMM) patients in China. Methods A retrospective observational study was performed on patients with NDMM treated at Zhongshan Hospital, Fudan University, from January 2013 to October 2021. The propensity score matching at a ratio of 1∶1 was employed to balance baseline confounders between the therapeutic group and the control group, and CVAEs incidences were compared between the corresponding groups. Independent risk factors for CVAEs were identified through Fine-Gray competing risk regression model. Kaplan-Meier survival curves and log-rank tests were used to assess overall survival and progression-free survival of patients. Results A total of 829 patients with NDMM were analyzed, with a median of 33.1 months of follow-up for survivors. CVAEs occurred in 65 patients (7.8%) during first-line treatment, and a total of 74 events were recorded, with 52.7% grade 3 or greater in severity. Arrhythmia (particularly atrial fibrillation), thrombotic event (TE), and heart failure were the most common types. The median time from treatment to the first occurrence of CVAEs was 26 days, while the medium occurrence time of TE was later than the other events (76 d vs 19 d, P＝0.003). The exposure to immunomodulatory drugs was related to a higher incidence of TEs, whereas other therapeutic regimens, including bortezomib, didn’t show the effect of cardiovascular toxicity. Results of multivariate analysis showed that Eastern Cooperative Oncology Group performance status ＞2, symptomatic heart diseases within three months before treatment, and estimated glomerular filtration rate≤50 mL·min⁻¹·(1.73 m²)⁻¹ were independent risk factors for CVAEs. Compared with patients without CVAE, patients who experienced CVAEs had significantly inferior progression-free survival and overall survival, and higher cardiovascular mortality (P＜0.001). Conclusions The incidence of CVAE is relatively high during first-line treatment in NDMM patients, and the prognosis of CVAE patients is poor. The risk of CVAE is significantly increased in patients with underlying cardiovascular diseases.

Objective To explore the metabolic characteristics and related factors in patients with diabetic retinopathy (DR). Methods A retrospective study was conducted on the clinical data of 467 diabetic patients hospitalized at the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2020 to September 2024. The patients were divided into the DR group (n＝150) and the non-DR group (n＝317). Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed using a transient elastography device, and graded into five levels. Basic data, LSM and CAP grading, and metabolic indicators were compared between the two groups. Univariate and multivariate logistic regression analyses were applied to identify factors influencing DR. Results Patients in the DR group were older than those in the non-DR group (P＜0.001). Compared with the non-DR group, fasting blood glucose (FBG), glycated hemoglobin A_1C (HbA_1C), and triglyceride (TG) levels were higher, while low-density lipoprotein cholesterol (LDL-C) was lower in the DR group (P＜0.05). Significant differences in LSM grading were observed between the two groups (P＝0.006). Multivariate logistic regression analysis revealed that LSM grading (grade 2: OR＝2.127, P＝0.002; grade 3: OR＝2.344, P＝0.030; grade 4: OR＝2.960, P＝0.038), FBG (OR=1.233, P＜0.001), and serum creatinine (OR＝1.013, P＝0.006) were independent factors associated with DR. Conclusions FBG, serum creatinine, and LSM are related factors of DR. In clinical practice, attention should be paid to the coordinated management of blood glucose control, renal function monitoring, and liver fibrosis assessment, with early interventions to reduce the risk of DR.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.