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 assess the nutritional status in elderly patients with chronic renal insufficiency (CRI) and reveal the key factors affecting the nutritional status. Methods A total of 310 elderly patients with CRI who received hospitalization treatment and outpatient follow-up in the hospital from January 2021 to June 2024 were selected as the investigation subjects. The nutritional status of patients was evaluated by mini-nutritional assessment (MNA) questionnaire, and the nutritional status and dietary structure of patients were comprehensively evaluated by anthropometric indicators [height, weight, body mass index (BMI), upper arm circumference, calf circumference], biochemical indicators [serum albumin (ALB), prealbumin (PA), hemoglobin (Hb), transferrin (TF)] and 24-hour dietary review method. According to the investigation results of nutritional status, the patients were divided into good nutrition group (MNA score≥24 points), nutritional risk group (MNA score of 17-23.5 points) and malnutrition group (MNA score<17 points). Univariate analysis was adopted to screen the potential influencing factors of elderly CRI. Multivariate logistic regression model was applied to analyze the influencing factors of malnutrition in elderly CRI patients. Results Among the 325 questionnaires were distributed, but only 310 valid questionnaires were recovered, with an effective recovery rate of 95.38%. Investigation results revealed that among the 310 patients, 29.35% (91 cases) had good nutritional status, and 42.26% (131 cases) had nutritional risk, and 28.39% (88 cases) had malnutrition. Univariate analysis indicated that there were statistical differences in BMI, CRI staging, serum ALB, PA, Hb, TF, protein intake and total calorie intake among the good nutrition group, the nutritional risk group and the malnutrition group (P<0.05). Multivariate logistic regression analysis suggested that low BMI (OR=0.903, 95%CI: 0.867-0.941), high CRI stage (OR=1.091, 95%CI: 1.053-1.130), low serum ALB (OR=0.907, 95%CI: 0.867-0.948), PA (OR=0.918, 95%CI: 0.888-0.949), Hb (OR=0.944, 95%CI: 0.909-0.997), TF (OR=0.912, 95%CI: 0.874-0.952), insufficient protein intake (OR=0.924, 95%CI: 0.882-0.969) and insufficient total calorie intake (OR=0.938, 95%CI: 0.909-0.968) were influencing factors for malnutrition in elderly patients with CRI (all P<0.05). Drawing ROC curve of malnutrition in elderly patients with CRI according to the prediction probability of logistic regression model found that the AUC, sensitivity, specificity, 95%CI and Youden index were 0.976, 93.18%, 92.34%, 0.953-0.990 (P<0.05) and 0.855. Conclusion The incidence rate of malnutrition is high in elderly patients with CRI, and is mainly affected by factors such as low BMI, high CRI stage, low serum ALB, PA, Hb and TF levels and insufficient protein and total calorie intakes. In addition, logistic regression model has high predictive value and can provide a reference for early clinical identification of high-risk population with malnutrition among elderly patients with CRI.

The patient, a 10-year-old and 4-month-old boy, was admitted to the hospital "with a history of 19 days since tonsil surgery and 11 days of recurrent hematemesis". 19 days ago, bilateral endoscopic tonsil + adenoid plasma melting and bilateral tonsil fossa inferior pole suture were performed in the outer hospital, and recurrent hematemesis occurred 11 days ago, accompanied by transient fatigue and abdominal pain, diagnosis: ①Hematemesis to be investigated: postoperative tonsil bleeding? Upper gastrointestinal bleeding?②Acute moderate hemorrhagic anemia. On the first and third days of admission, the child had two sudden episodes of massive hematemesis, both of which were more than 1 000 mL, with pale lips, fatigue, and hemorrhagic shock. Bleeding was rapid and can terminate spontaneously, and emergency physical examination does not reveal a clear point of bleeding. Bilateral inferior pole sutures in the tonsillar fossa are in place. There were no obvious abnormalities in the emergency digestive endoscopy, no obvious bleeding points were detected in the tonsils and adenoids surgical area, and no obvious abnormalities were found in the neck CT angiography（CTA）. Emergency DSA-guided percutaneous selective external carotid artery intervention was performed, during which about 5 mm contrast agent overflowed at the origin of the facial artery, and a coil was implanted. The child had no active bleeding after the operation, and his life was as usual at 2 months of follow-up.
Humans ; Male ; Child ; Tonsillectomy/adverse effects* ; Postoperative Hemorrhage/therapy* ; Palatine Tonsil/surgery* ; Recurrence

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To investigate the application value of peripheral blood soluble human leukocyte antigen-G(sHLA-G)combined with immune cytokines in the differential diagnosis of renal transplant rejection.Methods This case-control study retrospectively analyzed 81 renal transplant patients hospitalized in the Department of Organ Transplantation,the Second Affiliated Hospital of Naval Medical University from April 2020 to December 2023,due to elevated serum creatinine.Among them,32 patients were diagnosed with acute rejection(acute rejection group),29 with chronic rejection(chronic rejection group),and 20 with elevated creatinine due to non-rejection causes(non-rejection group).Fifty renal transplant inpatients and outpatients with normal and stable serum creatinine were selected as control group during the same period.Clinical data such as gender,age,serum creatinine,estimated glomerular filtration rate(eGFR),and urine protein positive rate,etc.were collected.Peripheral blood of patients was sampled to measure the levels of plasma sHLA-G and immune cytokines[interferon-γ(IFN-γ),tumor necrosis factor-β(TNF-β),interleukin(IL)-2,IL-4,IL-10,IL-5,IL-6,IL-17]using enzyme-linked immunosorbent assay(ELISA).Stratify and compare the differences in sHLA-G levels among different groups and all renal transplant inpatients by gender.Results Compared with control group,serum creatinine levels and urine protein positive rate were significantly higher in acute rejection group,chronic rejection group,and non-rejection group,while eGFR was significantly lower,serum creatinine levels in chronic rejection group and non-rejection group were higher than those in acute rejection group,while eGFR was lower than that in acute rejection group,with statistically significant differences(P<0.05).No statistically significant differences were observed in gender,age,blood type,body mass index,transplantation duration,and immunosuppressive agent use among acute rejection,chronic rejection,non-rejection,and control groups(P>0.05).Plasma sHLA-G levels in acute rejection and chronic rejection groups were significantly lower than those in control group[(19.665±11.233)U/ml vs.(24.785±21.668)U/ml vs.(44.918±39.898)U/ml,P<0.05].The sHLA-G/IL-2 ratio in chronic rejection group was significantly higher than that in acute rejection group(5.844±6.248 vs.1.825±1.574,P<0.05),and the sHLA-G/IFN-γ ratio in non-rejection group was significantly higher than that in chronic rejection group(3.452±3.283 vs.1.543±2.030,P<0.05).Among 131 renal transplant inpatients,female sHLA-G levels were significantly higher than male(P<0.05).Within each group,female sHLA-G levels in chronic rejection group were significantly higher than male(P<0.05).Although female sHLA-G levels in acute rejection,non-rejection,and control groups were higher than those of male,the gender difference was not statistically significant(P>0.05).Conclusions Peripheral blood sHLA-G levels are correlated with renal transplantation rejection.The application of sHLA-G/IL-2 and sHLA-G/IFN-γ ratios has potential value in the diagnosis and differentiation of elevated creatinine caused by acute/chronic rejection,chronic rejection and non-rejection causes,respectively.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female