Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P＝0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P＜0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Cantharidin(CTD),a natural compound used to treat multiple tumors in the clinic setting,has been limited due to acute kidney injury(AKI).However,the major cause of AKI and its underlying mechanism remain to be elucidated.Serum creatinine(SCr)and blood urea nitrogen(BUN)were detected through pathological evaluation after CTD(1.5 mg/kg)oral gavage in mice in 3 days.Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to investigate lipids disorder after CTD exposure in mice.Then,spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI)was used to detect the kidney spatial distribution of lipids.Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro.The results showed that the levels of SCr and BUN were increased,and tubular necrosis was observed in mouse kidneys,resulting in acute tubular necrosis(ATN)in CTD-induced AKI.Then,lipidomics results revealed that after CTD exposure,232 differential lipid metabolites and 11 pathways including glycerophospholipid(GP)and sphingolipid(SL)metabolism were disrupted.Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed.Subsequently,integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla,whereas SL metabolism was inhibited in the renal cortex.Up-regulated lysophosphatidylcholine(LysoPC)(18∶2(9Z,12Z)),LysoPC(16∶0/0∶0),glycerophosphocholine,and down-regulated sphingomyelin(SM)(d18∶0/16:0),SM(d 18∶1/24:0),and SM(d42∶1)were key differential lipids.Among them,LysoPC(16∶0/0∶0)was increased in the CTD group at 1.1196 μg/mL,which aggravated CTD-induced ATN in human kidney-2(HK-2)cells.LysoPC acyltransferase was inhibited and choline phos-photransferase 1(CEPT1)was activated after CTD intervention in mice and in HK-2 cells.CTD induces ATN,resulting in AKI,by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla,LysoPC(16:0/0:0),LysoPC acyltransferase,and CEPT1 may be the therapeutic targets.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To investigate the relationship between symptoms of vertigo and vestibular functions and short-term hearing outcomes in patients with flat descending sudden sensorineural hearing loss （SSNHL）. Methods:A retrospective review was conducted of the vestibular symptoms observed in 48 patients with unilateral flat-down sudden sensorineural hearing loss treated at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Symptoms of vertigo and the results of cervical vestibular-evoked myogenic potentials （cVEMP）, ocular VEMP （oVEMP）, caloric test and video head-impulse test （vHIT） were collected to determine whether these factors could predict therapeutic efficacy. Results:The symptoms of vertigo was not correlated with prognosis （P>0.05） or with abnormal vestibular functions （P>0.05）. Patients with abnormal cVEMP, oVEMP, caloric test or vHIT showed significantly lower effective rates （32.0%, 44.0%, 32.0%, and 24.0%, respectively）; the greater the number of abnormal tests, the poorer the outcome. Patients with all four tests abnormal gained only （3.13±15.97） dB HL in hearing recovery, whereas those with normal cVEMP, oVEMP, caloric test or vHIT showed better chances of hearing improvements by （29.22±20.31）, （31.18±21.59）, （26.17±21.31）, and （26.38±24.05） dB HL, respectively. Conclusion:Vestibular function effectively predicts prognosis in flat descending SSNHL. Patients with abnormal vestibular tests, regardless of symptoms of vertigo, responded poorly to treatment, whereas those with normal cVEMP, oVEMP, caloric test and vHIT results achieved better hearing recovery. Abnormal vestibular function implies more extensive and severe inner-ear lesions in patients with SSNHL.
Humans ; Male ; Female ; Retrospective Studies ; Prognosis ; Adult ; Middle Aged ; Vertigo/diagnosis* ; Hearing Loss, Sensorineural/diagnosis* ; Young Adult ; Hearing Loss, Sudden/diagnosis* ; Adolescent ; Aged ; Vestibular Evoked Myogenic Potentials

Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.