Objective:Inflammation has been confirmed to play an important role in the occurrence and development of sudden sensorineural hearing loss（SSNHL）, and the neutrophil-to-lymphocyte ratio（NLR） is a biomarker positively correlated with the degree of inflammation. This study aims to identify the difference in serum NLR between patients with SSNHL and normal population, and to evaluate the predictive efficacy of NLR for the occurrence and prognosis of SSNHL, thereby guiding the clinical diagnosis and treatment of SSNHL. Methods:In this study, 96 patients diagnosed with SSNHL admitted to our department from January 2023 to March 2024 and 96 patients diagnosed with vocal cord polyps admitted to our department during the same period were recruited as a control group. Multivariate Logistic regression was used to evaluate independent related factors, and a nomogram was constructed to predict the probability of SSNHL. The receiver operating characteristic（ROC） curve and calibration curve were used to evaluate the accuracy of prediction. Results:Multivariate logistic regression analysis showed that a high level NLR（OR2.215; 95%CI1.597-3.073; P<0.001） were independently associated with the presence of SSNHL. High age（OR1.036; 95%CI1.009-1.067; P=0.012）, high FIB（OR2.35; 95%CI1.176-4.960; P=0.019） were the risk factor for SSNHL. Incorporating these 3 factors, a forest plot and a nomogram were generated. The ROC curve, nomogram and calibration curve showed that the model had good clinical practicability. A low NLR（OR0.598; 95%CI0.439-0.816; P<0.001） was significantly associated with a favorable prognosis of SSNHL. Conclusion:Elevated NLR can serve as an promising biomarker for assessing the risk of SSNHL. The nomograms calculation model may be utilized as a tool to estimate the probability of SSNHL. Low level NLR is significantly associated with a good prognosis of SSNHL.
Humans ; Neutrophils ; Female ; Male ; Lymphocytes ; Hearing Loss, Sensorineural/blood* ; Hearing Loss, Sudden/diagnosis* ; Middle Aged ; Prognosis ; Nomograms ; ROC Curve ; Adult ; Logistic Models ; Biomarkers/blood* ; Lymphocyte Count ; Inflammation/blood* ; Clinical Relevance

Objective:To evaluate the bioequivalence and safety of domestic and original pyrazinamide tablets under fasting condition.Methods:A single center, randomized, open-label, two period self-crossover trial was conducted in healthy adult volunteers. The test preparation (T) of pyrazinamide tablets was produced by Taicang Pharmaceutical Factory and the reference preparation (R) was produced by A&Z Pharmaceutical Inc. (Pyrazinamide ?). The healthy subjects were randomly divided into 2 groups and took the drugs for 2 times with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 8) and T-R group (subjects took T on day 1 and then R on day 8). Pharmacokinetic parameters were used as endpoints to assess the bioequivalence. Peripheral venous blood samples (3 ml) were collected from subjects within 1 hour before taking the drug and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 210 minutes and 4, 5, 6, 8, 12, 24, 36, and 48 hours after taking the drug. Plasma was frozen after centrifugation of the blood samples. The plasma pyrazinamide concentrations were determined by a tandem liquid chromatography-mass spectrometry method and the main pharmacokinetic parameters such as peak concentration ( Cmax) and the area under the concentration-time curve (AUC), including AUC from time zero (pre-dose) to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞), were calculated. The test and reference preparations were judged as bioequivalence when the 90% confidence intervals ( CI) of geometric mean ratios for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.80 to 1.25. Adverse events occurred in subjects during the trial were observed and recorded. Results:A total of 24 healthy volunteers were enrolled in the trial, including 16 males and 8 females aged 18-50 years, with 12 in the R-T and T-R groups, respectively. All subjects completed the trial. After taking medicine under fasting condition, the 90% CI of the geometric mean ratios of Cmax, AUC 0-t, and AUC 0-∞ for the test and reference preparations were 0.93-1.09, 0.98-1.03, and 0.98-1.03, respectively. During the trial, the incidence of adverse events was 25.0% (6/24) and 3 cases occurred after taking the test and reference preparations respectively, which were grade 1 in severity. Conclusion:The domestic and original pyrazinamide tablets were bioequivalence and with good safety when taken under fasting condition.

Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Doxorubicin/therapeutic use* ; Etoposide ; Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prednisone/therapeutic use* ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Vincristine/therapeutic use*

Objective:To evaluate the bioequivalence and safety of domestic and original pyrazinamide tablets under fasting condition.Methods:A single center, randomized, open-label, two period self-crossover trial was conducted in healthy adult volunteers. The test preparation (T) of pyrazinamide tablets was produced by Taicang Pharmaceutical Factory and the reference preparation (R) was produced by A&Z Pharmaceutical Inc. (Pyrazinamide ?). The healthy subjects were randomly divided into 2 groups and took the drugs for 2 times with different order in each group, which were R-T group (subjects took R on day 1 and then T on day 8) and T-R group (subjects took T on day 1 and then R on day 8). Pharmacokinetic parameters were used as endpoints to assess the bioequivalence. Peripheral venous blood samples (3 ml) were collected from subjects within 1 hour before taking the drug and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, and 210 minutes and 4, 5, 6, 8, 12, 24, 36, and 48 hours after taking the drug. Plasma was frozen after centrifugation of the blood samples. The plasma pyrazinamide concentrations were determined by a tandem liquid chromatography-mass spectrometry method and the main pharmacokinetic parameters such as peak concentration ( Cmax) and the area under the concentration-time curve (AUC), including AUC from time zero (pre-dose) to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞), were calculated. The test and reference preparations were judged as bioequivalence when the 90% confidence intervals ( CI) of geometric mean ratios for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.80 to 1.25. Adverse events occurred in subjects during the trial were observed and recorded. Results:A total of 24 healthy volunteers were enrolled in the trial, including 16 males and 8 females aged 18-50 years, with 12 in the R-T and T-R groups, respectively. All subjects completed the trial. After taking medicine under fasting condition, the 90% CI of the geometric mean ratios of Cmax, AUC 0-t, and AUC 0-∞ for the test and reference preparations were 0.93-1.09, 0.98-1.03, and 0.98-1.03, respectively. During the trial, the incidence of adverse events was 25.0% (6/24) and 3 cases occurred after taking the test and reference preparations respectively, which were grade 1 in severity. Conclusion:The domestic and original pyrazinamide tablets were bioequivalence and with good safety when taken under fasting condition.

Objective: To compare and correlate the findings of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging and arterial spin labeling (ASL) imaging in characterizing parotid gland tumors. Materials and Methods: We retrospectively reviewed 56 patients with parotid gland tumors evaluated by MR imaging. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and fraction of perfusion (f) values of IVIM imaging and tumor-to-parotid gland signal intensity ratio (SIR) on ASL imaging were calculated. Spearman rank correlation coefficient, chi-squared, Mann-Whitney U, and Kruskal-Wallis tests with the post-hoc Dunn-Bonferroni method and receiver operating characteristic curve assessments were used for statistical analysis. Results: Malignant parotid gland tumors showed significantly lower D than benign tumors (p = 0.019). Within subgroup analyses, pleomorphic adenomas (PAs) showed significantly higher D than malignant tumors (MTs) and Warthin’s tumors (WTs) (p < 0.001). The D* of WTs was significantly higher than that of PAs (p = 0.031). The f and SIR on ASL imaging of WTs were significantly higher than those of MTs and PAs (p < 0.05). Significantly positive correlation was found between SIR on ASL imaging and f (r = 0.446, p = 0.001). In comparison with f, SIR on ASL imaging showed a higher area under curve (0.853 vs. 0.891) in discriminating MTs from WTs, although the difference was not significant (p = 0.720). Conclusion IVIM and ASL imaging could help differentiate parotid gland tumors. SIR on ASL imaging showed a significantly positive correlation with f. ASL imaging might hold potential to improve the ability to discriminate MTs from WTs.

Objective:To evaluate the postprandial bioequivalence of domestic and original glucosamine sulfate capsules in Chinese healthy volunteers.Methods:The trial was a single-center, randomized, open-label, single-dose, 2-preparation, 3-sequence, 3-period, partially repeated crossover design. The trialed drugs were domestic glucosamine sulfate capsules Yisuojia (test preparation) and original glucosamine sulfate capsules Viartril ? (reference preparation). Healthy subjects were randomly divided into 3 groups, each group took medicine in 3 periods, but the order of taking test preparation (T) and reference preparation (R) was different, which were TRR, RTR and RRT groups. The healthy volunteers in the TRR, RTR, and RRT groups received the trialed drugs orally 30 minutes after diet supply on day 1, 4, and 7, respectively. Peripheral venous blood samples 4 ml were collected at 1-2 hours after dinner the day before medication (baseline 1), within 60 minutes before medication (baseline 2), and 15, 30, 45, 60, 90, 120, and 150 minutes and 3, 4, 5, 6, 8, 10, 14, and 16 hours after medication, respectively. Plasma was collected after centrifugation, frozen, and stored. Liquid chromatography-tandem mass spectrometry was used for the determination of glucosamine concentrations in plasma samples and main pharmacokinetic parameters such as the area under the concentration-time curve(AUC), including areas from time zero (pre-dose) to the last measurable concentration (AUC 0-t) and extrapolated to infinite time (AUC 0-∞), and peak concentration ( Cmax) were calculated. Because glucosamine was an endogenous substance in humans, the measured blood concentration of glucosamine was corrected by subtracting the baseline value before medication (the average of baseline 1 and baseline 2). The test and reference preparations were equivalent when the geometric mean ratios ( GMR) and their 90% confidence intervals ( CI) for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.800 to 1.250. Results:A total of 30 healthy volunteers were enrolled in the study, including 20 males and 10 females, aged (31±7) years with a range of 18-45 years. Ten volunteers were included in each TRR, RTR, and RRT group. One volunteer fell off in the TRR group after the first period of medication and the remaining 29 volunteers completed the trial. The baseline uncorrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax for the test and the reference preparations were 0.985 (0.941-1.031), 1.014 (0.961-1.070), and 0.937 (0.827-1.062), respectively; the baseline corrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax of the test and the reference preparations were 0.977 (0.923-1.035), 0.976 (0.922-1.032), and 0.932 (0.817-1.063), respectively, which all fell within the equivalence range (0.800-1.250). During the trial, no adverse events related to the trialed drugs occurred in the 3 groups. Conclusion:Domestic glucosamine sulfate capsules were bioequivalent to the original when taken after diet and had a good safety profile.

Objective:To evaluate the postprandial bioequivalence of domestic and original glucosamine sulfate capsules in Chinese healthy volunteers.Methods:The trial was a single-center, randomized, open-label, single-dose, 2-preparation, 3-sequence, 3-period, partially repeated crossover design. The trialed drugs were domestic glucosamine sulfate capsules Yisuojia (test preparation) and original glucosamine sulfate capsules Viartril ? (reference preparation). Healthy subjects were randomly divided into 3 groups, each group took medicine in 3 periods, but the order of taking test preparation (T) and reference preparation (R) was different, which were TRR, RTR and RRT groups. The healthy volunteers in the TRR, RTR, and RRT groups received the trialed drugs orally 30 minutes after diet supply on day 1, 4, and 7, respectively. Peripheral venous blood samples 4 ml were collected at 1-2 hours after dinner the day before medication (baseline 1), within 60 minutes before medication (baseline 2), and 15, 30, 45, 60, 90, 120, and 150 minutes and 3, 4, 5, 6, 8, 10, 14, and 16 hours after medication, respectively. Plasma was collected after centrifugation, frozen, and stored. Liquid chromatography-tandem mass spectrometry was used for the determination of glucosamine concentrations in plasma samples and main pharmacokinetic parameters such as the area under the concentration-time curve(AUC), including areas from time zero (pre-dose) to the last measurable concentration (AUC 0-t) and extrapolated to infinite time (AUC 0-∞), and peak concentration ( Cmax) were calculated. Because glucosamine was an endogenous substance in humans, the measured blood concentration of glucosamine was corrected by subtracting the baseline value before medication (the average of baseline 1 and baseline 2). The test and reference preparations were equivalent when the geometric mean ratios ( GMR) and their 90% confidence intervals ( CI) for AUC 0-t, AUC 0-∞, and Cmax all ranged from 0.800 to 1.250. Results:A total of 30 healthy volunteers were enrolled in the study, including 20 males and 10 females, aged (31±7) years with a range of 18-45 years. Ten volunteers were included in each TRR, RTR, and RRT group. One volunteer fell off in the TRR group after the first period of medication and the remaining 29 volunteers completed the trial. The baseline uncorrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax for the test and the reference preparations were 0.985 (0.941-1.031), 1.014 (0.961-1.070), and 0.937 (0.827-1.062), respectively; the baseline corrected GMR (90 %CI) of AUC 0-t, AUC 0-∞, and Cmax of the test and the reference preparations were 0.977 (0.923-1.035), 0.976 (0.922-1.032), and 0.932 (0.817-1.063), respectively, which all fell within the equivalence range (0.800-1.250). During the trial, no adverse events related to the trialed drugs occurred in the 3 groups. Conclusion:Domestic glucosamine sulfate capsules were bioequivalent to the original when taken after diet and had a good safety profile.

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and β cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).
Adolescent ; Adult ; Age Factors ; Aged ; Antineoplastic Agents/adverse effects* ; Diabetes Mellitus/chemically induced* ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality* ; Young Adult

OBJECTIVE: To compare various models of diffusion-weighted imaging including monoexponential apparent diffusion coefficient (ADC), biexponential (fast diffusion coefficient [Df], slow diffusion coefficient [Ds], and fraction of fast diffusion), stretched-exponential (distributed diffusion coefficient and anomalous exponent term [α]), and kurtosis (mean diffusivity and mean kurtosis [MK]) models in the differentiation of renal solid masses. MATERIALS AND METHODS: A total of 81 patients (56 men and 25 women; mean age, 57 years; age range, 30–69 years) with 18 benign and 63 malignant lesions were imaged using 3T diffusion-weighted MRI. Diffusion model selection was investigated in each lesion using the Akaike information criteria. Mann-Whitney U test and receiver operating characteristic (ROC) analysis were used for statistical evaluations. RESULTS: Goodness-of-fit analysis showed that the stretched-exponential model had the highest voxel percentages in benign and malignant lesions (90.7% and 51.4%, respectively). ADC, Ds, and MK showed significant differences between benign and malignant lesions (p < 0.05) and between low- and high-grade clear cell renal cell carcinoma (ccRCC) (p < 0.05). α was significantly lower in the benign group than in the malignant group (p < 0.05). All diffusion measures showed significant differences between ccRCC and non-ccRCC (p < 0.05) except Df and α (p = 0.143 and 0.112, respectively). α showed the highest diagnostic accuracy in differentiating benign and malignant lesions with an area under the ROC curve of 0.923, but none of the parameters from these advanced models revealed significantly better performance over ADC in discriminating subtypes or grades of renal cell carcinoma (RCC) (p > 0.05). CONCLUSION: Compared with conventional diffusion parameters, α may provide additional information for differentiating benign and malignant renal masses, while ADC remains the most valuable parameter for differentiation of RCC subtypes and for ccRCC grading.
Carcinoma, Renal Cell ; Diffusion ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; ROC Curve

OBJECTIVES: We analyzed the chromosomal-arm-level copy number alterations (CNAs) in the cervical exfoliative cell and tissue samples by using the low-coverage whole genomic sequencing technique. METHODS: In this study, we retrospectively collected 55 archived exfoliated cervical cell suspension samples and the corresponding formalin-fixed and paraffin-embedded tissue section samples including 27 invasive cervical cancer and 28 control cases. We also collected 19 samples of the cervical exfoliative cells randomly from women to verify the new algorithm model. We analyzed the CNAs in cervical exfoliated cell and tissue samples by using the low-coverage next generation of sequencing. RESULTS: In the model-building study, multiple chromosomal-arm-level CNAs were detected in both cervical exfoliated cell and tissue samples of all cervical cancer cases. By analyzing the consistency of CNAs between exfoliated cells and cervical tissue samples, as well as the heterogeneity in individual patient, we also established a C-score algorithm model according to the chromosomal-arm-level changes of 1q, 2q, 3p, 7q. The C-score model was then validated by the pathological diagnosis of all 74 exfoliated cell samples (including 55 cases in model-building group and 19 cases in verification group). In our result, a cutoff value of C-score > 6 showed 100% sensitivity and 100% specificity in the diagnosis of cervical cancer. CONCLUSION: In this study, we found that CNAs of cervical exfoliated cell samples could robustly distinguish invasive cervical cancer from cancer-free tissues. And we have also developed a C-score algorithm model to process the sequencing data in a more standardized and automated way.
Diagnosis ; DNA Copy Number Variations ; Female ; Genome* ; High-Throughput Nucleotide Sequencing ; Humans ; Mass Screening ; Population Characteristics ; Retrospective Studies ; Sensitivity and Specificity ; Uterine Cervical Neoplasms*