Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To analyze the influencing factors of diabetes insipidus after pituitary tumor surgery,thereby providing evidence for enhancing perioperative management of pituitary tumor surgery and preventing diabetes insipidus after pituitary tumor surgery.Methods The clinical data of patients who underwent pituitary tumor surgery in our hospital from January 2014 to December 2024 were retrospectively analyzed.The relationship between each variable and postoperative diabetes insipidus was explored through univariate analysis,and multi-variate regression analysis was used to identify the independent risk factors for the occurrence of postoperative diabetes insipidus.Results Univariate analysis showed that the occurrence of diabetes insipidus after pituitary tumor surgery was related to tumor invasiveness,tumor growth direction,surgical resection degree,surgical time and surgical method(P<0.05).Logistic regression analysis showed that the surgical time>4 hours(P=0.001)and tumor growth breaking through diaphragma sellae(P=0.004)were independent risk factors for the occurrence of postoperative diabetes insipidus.Conclusion The surgical time and tumor growth direction are closely related to diabetes insipidus after pituitary tumor surgery;therefore,in order to reduce the incidence of diabetes insipidus after pituitary tumor surgery,a thorough evaluation should be conducted preoperatively to clarify the direction of tumor growth;minimally invasive surgery should be adopted as much as possible during the operation and the skills of surgeons should be improved to shorten the surgical time;and close observation should performed after surgery.

Objective To analyze the influencing factors of diabetes insipidus after pituitary tumor surgery,thereby providing evidence for enhancing perioperative management of pituitary tumor surgery and preventing diabetes insipidus after pituitary tumor surgery.Methods The clinical data of patients who underwent pituitary tumor surgery in our hospital from January 2014 to December 2024 were retrospectively analyzed.The relationship between each variable and postoperative diabetes insipidus was explored through univariate analysis,and multi-variate regression analysis was used to identify the independent risk factors for the occurrence of postoperative diabetes insipidus.Results Univariate analysis showed that the occurrence of diabetes insipidus after pituitary tumor surgery was related to tumor invasiveness,tumor growth direction,surgical resection degree,surgical time and surgical method(P<0.05).Logistic regression analysis showed that the surgical time>4 hours(P=0.001)and tumor growth breaking through diaphragma sellae(P=0.004)were independent risk factors for the occurrence of postoperative diabetes insipidus.Conclusion The surgical time and tumor growth direction are closely related to diabetes insipidus after pituitary tumor surgery;therefore,in order to reduce the incidence of diabetes insipidus after pituitary tumor surgery,a thorough evaluation should be conducted preoperatively to clarify the direction of tumor growth;minimally invasive surgery should be adopted as much as possible during the operation and the skills of surgeons should be improved to shorten the surgical time;and close observation should performed after surgery.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To compare the effectiveness of cylindrical-shaped and conical-shaped cuff catheters for airway closure using different pressure measurement methods at the lowest safe pressure and to guide the clinical application.Methods:Twenty-four patients with endotracheal intubation admitted to the intensive care unit (ICU) of Guangxi Medical University Cancer Hospital from December 2021 to January 2022 were enrolled. Leakage test in vitro was performed on the secretion on the patients' cuff. The needle and plunger from 20 mL syringe was separated, the syringe was sealed with adhesive, and the syringe nozzle was filled thoroughly to create a tracheal model. Consecutively, both cylindrical-shaped and conical-shaped cuff catheters were inserted into the simulated trachea, and the cuff pressure was calibrated to 20 cmH 2O (1 cmH 2O≈0.098 kPa) before commencing the experiment. The viscosity of the secretion on the patients' cuff was classified (grade Ⅰ was watery subglottic secretion, grade Ⅱ was thick subglottic secretion, grade Ⅲ was gel-like subglottic secretion), and the same viscosity secretion was injected into the catheter cuff. Utilizing a self-control approach, intermittent pressure measurement was initially conducted on both the cylindrical-shaped and conical-shaped cuff by improved pressure measurement method (intermittent pressure measurement group), followed by continuous pressure measurement experiment (continuous pressure measurement group). The leakage volume of the three viscosity subglottic secretions and the values of cuff pressure measurement of different shaped cuff catheters at 4, 6, 8 hours of inflation were recorded. Results:A total of 180 retention samples were extracted from 24 patients with tracheal intubation during ventilation, with 90 samples in each of the two groups using different pressure measurement methods, and 30 samples of retention materials with different viscosities in each group. In the intermittent pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ and grade Ⅱ on cylindrical-shaped cuff leaked, while 3 samples of secretion with grade Ⅲ also leaked. For conical-shaped cuff, 28 samples of secretion with grade Ⅰ leaked, only 2 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. At 6 hours of inflation, all samples of the three viscosity secretions on different shaped cuffs leaked. The leakage was gradually increased with the prolongation of inflation time. In the continuous pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ on cylindrical-shaped cuff leaked, while 29 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. For the conical-shaped cuff, 26 samples of secretion with grade Ⅰ leaked, and there was no leak for secretion with grade Ⅱ and grade Ⅲ. At 6 hours of inflation, the conical-shaped cuff still had no leak for secretion with grade Ⅲ. As the inflation time prolonged, the leakage of subglottic secretion on different shaped cuffs in both groups was gradually increased. At 8 hours of inflation, all samples experienced leakage, but the leakage of subglottic secretion on different shaped cuffs in the continuous pressure measurement group was significantly reduced as compared with the intermittent pressure measurement group [leakage for secretion with grade Ⅲ (mL): 1.00 (0.00, 1.25) vs. 2.00 (1.00, 2.00) on the cylindrical-shaped cuff, 1.00 (0.00, 1.00) vs. 2.00 (2.00, 2.00) on the conical-shaped cuff, both P < 0.01]. The values of pressure measurement of cuffs with different shapes at different time points of inflation in the continuous pressure measurement group were within the set range (20-21 cmH 2O). The cuff pressure at 4 hours of inflation in the intermittent pressure measurement group was significantly lower than the initial value (cmH 2O: 18.3±0.6 vs. 20.0±0.0 in the cylindrical-shaped cuff, 18.4±0.6 vs. 20.0±0.0 in the conical-shaped cuff, both P < 0.01), and the cuff pressure in both shaped cuffs showed a significant decrease tendency as inflation time prolonged. However, there was no statistically significant difference in values of pressure measurement between the different shaped cuff catheters. Conclusions:Continuous pressure monitoring devices can maintain the effective sealing of conical-shaped cuff catheters at the lowest safe pressure. When using an improved pressure measurement method for intermittent pressure measurement and/or using a cylindrical cuff catheter, the target pressure should be set at 25-30 cmH 2O, and the cuff pressure should be adjusted regularly.

To review the concept development,characteristics,measurement tools,influencing factors,effects,and cultivation of moral resilience among medical staff at home and abroad.The characteristics of moral resilience of medical staff include personal integrity,adaptability,self-regulation,self-management,and moral efficacy of medical personnel,as well as the relational integrity of the medical team.The influencing factors of medical staff's moral resilience include the support system of the medical team,personal qualities of medical staff,and their understanding of events.Moral resilience can promote the physical and mental health of medical staff,effectively cope with moral injury,reduce occupational fatigue and turnover intention of medical staff,as well as alleviate the moral dilemmas of medical staff.Cultivate moral resilience to enhance the ability of medical staff to resist moral dilemmas.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective: To understand the status quo of school bullying among middle school students in Anhui Province and its correlation with family environment and education methods of students related to school bullying, so as to provide corresponding prevention and controlling measures against school bullying. Methods: The investigation has been conducted on the occurrence of school bullying among middle school students ranging from junior grade one to senior grade three in Hefei, Wuhu, Fuyang of Anhui Province, during which up to 1 826 students information has been gathered through Questionnaire Atar Platform using the school bullying scale and self designed questionnaire. SPSS 26.0 statistical software has been applied for data analysis. Results: The incidence of bullying was 41.40%, and among them, 14.46% were reported to bully others, 39.59% of them were of being bullied, and 12.65% of them were reported of bullying others and being bullied at the same time. Multivariate Logistic regression corrected model showed that quiet relationship with mother ( OR=1.76, 95%CI =1.22-2.53) was a risk factor for the bully, quiet relationship with father( OR=1.89, 95%CI=1.47-2.43 ), reorganized family ( OR=2.28, 95%CI =1.22-4.29) were the risk factors for the bullied, quiet/poor relationship between parents ( OR=1.52, 95%CI=1.06-2.17; OR=3.15, 95%CI =1.79-5.57) was a risk factor for the bully-bullied; Punishment and abuse( OR=1.45, 95%CI=1.10-1.90; OR=1.82, 95%CI=1.48-2.23; OR=1.47, 95%CI = 1.10- 1.96) were risk factors for the above three behaviors( P <0.05). Conclusion The incidence of school bullying is influenced by family environment and rearing style. In daily life, parents should be mindful of maintaining a good family relationship, fostering active communication with child, which can reduce the occurrence of school bullying.

Humans ; Hemoglobinopathies ; Hemoglobins, Abnormal/genetics* ; Oxygen