Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Humans ; Adolescent ; Fractures, Avulsion ; Fractures, Bone ; Fracture Fixation, Internal ; Ischium/surgery*

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Nutritional therapy is a core component of critically ill patient management,and the enteral route has become the preferred method due to its dual roles of nutrition and non-nutrition. The use of vasoactive medications makes enteral nutrition decisions more challenging for these patients. This review systematically examines the pathophysiological effects of vasoactive medications on gastrointestinal tract of critically ill patients,the current value and safety of enteral nutrition in this patient's population,summarizes the optimal strategies for implementing enteral nutrition in these patients for clinical reference.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*