Objective To study the bioequivalence of two glipizide tablets in healthy Chinese subjects.Methods Randomized,open,single-administration,two-period,self-cross-over trial design was used in the study.There were 28 Chinese healthy subjects in the fasted state and 28 in the fed state,complete repeat cross single dose oral glipizide tablets test preparation or reference preparation 5 mg.The plasma concentration of glipizide was determined by liquid chromatography/tandem mass spectrometry at different time points after administration.The non-compartmental model was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two formulations.Results The main pharmacokinetic parameters of glipizide in the fasted state were as follows:Cmax were(551.60±91.26)and(518.10±105.10)ng·mL-1;AUC0-t were(3 074.33±861.91)and(3 026.77±934.25)h·ng·mL-1;AUC0-∞ were(3 204.85±990.78)and(3 166.35±1 107.36)h ng·mL-1.The parameters of glipizide in the fed state were as follows:Cmax were(517.30±98.97)and(472.80±114.48)ng·mL-1;AUC0-t were(3 001.12±830.87)and(2 932.79±736.35)h·ng·mL-1;AUC0-∞ were(3 067.00±918.84)and(2 997.44±819.14)h·ng·mL-1.The 90％confidence interval of the Cmax,AUC0-t and AUC0-∞ of the test formulation and the reference formulation were from 80.00％to 125.00％.The incidence of adverse events in fasted group and fed group was no serious adverse events.Conclusion The two glipizide tablets were bioequivalent under fasted and fed conditions,and good security.

ObjectiveCoronavirus is a class of long-standing pathogens, which are enveloped single-stranded positive-sense RNA viruses. The genome all encodes 4 structural proteins: spike protein (S), nucleocapsid protein (N), membrane protein (M), and envelope protein (E). The nucleocapsid protein (NP) serves as a key structural component of coronaviruses, playing a vital function in the viral life cycle. NP acts as an RNA-binding protein, with a critical role in identifying specific sequences within the viral genome RNA, facilitating the formation of ribonucleoprotein (RNP) complexes with viral RNA to stabilize the viral genome and contribute to viral particles assembly. The NP consists of two primary structural domains, the N-terminal domain (NTD) and the C-terminal domain (CTD). The NTD is primarily responsible for RNA binding, whereas the CTD is involved in polymerization. The N protein demonstrated to trigger the host immune response and to modulate the cell cycle of infected cells by interacting with host proteins. The NP, one of the most abundant protein in coronaviruses, is essential in understanding the pathogenic mechanism of coronaviruses through its interaction with host factors, which response for determining the virus pathogenicity. HCoV-229E is a widely distributed coronavirus that typically causes mild upper respiratory tract diseases, accounting for a significant portion of common cold cases. However, its pathogenicity is notably lower compared to other coronaviruses like MERS-CoV, SARS-CoV, and SARS-CoV-2. The exact molecular mechanism behind remains unexplained, and how HCoV-229E N protein influences virus replication, host antiviral immunity, and pathogenesis need to be further explored. MethodsProximity labeling-mass spectrometry technique and bioinformatics analysis were used to screen for potential host factors interacting with the NP of human coronavirus 229E (HCoV-229E). In this study, a recombinant adenovirus Ad-V5-NP^HCoV-229E-TurboID was constructed to express the fusion protein of HCoV-229E NP and biotin ligase (TurboID). A549 cells were infected with the Ad-V5-NP^HCoV-229E-TurboID. After 30 min biotin treatment, NP interacting proteins were labeled with biotin by biotin ligase, and subsequently isolated with streptavidin cross-linked magnetic beads. The potential interacting proteins were identified using label-free proteomic mass spectrometry and further validated through immunoprecipitation and immunofluorescence assays. ResultsWe identified a total of 584 potential interacting proteins. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the enrichment of glycogen synthase kinase (GSK)3A and GSK3B in the glycolysis/gluconeogenesis pathway, indicating HCoV-229E NP connection to diabetes through aberrant activity. Moreover, SARS-CoV-2 infection can exacerbate hyperglycemia and metabolic dysregulation in diabetic individuals by activating the ACE2 receptor. Moreover, SARS-CoV-2 was observed to cause potentially harm to pancreatic β‑cells and leading to insulin deficiency, which not only worsens the condition of diabetic patients but also raises the possibility of new-onset diabetes in non-diabetic individuals. We demonstrated that GSK3A and GSK3B interacted with NP of HCoV-229E, suggesting that the NP may engage in various coronavirus pathogenic processes by interacting with GSK3. ConclusionThese findings suggest that proximity labeling-mass spectrometry technique is a valuable tool for identifying virus-host interaction factors, and lay the foundation for future investigations into the mechanisms underlying coronavirus replication, proliferation, and pathogenesis.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

The wearable electrochemical sensors exhibit many advantages such as flexibility,miniaturization,portability,biocompatibility and low cost,and can be used for accurate,safe,real-time,and non-invasive monitoring of physiological signals in sweat,which are very helpful to monitor various physiological indicators of athletes during training,predict sports risks,prevent sports injuries and scientifically guide sports training,showing enormous potential in the field of sports monitoring. In this paper,the latest research progress of wearable electrochemical sweat sensors based on the relationship between biomarkers in sweat and exercise training was reviewed,such as the sensor substrate materials,sweat sampling strategies,sensing unit,signal transmission,and power supply systems. In addition,the current application status,the opportunities and challenges in the field of motion monitoring of wearable electrochemical sensors were discussed,and their future development was prospected.

Non-functional pituitary adenomas(NFPAs)are relatively common intracranial sellar tumors.The diagnostic rate of NFPAs has significantly increased in recent years due to the widespread application of computed tomography(CT)and magnetic resonance imaging(MRI)in clinical practice.NFPAs do not exhibit increased biochemical hormone secretion,so they may not present with obvious clinical manifestations.However,as the tumor grows,it can cause mass effect symptoms,such as headache,visual impairment,and related pituitary target gland dysfunction,and even life-threatening pituitary stroke.The evaluation of pituitary function in patients with NFPAs and the selection of treatment plans require close collaboration and scientific management by a multidisciplinary team.The genetic and epigenetic mechanisms underlying the occurrence and development of NFPAs have not yet been fully elucidated.New treatment strategies may be developed through technologies such as whole-genome sequencing combined with chromatin structure analysis.This review systematically summarizes the research progress in epidemiology,histopathology,clinical diagnosis,treatment,and prognosis of NFPAs,aiming to provide reference and guidance for clinical management.

objective To compare the surgical effect of short median incision approach and mini-incision approach in patients with medial unicompartmental knee arthroplasty.Methods A total of 65 patients with knee medial compartment osteoarthritis were treated with Oxford third-generation artificial unicondylar joint from April 2012 to July 2016 in PLA 960 hospital were enrolled.Among them,31 patients were treated with mini-incision approach and 34 patients were treated with short median incision approach.The postoperative incision healing and follow-up status of patients in the two groups were compared.The operating time of two incision approaches was counted,and the total blood loss during and after operation were calculated by Gross equation.The time to get out of bed after operation,the visual analogue scale(VAS)scores before operation,1 day after operation,1 week after operation and 1 month after operation,and the hospital for special surgery(HSS)scores before operation,1 month after operation,3 months after operation and at the last follow-up were counted.Results Three patients with previous diabetes had delayed incision healing after surgery,one patient in the mini-incision group suffered pad dislocation 6 months after operation,and three patients died of other medical diseases within 3 years after operation.The 5-year survival rate of the prosthesis was 93.85%.In the mini-incision group,the average preoperative muscle strength of quadriceps femoris was(3.10±0.60)level,and the average postoperative time to get out of bed was(1.32±0.35)days;In the short median incision group,the average preoperative muscle strength of quadriceps femoris was(3.18±0.63)level,and the average postoperative time to get out of bed was(1.37±0.41)days.There was no statistically significant difference in the postoperative time to get out of bed,operation time,total blood loss during and after operation,VAS score,HSS score of patients between the two groups(P>0.05).Conclusion The short median incision approach and mini-incision approach for unicompartmental knee arthroplasty have similar clinical effects.The short median incision approach has clearer exposure during operation,and the patellofemoral joint can be better treated,which provides conditions for modifying the surgery;the mini-incision approach is highly accepted by patients and minimizes soft tissue damage.Both of them have their own advantages.

Objective To explore the clinical efficacy and safety of early surgical treatment for spinal thoracolumbar fracture without nerve injury.Methods The clinical data of 80 patients with spinal thoracolumbar fracture without nerve injury who were admitted to the department of spinal surgery in our hospital were retrospectively analyzed.According to the different operation timing,those who underwent surgery within 72 hours after fracture were included in the early operation group(n=41),and those who underwent surgery 72 hours to 2 weeks after fracture were included in the elective operation group(n=39).All operations were performed through the Wiltse approach for short-segment pedicle screw fixation on the injured vertebra.The operation time,intraoperative blood loss,hospital stay and incidence of complication of the two groups were compared.The visual analogue scale(VAS)scores,Oswestry disability index(ODI),compression rate of the anterior edge height of the injured vertebra,and the Cobb angle in the sagittal position of the injured vertebra before surgery,1 week after surgery and 1 year after surgery were compared between the two groups.The improvement rates of the anterior edge height compression and the Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery were compared between the two groups.Results There was no significant difference in the operation time,intraoperative blood loss or total incidence of complications between the two groups(P>0.05).The hospital stay in the early operation group was shorter than that in the elective operation group,and the difference was statistically significant(P<0.05).The VAS scores and ODI 1 week and 1 year after surgery of the two groups were better than those before surgery,and the differences were statistically significant(P<0.05).There was no significant difference in the VAS scores or ODI at each time point before and after surgery between the two groups(P>0.05).The compression rate of the anterior edge height and Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the two groups were lower/smaller than those before surgery,with statistically significant differences(P<0.05).There was no statistically significant difference in the compression rate of the anterior edge height or Cobb angle before surgery in the sagittal position of the injured vertebrae between the two groups(P>0.05).The compression rate of the anterior edge height and Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the early operation group were lower/smaller than those in the elective operation group,and the differences were statistically significant(P<0.05).The improvement rates of the anterior edge height compression and the Cobb angle in the sagittal position of the injured vertebra 1 week and 1 year after surgery in the early operation group were better than those in the elective operation group,and the differences were statistically significant(P<0.05).Conclusion Early surgical treatment for spinal thoracolumbar fracture without nerve damage is safe,it can significantly shorten hospitalization time,obtain good fracture reduction quality and definite therapeutic effects.However,a comprehensive preoperative evaluation of the patients' condition is necessary to ensure surgical safety.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Background: Psoriasis imposes a significant treatment burden on patients, particularly impacting well-being and quality of life (QoL). The psychosocial impact of psoriasis treatments remains unexplored in most patient populations. Objective: To assess the impact of adalimumab on health-related QoL (HRQoL) in Korean patients with psoriasis. Methods: This 24-week, multicenter, observational study, assessed HRQoL in Korean patients treated with adalimumab in a real-world setting. Patient-reported outcomes (PROs) including European Quality of Life-5 Dimension scale (EQ-5D), EQ-5D VAS, SF-36, and DLQI were evaluated at week 16 and 24, versus baseline. Patient satisfaction was assessed using TSQM. Results: Among 97 enrolled patients, 77 were assessed for treatment effectiveness. Most patients were male (52, 67.5%) and mean age was 45.4 years. Median baseline body surface area and Psoriasis Area and Severity Index (PASI) scores were 15.00 (range 4.00~80.00) and 12.40 (range 2.70~39.40), respectively. Statistically significant improvements in all PROs were observed between baseline and week 24. Mean EQ-5D score improved from 0.88 (standard deviation [SD], 0.14) at baseline to 0.91 (SD, 0.17) at week 24 (p=0.0067). The number of patients with changes in PASI 75, 90, or 100 from baseline to week 16 and 24 were 65 (84.4%), 17 (22.1%), and 1 (1.3%); and 64 (83.1%), 21 (27.3%), and 2 (2.6%), respectively. Overall treatment satisfaction was reported, including effectiveness and convenience. No unexpected safety findings were noted. Conclusion Adalimumab improved QoL and was well-tolerated in Korean patients with moderate to severe psoriasis, as demonstrated in a real-world setting. Clinical trial registration number (clinicaltrials.gov: NCT03099083).

OBJECTIVE: To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1β, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke. METHODS: Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD₃ group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD₃ group were treated with intragastric administration of 1,25-dihydroxyvitamin D₃ (1,25-VitD₃) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1β, and IL-10 in the ischemic cortex. RESULTS: Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD₃ group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD₃ group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1β, and IL-10 in the ischemic cortex (P<0.01, P<0.05). CONCLUSION ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Ischemic Stroke ; Interleukin-10 ; Interleukin-6/genetics* ; Microglia ; Scalp ; Acupuncture Therapy ; Vitamins ; Infarction, Middle Cerebral Artery