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.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To assess the effectiveness and viability of 5G-enabled robot-assisted thoracolumbar internal fixation surgery, scrutinizing its benefits and potential limitations in a clinical setting.Methods:This retrospective case series study analyzed 61 patients who underwent robot-assisted remote thoracolumbar internal fixation surgery between April and December 2021. The orthopaedic robotic telesurgery system, centered at Beijing Jishuitan Hospital and utilizing 5G technology for network transmission, was used to assist in screw placement. The surgeries, distributed across ten hospitals and executed over an average distance of 1 617 km (maximum exceeding 3 000 km), were appraised by examining the accuracy of screw placement, intraoperative communication efficacy, complication rates, among other metrics, and benchmarked against traditional local procedures.Results:Telesurgery was completed successfully in all patients, averaging 92±32 minutes per operation. Out of 354 screws placed, 89.8% were positioned perfectly and 97.5% were deemed clinically acceptable. The 61 patients, followed-up for an average of 18.9±1.9 months, exhibited significant postoperative improvement in pain. The preoperative visual analogue scale (VAS) pain score was 5.74±1.30 and improved to 2.30±0.90 at discharge, a statistically significant difference ( t=11.002, P<0.001). 6 patients with thoracolumbar degenerative spine disease showed significant relief of claudication and pain symptoms postoperatively. 55 patients with thoracolumbar spine fractures had a preoperative height ratio of 62.78%±12.60% at the anterior margin of the injured vertebrae, which recovered to 85.36%±8.35% postoperatively, a statistically significant difference ( t=16.977, P<0.001). All fractures were healed at final follow-up. No perioperative complications, such as vascular or nerve injuries or infections, occurred. Additionally, there were no complications related to the use of the robot. The 5G network ensured stable transmission of robotic control signals, images, and audio signals during the procedure, with no signal delays or communication failures observed. The perfect rate (90.2% vs. 93.8%, χ 2=0.169, P=0.681) and clinical acceptability rate (99.0% vs. 100.0%, P=1.000) of remote versus local robotic-assisted screw placement in participating hospital 1 (Shantou Xin Sheng Orthopaedic Hospital) were similar. The perfect rate (87.0% vs. 85.4%, χ 2=0.075, P=0.784) and clinical acceptability rate (100.0% vs. 96.6%, χ 2=0.580, P=0.446) of remote versus local robotic-assisted screw placement in participating hospital 2 (Guizhou Provincial People's Hospital) were similar. Conclusion:5G technology enhances the remote application of robotic thoracolumbar surgery without compromising patient safety or outcome quality. It underscores the potential for broader adoption of surgical robotics, aiding in the standardization of medical practices across China, boosting healthcare efficiency, and aligning with the Healthy China strategy.

Objective:To evaluate the precision of robot-assisted axis pedicle screw placement and to evaluate the factors influencing the accuracy of the placement.Methods:The medical records of 27 consecutive patients who underwent posterior internal fixation of the upper cervical spine for atlantoaxial instability with intraoperative robot-assisted axis pedicle screw placement from January 2017 to December 2020 at Beijing Jishuitan Hospital were retrospectively analyzed. T The cohort comprised 10 males and 17 females, aged 41.3±16.6 years (range 12-75 years), with a body mass index (BMI) of 23.0±2.9 kg/m 2 (range 18.9-30.0 kg/m 2). There were 16 cases of traumatic atlantoaxial instability and 11 cases of atlantoaxial instability caused by deformity. The accuracy of robot-assisted axis pedicle screw placement was evaluated by postoperative CT using Gertzbein-Robbins scale. Factors potentially affecting placement accuracy were initially identified via univariate analysis, with significant factors ( P<0.200) subsequently analyzed through multivariate modeling using generalized estimating equations. Results:A total of 49 axis pedicle screws were placed in 27 patients, with 35 (71.4%) in Gertzbein-Robbins scale grade A, 12 (24.5%) in grade B, 2 (4.1%) in e grade C, and 0 in grades D and E. The clinically acceptable rate (Gertzbein-Robbins grades A and B) was 95.9%. No patient experienced vascular or neurologic injury due to screw displacement. The results of univariate analysis showed no statistical significance for patient factors (age, gender, BMI, preoperative cervical curvature, and causes of atlantoaxial instability); no statistical significance for the surgical factors of tracker position, screw position, screw type, and screw placement approach ( P>0.05), and a statistically significant difference for the difference between the effective width of the axis pedicle and the screw diameter ( t=3.484, P<0.001). The results of multifactorial analysis showed that tracker fixation to the Mayfield frame in robot-assisted axis pedicle screw placement over the axis spinous process resulted in more accurate screw placement [ OR=83.231, 95% CI(3.898, 1776.952), P=0.005]; and the greater the difference between the effective width of the axis pedicle and the diameter of the screw, the greater the accuracy of screw placement [ OR=5.330, 95% CI(1.648, 17.243), P=0.005]. Conclusion:Robot-assisted axis pedicle screw placement is both precise and safe. Securing the tracker to the Mayfield clamp rather than the axis spinous process enhances the accuracy of screw placement. A greater discrepancy between the axis pedicle's effective width and the screw diameter decreases the likelihood of cortical violation. Preoperative planning, including the selection of appropriate screw types and adjusting the trajectory in three dimensions to maximize the difference between the pedicle's effective width and the screw diameter, can mitigate the risk of cortical breach and subsequent vascular and neurological injury.

Objective:To investigate the efficacy and safety of Guihuang Formula(GHF)in the treatment of type Ⅲ prostatitis with the syndrome of damp-heat stasis in the essence chamber.Methods:This study included 120 cases of type Ⅲ prostatitis with damp-heat stasis syndrome in the essence chamber,which were randomly and equally divided into a GHF and a control group,the for-mer treated with GHF and the latter with Tamsulosin Hydrochloride Sustained-Release Capsules,both for 6 successive weeks.We fol-lowed up the patients for 4 weeks,recorded the NIH-CPSI,TCM symptom scores,and results of prostatic fluid routine,blood and u-rine routine,liver and kidney function and electrocardiogram examinations,and compared them between the two groups of patients be-fore and after treatment.Results:Compared with the baseline,the total NIH-CPSI scores were significantly decreased in both the GHF and control groups after 6 weeks of treatment,even more significantly in the former group(28.34±9.23 vs 6.78±3.53,P＜0.05)than in the latter(27.81±8.28 vs 14.48±4.27,P＜0.05),so were the scores on pain,voiding symptoms,quality of life(QOL)impact,TCM symptoms and WBC count(all P＜0.05),while the number of lecithin bodies remarkably increased(P＜0.05).There were statically significant differences in the above parameters at 4,6 and 10 weeks of medication(P＜0.05),but not at 2 weeks(P＞0.05).No obvious abnormalities or adverse reactions were observed in either of the two groups during the treatment.Conclusion:Guihuang Formula is safe and effective in the treatment of type Ⅲ prostatitis with the syndrome of damp-heat stasis in the essence chamber.

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
Humans ; Liposomes ; Hepatic Stellate Cells ; Glycyrrhetinic Acid/pharmacology* ; Liver ; Liver Cirrhosis/genetics* ; Collagen/pharmacology*

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

Aim To explore the protective effect of Zishen Huoxue Prescription on OGD/R-induced primary hippocampal neuron damage in rats and the possible mechanism. Methods After the isolated primary hippocampal neurons were identified by immunofluorescence, OGD/R induced neuronal damage, and the changes of autophagic flux at different re-oxygenation time were observed by confocal laser scanning microscopy. After OGD/R-induced primary hippocampal neurons were intervened with serum containing Zishen Huoxue Prescription, cell viability was detected by CCK-8, cell apoptosis was detected by flow cytometry, autophagosomes were detected by transmission electron microscopy, and autophagy-related protein expressions were detected by Western blot. Results 10% Zishen Huoxue Prescription-containing serum could significantly improve cell viability and reduce the proportion of cell apoptosis, increase the number of autophagosomes in neurons, and up-regulate the expression of autophagy-related protein PINK1, Parkin, and pATG16L1. Conclusions Zishen Huoxue Prescription can effectively resist OGD/R-induced apoptosis of primary hippocampal neurons in rats, and its effect may be related to the regulation of PINK1-Parkin pathway to promote mitophagy.

Objective:To explore the repairing effects of 3D-printed nano-β-tricalcium phosphate (β-TCP) scaffolds loaded with vancomycin and bone morphogenetic protein-2 (BMP-2) for seawater -soaked tibial bone defects in rabbits. Methods:A total of 27 male New Zealand White rabbits were assigned to the normal group using a random number table method, with each group consisting of 9 rabbits. The rabbit tibial bone defect model was created using the osteotomy surgical method. Eight hours after operation, the wounds in the control group and seawater group were immersed in seawater for 2 hours, and those in the normal group were not immersed. After an observation period of 5-7 days, no significant redness or purulent discharge was observed in the wound appearance, then debridement was performed followed by corresponding implantations: the control group with gelatin sponges loaded with vancomycin and BMP-2, and the other two groups with 3D-printed nano-β-TCP scaffolds loaded with vancomycin and BMP-2. After filling the bone defects with the respective materials, all groups underwent layer-by-layer suturing of the wound, followed by disinfection with iodine and injection of gentamicin to prevent infection. The affected limbs were then immobilized using a plaster cast. The affected limbs were imaged using anteroposterior X-ray at 4, 8 and 16 weeks after operation, and the repair effects were evaluated using the Lane-Sandhu X-ray scoring system. At 16 weeks after operation, the bone defect tissues were collected for HE staining to observe bone tissue growth.Results:At 4 weeks after operation, the Lane-Sandhu X-ray score in the control group was significantly lower than that in the normal group [(2.8±1.1)points vs. (1.1±0.9)points] ( P<0.05), and that in the seawater group [(2.2±1.0)points] was not significantly different from those in the other two groups (all P>0.05). At 8 weeks after operation, the seawater group [(6.1±0.9)points] and the control group [(2.8±1.0)points] exhibited lower Lane-Sandhu X-ray score compared to the normal group [(8.2±1.0)points] (all P<0.05), and the seawater group showed a higher score compared to the control group ( P<0.05). At 16 weeks after operation, the control group [(3.8±1.0)points] exhibited a lower Lane-Sandhu X-ray score compared to the normal group [(10.0±1.3)points] and the seawater group [(9.3±1.2)points] (all P<0.05), while no significant difference was noted between the latter two ( P>0.05). At 16 weeks after operation, histological observations revealed varying degrees of bone tissue formation in three groups, with the normal group showing the best bone defect repair effect, followed by the seawater group. Conclusion:The 3D-printed nano-β-TCP scaffolds loaded with vancomycin and BMP-2 are effective for the treatment of seawater -soaked bone defects, which can promote bone tissue repair.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*