Height， as one of the crucial indicators for assessing children’s growth and development， has consistently been a global focus. With economic development and improvements in social living standards， the clinical management needs for children with short stature have been increasingly growing. While growth hormone brings hope to children with short stature， it also triggers ethical challenges such as medical standardization， expansion of indications， equitable accessibility， and informed consent. To avoid the ethical issues related to the use of pediatric growth hormone， multidimensional and comprehensive clinical management should be implemented for children with short stature， including strictly adhering to medical standards and ethical guidelines， enhancing public awareness， and promoting the standardized development of recombinant human growth hormone （rhGH） therapy and ethics.

OBJECTIVE: To investigate the effectiveness of using 3 hollow compression screws combined with 1 screw off-axis fixation under the guidance of three-dimensional (3D) printed guide plate with mortise-tenon joint structure (mortise-tenon joint plate) for the treatment of Pauwels type Ⅲ femoral neck fractures. METHODS: A clinical data of 78 patients with Pauwels type Ⅲ femoral neck fractures, who were admitted between August 2022 and August 2023 and met the selection criteria, was retrospectively analyzed. The operations were assisted with mortise-tenon joint plates in 26 cases (mortise-tenon joint plate group) and traditional guide plates in 28 cases (traditional plate group), and without guide plates in 24 cases (control group). There was no significant difference in the baseline data of gender, age, body mass index, cause of injury, and fracture side between groups ( P>0.05). The operation time, intraoperative blood loss, frequency of intraoperative fluoroscopy, incision length, incidence of postoperative deep vein thrombosis of lower extremity, pain visual analogue scale (VAS) score at 1 week after operation, and Harris score of hip joint at 3 months after operation were recorded and compared. X-ray re-examination was taken to check the quality of fracture reduction, fracture healing, and the shortening length of the femoral neck at 3 months after operation, and the incidences of internal fixation failure and osteonecrosis of the femoral head during operation. RESULTS: Compared with the control group, the operation time, intraoperative blood loss, and frequency of intraoperative fluoroscopy reduced in the two plate groups, and the quality of fracture reduction was better, but the incision was longer, and the differences were significant ( P<0.05). The operation time and intraoperative blood loss were significantly higher in the traditional plate group than in the mortise-tenon joint plate group ( P<0.05), the incision was significantly longer ( P<0.05); and the difference in fracture reduction quality and the frequency of intraoperative fluoroscopy was not significant between two plate groups ( P>0.05). There was 1 case of deep vein thrombosis of lower extremity in the traditional plate group and 1 case in the control group, while there was no thrombosis in the mortise-tenon joint plate group. There was no significant difference in the incidence between groups ( P>0.05). All patients were followed up 12-15 months (mean, 13 months). There was no significant difference in VAS score at 1 week and Harris score at 3 months between groups ( P>0.05). Compared with the control group, the fracture healing time and the length of femoral neck shortening at 3 months after operation were significantly shorter in the two plate groups ( P<0.05). There was no significant difference between the two plate groups ( P>0.05). There was no significant difference in the incidences of non-union fractures, osteonecrosis of the femoral head, or internal fixation failure between groups ( P>0.05). CONCLUSION For Pauwels type Ⅲ femoral neck fractures, the use of 3D printed guide plate assisted reduction and fixation can shorten the fracture healing time, reduce the incidence of postoperative complications, and be more conducive to the early functional exercise of the affected limb. Compared with the traditional guide plate, the mortise-tenon joint plate can reduce the intraoperative bleeding and shorten the operation time.
Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Bone Screws ; Adult ; Aged ; Treatment Outcome ; Printing, Three-Dimensional ; Operative Time

B and T lymphocyte attenuator (BTLA) is an inhibitory immune checkpoint, which typically interacts with herpesvirus entry mediator (HVEM) and plays a crucial role in regulating immune balance. BTLA interacts with its ligand HVEM in a cis manner on the surface of the same immune cell to maintain immune tolerance, while trans interactions on the surface of different immune cells mediate immunosuppressive effects. Dysregulation of the BTLA/HVEM axis can impair the functions of immune cells, particularly T lymphocytes, promoting immune escape of tumor cells and ultimately leading to tumor progression. Researchers have found that BTLA and HVEM are abnormally expressed in various tumors and are associated with prognosis, suggesting that they may be potential targets for tumor immunotherapy. This review summarizes the molecular structures of BTLA and HVEM, immunomodulatory mechanisms, recent advances in hematologic malignancies, potential inhibitors of BTLA/HVEM interaction, and their applications in immunotherapy for hematologic malignancies.
Humans ; Receptors, Tumor Necrosis Factor, Member 14/chemistry* ; Receptors, Immunologic/immunology* ; Hematologic Neoplasms/genetics* ; Immunotherapy/methods* ; Animals

Alzheimer's disease (AD) is the leading cause of dementia, and no effective treatment has been developed for it thus far. Recently, the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions. Accordingly, the potential therapeutic effect of pterostilbene (PTS) on AD has been demonstrated in multiple in vivo and in vitro experiments. In this study, we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD. Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation. Moreover, PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha (PPAR-α), monoamine oxidase B (MAO-B), silent information regulator sirtuin 1 (SIRT1), and phosphodiesterase 4A (PDE4A). Furthermore, to further elucidate the potential therapeutic mechanisms of PTS in AD, we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins, and the obtained binding energies ranged from -2.83 to -5.14 kJ/mol, indicating that these proteins exhibit good binding ability with PTS. Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD. In summary, by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD, it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD, either using PTS or other developed drug interventions.

LC-MS/MS methods for the quantitative determination of mecobalamin and ceftriaxone in rat plasma were established, and utilized to assess the pharmacokinetic behaviors of the two drugs in rats and to determine whether there were pharmacokinetics-based drug-drug interactions between them. Methanol was used as a protein precipitant to process rat plasma samples. For mecobalamin, acetonitrile containing 0.1% formic acid was used as the organic phase, while an aqueous solution of 0.1% formic acid and 2 mmol/L ammonium acetate served as the aqueous phase. For ceftriaxone, the organic phase was acetonitrile with 0.1% formic acid, and the aqueous phase was a 1% formic acid aqueous solution. LC-MS/MS quantitative analysis methods for both drugs were developed under the positive ion mode, followed by comprehensive methodological validation. Single-dose administration (either alone or in combination) was carried out via caudal vein injection. The dosing regimens were 0.03, 0.1, and 0.3 mg/kg for mecobalamin and 90 mg/kg for ceftriaxone. The results of methodological validation indicated that mecobalamin exhibited good linearity in the range of 3−3000 ng/mL (r = 0.9991), and ceftriaxone showed excellent linearity in the range of 0.5~500 μg/mL (r = 1). The selectivity, precision, accuracy, extraction recovery, matrix effect, and stability of the analytical methods for both substances met the relevant requirements. The pharmacokinetic study revealed that, compared with single-drug administration, the average plasma concentration-time profiles of the two drugs almost overlapped during single-dose combined administration. Statistical analysis, specifically one-way analysis of variance, demonstrated no significant differences in major pharmacokinetic parameters (t1/2, AUC0−∞, etc.) (P > 0.05). This study confirmed that no pharmacokinetic-based drug-drug interactions occurred when mecobalamin and ceftriaxone were co-administered in rats. The findings of this research offer a reliable pharmacokinetic foundation for the rational clinical co-use of these two drugs, thus providing valuable insights into optimizing therapeutic strategies.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To study the biological role and related mechanism of autophagy in acute lung injury (ALI) of hemorrhagic shock mice.Methods:According to random number table method, wild-type male C57BL/6 mice were divided into control group, ALI group, rapamycin group and 3-methyladenine (3-MA) group, with 8 mice in each group. Light chain 3 (LC3) gene knockout mice with C57BL/6 background were divided into LC3 knockout group and LC3 knockout+ALI group, with 8 mice in each group. Control group, ALI group, LC3 knockout group, LC3 knockout+ALI group were intraperitoneally injected with 2 mL/kg normal saline, rapamycin group was intraperitoneally injected with 3 mg/kg autophagy activator rapamycin, 3-MA group was intraperitoneally injected with 15 mg/kg autophagy inhibitor 3-MA, all of which were given for 3 consecutive days. 2 hours after the last administration, the hemorrhagic shock induced ALI model was established. 24 hours after modeling, the lung index was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue and lung injury score was performed. The expressions of autophagy genes LC3-Ⅱ/LC3-Ⅰ and Beclin-1 in lung tissue were detected by Western blotting. The contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) in lung tissue were detected according to the steps of the kit.Results:Compared with the control group, the lung tissue structure was destroyed and exudation increased, lung index, lung injury score, the expressions of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and the contents of TNF-α, IL-6 and MDA in lung tissue significantly increased in the ALI group. Compared with the ALI group, the structural damage and exudation of lung tissue were reduced in the rapamycin group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue decreased, while the expressions of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 in lung tissue increased [lung index: (7.56±0.39)% vs. (9.12±0.59)%, lung injury score: 3.04±0.58 vs. 9.32±2.14, TNF-α (ng/mg): 1.85±0.32 vs. 3.51±0.62, IL-6 (ng/mg): 1.61±0.32 vs. 2.52±0.44, MDA (nmol/mg): 1.03±0.16 vs. 1.88±0.24, LC3-Ⅱ/LC3-Ⅰ: 1.21±0.12 vs. 0.39±0.05, Beclin-1/β-actin: 1.10±0.12 vs. 0.58±0.06, all P < 0.05], while lung tissue structure damage was aggravated and exudation was further increased in the 3-MA group, lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue increased, the expressions of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 in lung tissue decreased [lung index: (10.44±0.62)% vs. (9.12±0.59)%, lung injury score: 11.59±2.28 vs. 9.32±2.14, TNF-α (ng/mg): 4.77±0.71 vs. 3.51±0.62, IL-6 (ng/mg): 3.44±0.52 vs. 2.52±0.44, MDA (nmol/mg): 2.71±0.42 vs. 1.88±0.24, LC3-Ⅱ/LC3-Ⅰ: 0.25±0.04 vs. 0.39±0.05, Beclin-1/β-actin: 0.21±0.03 vs. 0.58±0.06, all P < 0.05]. Lung index, lung injury score and the contents of TNF-α, IL-6 and MDA in lung tissue of LC3 knockout ALI mice were higher than those of wild-type ALI mice [lung index: (10.44±0.75)% vs. (9.12±0.59)%, lung injury score: 12.41±2.86 vs. 9.32±2.14, TNF-α (ng/mg): 4.85±0.72 vs. 3.51±0.62, IL-6 (ng/mg): 3.28±0.51 vs. 2.52±0.44, MDA (nmol/mg): 2.75±0.41 vs. 1.88±0.24, all P < 0.05]. Conclusion:Autophagy plays a protective role in ALI of hemorrhagic shock mice, and the related molecular mechanism is the inhibition of inflammatory response and oxidative stress response.

Objective:To evaluate the role of autophagy in hydrogen-rich solution-induced reduction of remifentanil-induced hyperalgesia in rats.Methods:Thirty-two clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were divided into 4 groups ( n=8 each) by a random number table method: incisional pain group (group I), remifentanil+ incisional pain group (group RI), hydrogen-rich solution+ remifentanil+ incisional pain group (group HRI), and hydrogen-rich solution + autophagy inhibitor+ remifentanil+ incisional pain group (MHRI group). The tail vein was catheterized, the equal volume of normal saline was intravenously infused for 60 min while the incisional pain model was developed in group I, and remifentanil was intravenously infused at a rate of 1 μg·kg -1·min -1 for 60 min while the incisional pain model was developed in RI, HRI and MHRI groups, hydrogen-rich solution 10 ml/kg was intraperitoneally injected at 10 min before preparing the model in group HRI, and 3-MA 15 mg/kg was intraperitoneally injected at 1 h before preparing the model in MHRI group, and the other treatments were similar to those previously described in group HRI. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were determined at 24 h before and 2, 6, 24 and 48 h after the end of infusion. The rats were sacrificed under anesthesia after the behavioral testing, and the lumbar enlargement segment of the spinal cord was removed for determination of the expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), Beclin-1 and P62 by Western blot. Results:Compared with the baseline at T 0, the MWT was significantly decreased and TWL was shortened at T 1-4 in the four groups ( P<0.05). Compared with group I, the MWT was significantly decreased and TWL was shortened at T 1-4, the expression of LC3 II and Beclin-1 was up-regulated, and the expression of P62 was down-regulated in group RI and group HRI ( P<0.05). Compared with group RI, the MWT was significantly increased and TWL was prolonged at T 1-4 in group HRI and group MHRI, the expression of LC3 II and Beclin-1 was significantly up-regulated, and the expression of P62 was down-regulated in group HRI, and the expression of LC3 II and Beclin-1 was significantly down-regulated, and the expression of P62 was up-regulated in group MHRI ( P<0.05). Compared with group HRI, the MWT was significantly decreased and TWL was shortened at T 1-4, the expression of LC3 II and Beclin-1 was down-regulated, and the expression of P62 was up-regulated in group MHRI ( P<0.05). Conclusions:The mechanism by which hydrogen-rich solution alleviates hyperalgesia may be related to enhancing the level of autophagy in the spinal cord of rats with incisional pain induced by remifentanil.

Objective To screen ischemia and hypoxiarelated genes(IAHRGs)after spinal cord injury(SCI)and analyze their immune infiltration patterns by bioinformatics methods.Methods The expression profiles of SCI-related GSE5296,GSE47681 and GSE217797 were downloaded from the Gene Expression Omnibus(GEO)database,where GSE5296,GSE47681 samples were used as the test set and GSE217797 samples as the validation set,and the differentially expressed genes(DEGs)between SCI and healthy samples were obtained.IAHRGs were screened in GeneCards and MSigDB databases.The intersection of DEGs and IAHRGs yielded ischemic and hypoxia related differentially expressed genes(IAHRDEGs).Based on the IAHRDEGs,the key genes were jointly screened by LASSO model and SVM analysis.The key genes were subjected to logistic regression analysis and a diagnostic model was constructed.The diagnostic ability of the diagnostic model was analyzed by Nomogram and the column line graph of Logistic predictive values was plotted.The diagnostic value of the diagnostic model and key genes for SCI was evaluated using the receiver operating characteristics(ROC).Immune cell infiltration patterns of the disease were analyzed using the CIBERSORT tool.Results A total of 388 IAHRGs were screened,313 differentially expressed genes were detected between SCI and healthy samples,among which 312 were up-regulated and 1 was down-regulated.A sum of 27 up-regulated IAHRDEGs genes were obtained.Five key genes related to ischemia and hypoxia after SCI(Abca1,Caspl,Lpl,Procr,Tnfrsf1a)were screened by LASSO model and SVM analysis based on IAHRDEGs.Nomogram analysis confirms the effect of logistics diagnosis model.ROC curve analysis showed that Casp1,Lpl and Tnfrsf1a had higher diagnostic efficacy(AUC＞0.9),followed by Abca1 and Procr(AUC:0.7～0.9),and the logistics linear predictors had the best diagnostic effect(AUC=0.964).CIBERSORT analysis showed that five key genes were associated with the infiltration of eight types of immune cells(neutrophil cells,B cells naive,plasma cells,M0 macrophage,T cells CD4 naive,T cells CD4 follicular,Th17 cells,and NK resting).Conclusion The five key genes of Abcal,Caspl,Lpl,Procr,and Tnfrsfla,may be closely related to ischemic-hypoxic pathogenesis after SCI,and can be used as candidate molecular markers for the diagnosis and treatment after SCI.