ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Chest CT pulmonary angiography (CTPA) has certain auxiliary diagnostic value for the clinical diagnosis of invasive pulmonary aspergillosis (IPA) . Three patients with hematological malignancies were reported, including 2 ones after allogeneic hematopoietic stem cell transplantation and 1 ones after chemotherapy for refractory recurrent leukemia. Each patient was treated with antibiotics for at least 48 hours after the onset of fever, they all underwent chest high-resolution CT (HRCT) scans without fever resolution. CT revealed at least one dense pulmonary consolidation shadow with a diameter greater than 10 mm, and subsequently a CTPA examination was performed to observe the effect of CTPA imaging signs for the diagnosis of IPA. There were 2 patients with positive vascular occlusion sign (VOS) and 1 patient with negative VOS detected by CTPA. Among them, 2 patients with positive VOS were diagnosed with possible IPA and received with diagnosis-driven antifungal treatment, which improved their conditions. One patient with negative VOS sign was diagnosed with diffuse large B-cell lymphoma involving the lungs. After receiving anti-lymphoma treatment, the lesions significantly reduced in size. The vascular occlusion sign detected by CTPA is relatively characteristic. For high-risk IPA patients, it helps to improve the specificity of imaging diagnosis and guide clinical treatment decisions.

Glycoengineering was carried out in the mammalian cell line CHO for the production of pro-tein-based drugs.Firstly,the genome sequence of the Rosa26 locus of CHO cells was determined,the gRNA sequences were designed,and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology.Three targeting vectors co-expressed by glycosyltransferases,which are β-1,4 galactosyltransferase(B4GALT1),α-2,6-sialyltransferase 1(ST6GAL1)and N-acetaminoglycosyl-transferase Ⅲ(GnT Ⅲ),were constructed by overlapping PCR and seamless ligation technology,and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology.PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site.The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR,and the protein expression levels of the three glycosyltrans-ferases were more than 4-fold via western blotting(P＜0.001).A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China,providing a reference for promoting enterprise R&D and production,as well as improving the supply guarantee mechanism for pediatric medicines.METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval,Pharnexcloud biomedical database,and National Medical Insurance Drug Directory,this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing.RESULTS As of June 30,2024,a total of 68 pediatric medicines had been approved through the priority review and approval process,covering 12 therapeutic areas,with oral dosage forms accounting for 64.71％.The median time from application to inclusion in priority review was 35.50 days,with an average of 41.69 days.The median time from inclusion in priority review to market approval was 1.24 years,with an average of 1.42 years.This included 12 domestic new medicines,21 domestic generic medicines,35 imported medicines,as well as 29 pediatric-specific medicines and 21 orphan medicines.Additionally,31 of these medicines had been included in the medical insurance catalog,representing a proportion of 45.59％.CONCLUSIONS Currently,a trend of differentiated competition is emerging between domestic and imported pediatric medicines.The therapeutic areas for pediatric medicines are continuously expanding,and the dosage forms are becoming more tailored to children's needs.However,there are still issues such as slow progress in new medicine development,insufficient stability in the medicine review and approval process,and a need to increase the proportion of medicines included in medical insurance.

Objective:To explore the position and length of anchor placement during the repair of anterior talofibular ligament (ATFL) in adolescents with unclosed epiphyseal plates by measuring the relevant data in three-dimensional CT.Methods:A total of 100 three-dimensional CT images of adolescent patients with unclosed epiphyseal plates were collected from the database of the Radiology Center of Renhe Hospital Affiliated to China Three Gorges University from January 1, 2017 to January 1, 2024. There were 69 males and 31 females, aged 12.38±0.90 years (range, 11-14 years), 47 on the left side and 53 on the right side, with a height of 155.72±5.84 cm (range, 145-175 cm), a weight of 48.02±5.93 kg (range, 40-72 kg), and a body mass index (BMI) of 19.77±1.61 kg/m 2 (range, 17.69-24.91 kg/m 2). The built-in measurement tool of the picture archiving and communication system (PACS) was used to measure the angle (α) between the direction of the nail placement and the longitudinal axis of the fibula, the distance between the nail placement point and the posterior edge of the fibula ( d), and the height from the nail placement point to the level of the fibula tip ( h) to evaluate the position and length of the anchor placement. Results:In adolescent patients, α was 47.50°±3.28° (range, 40.00°-56.00°), d was 17.12±1.80 mm (range, 11.70-21.90 mm), and h was 5.21±1.17 mm (range, 3.40-7.90 mm). The α, d and h of male patients were 47.48°±3.13° (range, 42.00°-56.00°), 17.49±1.54 mm (range, 14.45-21.90 mm) and 5.25±1.07 mm (range, 3.70-7.90 mm), respectively. Those of female patients were 47.55°±3.66° (range, 40.00°-53.00°), 16.30±2.07 mm (range, 11.65-20.30 mm) and 5.07±1.56 mm (range, 3.40-7.00 mm), respectively. There was a significant difference in d between male and female patients ( t=3.193, P=0.002), but there was no significant difference in α and h ( t=0.098, P=0.922; t=0.296, P=0.770). Conclusions:The safe range of anchor placement during ATFL anatomical repair in adolescents with unclosed epiphyseal plates is about 3.40-7.90 mm above the tip of fibula and 56°-90° with the longitudinal axis of fibula. Male patients with unclosed epiphyseal plates should choose anchors with a length of 14 mm and shorter, while females should choose anchors with a length of 10.8 mm.

Chest CT pulmonary angiography (CTPA) has certain auxiliary diagnostic value for the clinical diagnosis of invasive pulmonary aspergillosis (IPA) . Three patients with hematological malignancies were reported, including 2 ones after allogeneic hematopoietic stem cell transplantation and 1 ones after chemotherapy for refractory recurrent leukemia. Each patient was treated with antibiotics for at least 48 hours after the onset of fever, they all underwent chest high-resolution CT (HRCT) scans without fever resolution. CT revealed at least one dense pulmonary consolidation shadow with a diameter greater than 10 mm, and subsequently a CTPA examination was performed to observe the effect of CTPA imaging signs for the diagnosis of IPA. There were 2 patients with positive vascular occlusion sign (VOS) and 1 patient with negative VOS detected by CTPA. Among them, 2 patients with positive VOS were diagnosed with possible IPA and received with diagnosis-driven antifungal treatment, which improved their conditions. One patient with negative VOS sign was diagnosed with diffuse large B-cell lymphoma involving the lungs. After receiving anti-lymphoma treatment, the lesions significantly reduced in size. The vascular occlusion sign detected by CTPA is relatively characteristic. For high-risk IPA patients, it helps to improve the specificity of imaging diagnosis and guide clinical treatment decisions.

Glycoengineering was carried out in the mammalian cell line CHO for the production of pro-tein-based drugs.Firstly,the genome sequence of the Rosa26 locus of CHO cells was determined,the gRNA sequences were designed,and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology.Three targeting vectors co-expressed by glycosyltransferases,which are β-1,4 galactosyltransferase(B4GALT1),α-2,6-sialyltransferase 1(ST6GAL1)and N-acetaminoglycosyl-transferase Ⅲ(GnT Ⅲ),were constructed by overlapping PCR and seamless ligation technology,and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology.PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site.The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR,and the protein expression levels of the three glycosyltrans-ferases were more than 4-fold via western blotting(P＜0.001).A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.

Objective:To investigate the clinical efficacy and safety of ultrasonic bone scalpel in nasal osteotomy.Methods:A retrospective analysis was conducted on clinical data from the patients who received ultrasonic bone scalpel-assisted nasal osteotomy in the Nasal Plastic & Reconstructive Surgery Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2023 and April 2024. All patients underwent open lateral approach osteotomy using an ultrasonic bone scalpel under direct vision, combined with augmentation rhinoplasty using autologous costal cartilage grafting. Intraoperatively, the nasal dorsum was fully exposed, and the lateral nasal cartilage was separated from the nasal septum, followed by precise bone tissue incision using the ultrasonic bone scalpel. Parameters recorded included operative time, and postoperative complications. Based on the standardized photographs taken before the operation and during the 6-month follow-up after the operation, the observer global aesthetic improvement scale (GAIS) was evaluated by a third-party doctor, with a score ranging from 1 to 5. The smaller the score, the more significant the improvement compared to before the operation. The satisfaction of patients with the surgical outcome was evaluated and classified into four levels: very satisfied, satisfied, dissatisfied, and very dissatisfied.Results:A total of 25 female patients were enrolled, aged 20 to 38 years, with an average age of 27.1 years. All procedures were completed successfully, with a mean operative time of (25.4±4.2) minutes. Postoperative localized swelling of varying degrees was observed. Follow-up ranged from 6 to 18 months, with nasal contour and curvature stabilizing by 6 months postoperatively. No complications, such as infection, nasolacrimal duct, lacrimal sac, medial canthal ligament, nerve injuries, or sensory disturbances, were reported. Two cases exhibited mild nasal bone widening at the 6-month follow-up, though no surgical revision was requested. Significant improvement in external nasal morphology was achieved in all patients, with high satisfaction rates. The patients satisfaction survey showed that 18 cases (72%) were very satisfied and 7 cases (28%) were satisfied with the surgical outcome. GAIS scores reflected positive evaluations [(1.24±0.51) points].Conclusion:The ultrasonic bone scalpel for nasal osteotomy offers the advantages of high-precision cutting and efficient hemostasis. It is highly effective in reshaping the nasal contour, with shorter osteotomy time, reduced intraoperative bleeding, and a lower postoperative complication rate. This study provides some insights into plastic surgeons in optimizing nasal bone modification strategies.

Objective:To explore the position and length of anchor placement during the repair of anterior talofibular ligament (ATFL) in adolescents with unclosed epiphyseal plates by measuring the relevant data in three-dimensional CT.Methods:A total of 100 three-dimensional CT images of adolescent patients with unclosed epiphyseal plates were collected from the database of the Radiology Center of Renhe Hospital Affiliated to China Three Gorges University from January 1, 2017 to January 1, 2024. There were 69 males and 31 females, aged 12.38±0.90 years (range, 11-14 years), 47 on the left side and 53 on the right side, with a height of 155.72±5.84 cm (range, 145-175 cm), a weight of 48.02±5.93 kg (range, 40-72 kg), and a body mass index (BMI) of 19.77±1.61 kg/m 2 (range, 17.69-24.91 kg/m 2). The built-in measurement tool of the picture archiving and communication system (PACS) was used to measure the angle (α) between the direction of the nail placement and the longitudinal axis of the fibula, the distance between the nail placement point and the posterior edge of the fibula ( d), and the height from the nail placement point to the level of the fibula tip ( h) to evaluate the position and length of the anchor placement. Results:In adolescent patients, α was 47.50°±3.28° (range, 40.00°-56.00°), d was 17.12±1.80 mm (range, 11.70-21.90 mm), and h was 5.21±1.17 mm (range, 3.40-7.90 mm). The α, d and h of male patients were 47.48°±3.13° (range, 42.00°-56.00°), 17.49±1.54 mm (range, 14.45-21.90 mm) and 5.25±1.07 mm (range, 3.70-7.90 mm), respectively. Those of female patients were 47.55°±3.66° (range, 40.00°-53.00°), 16.30±2.07 mm (range, 11.65-20.30 mm) and 5.07±1.56 mm (range, 3.40-7.00 mm), respectively. There was a significant difference in d between male and female patients ( t=3.193, P=0.002), but there was no significant difference in α and h ( t=0.098, P=0.922; t=0.296, P=0.770). Conclusions:The safe range of anchor placement during ATFL anatomical repair in adolescents with unclosed epiphyseal plates is about 3.40-7.90 mm above the tip of fibula and 56°-90° with the longitudinal axis of fibula. Male patients with unclosed epiphyseal plates should choose anchors with a length of 14 mm and shorter, while females should choose anchors with a length of 10.8 mm.

The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*