OBJECTIVE To investigate the mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture based on the AMP-activated protein kinase （AMPK）/silencing information regulatory factor 1 （SIRT1）/ peroxisome proliferator activated-receptor-γ coactivator-1α （PGC-1α） signaling pathway. METHODS Rats with hip fracture surgery were assigned into model group， esketamine group （10 mg/kg）， inhibitor group （250 μg/mL AMPK inhibitor Compound C）， and esketamine+inhibitor group （10 mg/kg esketamine + 250 μg/mL Compound C）， and rats undergoing sham surgery were used as the control group， with 12 rats in each group. New object recognition and Barnes maze experiments were used to E-mail：448231@163.com evaluate cognitive function in rats. The levels of serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β），superoxide dismutase （SOD）， malondialdehyde （MDA）， gamma-aminobutyric acid （GABA）， dopamine （DA） and glutamate （Glu）， and the apoptosis of hippocampal neurons were detected. The pathological morphology of the hippocampal tissue and the ultrastructure of mitochondria were observed. The mRNA expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax），the mRNA and protein expression of AMPK， SIRT1 and PGC-1α， as well as the expression of phosphorylated （p）-AMPK in hippocampal tissue， were detected. RESULTS Compared with the control group， the hippocampal neurons in the model group of rats were disordered， with more neurons necrotic and swollen mitochondria；the new object recognition index， the SOD， GABA， DA levels， Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly reduced， while the latency and number of errors for locating unknown holes， the TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly increased/prolonged （P＜0.05）. Compared with the model group， the esketamine group showed reduced pathological damage to the hippocampal tissue of rats， and the new object recognition index， the SOD， GABA and DA levels， the Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly increased，while the latency and error frequency for locating unknown holes， TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly decreased （P＜0.05）；the inhibitor group showed the opposite trend of changes in these indicators compared to the esketamine group （P＜0.05）.AMPK inhibitor could reverse the improvement effect of esketamine on the above indicators after hip fracture surgery in rats （P＜0.05）. CONCLUSIONS Esketamine may improve postoperative inflammatory response and oxidative stress levels in rats with hip fracture by activating the AMPK/SIRT1/PGC-1α signaling pathway， inhibiting neuronal cell apoptosis， improving mitochondrial structure， and promoting postoperative cognitive function recovery.

BACKGROUND:Aside from iron chelating,deferoxamine is also considered as an effective hypoxia mimetic agent and hypoxia inducible factor-1α stabilizer.Deferoxamine has played a favorable effect on bone regeneration in both basic and clinical research recently.Deferoxamine solutions or deferoxamine loaded bio-scaffolds have been locally applied in bone tissue engineering,and their promotion of bone repair involves various functional properties and molecular mechanisms which have not been entirely clarified.Moreover,their advances in research of bone regeneration lack comprehensive summary as well. OBJECTIVE:To review the functional properties,relative merits and advances in basic research and clinical practice of deferoxamine applied in bone regeneration,attempting to provide references and strategies for further studies. METHODS:Relevant articles were searched with the key words of"deferoxamine OR desferrioxamine OR desferal OR DFO,""bone tissue engineering OR bone regeneration OR bone remodeling OR bone repair OR bone healing OR osteogenesis,""angiogenesis OR vascularized bone regeneration OR angiogenic-osteogenic coupling"in English and Chinese by using PubMed,WanFang and CNKI databases.Eventually,88 articles were selected for review. RESULTS AND CONCLUSION:Deferoxamine can recruit stem cells and regulate their function,activate relevant signaling pathways to advance hypoxia adaptation of the cells,exert anti-inflammatory and antioxidant properties to improve local inflammatory environment,and promote bone regeneration by coupling osteogenesis and angiogenesis as well as inhibiting bone resorption.Compared with growth factors or peptides loaded in conventional bone tissue engineering,deferoxamine has its unique advantages as a small molecule drug,while it also has toxic reactions and application limitations.Therefore,it is necessary to optimize its loading form and dosagey.The unique angiogenic-osteogenic coupling ability of deferoxamine can be used in different types of bone injuries including fractures,osteonecrosis,distraction osteogenesis,bone grafting,oral related osteogenesis,and bone defects.Due to the enhancement of angiogenesis,this ability enables deferoxamine to better adapt and solve the difficulties in bone repair caused by the complex and variable clinical situations and individual differences.However,it is also necessary to compare and optimize the application methods and safe dosage of deferoxamine to expand its application scope and enhance its clinical value.

Objective:To explore the clinical characteristics, pathological features, and diagnosis and treatment strategies of nasal chondromesenchymal hamartoma (NCMH) in infants and young children.Methods:A retrospective analysis was conducted on seven cases of NCMH infants and young children admitted to Beijing Children′s Hospital, Capital Medical University from April 2015 to January 2022. The cohort included 5 males and 2 females, aged from 6 days to 2 years and 3 months. General information, clinical symptoms, imaging findings, treatment plans, postoperative complications, recurrence and follow-up time were collected, summarized and analyzed. Additionally, immunohistochemical characteristics of the lesion were examined.Results:The clinical symptoms of 7 children included nasal congestion, runny nose, open mouth breathing, snoring during sleep, difficulty feeding, and strabismus. All patients underwent electronic nasopharyngoscopy examination, with 5 cases of tumors located in the right nasal cavity and 2 cases in the left nasal cavity. No case of bilateral nasal cavity disease was found. All 7 patients underwent complete imaging examinations, with 5 patients underwent MRI and CT examinations, 1 patient underwent CT examination only, and 1 patient underwent MRI examination only. The CT results showed that all tumors were broad-based, with uneven density, multiple calcifications and bone remodeling, and some exhibited multiple cystic components. The MRI results showed that the tumor showed low signal on T1 weighted imaging and high or slightly high signal on T2 weighted imaging. All patients were diagnosed through histopathological examination and immunohistochemistry, including 7 cases of Ki-67 and SMA (+), 5 cases of S-100 and Vimentin (+), and all EMA and GFAP were negative. All patients underwent endoscopic resection surgery through the nasal approach, with 3 cases using navigation technology. Five cases of tumors were completely removed, and two cases of tumors were mostly removed. No nasal packing was performed after surgery, and no postoperative nasal, ocular, or intracranial complication occurred in all patients. Follow up assessments conducted 6 to 84 months post-surgery revealed no instances of tumor recurrence in any of the patients.Conclusions:The clinical symptoms of children with NCHM mainly depend on the size and location of the tumor. Nasal endoscopic surgery is the main treatment method. In cases where critical structures like the skull base or orbit are implicated, staged surgical interventions may be warranted. Long-term follow-up is strongly advised to monitor for any potential recurrence or complications.

Background and Aims:In recent years,function-preserving proximal gastrectomy with reconstruction has become an important approach for the treatment of early gastric cancer.However,there is no standardized surgical technique,and the short-and long-term outcomes of various new procedures remain unclear.This study was performed to evaluate the safety and short-term efficacy of laparoscopic proximal gastrectomy plus esophagogastrostomy with single-flap technique for early gastric cancer. Methods:The clinical data and follow-up records of 7 patients who underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy in the First Affiliated Hospital of Soochow University between December 2021 and December 2022 were retrospectively analyzed.Perioperative safety,postoperative reflux,anastomotic stricture at 6 months,and related nutritional parameters were assessed.The nutrition-related indicators of this group of patients were compared with those of 11 patients who underwent total gastrectomy with Roux-en-Y anastomosis for early gastric cancer during the same period. Results:All 7 patients successfully underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy.The average operative time was(212.9±20.6)min,with anastomosis taking(54.7±10.5)min;the mean intraoperative blood loss was(28.6±9.0)mL.No Clavien-Dindo grade Ⅲ or higher complications were observed during hospitalization.None of the patients experienced significant reflux symptoms,although 1 patient developed anastomotic stricture 3 months after operation.There were no statistically significant differences in hemoglobin concentration,albumin level,prealbumin level,total protein concentration,and lymphocyte count between preoperative and 6-month postoperative measurements(all P＞0.05).Compared to patients who underwent total gastrectomy with Roux-en-Y anastomosis,those who had the proximal gastrectomy with single-flap esophagogastrostomy showed a lower percentage decrease in body weight,skeletal muscle area at the third lumbar vertebra(L3),visceral fat area at L3,and hemoglobin concentration at 1 year after operation(all P＜0.05). Conclusion:Laparoscopic proximal gastrectomy with single-flap esophagogastrostomy is a safe and feasible surgical option for early gastric cancer,offering effective anti-reflux outcomes while minimizing the risk of anastomotic stricture.This procedure has a lower impact on postoperative nutritional status compared to total gastrectomy.

Background::Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19).Methods::This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal.Results::The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio= 7.384, 95% confidence interval = 1.732–31.488, P = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P = 0.143). Conclusions::PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.

Thyroid cancer is the most common malignant tumor of the endocrine system, and the incidence is increasing year by year, which seriously threatens people's health. Autophagy is a programmed mode of death that can be used as a potential target for anti-tumor therapy and plays an important regulatory role. Leucine-rich repeat kinase 2 (LRRK2) is a protein kinase encoded by PARK8 gene. The recent studies have confirmed that autophagy is closely related to thyroid cancer. This paper analyzes the possible regulatory mechanism of LRRK2 affecting thyroid cancer through autophagy, providing new ideas for basic research and clinical diagnosis and treatment of thyroid cancer.

Objective:To analyze the serum anti-Müllerian hormone (AMH) levels in women of childbearing age in different age groups in Henan, and establish the medical reference intervals based on measurement results from this population.Methods:From January to June 2017, 620 healthy women of childbearing age (20-34 years old), who underwent pre-pregnancy eugenics and pre-marital checkups in 13 project sites in Henan, were included in this study. Participants were divided into 3 age groups: 20-24 years group ( n=210), 25-29 years group ( n=207), and 30-34 years group ( n=203). Spearman correlation coefficient was used to evaluate the correlation between serum AMH level and age; Kruskal-Wallis H test was used to compare the serum AMH levels of different age groups; Wilcoxon test was used for comparison between pairs; the percentile method ( P2.5, P97.5) was used to establish medical reference interval of serum AMH in women of childbearing age for the whole population and different age groups, respectively. Results:The correlation coefficient between serum AMH and age in women of childbearing age (20-34 years old) is -0.17 ( P<0.001). There was a statistically significant difference in the overall frequency distribution of serum AMH levels among the three different age groups ( H=21.978, P<0.05). Among them, there is a statistically significant difference between the 20-24 years group and the 30-34 years group ( Z=4.292, P<0.05). There is a statistically significant difference between the 25-29 years group and the 30-34 years group ( Z=3.803, P<0.05). The reference range of serum AMH is 0.281-9.693 μg/L in this cohort; the reference range of serum AMH is 0.524-10.760, 0.229-9.200, 0.115-8.200 μg/L for women of childbearing age at 20-24, 25-29 and 30-34 years, respectively. Conclusion:The serum AMH level of women of childbearing age (20-34 years old) decreases with age. It is of great significance to establish the serum AMH reference interval for women of childbearing age in different age groups in Henan.

Objective:To study the effect of sublingual immunotherapy on children with mite allergic rhinitis.Methods:Four hundred and ninety patients with mite allergic rhinitis have been recruited by Beijing Children′s Hospital from March 2014 to September 2019 and divided into 4 groups of young children group, different treatment duration group, individualized dose adjustment group and multiple allergy evaluation group, the clinical scores of total nasal symptoms score (TNSS), visual analogue scale scores (VAS) and total medication score were recorded at the first visit, 12 months, 24 months and 36 months after treatment, and the combined symptom and medication score(CSMS) score was calculated.Results:A total of 374 patients (76.32%) completed this study.Among them, the CSMS(2.20±1.61, 2.50±1.78), TNSS(2.80±2.32, 3.60±2.71) and VAS(3.50±1.16, 3.90±1.43) in ≤3-year-old group and children over 3-year-old group of young children set after use of 12 months were significantly lower than the score at the first time of diagnosis (respectively CSMS: 4.50±1.44, 5.30±1.32; TNSS: 6.20±1.89, 7.50±2.19; VAS: 5.40±2.33, 5.90±1.61). In addition, in the duration and efficacy set, the patients who completed the immunotherapy for 36 months can only be observed in the 3-year group, the scores were TNSS(0.90±0.97), VAS (1.30±1.19), CSMS (1.70±1.28); the scores of patients who completed the immunotherapy for 24 months in 2-year group and 3-year group were TNSS (2.10±0.95, 2.00±0.97), VAS (3.00±1.56, 3.10±1.68) and CSMS (3.10±1.15, 2.90±1.19) and the patients who completed 12-month immunotherapy were scored in 1-year group, 2-year group and 3-year group with TNSS(3.20±1.27, 3.10±1.41, 3.20±1.41), VAS(4.50±2.11, 4.70± 2.19, 4.50±2.17) and CSMS(4.20±1.39, 3.70±1.32, 4.10±1.39) respectively; patients with poor efficacy in sublingual immunotherapy achieved a score similar to the control group after 6 months of dose adjustment (equals to 12 months after treatment), that were CSMS(2.90±1.56, 2.90±1.88, 2.40±1.69), TNSS(4.70±2.98, 3.90±2.77, 3.80±2.45) and VAS(4.20±1.29, 4.50±1.65, 4.20±1.14) of 4 drops group, 5 drops group and control group; sublingual immunotherapy for patients with multiple allergens for 2 years finally achieved similar efficacy to patients with single allergen, with CSMS (2.30±0.50, 2.10±1.01, 1.90±1.01), TNSS (3.50±2.62, 3.70±2.62, 3.20±2.82) and VAS (4.50±1.00, 4.10±1.57, 3.80±1.54) in single allergen group, combined with 1-2 allergens group and combined with 3+ allergens group.Conclusions:Sublingual immunotherapy plays a corresponding role in the treatment of low-age children, multiple allergy children, and some children get better after dose adjustment.

Objective:To explore the influences of neutrophilic granule protein (NGP) on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages and the regulatory mechanism.Methods:NGP highexpression RAW264.7 cells (NGP/RAW) and negative control empty vector cells (NC/RAW), NGP knockout RAW264.7 cells (NGP KO/RAW) and wild-type cells (WT/RAW) were cultured in vitro. Cells in logarithmic phase were stimulated with 10 mg/L LPS (LPS group) or phosphate buffered saline (PBS group) respectively. The content of NO in the supernatant was detected by Griess method. The mRNA expression of inducible nitric oxide synthase (iNOS) was detected by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The protein expressions of iNOS and phosphorylated signal transducer and activator of transcription 1 (p-STAT1) were detected by Western blotting.Results:Compared with PBS group, iNOS mRNA and NO expression were significantly increased at different time after LPS stimulation, the mRNA expression of iNOS peaked at 12 hours after LPS stimulation (2 -ΔΔCt: 38.45±1.34 vs. 1.00±0.00 in NC/RAW cells, 56.24±2.41 vs. 1.45±0.30 in NGP/RAW cells, 37.84±1.52 vs. 1.00±0.00 in WT/RAW cells, 5.47±0.62 vs. 0.98±0.40 in NGP KO/RAW cells, all P < 0.05), and the production of NO peaked at 24 hours after LPS stimulation (μmol/L: 24.15±1.26 vs. 0.15±0.04 in NC/RAW cells, 58.80±2.11 vs. 0.18±0.02 in NGP/RAW cells, 25.04±1.80 vs. 0.16±0.02 in WT/RAW cells, 2.42±0.38 vs. 0.12±0.03 in NGP KO/RAW cells, all P < 0.05). After being stimulated by LPS, the expression of iNOS mRNA and NO in NGP/RAW cells were increased significantly compared with NC/RAW cells [iNOS mRNA (2 -ΔΔCt): 8.42±0.59 vs. 4.63±0.37 at 2 hours, 27.16±1.60 vs. 14.25±1.02 at 6 hours, 56.24±2.41 vs. 38.45±1.34 at 12 hours; NO (μmol/L): 4.12±0.25 vs. 2.23±0.17 at 6 hours, 16.50±1.52 vs. 6.35±0.39 at 12 hours, 58.80±2.11 vs. 24.15±1.26 at 24 hours, all P < 0.05]. At the same time, the protein expressions of p-STAT1 and iNOS were also significantly enhanced (p-STAT1/GAPDH: 4.26±1.84 vs. 1.00±0.32 at 0 hours, 20.59±4.97 vs. 0.93±0.21 at 2 hours, 141.99±10.99 vs. 11.17±2.11 at 6 hours; iNOS/GAPDH: 1.27±0.86 vs. 1.00±0.22 at 0 hours, 7.94±1.94 vs. 2.01±0.92 at 2 hours, 24.24±4.88 vs. 3.72±1.11 at 6 hours, all P < 0.05), indicating that NGP might increase the expression of iNOS by promoting the phosphorylation of the signal transducer and activator of transcription 1 (STAT1) pathway, thereby increasing the production of NO. After being stimulated by LPS, the expression of iNOS mRNA and NO in NGP KO/RAW cells were significantly lower than that of WT/RAW cells [iNOS mRNA (2 -ΔΔCt): 2.46±0.31 vs. 4.22±0.18 at 2 hours, 3.61±0.44 vs. 13.02±1.34 at 6 hours, 5.47±0.62 vs. 37.84±1.52 at 12 hours; NO (μmol/L): 1.22±0.19 vs. 2.01±0.12 at 6 hours, 1.60±0.44 vs. 5.15±0.62 at 12 hours, 2.42±0.38 vs. 25.04±1.80 at 24 hours, all P < 0.05]. It showed that iNOS activation was reduced after NGP knockout, which in turn reduced NO production. Conclusion:NGP can positively regulate NO production in activated macrophages by activating the STAT1/iNOS pathway.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,