This paper aimed to systematically evaluate the effects of hypoxic training at different fraction of inspired oxygen (FiO₂) on body composition, glucose metabolism, and lipid metabolism in obese individuals, and to determine the optimal oxygen concentration range to provide scientific evidence for personalized and precise hypoxic exercise prescriptions. A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and CNKI databases for randomized controlled trials and pre-post intervention studies published up to March 31, 2025, involving hypoxic training interventions in obese populations. Meta-analysis was performed using RevMan 5.4 software to assess the effects of different fraction of inspired oxygen (FiO₂≤14% vs. FiO₂>14%) on BMI, body fat percentage, waist circumference, fasting blood glucose, insulin, HOMA-IR, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with subgroup analyses based on oxygen concentration. A total of 22 studies involving 292 participants were included. Meta-analysis showed that hypoxic training significantly reduced BMI (mean difference (MD)=-2.29,95%CI: -3.42 to -1.17, P<0.000 1), body fat percentage (MD=-2.32, 95%CI: -3.16 to -1.47, P<0.001), waist circumference (MD=-3.79, 95%CI: -6.73 to -0.85, P=0.01), fasting blood glucose (MD=-3.58, 95%CI: -6.23 to -0.93, P=0.008), insulin (MD=-1.60, 95%CI: -2.98 to -0.22, P=0.02), TG (MD=-0.18, 95%CI: -0.25 to -0.12, P<0.001), and LDL-C (MD=-0.25, 95%CI: -0.39 to -0.11, P=0.000 3). Greater improvements were observed under moderate hypoxic conditions with FiO₂>14%. Changes in HOMA-IR (MD=-0.74, 95%CI: -1.52 to 0.04,P=0.06) and HDL-C (MD=-0.09, 95%CI: -0.21 to 0.02, P=0.11) were not statistically significant. Hypoxic training can significantly improve body composition, glucose metabolism, and lipid metabolism indicators in obese individuals, with greater benefits observed under moderate hypoxia (FiO>14%). As a key parameter in hypoxic exercise interventions, the precise setting of oxygen concentration is crucial for optimizing intervention outcomes.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

OBJECTIVE To analyze and identify the metabolites of pirtobrutinib （PTN） in rats， and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma， urine， and feces. RESULTS A total of 29 PTN metabolites were identified， including 17， 19 and 22 metabolites in plasma， urine and feces， respectively. The metabolic pathways of PTN mainly included oxidation， sulfation， glucuronidation， etc.， and its metabolites were mostly combination products of two or more different metabolic forms. In detail， a total of 26 metabolites were associated with phase Ⅰ metabolic reactions （14 oxidation metabolites， 9 reduction/dehydrogenation metabolites， 8 demethylation metabolites， and 5 hydrolysis metabolites）. Meanwhile， a total of 20 products were involved in phase Ⅱ metabolites （14 sulfation metabolites and 8 glucuronic acid binding metabolites）. CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples， with the primary metabolic pathways being oxidation， sulfation， glucuronidation， and others.

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Objective To assess the pharmacokinetic characteristics of two types of tofacitinib citrate tablets in healthy individuals and evaluate their bioequivalence and safety.Methods A randomized,two-period,self-crossing design was used with 36 subjects in two groups in both fasting and postprandial conditions.Each group received 5 mg tofacatile citrate tablets of either generic tofacitinib citrate tablets(T)or the reference product(R)per period,and the plasma concentration of tofacatile tablets was detected by LC-MS/MS.Phoenix WinNonlin software was used to calculate pharmacokinetic parameters and evaluate its bioequivalence.Results After single oral administration of test and reference preparations,the main pharmacokinetic parameters were as follows:Cmax values in fasting group were(57.54±13.95)and(59.17±12.31)ng·mL-1,respectively;AUC0,values were(143.83±34.58)and(142.13±33.00)ng·h·mL-1,respectively;AUC0-∞ values were(147.39±35.27)and(146.15±34.64)ng·h·mL-1,respectively;tmax was 0.5 h for both;Cmax values in the postprandial group were(57.16±17.56)and(55.19±21.98)ng·mL-1;AUC0-t values were(165.47±41.63)and(162.04±41.84)ng·h·mL-1;AUC0-∞ values were(171.88±44.15)and(168.05±44.21)ng·h·mL-1;The t max was 1.0 h for both.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ in fasting group and postprandial group were 96.35％(90.11％-103.03％)and 105.91％(95.20％-117.83％),101.02％(98.76％-103.34％)and 102.23％(99.67％-104.86％),100.77％(98.53％-103.06％)and 102.40％(99.81％-105.06％),all within the range of 80.00％-125.00％.Conclusion Both types of generic tofacitinib citrate tablets are bioequivalent and safe in Chinese healthy individuals.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

BACKGROUND:N6-methyladenosine(m6A)is a hot research topic in the mechanism of pathological cardiac remodeling and plays an important role in the development of cardiovascular diseases. OBJECTIVE:To summarize the possible mechanism by which m6A modification in non-coding RNAs regulates the main processes of pathological cardiac remodeling,such as pathological cardiac hypertrophy,cardiomyocyte death,myocardial fibrosis and vascular remodeling. METHODS:"m6A,non-coding RNA,pathological cardiac hypertrophy,cardiomyocyte apoptosis,cardiomyocyte pyroptosis,cardiomyocyte ferroptosis,myocardial fibrosis,vascular remodeling"were used as search terms in Chinese and English.Relevant literature from CNKI,PubMed and Web of Science databases published from January 1974 to April 2023 was retrieved,and finally 86 eligible articles were reviewed. RESULTS AND CONCLUSION:m6A modification is a highly dynamic and reversible modification.Pathological cardiac remodeling mainly involves pathological cardiac hypertrophy,cardiomyocyte apoptosis,cardiomyocyte pyroptosis,cardiomyocyte ferroptosis,myocardial fibrosis and vascular remodeling.m6A-related enzymes can regulate pathological cardiac remodeling processes through various non-coding RNAs and different signaling pathways,which can be used as a new potential intervention for cardiovascular diseases.In pathological cardiac remodeling,research on the regulatory relationship between m6A modification and non-coding RNAs is still in its infancy.With the development of epigenetics,m6A modification in non-coding RNAs is expected to have a new development in the regulation of pathological cardiac remodeling.

Objective:To explore the factors influencing lymph node metastasis and prognosis in patients with Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG).Methods:A retrospective analysis was conducted on clinical data of 239 patients with Siewert Type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction who underwent surgical treatment at Beijing Friendship Hospital, Capital Medical University, from July 2013 to December 2022. Among them, there were 204 males and 35 females. The patients′ ages ranged from 27 to 83 years, with a mean age of 63.1 years. Statistical analysis was performed using SPSS 26.0 software, with categorical data presented as n(%) and compared using χ2 tests, corrected χ2 tests, or Fisher′s exact tests. Ordinal data were expressed as frequencies and percentages and compared using rank-sum tests. Multivariate analysis was conducted using Logistic regression, and survival analysis was performed using the Cox regression model. Follow-up was conducted every 6 months, with the last follow-up conducted in November 2023. Results:Multivariate analysis identified infiltration depth ( OR=0.038, 95% CI: 0.011-0.139, P<0.001), tumor deposit ( OR=0.101, 95% CI: 0.011-0.904, P=0.040) and intravascular cancer embolus ( OR=0.234, 95% CI: 0.108-0.507, P<0.001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert Ⅲ AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert Ⅱ. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert Ⅱ AEG, with rates of 5.45% and 3.64%, respectively. A three-year survival analysis underscored LNM as a significant prognostic factor ( P=0.001). Conclusions:Siewert Ⅱ AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert Ⅲ AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No.5 and No.6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.

Objective:To explore the perioperative safety and postoperative short-and long-term efficacy of stomach-partitioning gastrojejunostomy (SPGJ) with distal selective vagotomy (DSV) for treating benign gastric outlet obstruction (GOO).Methods:The clinical data of 26 benign GOO patients treated by Beijing Friendship Hospital, Capital Medical University from January 2019 to July 2023 were retrospectively analyzed. There were 20 males (76.9%) and 6 females (23.1%), aged from 25 to 75 years, with an average age of (55.8±13.6) years, and an average body mass index (BMI) of (20.1±3.4) kg/m 2. There were 12 cases in SPGJ-DSV group and 14 cases in SPGJ group. The main outcome was the gastrointestinal quality of life index (GIQLI) 1 year after surgery in both groups. Independent sample t-test was used to test the difference between the continuous variables with normal distribution. The comparison between groups of non-normal distribution continuous variables was tested by Mann-Whitney U test. Counting data were compared using Chi-square test or Fisher exact test. Results:There were no significant differences between the two groups in terms of operative time ( P=0.071), intraoperative blood loss ( P=0.422), time to pass gas ( P=0.538), time to liquid intake ( P=0.386), postoperative hospitalization ( P=0.431), complications within 30 days after surgery ( P=0.999), and postoperative GOOSS grade ( P=0.483). Among them, postoperative DGE occurred in one patient in each of the two groups, both of which were grade A. In the follow-up results, compared with the SPGJ group, SPGJ-DSV group had a significant advantage in GIQLI score, and the difference was statistically significant ( P=0.028). The incidence of gastric ulcer, reflux esophagitis, bile reflux and gastritis in SPGJ-DSV group was 8.3%, 8.3%, 8.3% and 58.3%, while that in SPGJ group was 35.7%, 21.4%, 21.4% and 57.1%, respectively, but there was no statistical significance between groups. Conclusion:In the treatment of benign GOO patients, SPGJ with DSV did not significantly increase the difficulty of laparoscopic procedures, operative time and intraoperative blood loss. Moreover, it showed a significant advantage in gastrointestinal quality of life 1 year after surgery. In addition, the incidence rates of gastric ulcers and reflux esophagitis were lower in the SPGJ-DSV group 1 year after surgery, but further confirmation is needed in large sample studies.

ObjectiveBased on the ultrastructure of enteric nervous system （ENS）-platelet-derived growth factor receptor α positive （PDGFRα⁺） cell - smooth muscle cell （SMC） network， the effect and mechanism of Shuwei Decoction （舒胃汤） for rats with functional dyspepsia （FD） of liver-depression and spleen-deficiency syndrome were explored. MethodsFifty SD rats were divided into blank group， model group， low-， medium- and high-dose Shuwei Decoction groups randomly， with 10 rats in each group. The blank group was not set up， and the other 4 groups were set up with the modified composite cause （chronic restraint stress + tail irritation + excessive fatigue + diet disorder） for 21 days， resulting in FD model rats with liver-depression and spleen-deficiency syndrome. After successful modelling， rats in the low-， medium- and high-dose groups were given 3.78， 7.56 and 15.12 g/（kg·d） of Shuwei Decoction by gavage， respectively， while rats in the blank group and the model group were given 10 ml/（kg·d） of saline by gavage； all of them were given gavage once a day for 14 days. Body mass increase were collected before and after gavage， and compared after the experiment； the elevated cross maze experiment was conducted to observe the percentage of staying time and the percentage of times entering the open arm of rats； the gastric emptying rate and small intestinal propulsion rate were measured by black semi-solid paste； HE staining was used to observe histopathology of the gastric antrum； the Western Blotting and RT-qPCR were used to detect the expression levels of PDGFRα， small conductance calcium activated potassium （SK3）， and purinergic G protein-coupled receptor P2Y1 （P2Y1 R）， and mRNA expression in gastric antrum； immunofluorescence double staining was used to detect the co-localization of PDGFRα with receptor tyrosine kinase （C-kit）， protein gene product 9.5 （PGP9.5）， Sk3， and smooth muscle cells （SMCs） in gastric sinusoidal tissues； and transmission electron microscopy was used to observe the ultrastructure of the ENS-PDGFRα⁺ cell-SMC network. ResultsHE staining results showed that the mucosal folds of gastric tissue were clear in all groups， no organic lesions such as bleeding， ulceration and swelling were observed， and the arrangement of gastric glands in the lamina propria of gastric sinusoidal tissues in model group and low-dose Shuwei Decoction group was disordered. The arrangement of gastric glands in lamina propria in medium- and high-dose Shuwei Decoction groups was more orderly， and the lesion degree was less than that in model group and low-dose Shuwei Decoction group. Compared with the blank group， the growth value of body mass， the percentage of open arm retention time， the percentage of times entering the open arm， the small intestine propulsion rate， and the gastric empty rate of rats in the model group significantly decreased after gavage； the expressions of PDGFRα， Sk3， P2Y1 protein and mRNA in gastric sinusoidal tissues decreased； the co-localization expression of PDGFRα with C-kit， Sk3， SMC and PGP9.5 significantly decreased （P＜0.05 or P＜0.01）； the ultrastructure of ENS-PDGFRα⁺ cell-SMC network was damaged without gap junction. Compared with model group and low-dose Shuwei Decoction group， the growth value of body mass， the percentage of open arm retention time， the percentage of times entering the open arm， the small intestine propulsion rate， and the gastric empting rate of rats in medium- and high-dose Shuwei Decoction groups increased after gavage； the expressions of PDGFRα， Sk3， P2Y1 protein and mRNA in gastric sinusoidal tissues increased； the co-localization expression of PDGFRα with C-kit， Sk3， SMC and PGP9.5 significantly increased （P＜0.05 or P＜0.01）； the ultrastructure of ENS-PDGFRα⁺ cell-SMC network was intact. Compared with medium-dose Shuwei Decoction group， the protein expressions of PDGFRα， Sk3 and P2Y1， the mRNA expressions of PDGFRα and Sk3， and the co-localization expressions of PDGFRα and C-kit， Sk3， SMC， and PGP9.5 in high-dose Shuwei Decoction group increased （P＜0.05 or P＜0.01）. ConclusionShuwei Decoction can improve the pathological lesion of the gastric antrum in the FD model rats with liver-depression and spleen-deficiency syndrome and increase the gastric emptying rate as well as the small intestinal propusion rate. The mechanism of Shuwei Decoction on FD rats with liver-depression and spleen-deficiency syndrome is related to the protection of the ultrastructural integrity of ENS-PDGFRα⁺ cell-SMC network.