ObjectiveTo investigate the mechanisms by which Jianpi Yangzheng Xiaozheng prescription （JPYZXZ） treats poorly cohesive gastric carcinoma （PC-GC） through regulation of ubiquitin-specific peptidase 51 （USP51）. MethodsIn vitro experiments： Cell viability and proliferation of PC-GC cell lines （MKN-45 and HGC-27） treated with different concentrations of JPYZXZ （2， 4， 6 g·L^-1） were assessed using Cell Counting Kit-8 （CCK-8） and colony formation assays. Cell migration was evaluated by wound healing （scratch） and Transwell assays. The mRNA and protein expression levels of USP51， zinc finger E-box-binding homeobox 1 （ZEB1）， and epithelial-mesenchymal transition （EMT）-related markers （e.g.， E-cadherin） were detected by quantitative real-time PCR （Real-time PCR） and Western blot， respectively. Subsequently， stable MKN-45 and HGC-27 cell lines with USP51 knockdown （sh-USP51） and overexpression （oe-USP51） were constructed. Their migration ability and EMT-related protein expression were further evaluated by scratch assay， Transwell assay， and Western blot. In vivo experiments： A subcutaneous xenograft model of MKN-45 human gastric cancer was established in BALB/c nude mice. Thirty mice were randomly divided into six groups （NC， NC + JPYZXZ， sh-USP51， sh-USP51 + JPYZXZ， oe-USP51， and oe-USP51 + JPYZXZ）， with five mice in each group. After successful modeling， mice in the treatment groups were administered JPYZXZ （30 g·kg^-1） by gavage for 28 days. Body weight and tumor volume were monitored during the experiment. The expression levels of USP51 and EMT-related proteins in tumor tissues were detected by Western blot and immunohistochemistry （IHC）. ResultsCompared with the blank group， the colony formation rate， wound healing rate， and number of migrated cells in MKN-45 and HGC-27 cells were significantly reduced in all JPYZXZ groups and the 5-fluorouracil （5-FU） group （P<0.05）. The mRNA and protein expression levels of USP51 were decreased （P<0.05）. The expression of ZEB1 and mesenchymal phenotype proteins （e.g.， N-cadherin and vimentin） was reduced （P<0.05）， whereas the expression of the epithelial marker E-cadherin was increased （P<0.05）. Compared with the control group， USP51 expression was decreased in the sh-USP51 group and increased in the oe-USP51 group （P<0.05）. Compared with the NC group， USP51 knockdown significantly reduced the migration and proliferation of gastric cancer cells （P<0.01）， decreased the expression of ZEB1 and EMT-related proteins， and increased E-cadherin expression （P<0.05）. In vivo results showed that JPYZXZ significantly inhibited the growth of xenograft tumors in nude mice （P<0.05） and markedly reversed the abnormal expression of EMT-related proteins in tumor tissues （P<0.05）. ConclusionThe therapeutic mechanisms of JPYZXZ in PC-GC may be associated with inhibition of the EMT process via regulation of the USP51-ZEB1 signaling pathway.

Objective To establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. Methods The EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. Results The 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. Conclusion The EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.

Farrerol is a dihydroflavone compound extracted from the dried leaves of Rhododendron dauricum belonging to the Ericaceae family. This article systematically reviews relevant research on farrerol both domestically and internationally， summarizes its pharmacological activities and mechanisms of action， and finds that it exerts cardiovascular and cerebrovascular protective effects by maintaining the homeostasis of vascular endothelial function and inhibiting vascular intimal hyperplasia； exerts renal protective effects by activating the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway to reduce renal damage； exerts liver protective effects by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway， activating the Nrf2 signaling pathway， improving insulin resistance， and reducing lipid deposition in the liver； exerts neuroprotective effects by activating the Nrf2/Keap1 signaling pathway， inhibiting the Toll-like receptor 4 and cyclic GMP-AMP synthase/stimulator of interferon genes signaling pathways to reduce neuroinflammatory damage； exerts bone protective effects by promoting tendon formation and inhibiting osteoclast differentiation； exerts antitumor effects by inducing tumor cell apoptosis and weakening tumor cell invasion and metastasis； and exerts antibacterial effects by downregulating α -toxin expression， interfering with β -lactamase/penicillin-binding protein 2a （PBP2a）， and inhibiting PBP2a oligomerization. Currently， research on the pharmacological effects of farrerol is still mainly focused on animal and cell experiments. Further mechanistic studies and clinical trials are needed to provide theoretical basis for its new drug development and clinical application.

Farrerol is a dihydroflavone compound extracted from the dried leaves of Rhododendron dauricum belonging to the Ericaceae family. This article systematically reviews relevant research on farrerol both domestically and internationally， summarizes its pharmacological activities and mechanisms of action， and finds that it exerts cardiovascular and cerebrovascular protective effects by maintaining the homeostasis of vascular endothelial function and inhibiting vascular intimal hyperplasia； exerts renal protective effects by activating the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway to reduce renal damage； exerts liver protective effects by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway， activating the Nrf2 signaling pathway， improving insulin resistance， and reducing lipid deposition in the liver； exerts neuroprotective effects by activating the Nrf2/Keap1 signaling pathway， inhibiting the Toll-like receptor 4 and cyclic GMP-AMP synthase/stimulator of interferon genes signaling pathways to reduce neuroinflammatory damage； exerts bone protective effects by promoting tendon formation and inhibiting osteoclast differentiation； exerts antitumor effects by inducing tumor cell apoptosis and weakening tumor cell invasion and metastasis； and exerts antibacterial effects by downregulating α -toxin expression， interfering with β -lactamase/penicillin-binding protein 2a （PBP2a）， and inhibiting PBP2a oligomerization. Currently， research on the pharmacological effects of farrerol is still mainly focused on animal and cell experiments. Further mechanistic studies and clinical trials are needed to provide theoretical basis for its new drug development and clinical application.

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

Objective The aim of this study was to characterize the basic molecular and biochemical parameters for a cyclophilin protein in Cryptosporidium parvum called CpCyP1.Methods CpCyP1 expression patterns during the parasite life cycle were evaluated using qRT-PCR with total RNA isolated from different developmental stages of C.parvum.Native CpCyP1 protein in sporozoites was detected using western blot.The localization of CpCyP1 was performed using the immunofluorescence assay,with an affinity-purified rabbit polyclonal antibody against a synthetic peptide.The peptidyl-prolyl cis-trans isomerase(PPIase)activity of His-tagged recombinant CpCyP1 was evaluated using absorbance colorimetry,and the effect of cyclosporin A(CsA)on the activity of CpCyP1 was determined.Results CpCyP1 was expressed in all parasite developmental stages,whereas CpCyP1 was present mainly in the cytosol of sporozoites,meronts,and gamonts.CpCyP1 displayed Michaelis-Menten kinetics towards N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide for its PPIase activity(Km=456.4 μmol/L;Vmax=1.981 U).CsA inhibited PPIase activity,showing lower micromolar inhibitory activity and binding affinity(Kd=5.122 μmol/L;IC50=1.004 μmol/L).Conclusions These results imply that CpCyP1 in the parasite may be the target for the previously reported anti-cryptosporidial efficacy of CsA and suggest that C.parvum cyclophilins could be evaluated as candidate drug targets.

Objective:To explore the predictive value of preoperative CT angiography (CTA) for incomplete endothelialization of the occluder after left atrial appendage closure (LAAC) in patients with atrial fibrillation.Methods:The clinical data of 92 atrial fibrillation patients underwent LAAC in the Tangdu Hospital of Air Force Military Medical University from January 2022 to June 2024 were retrospectively analyzed. CTA examinations were performed both before operation and 3 months after operation. Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening, diameter of anchoring area and effective depth were measured. After operation, the condition of occluder endothelialization was evaluated, and the patients were divided into the completely endothelialization group and the incomplete endothelialization group. Multivariate Logistic regression analysis was used to analyze the independent risk factors of occluder incomplete endothelialization after LAAC in patients with atrial fibrillation. The predictive value of independent risk factors was evaluated by the receiver operating characteristic (ROC) curve.Results:Among the 92 patients, CTA 3 months after the operation showed that 58 cases had complete occluder endothelialization (complete endothelialization group), and 34 cases had occluder incomplete endothelialization (incomplete endothelialization group). Before operation, the long diameter of left atrial appendage opening, short diameter of left atrial appendage opening, area of left atrial appendage opening and diameter of anchoring area in incomplete endothelialization group were significantly larger than those in complete endothelialization group: (28.35 ± 1.77) mm vs. (26.21 ± 2.21) mm, (22.09 ± 2.01) mm vs. (20.86 ± 1.75) mm, (512.76 ± 63.35) mm 2 vs. (453.83 ± 75.39) mm 2 and (24.71 ± 2.50) mm vs. (23.12 ± 2.40) mm, and there were statistical differences ( P<0.01); there was no statistical difference in effective depth between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the long diameter of left atrial appendage opening before operation was an independent risk factor for occluder incomplete endothelialization after LAAC in patients with atrial fibrillation ( OR = 2.141, 95% CI 1.217 to 3.768, P<0.01). ROC curve analysis result showed that the area under the curve of the long diameter of left atrial appendage opening before operation for predicting occluder incomplete endothelialization after LAAC in patients with atrial fibrillation was 0.768 (95% CI 0.674 to 0.862, P<0.01), the optimal cut-off value was 26.5 mm, the sensitivity was 88.2%, and the specificity was 55.2%. Conclusions:A larger long diameter of left atrial appendage opening before operation can lead to occluder incomplete endothelialization after LAAC in patients with atrial fibrillation.

Objective To evaluate the clinical efficacy of hip-knee-ankle active and passive exercise therapy in patients with early-to mid-stage knee osteoarthritis(KOA).Methods A total of 180 patients with early to mid-stage knee osteoarthritis(KOA)were recruited from the First Affiliated Hospital of Hebei University of Tradi-tional Chinese Medicine between March 2023 and March 2024.Patients were randomly assigned to one of four groups:active movement group,passive movement group,combined movement group,and control group,with 45 patients in each group.The active movement group received hip-knee-ankle active movement therapy daily until the end of follow-up.The passive movement group underwent hip-knee-ankle passive movement therapy three times per week for two weeks.The combined movement group received both active and passive therapies.The control group was administered oral celecoxib capsules(200 mg once daily for two weeks).Joint function was assessed in all four groups before treatment,at two weeks post-treatment,and at 14 weeks post-treatment.The primary outcome measure was the WOMAC joint function score,while secondary outcomes included the WOMAC pain score,stiffness score,and quality of life score(SF-12).Results A total of 160 patients completed the trial,with 39 in the active group,42 in the passive group,40 in the combined group,and 39 in the control group.There were no significant differences in baseline characteristics among the groups(P>0.05).Compared to baseline,the WOMAC scores for function,pain,and stiffness in the passive,combined,and control groups decreased significantly at both 2 and 14 weeks post-treatment(P<0.05),while the SF-12 scores increased significantly(P<0.05).Between 2 and 14 weeks post-treat-ment,the active and combined groups showed further significant decreases in WOMAC function,pain,and stiffness scores(P<0.05)and increases in SF-12 scores(P<0.05).At 2 weeks post-treatment,compared to the control group,the passive and combined groups exhibited significantly lower WOMAC function scores(P<0.05),with no significant difference between the passive and combined groups(P>0.05).By 14 weeks post-treatment,the active and combined groups demonstrated significantly lower WOMAC function scores(P<0.05),with the combined group showing a significantly lower score than the active group(P<0.05).Conclusion The four therapeutic approaches demonstrate a certain degree of efficacy in improving joint function for patients with early and mid-stage KOA.The passive therapy group exhibits superior short-term outcomes,while the active therapy group shows better long-term benefits.The combined therapy group presents notable advantages in both short-term and long-term effi-cacy,although its short-term effectiveness does not surpass that of the passive therapy group.It is recommended for patients with early and mid-stage KOA who have underlying gastrointestinal and cardiovascular conditions.

Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.