ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

Objective:To investigate the safety and effectiveness of the clinical application of minimally invasive transcatheter patent foramen ovale occlusion.Methods:A total of 123 patients who underwent transcatheter patent foramen ovale (PFO) occlusion at the Department of Cardiac Surgery of Beijing Anzhen Hospital from January 1, 2023, to December 31, 2023, were retrospectively analyzed. According to the surgical protocol, this study divided the patients into the conventional occlusion group (Group A, 53 cases) and the minimal invasive occlusion group (Group B, 70 cases). The patients were followed up for at least six months after surgery to evaluate the safety and effectiveness of the new method.Results:The surgical success rate was 100% in both groups. Intraoperative fluoroscopy time decreased by over 50% (7 min in group A and 3 min in group B, P<0.001). At the six-month postoperative follow-up, contrast-enhanced transcranial Doppler ultrasound sonography revealed seven positive results, two of which indicated large shunts. It was further reviewed for combined pulmonary arteriovenous fistula. One patient experienced a recurrence of stroke after the surgery. The patients' overall migraine and transient ischemia attack (TIA) were significantly relieved, and their overall VAS scores decreased significantly compared to the previous ones. Conclusion:The minimally invasive transcatheter PFO occlusion procedure is safe, reliable, and cost-effective. It warrants further follow-up and promotion. Meanwhile, transcatheter PFO occlusion is an effective treatment for preventing recurrent stroke and relieving symptoms like migraine and TIA in patients.

Objective To investigate the changes of anti-Müllerian hormone(AMH),inhibin-B(INHB)and inhibin-A(INHA)levels in boys with cryptorchidism,analyze their clinical application value,and provide labo-ratory data for the diagnosis and treatment of cryptorchidism.Methods A total of 1 310 boys with cryp-torchidism who were hospitalized or visited the outpatient department in the hospital from July 2020 to July 2023 were included in the case group.Another 50 boys who underwent physical examination at the hospital and had no abnormalities in reproductive system development such as testicles were selected as the control group.Venous blood was collected from all the research subjects in a fasting state and placed into biochemical tubes.After centrifuging the serum,the changes in the levels of anti-Müllerian hormone(AMH),Inhibin B(INHB),and Inhibin A(INHA)in the two groups were detected by the chemiluminescence method.The differences between the two groups were analyzed,and the receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of AMH,INHB,and INHA for cryptorchidism.Results The AMH lev-els in boys with cryptorchidism were significantly higher than those in the control group(P＜0.01),while the INHB and INHA levels were significantly lower than those in the control group(P＜0.01).ROC curve analy-sis showed that the area under the curve(AUC)of AMH was 0.65(95％CI:0.56-0.74,P＜0.01).When the Youden index was 26.85％and the cut off value was 37.19 ng/mL,it had relatively good sensitivity(88.85％)but relatively low specificity(38.00％).The AUC of INHB was 0.63(95％CI:0.57-0.70,P＜0.01).When the Youden index was 24.17％and the cut off value was 77.17 pg/mL,it had relatively poor sensitivity(38.17％)but relatively good specificity(86.00％).Both AMH and INHB have certain clinical val-ue in the differential diagnosis of boys with cryptorchidism.The AUC of INHA was 0.81(95％CI:0.79-0.84,P＜0.01).When the Youden index was 75.86％and the cut off value was 5.165 pg/mL,it had a rela-tively good sensitivity(77.86％)and specificity(98.00％).Conclusion The changes in the levels of serum AMH and INHB have certain diagnostic value for boys with cryptorchidism,while INHA has a good diagnos-tic value and can be used as an auxiliary diagnostic indicator for boys with cryptorchidism.

While multiple step saccades (MSS) are occasionally reported in the healthy population, they are more evident in patients with Parkinson's disease (PD). Therefore, MSS has been suggested as a biological marker for the diagnosis of PD. However, the lack of clarity on the neural mechanism underlying the generation of MSS largely impedes their application in the clinic. We have proposed recently that MSS are triggered by the discrepancy between desired and executed saccades. Accordingly, brain regions involved in saccadic planning and execution might play a role in the generation of MSS. To test this hypothesis, we explored the role of the prefrontal (PFC) and posterior parietal cortex (PPC) in generating MSS by conducting two experiments: electroencephalographic recording and single-pulse transcranial magnetic stimulation in the PFC or PPC of humans while participants were performing a gap saccade task. We found that the PFC and PPC are involved in the generation of MSS.
Humans ; Parietal Lobe/physiology* ; Saccades/physiology* ; Prefrontal Cortex/physiology* ; Male ; Transcranial Magnetic Stimulation ; Female ; Electroencephalography ; Adult ; Young Adult

Purpose To investigate correlation of ADP ribosylation-like factor 6 interacting protein 4(ARL6IP4)expression with the pathological characteristics and clinical prognosis in primary colon cancer.Methods The ARL6IP4 mRNA expression in tumor and adjacent normal tissues of 133 colon cancer patients was analyzed by RT-qPCR,and its relationship with tumor location,pathological TNM stage,and 3-year survival prognosis was assessed.Additionally,ARL6IP4 protein expression was analyzed by immunohistochemistry in 30 cases,of which 16 cases were analyzed by immunofluorescence.Results The colon cancer presented significantly higher mRNA and protein levels of ARL6IP4 than adjacent normal tissues(t=4.221,P=5.200 × 10-5;t=7.421,P=3.537 × 10-8).The relative ex-pression level of ARL6IP4 mRNA in colon cancer was positively correlated with pathological TNM stage,N stage and M stage(P＜0.05),and negatively correlated with 3-year cumulative survival probability(P＜0.01).Additionally,sig-moid colon cancer presented significantly higher ARL6IP4 expression than other colon cancers,and at the cellular lev-el,ARL6IP4 was predominantly expressed in the cell nucleus.Conclusion The ARL6IP4 expression in colon cancer is higher than that in adjacent normal tissues,which is closely related to tumor metastasis and clinical prognosis.

Objective Cheng's Juanbi Decoction(CSJBD)is a classic traditional Chinese medicine formula for treating rheumatoid arthritis(RA),exhibiting significant clinical efficacy,but the underlying mechanisms remain unclear.We investigated whether CSJBD inhibited RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis using a collagen-induced arthritis(CIA)mouse model and fibroblast-like synoviocytes(FLSs)derived from RA patients(RA FLSs)and examined the underlying mechanisms.Methods We conducted in vivo experiments.Male C57BL/6 mice weighing 17 to 20 g were used to establish the CIA model.The mice were assigned to 6 groups,including the normal group,the model(CIA)group,the model+CSJBD-L(8.1 g/kg)group,the model+CSJBD-M(16.2 g/kg)group,the model+CSJBD-H(32.4 g/kg)group,and the model+leflunomide(LEF)(0.05 mg/10 g)group,with 10 mice in each group.CSJBD was administered twice daily via gastric gavage,while LEF was administered once daily via gastric gavage,for a duration of 28 days.We also conducted in vitro experiments.RA FLSs were assigned to 4 groups,including the RA FLSs+CSJBDS-L group receiving 10%CSJBDS-containing serum,the RA FLSs+CSJBDS-M group receiving 15%CSJBDS-containing serum,the RA FLSs+CSJBDS-H group receiving 20%CSJBDS-containing serum,and the RA FLSs+NC group(negative control).To study whether WTAP regulated Wnt7b,RA FLSs were divided into the RA FLSs group,the RA FLSs+si-WTAP#3 group,the RA FLSs+si-WTAP#3+Wnt7b-OE group,and the RA FLSs+si-WTAP#3+Wnt7b-NC group.To study the underlying mechanism by which CSJBT affected RA FLSs,RA FLSs were divided into the RA FLSs group,the RA FLSs+CSJBDS-M group,the RA FLSs+CSJBDS-M+Wnt7b-OE group,and the RA FLSs+CSJBDS-M+NC group.We used ultra-high performance liquid chromatography(UPLC)to identify and quantify key monomer compounds from CSJBD as quality criteria for CSJBD preparation.Bioinformatics,CCK-8,RT-qPCR,Western blot,immunofluorescence,and related methods were employed to assess the therapeutic efficacy and underlying mechanisms of CSJBD in treating RA.Results According to the UPLC analysis,ferulic acid,osthole,mulberroside A,notopterol,and gentiopicroside were identified as quality control standards for the preparation of CSJBD formula.CSJBD improved RA pathology in CIA mice,reduced the levels of interleukin(IL)-6,IL-1β,IL-8,and tumor necrosis factor-α(TNF-α)in their serum,and decreased the expression of RA pathological genes MMP3 and fibronectin,with the difference between groups being statistically significant.Bioinformatics analysis suggested that CSJBD might inhibit RA pathology by suppressing the Wnt/β-catenin signaling pathway through Wnt7b.Experimental results showed that the expression of WTAP and Wnt7b was significantly increased in RA.After knocking down WTAP,the expression of Wnt7b was significantly reduced,and the Wnt/β-catenin signaling pathway was also inhibited,with the difference between groups being statistically significant(P<0.05),confirming that WTAP regulated the pathway via Wnt7b.According to experimental verification,CSJBD significantly inhibited the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs.Wnt7b overexpression reversed the inhibitory effect of CSJBD on the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs,indicating that Wnt7b is the direct target of CSJBD.Conclusion CSJBD inhibits RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis,with Wnt7b identified as a direct therapeutic target of CSJBD.

Objective To investigate the perspectives and consensus among high-level medical professionals in China regarding critical thinking skills,identify key factors influencing the cultivation of critical thinking skills among medical students,propose optimization strategies,and provide both theoretical and practical guidance for standardizing mechanisms of critical thinking training within the medical education system.Methods A mixed-methods approach was employed.Semi-structured in-depth interviews were conducted with 22 core personnel involved in critical thinking training from multiple medical universities,hospitals,and clinical research teams across China between March 2023 and June 2023.Grounded theory was applied to explore the influencing factors,and the decision-making trial and evaluation laboratory(DEMATEL)method was applied to construct a structural model of the influencing factors.Centrality and causality analyses were conducted to examine the interrelationships among factors.Results The grounded theory analysis revealed a shared conceptual understanding of critical thinking skills among the participants,who emphasized that the development of critical thinking skills was influenced by multiple factors,including individual traits,teaching methods,and institutional environments.According to the DEMATEL analysis,13 core factors influencing the development of critical thinking skills in high-level medical professionals were identified.Among these,knowledge foundation was the most important influencing factor,exhibiting the highest centrality(22.35).Curriculum design was the second most important influencing factor.Conclusion The cultivation of critical thinking skills in medical education exhibits a multi-level interactive structure that encompasses individual,organizational,and institutional dimensions.Future efforts should focus on reinforcing the cognitive scaffolding role of knowledge construction and interdisciplinary curriculum design.

Objective To explore the effects and underlying molecular mechanisms of high fat diet(HFD)on in-testinal barrier damage and inflammatory reaction in mice with irritable bowel syndrome(IBS)induced by sodium dextran sulfate(DSS).Methods C57BL/6 mice were randomly divided into four groups(n=6):Normal group,DSS group(1.5％DSS solution for one week),HFD+DSS group,and HFD+DSS+WY14643 group(intraperitone-ally injected daily with PPARα agonist WY14643 6 mg/kg).The body weight and liver weight of mice were measured.Colon pathology was observed by HE staining.The protein expression of zonula occludens-1(ZO-1)and occludin was detected by immunohistochemistry.The mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-β(IL-1β),and interleukin-17(IL-17)were determined by qRT-PCR.PPARα protein expression was determined by Western blot.Results The body weight and liver weight of mice in the HFD+DSS group were significantly higher than those in the DSS group(P＜0.001).HE staining showed normal colonic tissue structure in Normal group,while other three groups exhibited varying degrees of mucosal damage with a small amount of in-flammatory cell infiltration and epithelial cell shedding.Among these,the HFD+DSS group displayed the most se-vere intestinal mucosal damage and inflammatory infiltration.Compared with the DSS group,the HFD+DSS group showed decreased ZO-1 and Occludin protein expression(P＜0.001),elevated TNF-α,IL-1 β,and IL-17 mRNA levels(all P＜0.001),and downregulated PPARα protein expression(P＜0.01).Compared with the HFD+DSS group,mice in HFD+DSS+WY14643 group showed improvement in intestinal mucosal damage and reduced infiltration of inflammatory cells.The protein expression of ZO-1 and occludin in colon of mice in the HFD+DSS+WY14643 was increased(all P＜0.05),while the expression of TNF-α,IL-1 β,and IL-17 mRNA was downregulated(P＜0.01 or P＜0.05),and the protein expression of PPAR α was upregulated(P＜0.05).Conclusions HFD-induced obesity aggravates intestinal mucosal damage,intestinal barrier destruction and in-flammatory response in IBS mice,and its molecular mechanism is potentially related to downregulation of PPARαexpression in intestinal tissues.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.