BACKGROUND:Increasing evidence supports the association between different exercise intensities and the risk of osteoarthritis,but this may be affected by confounding and reverse causality,and the conclusions have not been unified. OBJECTIVE:To explore the causal association between different exercise intensities and osteoarthritis using Mendelian randomization method. METHODS:Data from genome-wide association studies associated with different exercise intensities were selected,and instrumental variables were screened with a threshold of P＜5×10-8.Causal associations between exposure and risk of outcome were assessed using five analysis methods of Mendelian randomization with inverse variance weighting as the primary analysis method.Selected instrumental variables were used to assess causal associations between different exercise intensities and osteoarthritis,and sensitivity analyses with inverse Mendelian randomization were performed. RESULTS AND CONCLUSION:In the analysis results of the inverse variance weighting method,low-intensity exercise showed a significant protective effect on knee osteoarthritis[odds ratio(OR)=0.14,95%confidence interval(CI):0.06-0.32,P＜0.001],while sedentary behavior without exercise intensity,such as watching TV,was confirmed to be a risk factor for knee osteoarthritis and hip osteoarthritis(OR=2.24,95%CI:1.74-2.88,P＜0.001;OR=1.34,95%CI:1.01-1.78,P=0.04).Through the reverse Mendelian randomization analysis of osteoarthritis to different exercise intensities,it was found that osteoarthritis was negatively correlated with low-intensity exercise and positively correlated with watching TV.The analysis results show that there is a two-way causal relationship between different exercise intensity and osteoarthritis risk.

Congenital heart disease (CHD) is a congenital malformation resulting from abnormal embryonic development of the heart and great vessels, accounting for approximately 25% of all congenital malformations. Children with CHD are often complicated by short stature. Although surgical treatment can improve their growth and development to a certain extent, some children still experience growth retardation after surgery. Recombinant human growth hormone (rhGH) is the main drug for treating short stature, but its efficacy and safety in the treatment of patients with concomitant CHD warrant further investigation. This article reports six cases of children with CHD and short stature who were treated with rhGH. Through a literature review, we summarize and discuss the therapeutic efficacy, follow-up experiences, and adverse reactions of rhGH treatment, aiming to provide references for clinicians in applying rhGH to treat patients with CHD and short stature.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

OBJECTIVES: To investigate the mechanism by which Guijianyu ameliorates podocyte injury in a mouse model of diabetic kidney disease (DKD) induced by advanced glycation endproducts (AGEs). METHODS: Sixty db/db mouse models of DKD were randomized equally into 5 groups for treatment with saline, Guijianyu extract at 3 doses or irbesartan for 12 weeks, and the changes in renal pathology and structure were observed using transmission electron microscopy, and the expressions of related genes and key proteins were detected using RT-qPCR and immunohistochemistry. In cultured MPC-5 cells incubated with 50 mg/L AGEs-BSA for 24 h, the effect of different concentrations of Guijianyu extract on cell viability was examined with CCK-8 assay; Western blotting was performed to detect the protein expressions of RAGE, VEGFA, TNF-α, NF-κB(p65), IL-6 and caspase-3, and the mRNA expressions of RAGE, NF-κB (p65), VEGFA and IL-6 were detected with RT-qPCR. RESULTS: In mouse models of DKD, treatment with high-dose Guijianyu extract significantly reduced renal expressions of RAGE, VEGFA, NF-κB(p65), and IL-6 proteins and the mRNA expressions of RAGE, NF-κB, and IL-6. In MPC-5 cells, exposure to AGEs significantly reduced cell viability and increased the protein expressions of RAGE, NF‑κB (p65), VEGFA, TNF-α, IL-6 and caspase-3 (P<0.05) and mRNA expressions of RAGE, NF-κB (p65), VEGFA, and IL-6. Treatment with Guijianyu extract obviously improved cell viability and reduced the expressions of RAGE, NF-κB(p65), VEGFA, TNF-α, IL-6, and caspase-3. Furthermore, Guijianyu extract effectively reversed RAGE agonist-induced elevation of protein expressions of RAGE, VEGFA, TNF-α, IL-6, and caspase-3 and mRNA expressions of RAGE, NF-κB (p65), IL-6, and VEGFA in MPC-5 cells. CONCLUSIONS Guijianyu extract ameliorates AGEs-induced mouse renal podocyte injury in DKD by inhibiting the activation of AGEs-RAGE signaling pathway and reducing the expressions of pro-inflammatory cytokines and vascular endothelial growth factors.
Animals ; Glycation End Products, Advanced ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Signal Transduction/drug effects* ; Podocytes/pathology* ; Diabetic Nephropathies/drug therapy* ; Receptor for Advanced Glycation End Products ; Vascular Endothelial Growth Factor A/metabolism* ; Interleukin-6/metabolism* ; Male

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective To analyze the effect of neurofeedback training based on early start Denver model(ESDM)on children with autism spectrum disorder(ASD). Methods From August,2020 to May,2024,a total of 60 children with ASD from Hangzhou Children's Hospital were randomly divided into control group(n=30)and observation group(n=30).The control group received ESDM intervention,while the observation group received neurofeedback training in addition,for six months.They were assessed with Autism Treatment Evaluation Checklist(ATEC)and Psycho-Educational Profile-3rd Edition(PEP-3). Results After treatment,the score of ATEC was lower in the observation group than in the control group(t=3.545,P<0.05),the scores of cognition(t=2.236,P=0.029),emotional expression(t=2.293,P=0.025)and problem be-havior(Z=2.099,P=0.036)were higher in the observation group than in the control group.The score differenc-es of ATEC(Z=3.620,P<0.001),and cognition(Z=2.920,P<0.05)and problem behaviors(Z=4.209,P<0.05)of PEP-3 before and after intervention were higher in the observation group than in the control group. Conclusion Combination of neurofeedback training could improve the effect of ESDM on ASD.

AIM: To understand the visual acuity and spectacle usage among primary and secondary school students in Xi'an city, providing scientific evidence for making myopia prevention and control efforts.METHODS:Vision screening and spectacles usage survey was conducted on 38 226 students in 119 primary and secondary schools from 16 counties and districts in Xi'an city, and uncorrected visual acuity, refractive power, glasses wearing rate, full correction rate were statistically analyzed.RESULTS:The myopia rate among primary and secondary school students in Xi'an city is 61.53%, showing an increasing trend as the grade level goes up(χ2trend=5332.203, P<0.01). Among them, the proportion of mild myopia decreases with the increase of grade level, while the proportion of moderate and high myopia shows an upward trend with the increase of grade level(χ2trend=2671.562, P<0.01). The glasses wearing rate among myopic students is 51.69%, showing an upward trend as the grade level goes up(χ2trend=1486.941, P<0.01). The spectacle prescription rate for female students is higher than that for male students(χ2=23.659, P<0.01), and the rate in urban areas is higher than that in suburban counties(χ2=102.241, P<0.01). The full correction rate among students wearing glasses is 67.08%, and the rate for students wearing glasses in urban areas is higher than that in suburban counties(χ2=4.980, P<0.05). Among myopic students, 63.66% had undergone visual acuity checks more than or equal to twice in the past year, with vocational high school students having the lowest frequency of twice vision screenings, accounting for 58.06%. There is a negative correlation between myopic students residing in suburban counties and their glasses wearing rate, while a higher grade level and increased frequency of annual vision checks are positively correlated with the glasses wearing rate among myopic students(all P<0.01).CONCLUSION:The situation of students' myopia prevention and control is severe in Xi'an city, with low rates of spectacles usage, full correction, and frequency of visual checks. Special attention needs to be paid to the vision correction status of students in suburban counties, primary schools, and vocational high schools.

Objective To investigate the clinical value of fat attenuation index (FAI) on coronary CT angiography (CCTA) in evaluating the degree of coronary artery stenosis and the diagnostic value of plaque vulnerability. Methods A total of 80 patients treated for coronary artery diseases from January 2021 to November 2023 were retrospectively included. All patients were diagnosed with non-calcified plaque (NCP) by CCTA examination. Patients were divided according to the severity of luminal stenosis (39 with mild stenosis, 24 with moderate stenosis, and 17 with severe stenosis). According to plaque vulnerability, the patients were divided into a vulnerable plaque group (27 cases) and a non-vulnerable plaque group (53 cases). A Spearman correlation analysis was used to evaluate the correlation between FAI and stenosis severity in patients with NCP, and a multivariate logistic regression analysis was used to explore the factors influencing vulnerable plaques. Results FAI was significantly lower in the severe stenosis group (−76.95 ± 7.91 HU) than in the mild stenosis group (−66.73 ± 7.69 HU) and the moderate stenosis group (−71.58 ± 8.65 HU), and FAI was significantly lower in the moderate stenosis group than in the mild stenosis group (t = 4.534, 2.190, 4.534, P < 0.05). The correlation analysis showed that FAI was negatively correlated with the severity of coronary artery stenosis (r = −0.726, P < 0.05). There were significant differences between vulnerable and non-vulnerable plaque groups in hypertension [23 (85.19%) vs. 30 (56.60%)], smoking history [8 (29.63%) vs. 4 (7.55)], and FAI (−67.64 ± 8.32 HU vs. −75.69 ± 7.88 HU) (t = 6.535, 6.841, 4.164, P < 0.05). The multivariate logistic regression analysis showed that FAI was a risk factor for vulnerable plaque (odds ratio = 1.439, P < 0.05). Conclusion FAI can be used to effectively assess the risk stratification of NCP and is of great significance in guiding the clinical management of patients.