BACKGROUND:Acupuncture is an effective method for lumbar pain in lumbar disc herniation,but its mechanism has not yet been clarified.Factors related to the JAK2/STAT3 signaling pathway regulate the body's inflammatory response and are involved in the process of neuropathic pain. OBJECTIVE:To study the mechanism of acupuncture on lumbar disc herniation in a rat model based on the JAK2/STAT3 signaling pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups:sham operation group,model group,acupuncture group,and acupuncture+agonist group,with 10 rats in each group.Animal models of L5 lumbar disc herniation was constructed through autologous disc cell transplantation in the model group,acupuncture group,and acupuncture+agonist group.Rats in the acupuncture group and the acupuncture+agonist group received acupuncture treatment(Yanglingquan,Shenshu,Huantiao,and Dachangshu acupoints)at 3 days after modeling,and acupuncture treatment was given once a day,20 minutes each,for 15 consecutive days.Rats in the acupuncture+agonist group were injected intrathecally with coumermycin A1,a JAK2 agonist,into the L4/L5 intervertebral space,once a day,20 minutes each,prior to the acupuncture at 6,12,and 18 days after modeling.Paw withdrawal mechanical threshold was detected before and 3,6,9,12,15,and 18 days after modeling.At 18 days after modeling,serum inflammatory factor levels were detected,hematoxylin-eosin staining was performed to observe the morphology of L5-L6 tissues,RT-PCR was performed to detect the expression of JAK2 and STAT3 mRNAs in L5-L6 tissues,and western blot was performed to detect the expression of JAK2,p-JAK2 and p-STAT3 proteins in L5-L6 tissues. RESULTS AND CONCLUSION:The paw withdrawal mechanical thresholds of rats in the model group at different time points after modeling were lower than those in the sham operation group(P<0.05),the paw withdrawal mechanical thresholds of rats in the acupuncture group were higher than those in the model group at 9,12,15,and 18 days after modeling(P<0.05),and the paw withdrawal mechanical thresholds of rats in the acupuncture+agonist group were lower than those in the acupuncture group at 9,12,15,and 18 days after modeling(P<0.05).The levels of interleukin 6,tumor necrosis factor α,neurotransmitter substance P,and brain neuropeptide Y were elevated in the model group compared with the sham operation group(P<0.05);the levels of all four inflammatory factors were reduced in the acupuncture group compared with the model group(P<0.05);and the levels of all four inflammatory factors were elevated in the acupuncture+agonist group compared with the acupuncture group(P<0.05).Hematoxylin-eosin staining showed that lumbar degeneration was obvious in the model group but reduced in the acupuncture group and the acupuncture+agonist group.Moreover,the reduction was more obvious in the acupuncture group compared with the acupuncture+agonist group.The JAK2 and STAT3 mRNA expression as well as the p-JAK2 and p-STAT3 protein expression were elevated in the model group compared with the sham operation group(P<0.05),were decreased in the acupuncture group compared with the model group(P<0.05),and were increased in the acupuncture+agonist group compared with the acupuncture group(P<0.05).To conclude,acupuncture can alleviate inflammation to exert analgesic effects in the rat model of lumbar disc herniation,and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Objective: To investigate the association of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin, so as to provide scientific evidence for childhood obesity prevention and intervention measures in the population. Methods: From January 2022 to June 2024, 296 children and adolescents with intellectual disabilities and autism spectrum disorders aged 2-18 years were recruited from special education schools and institutions in Tianjin. Height and weight were measured, and a standardized questionnaire was used to assess physical activity and screen time. Binary Logistic regression analysis was carried out to investigate the association of physical activity and screen time with overweight and obesity. Results: The prevalence of overweight and obesity among children and adolescents with special needs in Tianjin were 17.2% and 21.6%, respectively, and the combined prevalence of overweight and obesity was 38.9%. The median of moderatetovigorous physical activity (MVPA) time was 0.20 h/d, and physical activity sufficiency rate was 7.8%. The median of screen time was 1.79 h/d, and the screen time compliance rate was 68.2%. The binary Logistic regression results showed that lower levels of MVPA time and increased screen time were associated with a higher risk of overweight and obesity among children and adolescents with special needs [OR(95%CI)=1.80(1.06-3.07), 2.40(1.42-4.07),P<0.05]. Conclusions Insufficient physical activity and excessive screen time are associated with an increased risk of overweight and obesity among children and adolescents with special needs. Therefore, comprehensive intervention measures should be implemented as early as possible to prevent and reduce the incidence of overweight and obesity in this population.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Targeted covalent inhibitors, primarily targeting cysteine residues, have attracted great attention as potential drug candidates due to good potency and prolonged duration of action. However, their discovery is challenging. In this research, a database-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy was developed to quickly discover potential cysteine-targeting compounds. First, compounds with potential reactive groups were selected and incubated with N-acetyl-cysteine in microsomes. And the precursor ions of possible cysteine-adducts were predicted based on covalent binding mechanisms to establish in-house database. Second, substrate-independent product ions produced from N-acetyl-cysteine moiety were selected. Third, multiple reaction monitoring scan was conducted to achieve sensitive screening for cysteine-targeting compounds. This strategy showed broad applicability, and covalent compounds with diverse structures were screened out, offering structural resources for covalent inhibitors development. Moreover, the screened compounds, norketamine and hydroxynorketamine, could modify synaptic transmission-related proteins in vivo, indicating their potential as covalent inhibitors. This experimental-based screening strategy provides a quick and reliable guidance for the design and discovery of covalent inhibitors.