Objective: To systematically review the development and changes in mental health policies within the National Outline for Children s Development in China from 1992 to 2030, providing a reference basis for future formulation of mental health policies among children and adolescent in China. Methods: Based on the four editions of the National Outline for Children s Development in China across different periods from 1992 to 2030, word frequency analysis was used to reveal shifts in policy priorities, and an internationally recognized framework for adolescent health policy analysis was applied to conduct a textual review. Results: Word frequency analysis revealed that the term "psychological" appeared 6 times in the National Outline for Children s Development in China (2001-2010) but increased to 20 times in the National Outline for Children s Development in China (2021-2030) (abbreviated as the National Outline of 2021), while the term "health" rose from 4 times in the National Outline for Children s Development Plan in China in the 1990s to 68 times in the National Outline of 2021. The scope of mental health policy interventions expanded to encompass five key areas:health, safety, education, welfare and legal protection. Textual analysis highlighted that the policies of the National Outline for Children s Development in China were demand driven, prioritized vulnerable groups and continuously broadened their coverage, emphasizing sustainability and appropriateness, and monitoring/evaluation mechanisms. By 2023, 42.3% of primary schools and 64.8% of secondary schools employed full time mental health education teachers. However, the National Outline for Children s Development in China lacked direct evidence of children and adolescents participation in policy formulation, and publicly available mental health data disaggregated by age and gender remained limited. Conclusion Mental health policies of children and adolescents in China have evolved from nonexistence to gradual refinement, yet institutionalized channels for youth involvement in policy development and evaluation remain insufficient, and transparency in age and gender specific mental health data needs improvement.

ObjectiveThis study aims to analyze the pharmacodynamic material basis and multi-target mechanism of action of Banxia Baizhu Tianmatang combined with Danggui Shaoyaosan in the treatment of Meniere's disease（MD）. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS） （mobile phase： gradient elution with 0.1% formic acid aqueous solution-acetonitrile. Mass spectrometry scanning range： m/z 90-1 300） was used to identify the chemical components of the compound recipe and components absorbed into blood. The core mechanism was predicted by combining network pharmacology （target screening via SwissTargetPrediction and GeneCards databases， and construction of protein-protein interaction （PPI） network by STRING） and molecular docking （evaluated by Autodock， with binding energy ≤ -5.0 kcal·mol^-1）. For animal experiment validation， 36 Sprague Dawley （SD） rats were divided into a blank group， a model group （postauricular injection of lipopolysaccharide （LPS） at 1 mg·kg^-1）， low/medium/high-dose Chinese medicine groups （5.94， 11.88， and 23.76 g·kg^-1·d^-1， respectively）， and Western medicine group （betahistine at 0.1 mg·kg^-1·d^-1）. After eight weeks of intervention， the gene and protein expressions in cochlear tissue were detected. Results①A total of 2 831 chemical components and 173 components absorbed into blood were identified， with terpenoids showing the highest absorption rate into blood（10.28%）. ②60 common drug-disease targets were screened， with core targets including tumor necrosis factor-α（TNF-α），interleukin-6（IL-6）， Toll-like receptor 4（TLR4）， angiotensin-converting enzyme（ACE）， and endothelial nitric oxide synthase 3（NOS3）.These targets were enriched in the nuclear factor-κB（NF-κB） signaling pathway and renin-angiotensin system（P<0.05）. Molecular docking showed that the active component YC-1 had a strong binding ability to TNF（binding energy-9.66 kcal·mol^-1）. ③In animal experiments， the high-dose Chinese medicine group significantly down-regulated the expression of pro-inflammatory factors TNF mRNA（P<0.01）and up-regulated vascular regulatory factors NOS3 protein（P<0.01）， and alleviated cochlear pathological damage［hematoxylin eosin （HE） score： from 4 to 2］. ConclusionThis compound recipe synergistically regulates the TNF/NF-κB inflammatory pathway and ACE/NOS3 vascular homeostasis pathway through flavonoids， triterpenoids， and other components， thereby inhibiting endolymphatic hydrops and cochlear damage. It provides a scientific basis for the theory of "simultaneous treatment of phlegm and blood stasis" in traditional Chinese medicine.

Objective:To report a case of Kufor-Rakeb syndrome caused by novel ATP13A2 mutation, collect the cases related to ATP13A2 gene mutation published in recent years, summarize the clinical manifestations of the disease, and broaden the clinical diagnostic thinking. Methods:The clinical manifestations of a newly diagnosed patient with Kufor-Rakeb syndrome caused by ATP13A2 gene mutation admitted to Zhongda Hospital, Southeast University on November 26, 2021, were summarized. The related cases of ATP13A2 mutation published from January 2000 to December 2021 were searched through the PubMed and CNKI databases using the keywords "ATP13A2" and "Parkinson′s disease". The onset age, clinical symptoms, family history, genetic testing, and levodopa responsiveness results of the patients were collected. Results:The patient is a 52-year-old female with the main clinical symptoms of static tremor and bradykinesia. Physical examination showed a gear like increase in muscle tension in the right upper limb, involuntary shaking of the right hand and slow movement. She had good responsiveness to levodopa, and the magnetic resonance imaging and susceptibility weighted imaging of the head showed a lack of clear observation of bilateral black matter swallowtail sign. Whole exome sequencing showed that mutations c.3010A>G (p.S1004G) and c.1195+5G>A (splice) were found in the ATP13A2 gene, both of which were not reported. The c.3010A>G (p.S1004G) mutation originated from the mother, and the c.1195+5G>A (splice) mutation originated from the father. In the retrospective literature review, a total of 10 cases were collected, with onset ages ranging from 18 months to 24 years. Among them, 4/10 patients′ parents married close relatives, and the clinical manifestations were mainly motor symptoms of Parkinson′s disease. In addition, 5/10 patients had cognitive dysfunction, and 3/10 patients had mental symptoms. And demonstrations of most patients′ magnetic resonance imaging were normal in the early stage of the disease, and as the disease progressed, some patients′ imaging results showed specific changes, such as whole brain atrophy and changes in the corpus callosum. Meanwhile, 8/10 patients showed good responsiveness to levodopa. Conclusions:Kufor-Rakeb syndrome is a special type of adolescent levodopa responsive Parkinson′s disease caused by ATP13A2 mutation, which is an autosomal recessive disorder. In addition to motor symptoms such as static tremor and bradykinesia, its clinical manifestations may also be accompanied by non motor symptoms such as cognitive and psychiatric disorders. The disease responds well to treatment with levodopa.

Objective To investigate the effects of abdominal massage combined with electroacupuncture point-through-point method on the expressions of circadian clock genes of Clock,BMAL1,PER1 and neurotransmitters contents of ACh and Glu in insomnia rats and its possible mechanism.Methods Totally 50 SD male rats were randomly divided into normal group,model group,abdominal massage group,electroacupuncture point-through-point group and combination group,with 10 rats in each group.Except for the normal group,an insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine.Abdominal massage group received abdominal massage;electroacupuncture point-through-point group was treated with flat acupuncture,"Baihui"through"Shenting","Sanyinjiao"through"Yinlingquan"(bilateral),"Shenmen"through"Neiguan"(bilateral),the electroacupuncture instrument dilatational wave,frequency of 1 Hz/20 Hz was connected;the combination group was treated with electroacupuncture through acupoints after abdominal massage;1 time/d for each treatment group,a total of 7 days.The normal group and model group were not intervened.HE staining was used to observe the pathological changes of neurons in hypothalamic tissue,the expression of Clock,BMAL1 and PER1 mRNA were detected by RT-qPCR,the expressions of Clock,BMAL1 and PER1 in hypothalamic tissue were detected by immunohistochemical staining,the expression of Clock,BMAL1 and PER1 protein in hypothalamic tissue were detected by Western blot,the contents of ACh and Glu in serum were detected by ELISA.Results Compared with the normal group,the model group rats had a longer sleep latency,shorter sleep duration,severe damage to the cellular structure of the hypothalamic tissue,and a vacuolar like change,with a decrease in the number of neuronal cells,the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue increased,while the expressions of PER1 mRNA and protein decreased;the contents of serum ACh and Glu increased,with statistical significance(P<0.05).Compared with the model group,the abdominal massage group,electroacupuncture point-through-point group,and combination group could all shorten the sleep latency,prolong sleep duration,and improve the morphology of hypothalamic neurons,reduce the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue,up-regulate the expressions of PER1 mRNA and protein,and reduce the contents of serum ACh and Glu,with statistical significance(P<0.05),the combination group showed the most obvious effects(P<0.05).Conclusion Abdominal massage combined with electroacupuncture point-through-point method can improve insomnia.Its mechanism may be related to the regulation of circadian clock genes Clock,BMAL1,PER1 mRNA and protein expression,as well as neurotransmitter content.

Objective:To investigate the correlation between immune function and age-related pulmonary fibrosis, as well as the potential impact of bacterial lysates on this condition.Methods:Twenty-four healthy male C57BL/6 mice, aged 24, were randomly divided into three groups: a control group(Group N), a pulmonary fibrosis group(Group M), and a pulmonary fibrosis+ bacterial lysis product intervention group(Group P). Mice in Groups M and P were intratracheally injected with bleomycin(5 mg/kg)to induce a mouse pulmonary fibrosis model, while mice in Group N were injected with saline.After modeling, mice in Group P were orally administered 0.4 ml of a bacterial lysis product once a day.After 28 days, lung tissue and blood samples were collected for analysis.Pathological changes in lung tissue were assessed using hematoxylin and tosin staining(HE)and Masson staining and the Ashcroft score.The expression of CD4+ and CD8+ in lung tissue was evaluated using immunohistochemistry.The levels of serum interferon-γ(INF-γ), interleukin-3(IL-13), and immunoglobulin A(IgA)protein were measured using Enzyme-linked Immuno Sorbent Assay(ELISA). The levels of INF-γ and IL-13 mRNA in lung tissue were determined using Real-Time Quantitative Transcription PCR(RT-qPCR). Additionally, the protein expression levels of matrix metalloprotein-9(MMP-9)and tissue inhibitor of metalloproteincise 1(TIMP-1)in lung tissue were assessed using blot analysis.Results:The degree of lung fibrosis was significantly reduced in mice in group P compared with group M when treated with bacterial lysis products.Group M showed a significant decrease in the expression of CD4+ T cells and an increase in the expression of CD8+ T cells( P<0.05)compared to group N. Additionally, the content of IgA was decreased( P<0.05)in group M. On the other hand, group P showed a significant increase in the expression of CD4+ T cells and a decrease in the expression of CD8+ T cells( P<0.05)compared to group M. Furthermore, the content of IgA was elevated( P<0.05)in group P. After bacterial lysis product intervention, mRNA and protein expression levels of IFN-γ were elevated( P<0.05), while mRNA and protein expression levels of IL-13 were reduced( P<0.05). Moreover, protein expression of MMP-9 and TIMP-1 was significantly up-regulated in group M compared with group N( P<0.05), and decreased after bacterial lysis product intervention( P<0.05). Conclusions:It is well-known that immune mechanisms play a crucial role in the development of pulmonary fibrosis.The use of bacterial lysates has been found to effectively regulate immune balance and mitigate the severity of pulmonary fibrosis in elderly mice.

【Objective】 To evaluate the HBsAg detection results of HBsAg+ samples after 8 years refrigeration by ELISA and evaluate the effectiveness of the current storage policy of retained samples. 【Methods】 A total of 100 HBsAg+ plasma samples by ELISA from May 2014 to March 2015 and refrigerated at -20℃ were collected and retested for HBsAg using the same method after thawing in 2023. 【Results】 The HBsAg retest results of 100 plasma samples were all positive, with the concordance rate of 100%, though there was a significant decrease in the S/CO value after refrigeration(27.52 vs 19.03, P<0.05). 【Conclusion】 Long-term refrigeration can lead to a decrease in the S/CO value of HBsAg ELISA detection,but it does not affect the positive results.

Red blood cells(RBCs)are the primary mediators of oxygen transport in the human body,and their function is mainly achieved through conformational changes of hemoglobin(Hb).Hb is a tetramer composed of four subunits,with HbA being the predominant Hb in healthy adults,existing in two forms:tense state(T state)and relaxed state(R state).Endogenous regulators of Hb conformation include 2,3-diphosphoglyceric acid,carbon dioxide,protons,and chloride ions,while exogenous regulators include inositol hexaphosphate,inositol tripyrophosphate,benzabate,urea derivative L35,and vanillin,each with different mechanisms of action.The application of Hb conformational regulators provides new insights into the study of hypoxia oxygen supply issues and the treatment of sickle cell disease.

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.