BackgroundAdolescents with depressive disorder often engage in non-suicidal self-injury （NSSI） behaviors， which severely impacts their physical and mental health. Impulsivity and emotional regulation are key factors influencing NSSI behaviors. However， research on the mechanisms through which impulsivity and emotional regulation affect NSSI behaviors in adolescent depressive disorder patients with NSSI remains insufficient， limiting the development of effective intervention strategies. ObjectiveTo explore the differences in impulsivity and emotion regulation abilities between adolescent patients with depressive disorder accompanied by and without NSSI behaviors， and to analyze the association between NSSI behaviors and impulsivity and emotion regulation abilities in adolescent patients with depressive disorder accompanied by NSSI behaviors. MethodsA total of 184 adolescents hospitalized in the child and adolescent psychiatry department of Wuxi Mental Health Center from October 2023 to August 2024， who met the diagnostic criteria for depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were consecutively enrolled as study subjects. Based on the diagnostic criteria for NSSI in DSM-5， patients were divided into NSSI group （n=108） and non-NSSI group （n=76）. The Barratt Impulsiveness Scale-11 （BIS-11）， the Emotion Regulation Questionnaire （ERQ）， the Adolescent Self-Harm Questionnaire， and the Positive and Negative Suicide Ideation （PANSI） were used for assessment. Spearman correlation analysis was employed to explore the correlation between the scores of the Adolescent Self-Harm Questionnaire and the scores of BIS-11 and ERQ in the NSSI group. Multiple regression analysis was conducted to examine the effects of impulsivity and emotion regulation on NSSI behaviors in the NSSI group. ResultsCompared to the non-NSSI group， the NSSI group showed significantly higher scores in BIS-11 non-planned impulsivity （Z=-4.181， P<0.05）， action impulsivity （t=4.944， P<0.05）， cognitive impulsivity （Z=-3.392， P<0.05）， and total score （t=4.763， P<0.05）， and lower scores in the cognitive reappraisal of ERQ （t=-4.094， P<0.05） and total score （Z=-2.299， P<0.05）， and higher scores in the expression inhibition of ERQ （Z=-3.019， P<0.05）. The correlation analysis results showed that the score of the adolescent self-harm questionnaire in the NSSI group was positively correlated with the behavioral impulsivity factor score in the BIS-11 （r=0.434， P<0.05）. Multiple regression analysis indicated that action impulsivity factor was a significant correlate of self-injury behaviors in the NSSI group （B=0.855， P<0.05）， explaining 22.30% of the total variance. ConclusionAdolescent patients with depressive disorder accompanied by NSSI behaviors exhibit higher levels of impulsivity and poorer emotional regulation abilities. Action impulsivity may play a significant role in the mechanism of NSSI behaviors. ［Funded by Wuxi Municipal Health Commission Research Project （number， Q202320）］

OBJECTIVE To evaluate the clinical comprehensive value of four Chinese patent medicines （Xuezhikang， Zhibitai， Zhibituo， Jiangzhiling） in the treatment of hyperlipidemia， and provide a reference for rational clinical drug use. METHODS A clinical comprehensive evaluation index system was established in accordance with the Evidence and Value： Impact on Decision-Making （EVIDEM） framework and Technical Guideline for Clinical Comprehensive Evaluation of Cardiovascular Drugs （2022 edition， trial implementation）. CNKI， Wanfang data， VIP， PubMed， ScienceDirect， Embase and official websites were retrieved to collect the literature such as drug instructions， guidelines and consensus statements， and systematic reviews/meta-analyses for the four Chinese patent medicines. A comprehensive evaluation was conducted from seven dimensions： effectiveness， safety， economy， suitability， accessibility， innovation and characteristics of traditional Chinese medicine. RESULTS This evaluation index system included 7 first-level indicators， 15 second-level indicators and 30 third-level indicators. Xuezhikang achieved the highest comprehensive evaluation score of 81.4 points， and was classified as class Ⅰ recommendation. Zhibitai with 76.0 points and Zhibituo with 60.9 points were both classified as class Ⅱ recommendation. Jiangzhiling with 48.8 points was classified as class Ⅳ recommendation. CONCLUSIONS Xuezhikang demonstrates the optimal clinical comprehensive value for treating hyperlipidemia. Zhibitai exhibits certain advantages in terms of safety and characteristics of traditional Chinese medicine； Zhibituo shows a moderate performance in all aspects； Jiangzhiling has a relatively low score. Appropriate medicines can be selected clinically according to actual conditions and patients’ characteristics.

Based on the interactive ritual chain theory， this paper deeply analyzed the interactive characteristics between doctors， patients， and their families in the palliative care environment， as well as explored the role of emotional resonance， symbolic representation， and situational creation in psychological support. It also sorted out four primary issues currently present in psychological support for palliative care patients， including insufficient recognition of caregivers regarding patients’ psychological needs， limited psychological intervention methods， inadequate psychological support capabilities among medical staff， and an imperfect family and social support system. On this basis， a five-dimensional psychological support mechanism was constructed， encompassing emotional resonance， situational creation， team collaboration， environment building， and technological application. This aimed to provide palliative care patients with comprehensive and continuous psychological intervention by optimizing doctor-patient interaction， strengthening emotional connection， improving physical environment， and utilizing information technology， thereby contributing to alleviating the psychological distress patients confront in the terminal stage and improving their life dignity and quality of life.

OBJECTIVE: To observe the clinical effect of Jin's three-needle therapy combined with game therapy on children with autism spectrum disorder (ASD). METHODS: Sixty children with ASD were randomly divided into an observation group and a control group, with 30 cases in each. The children in the observation group received Jin's three-needle therapy combined with game therapy. The acupoints used in Jin's three-needle therapy included Zhisanzhen, Niesanzhen, Sishenzhen and Naosanzhen, and matches acupoints with syndromes. The acupoints included Shenting (GV24), Naohu (GV17) and bilateral Benshen (GB13), Naokong (GB19), Xinshu (BL15), Zusanli (ST36), etc. The needles were retained for 1 h for scalp acupuncture and not retained for body acupuncture. Game therapy included social interaction, music and dance, language stimulation, etc. The children in the control group were treated with the same game therapy in the observation group. Treatments were administered once daily, five times a week, with a three-month course considered as one treatment cycle, and a total of two cycles were provided. The scores of childhood autism rating scale (CARS), autism behavior scale (ABC) and 0-6-year-old Children's neuropsychological development assessment scale (children's psychological scale) were compared between the two groups before treatment and after 3 and 6 months of treatment. RESULTS: After 3 and 6 months of treatment, the CARS and ABC scores of both groups were lower than those before treatment (P<0.01). After 6 months of treatment, the CARS and ABC scores of the observation group were lower than those of the control group (P<0.05). After 3 and 6 months of treatment, the scores of gross motor, fine motor, adaptive ability, language, and social behaviors in both groups were higher than those before treatment (P<0.01). After 3 months of treatment, the observation group showed a greater improvement in gross motor, fine motor, adaptive ability, and social behaviors compared to the control group (P<0.05). After 6 months of treatment, the observation group showed a greater improvement in gross motor, fine motor, adaptive ability, language, and social behaviors compared to the control group (P<0.01, P<0.05). CONCLUSION Jin's three-needle therapy combined with game therapy is an effective method for the treatment of ASD, which shows more obvious advantages than simple game therapy in promoting the improvement of children's ability and reducing related behavior.
Humans ; Autism Spectrum Disorder/psychology* ; Male ; Acupuncture Therapy/instrumentation* ; Female ; Child ; Child, Preschool ; Acupuncture Points ; Treatment Outcome ; Play Therapy ; Combined Modality Therapy

Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

L-theanine is an important natural non-protein amino acid that is widely used in food and medicine. Although in previous studies, a microbial fermentation method for L-theanine without the addition of ethylamine has been developed, the conversion rate of this process needs to be further improved. In this study, we constructed a de novo synthesis pathway of L-theanine with glucose as the substrate. First, an in vitro transformation pathway containing ω-transaminase (TA) and γ-glutamylmethylamide synthetase (GMAS) was designed, optimized, and introduced into the chassis strain Escherichia coli K12 W3110 to achieve de novo synthesis of L-theanine. To improve the synthesis efficiency through metabolic engineering, we increased the copies of the GMAS gene gams and the TA gene spuC and enhanced the expression of the aldehyde dehydrogenase gene eutE to provide sufficient acetaldehyde substrate, knocked out the lactate dehydrogenase gene ldhA and the pyruvate formate lyase gene pflB to block bypass metabolism, and introduced the alanine dehydrogenase gene alD to recycle alanine. Furthermore, we over-expressed the phosphoenolpyruvate carboxylase gene ppc to enhance the carbon flux of the TCA cycle, knocked out the succinyl-CoA synthase gene sucCD to reduce the loss of downstream flux of TCA, and integrated the glutamate dehydrogenase gene gdh to enhance the supply of L-glutamate. Finally, the polyphosphate kinase gene ppk was introduced to the ATP cycle, which enhanced the energy supply in L-theanine production. The recombinant strain Tea11 produced 22.60 g/L L-theanine in a 5 L fermenter in 28 h, with a conversion rate of 41.71%. This synthetic pathway in this study balanced the relationship between the supply of ethylamine and the production of theanine, providing a new idea for metabolic engineering of microorganisms to produce L-theanine.
Glutamates/biosynthesis* ; Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Fermentation ; Transaminases/metabolism* ; Amide Synthases/metabolism* ; Glucose/metabolism*

Objective To investigate the regulatory mechanism of the central nervous system in patients with refractory overactive bladder (rOAB) using diffusion tensor imaging (DTI) and graph theory analysis. Methods A total of 43 rOAB patients (rOAB group) and 46 matched healthy controls (HC group) were recruited during May and Nov.2024. All participants were scanned with DTI, and surveyed with the overactive bladder symptom score (OABSS), and overactive bladder questionnaire (OAB-q). Their age, gender, height, weight, and educational years were collected.DTI plus graph theory analysis was employed to explore the alterations in global and local topological properties of the brain structural network in rOAB patients. Brain regions showing significant group differences in structural metrics [specifically, the right paracentral lobule (PCL.R) ]were further used as seed points for functional connectivity (FC) analysis. Correlations between the nodal clustering coefficient (NCp) of the identified region, FC strength, OABSS, and OAB-q score were investigated. Results The OABSS [8 (6,10) vs.0 (0,1) ]and OAB-q [71 (53,80) vs.20 (19,24) ]were higher in the rOAB group than the HC group (P<0.001). Graph theory analysis revealed no statistically significant differences in global network metrics between the two groups (P>0.05). However, the NCp was significantly higher in the PCL.R of rOAB group compared to HC group (P<0.05, FDR-corrected).FC analysis using the PCL.R as a seed region demonstrated significantly reduced FC value in the left cerebellar crus Ⅱ (Cerebelum_Crus2_L) of the rOAB group (P<0.05, FDR-corrected). Partial correlation analysis showed that the NCp of PCL.R was positively correlated with both OABSS (r=0.255, P=0.018) and OAB-q score (r=0.257, P=0.017). Conversely, the FC of Cerebelum_Crus2_L was significantly negatively correlated with OABSS (r=-0.545, P<0.001) and OAB-q score (r=-0.535, P<0.001). Conclusion Patients with rOAB exhibit distinct brain structural network alterations compared to healthy individuals, primarily manifestation in the NCp value of PCL.R increased, and the FC intensity of Cerebelum_Crus2_L is significantly weakened. These alterations in the topological properties of the structural network may be implicated in the pathogenesis of rOAB.

[摘 要] 目的：探究2'-岩藻糖基乳糖（2'-FL）对小鼠免疫检查点抑制剂（ICI）相关结肠炎（ICIC）的作用及其机制。方法：用随机数字表法将BALB/c小鼠随机分为对照组、葡聚糖硫酸钠（DSS）组、ICIC组、ICIC + 2'-FL组。DSS组连续7 d自由摄取含3.5% DSS的饮用水诱导结肠炎；ICIC组在摄取含3.5% DSS的饮用水的同时在实验第0天和第4天通过腹腔注射细胞毒性T淋巴细胞相关抗原4抗体（CTLA⁃4抗体，剂量为150 µg/只）构建ICIC模型；ICIC + 2'-FL组在ICIC造模同时从实验开始每日灌胃给予2'-FL[150 mg/(kg·d）]。统计分析小鼠体质量和疾病活动性评分（DAI）变化。第7天处死小鼠，测量结肠长度，用H-E染色法观察各组结肠组织学形态变化，用免疫组织化学（IHC）法检测CD3+ T细胞和CD19+B细胞在结肠组织中的浸润情况，用转录组学方法对结肠组织进行RNA测序，统计分析各组结肠组织中的差异表达基因（DEG）并进行基因本体论（GO）功能注释和京都基因与基因组百科全书（KEGG）富集分析。结果：与对照组和DSS组比较，ICIC组小鼠体质量明显下降、DAI评分上升、结肠长度更短（均P < 0.05），结肠黏膜完整性受损，呈现典型的溃疡性病变；与ICIC组比较，ICIC + 2'-FL组小鼠体质量下降显著缓解、DAI评分降低，结肠长度恢复（均P < 0.05)。转录组学检测结果显示，与ICIC组相比，2'-FL处理组有51个DEG，GO功能注释和KEGG富集分析提示，2'-FL缓解ICIC样症状与B细胞受体、B细胞增殖调控、炎症反应和修复相关通路的上调有关。结论：人乳寡糖2'-FL可显著缓解ICIC的病理进程，其可能通过B细胞受体相关信号通路及与炎症反应和修复相关通路减轻ICIC小鼠结肠组织的损伤。