Serotonin-selective reuptake inhibitors （SSRIs）， as widely used antidepressants in clinical practice， exhibit significant individual differences in antidepressant efficacy. Gut microbiota plays an important role in the development and progression of depression， and the use of SSRIs exerts a significant impact on the gut microbiota of patients with depression. Based on this， this article reviews the research progress on the interactions between the antidepressant effects of SSRIs and gut microbiota. It has been found that SSRIs can influence the diversity， abundance， and function of the gut microbiota directly or indirectly. Conversely， the composition of the gut microbiota and differences in its functional metabolic pathways， and other factors， can in turn affect the antidepressant effects of SSRIs. Therefore， in clinical practice， gut microbiota diversity can be utilized as a predictive indicator for the antidepressant effects of SSRIs. Probiotics can be employed as an adjunct therapy alongside SSRIs， and dietary adjustments， as well as fecal microbiota transplantation， can be used to enhance the therapeutic efficacy of SSRIs. In the future， large-scale， multicenter clinical studies should be conducted， enrolling a broadly representative cohort of patients with depression， to uncover the true association between the antidepressant effects of SSRIs and gut microbiota， thereby opening up more effective avenues for the comprehensive treatment of depression.

The modern Silk Road spirit advocating for win-win cooperative partnerships, aligns with the target of the “Belt and Road” Initiative, which provides new opportunities for collaboration on tropical disease control among countries along the “Belt and Road”. The modern Silk Road spirit may effectively facilitate tropical disease control programmes and improve disease control concepts and approaches through collaborative research, information sharing, infrastructure development, and joint efforts in pharmaceuticals and vaccine development; however, there are still multiple challenges that require to be overcome, including political and cultural differences, and data sharing. Therefore, countries participating in the “Belt and Road” Initiative need to work together with mutual respects, build effective collaborative mechanisms and improve communications to jointly facilitate the sustainable development of global tropical disease control programmes and cultural exchange, so as to contribute to global health and prosperities. This article discusses the contribution of the modern Silk Road spirit to facilitating global tropical disease control programmes in the context of the “Belt and Road” Initiative.

OBJECTIVES: To explore the clinical value of endoscopic findings under white light gastroscopy in diagnosing Helicobacter pylori (Hp) infection in children. METHODS: A retrospective analysis was conducted on the clinical data of 340 children who underwent gastroscopy and gastric mucosa tissue Hp culture from July 2022 to June 2023 in the Department of Gastroenterology at Wuxi Children's Hospital due to upper gastrointestinal symptoms. Based on the results of Hp culture, the children were categorized into an Hp-infected group (146 cases) and a non-infected group (194 cases). The detection rates of various endoscopic findings in the gastric mucosa between the two groups were compared, and the association between each endoscopic finding and different Hp infection statuses was analyzed, as well as the diagnostic value of each endoscopic finding under different Hp infection statuses. RESULTS: The proportions of white mucus, diffuse redness, mucosal edema, enlarged folds, chicken skin-like changes, and ulcers in the Hp-infected group were higher than those in the non-infected group (P<0.05), while the proportions of regular arrangement of collecting venules (RAC) and ridge-like redness were lower in the Hp-infected group compared to the non-infected group (P<0.05). Multivariate logistic regression analysis showed that diffuse redness, enlarged folds, mucosal edema, and chicken skin-like changes were closely associated with Hp infection (P<0.05), while RAC and ridge-like redness were closely associated with the absence of Hp infection (P<0.05). Receiver operating characteristic curve analysis indicated that the area under the curve for diffuse redness, enlarged folds, mucosal edema, and chicken skin-like changes in predicting Hp infection was 0.798, 0.731, 0.782, and 0.760, respectively (P<0.05). The area under the curve for RAC and ridge-like redness in predicting the absence of Hp infection was 0.861 and 0.589, respectively (P<0.05). CONCLUSIONS Endoscopic findings under white light gastroscopy are associated with Hp infection in children, with diffuse redness, mucosal edema, chicken skin-like changes, and enlarged folds showing significant diagnostic value for Hp infection.
Humans ; Helicobacter Infections/diagnostic imaging* ; Female ; Male ; Gastroscopy/methods* ; Child ; Helicobacter pylori ; Retrospective Studies ; Child, Preschool ; Adolescent ; Gastric Mucosa/pathology* ; Infant ; Logistic Models

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

As the chip of synthetic biology, enzymes play a vital role in the bio-manufacturing industry. The development of diverse functional enzymes can provide a rich toolbox for the development of synthetic biology. This article reports the construction of an artificial enzyme with the introduction of a non-natural cofactor. By introducing the 4-dimethylaminopyridine (DMAP) cofactor into the optimal protein skeleton via covalent bonds based on a click-chemistry strategy, we successfully constructed a novel artificial enzyme with the DMAP cofactor as the catalytic center. The artificial enzyme successfully catalyzed an unnatural asymmetric Morita-Baylis- Hillman (MBH) reaction between cycloketenone and p-nitrobenzaldehyde, with a conversion rate of 90% and enantioselectivity (e.e.) of 38%. This study not only provides an effective strategy for the design of new artificial enzymes but also establishes a theoretical basis for the development of unnatural biocatalytic MBH reactions.
Biocatalysis ; 4-Aminopyridine/chemistry* ; Enzymes/metabolism* ; Coenzymes/chemistry* ; Benzaldehydes/chemistry* ; Protein Engineering/methods* ; Click Chemistry

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*

[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。

Objective:To investigate the differences in gene mutations and functional clusters of gene mutations in patients with myelodysplastic syndromes (MDS) in the lower-risk and higher-risk groups.Methods:A retrospective case series study was conducted. Clinical data of 227 patients with MDS in Zhongda Hospital of Southeast University from January 2018 to August 2023 were retrospectively analyzed. According to the Revised International Prognostic Scoring System (IPSS-R), MDS patients were categorized into the lower-risk group (IPSS-R score ≤3.5 points, 96 cases) and the higher-risk group (IPSS-R score >3.5 points, 131 cases). Bone marrow specimens were tested for mutations of 58 common MDS genes using next-generation sequencing, and the 24 genes with the high mutation rates were included in the study, and the 24 mutated genes were categorized into 8 clusters according to gene function. The differences in clinical data, gene mutations and gene mutation functional clusters were compared between the lower-risk group and the higher-risk group.Results:At least 1 gene mutation was detected in 177 (78.0%) of 227 MDS patients, of which the 5 genes with high mutation rates were ASXL1 [21.6% (49/227)], TET2 [18.5% (42/227)], TP53 [15.4% (35/227)], DNMT3A [13.2% (30/227)], and U2AF1 [10.1% (23/227)] in turn. By gene function analysis, the most common mutation cluster was methylation-related genes [31.3% (71/227)], followed by spliceosome-related genes [24.7% (56/227)]. Platelet count and neutrophil count in the lower-risk group were higher than those in the higher-risk group, and the proportion of bone marrow primitive cells, the mutation rate and the presence of ≥3 mutations were lower than those in the higher-risk group (all P < 0.05). The 5 genes with high mutation rates in the lower-risk group were TET2 [21.9% (21/96)], DNMT3A [14.6% (14/96)], ASXL1 [13.5% (13/96)], SF3B1 [12.5% (12/96)], and U2AF1 [8.3% (8/96)] in turn. The 5 genes with high mutation rates in the higher-risk group were ASXL1 [27.5% (36/131)], TP53 [23.7% (31/131)], TET2 [16.0% (21/131)], DNMT3A [12.2% (16/131)], and U2AF1 [11.5% (15/131)] in turn, and the mutation rates of ASXL1, TP53, ETV6, and NRAS genes in the lower-risk group were lower than those in the higher-risk group (all P < 0.05). The mutation rate of methylation-related genes was the highest in both the lower-risk group and the higher-risk group, but the difference between the two groups was not statistically significant [32.3% (31/96) vs. 30.5% (40/131), χ2 = 0.08, P>0.05]. The differences in the proportions of tumor factor suppressor-related genes, transcription factor-related genes, chromatin-modification-related genes and RAS pathway-related genes mutations between the two groups were all statistically significant (all P < 0.05). Conclusions:The higher-risk group has a higher rate of common gene mutations and a greater number of gene mutations than the lower-risk group in MDS patients.

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.
Humans ; Gastrointestinal Microbiome/drug effects* ; Medicine, Chinese Traditional ; Animals ; Bacteroidetes ; Drugs, Chinese Herbal/pharmacology*