Depression, a prevalent mental disorder with significant socioeconomic burdens, underscores the urgent need for safe and effective non-pharmacological interventions. Recent advances in microbiome research have revealed the pivotal role of gut microbiota dysbiosis in the pathogenesis of depression. Concurrently, exercise, as a cost-effective and accessible intervention, has demonstrated remarkable efficacy in alleviating depressive symptoms. This comprehensive review synthesizes current evidence on the interplay among exercise, gut microbiota modulation, and depression, elucidating the mechanistic pathways through which exercise ameliorates depressive symptoms via the microbiota-gut-brain (MGB) axis. Depression is characterized by gut microbiota alterations, including reduced alpha and beta diversity, depletion of beneficial taxa (e.g., Bifidobacterium, Lactobacillus, and Coprococcus), and overgrowth of pro-inflammatory and pathogenic bacteria (e.g., Morganella, Klebsiella, and Enterobacteriaceae). Metagenomic analyses reveal disrupted metabolic functions in depressive patients, such as diminished synthesis of short-chain fatty acids (SCFAs), impaired tryptophan metabolism, and dysregulated bile acid conversion. For instance, Bifidobacterium longum deficiency correlates with reduced synthesis of neuroactive metabolites like homovanillic acid, while decreased Coprococcus abundance limits butyrate production, exacerbating neuroinflammation. Furthermore, elevated levels of indole derivatives from Clostridium species inhibit serotonin (5-HT) synthesis, contributing to depressive phenotypes. These dysbiotic profiles disrupt the MGB axis, triggering systemic inflammation, neurotransmitter imbalances, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Exercise exerts profound effects on gut microbiota composition, diversity, and metabolic activity. Longitudinal studies demonstrate that sustained aerobic exercise increases alpha diversity, enriches SCFA-producing genera (e.g., Faecalibacterium prausnitzii, Roseburia, and Akkermansia), and suppresses pathobionts (e.g., Desulfovibrio and Streptococcus). For example, a meta-analysis of 25 trials involving 1 044 participants confirmed that exercise enhances microbial richness and restores the Firmicutes/Bacteroidetes ratio, a biomarker of metabolic health. Notably, endurance training promotes Veillonella proliferation, which converts lactate into propionate, enhancing energy metabolism and delaying fatigue. Exercise also strengthens intestinal barrier integrity by upregulating tight junction proteins (e.g., ZO-1, occludin), thereby reducing lipopolysaccharide (LPS) translocation and systemic inflammation. However, excessive exercise may paradoxically diminish microbial diversity and exacerbate intestinal permeability, highlighting the importance of moderate intensity and duration. Exercise ameliorates depressive symptoms through multifaceted interactions with the gut microbiota, primarily via 4 interconnected pathways. First, exercise mitigates neuroinflammation by elevating anti-inflammatory SCFAs such as butyrate, which suppresses NF-κB signaling to attenuate microglial activation and oxidative stress in the hippocampus. Animal studies demonstrate that voluntary wheel running reduces hippocampal TNF‑α and IL-17 levels in stress-induced depression models, while fecal microbiota transplantation (FMT) from exercised mice reverses depressive behaviors by modulating the TLR4/NF‑κB pathway. Second, exercise regulates neurotransmitter dynamics by enriching GABA-producing Lactobacillus and Bifidobacterium, thereby counteracting neuronal hyperexcitability. Aerobic exercise also enhances the abundance of Lactobacillus plantarum and Streptococcus thermophilus, which facilitate 5-HT and dopamine synthesis. Clinical trials reveal that 12 weeks of moderate exercise increases fecal Coprococcus and Blautia abundance, correlating with improved 5-HT bioavailability and reduced depression scores. Third, exercise normalizes HPA axis hyperactivity by reducing cortisol levels and restoring glucocorticoid receptor sensitivity. In rodent models, chronic stress-induced corticosterone elevation is reversed by probiotic supplementation (e.g., Lactobacillus), which enhances endocannabinoid signaling and hippocampal neurogenesis. Furthermore, exercise upregulates brain-derived neurotrophic factor (BDNF) via microbial metabolites like butyrate, promoting histone acetylation and synaptic plasticity. FMT experiments confirm that exercise-induced microbiota elevates prefrontal BDNF expression, reversing stress-induced neuronal atrophy. Fourth, exercise reshapes microbial metabolic crosstalk, diverting tryptophan metabolism toward 5-HT synthesis instead of neurotoxic kynurenine derivatives. Butyrate inhibits indoleamine 2,3-dioxygenase (IDO), a key enzyme in the kynurenine pathway linked to depression. Concurrently, exercise-induced Akkermansia enrichment enhances mucin production, fortifies the gut barrier, and reduces LPS-driven neuroinflammation. Collectively, these mechanisms underscore exercise as a potent modulator of the microbiota-gut-brain axis, offering a holistic approach to alleviating depression through microbial and neurophysiological synergy. Current evidence supports exercise as a potent adjunct therapy for depression, with personalized regimens (e.g., aerobic, resistance, or yoga) tailored to individual microbiota profiles. However, challenges remain in optimizing exercise prescriptions (intensity, duration, and type) and integrating them with probiotics, prebiotics, or FMT for synergistic effects. Future research should prioritize large-scale randomized controlled trials to validate causality, multi-omics approaches to decipher MGB axis dynamics, and mechanistic studies exploring microbial metabolites as therapeutic targets. The authors advocate for a paradigm shift toward microbiota-centric interventions, emphasizing the bidirectional relationship between physical activity and gut ecosystem resilience in mental health management. In conclusion, this review underscores exercise as a multifaceted modulator of the gut-brain axis, offering novel insights into non-pharmacological strategies for depression. By bridging microbial ecology, neuroimmunology, and exercise physiology, this work lays a foundation for precision medicine approaches targeting the gut microbiota to alleviate depressive disorders.

Objective To analyze the risk factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn and its predictive efficiency.Methods A total of 100 patients with extensive deep burn who underwent Meek skin grafting from August 2018 to November 2024 were selected,and they were divided into the normal group(n=79)and the delayed group(n=21)according to the wound healing time.The clinical data of all patients were collected,and the influencing factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn were analyzed by Logistic regression model,and the efficiency of the model was analyzed by the receiver operating characteristic(ROC)curve and the Hosmer-Lemeshow goodness-of-fit test,respectively.Results There were statistically significant differences in the body mass index,hospitalization time,burn index,burn area,donor skin area,number of postoperative dressing change,postoperative nutritional support,postoperative pain scores,and hospitalized blood glucose levels between the two groups(P<0.05).Logistic regression analysis showed that high burn index(OR=1.086,β=0.082),large burn area(OR=1.155,β=0.144),fewer postoperative dressing change(OR=0.746,β=-0.293),lack of postoperative nutritional support(OR=6.439,β=1.862),high postoperative pain score(OR=4.483,β=1.500),and high level of hospitalized blood glucose(OR=2.251,β=0.811)were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn(P<0.05).The ROC curve revealed that the combined prediction of the above six influencing factors for delayed postoperative wound recovery had an area under the ROC curve(AUC)of 0.896,with a sensitivity and specificity of 88.00%and 89.10%,respectively;and the Hosmer-Lemeshow test result showed:χ2=10.641,and P=0.223,indicating a high predictive efficacy and a certain calibration ability of the model.Conclusion The high burn index,large burn area,fewer postoperative dressing change,lack of postoperative nutritional support,high postoperative pain score and hospitalized blood glucose level were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn,and the prediction model constructed by the above factors has good predictive ability,which can provide a reference for clinical treatment.

Objective To analyze the risk factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn and its predictive efficiency.Methods A total of 100 patients with extensive deep burn who underwent Meek skin grafting from August 2018 to November 2024 were selected,and they were divided into the normal group(n=79)and the delayed group(n=21)according to the wound healing time.The clinical data of all patients were collected,and the influencing factors of delayed wound recovery after Meek skin grafting in patients with extensive deep burn were analyzed by Logistic regression model,and the efficiency of the model was analyzed by the receiver operating characteristic(ROC)curve and the Hosmer-Lemeshow goodness-of-fit test,respectively.Results There were statistically significant differences in the body mass index,hospitalization time,burn index,burn area,donor skin area,number of postoperative dressing change,postoperative nutritional support,postoperative pain scores,and hospitalized blood glucose levels between the two groups(P<0.05).Logistic regression analysis showed that high burn index(OR=1.086,β=0.082),large burn area(OR=1.155,β=0.144),fewer postoperative dressing change(OR=0.746,β=-0.293),lack of postoperative nutritional support(OR=6.439,β=1.862),high postoperative pain score(OR=4.483,β=1.500),and high level of hospitalized blood glucose(OR=2.251,β=0.811)were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn(P<0.05).The ROC curve revealed that the combined prediction of the above six influencing factors for delayed postoperative wound recovery had an area under the ROC curve(AUC)of 0.896,with a sensitivity and specificity of 88.00%and 89.10%,respectively;and the Hosmer-Lemeshow test result showed:χ2=10.641,and P=0.223,indicating a high predictive efficacy and a certain calibration ability of the model.Conclusion The high burn index,large burn area,fewer postoperative dressing change,lack of postoperative nutritional support,high postoperative pain score and hospitalized blood glucose level were the influencing factors for delayed wound recovery after Meek skin grafting in patients with extensive deep burn,and the prediction model constructed by the above factors has good predictive ability,which can provide a reference for clinical treatment.

Background: Ophiopogon japonicus (L.f) Ker-Gawl. growing in Zhejiang is recognized as the Dao-di medicinal herb for the production of Ophiopogonis Radix. Borneol-7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, a prominent pharmacologically active compound, serves as a marker distinguishing O. japonicus in Zhejiang from those in other geographical areas. It is synthesized from borneol through glycosylation, with terpene synthase (TPS) being the critical enzyme catalyzing the conversion of terpene precursors into borneol. Objective: The aim of the study was to define key genes involved in biosynthesis of borneol in O. japonicus. Methods: The candidate terpene synthase genes were identified from the root and leaf transcriptome data of O. japonicus in Zhejiang and the functions of these enzymes were identified using engineered Escherichia coli. Results: This study developed a rapid expression system for monoterpene and sesquiterpene synthases based on engineered E. coli. Seven terpene synthase genes (OjTPS1 to OjTPS7) were identified in different terpene synthase subfamilies, including 2 from TPS-a, 4 from TPS-b, and 1 from TPS-g. Biochemical analysis using an engineered system E. coli demonstrated that all the 7 terpene synthases produced monoterpenes, and OjTPS3, OjTPS5, and OjTPS6 also yielded sesquiterpenes. Conclusions: These 7 terpene synthases produced 13 monoterpenes and 8 sesquiterpenes. Notably, OjTPS1 produced borneol establishing the groundwork for elucidating the biosynthetic pathways of borneol-7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside and other volatile oil components.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Skin, as the body's largest organ, acts as the primary defense mechanism against infection and injury. The maintenance of skin health heavily relies on the regulation of epidermal stem cells, crucial for ensuring epidermal homeostasis, hair regeneration, and the repair of epidermal injuries. Recent studies have placed a growing emphasis on G protein-coupled receptor (GPCR) in the context of understanding epidermal stem cells, uncovering its significant role in determining their fate. The activation of GPCR triggers the subsequent dissociation of the βγ subunits from the α subunit of G protein, leading to the modulation of various downstream signaling pathways, such as the WNT-BMP signaling crosstalk and the Gαs-PKA signaling pathway. These pathways collectively influence the fate of epidermal stem cells. Consequently, targeted GPCR therapy has emerged as a promising strategy for improving skin health by orchestrating the fate of epidermal stem cells, unveiling potential therapeutic targets that demand further investigation.
Humans ; Stem Cells/cytology* ; Receptors, G-Protein-Coupled/physiology* ; Animals ; Epidermal Cells/physiology* ; Signal Transduction ; Epidermis/physiology* ; Skin/cytology*

Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
Cinnamomum camphora/enzymology* ; Alkyl and Aryl Transferases/chemistry*

ObjectiveTo study the effect of Xiaoyusan new formula on the articular cartilage of knee osteoarthritis (KOA) rabbits and its mechanism. MethodsA total of 42 New Zealand white rabbits aged 6 months were randomly divided into normal group, model group, ointment of Xiaoyusan group, and ointment of Xiaoyusan new formula group, with 10 rabbits in each group (the other 2 rabbits were used for model validation). Except for the normal group, the right knee joints of all rabbits in the other groups were prepared as KOA models according to the modified Hulth method. After 5 weeks of molding, the rabbits in ointment of Xiaoyusan group, ointment of Xiaoyusan New Formula group were given corresponding ointments for knee arthritis treatment, once a day, each time for 10 hours. After 2-week continuous administration and treatment, the knee joint cartilage of the four groups of rabbits was taken and the cartilage damage of each group was evaluated by Outerbridge grading method. The pathological changes of the cartilage, calcified layer and subchondral bone of the knee joint of rabbits in each group were observed by HE staining method under the light microscope, and the degree of cartilage degeneration was evaluated by Mankin's method. The expression of matrix metalloproteinase-13 (MMP-13) in the cartilage of rabbit knee joint in each group was deteced by immunohistochemistry. Results After the general observation of articular cartilage, the Outerbridge grading showed that the number of high-grade animals in ointment of Xiaoyusan group was reduced compared with the model group (P<0.05), and the number of high-grade animals in ointment of Xiaoyusan new formula group was also reduced (P<0.05) compared with ointment of Xiaoyusan group. HE staining showed that Mankin's scores of articular cartilage in the four groups ranked from high to low: model group (10.82±1.76), ointment of Xiaoyusan group (6.19±1.23), ointment of Xiaoyusan new formula group (2.64±1.18) and normal group (0.28±0.17). The difference among four groups was statistically significant (P<0.05). Immunohistochemical detection showed that the positive rates of MMP-13 expression in rabbit articular cartilage tissues in each group were (67.90±13.94)% of model group, (37.10±19.16)% of ointment of Xiaoyusan group, (13.60±3.10)% of ointment of Xiaoyusan new formula group and (3.20±2.39) % of normal group, ranking from high to low, and the difference among four groups was statistically significant (P<0.05). ConclusionXiaoyusan new formula can repair articular cartilage degeneration in KOA rabbits and decrease the expression of MMP-13 in cartilage, which may be one of the mechanisms of the treatment.

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia