Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Objective To explore the causal relationship between gut microbiota and colorectal cancer,and to investigate whether metabolites have a mediating effect through Mendelian randomization(MR)analysis.Methods Genome-wide association studies data of 473 gut microbiota,233 metabolites,and colorectal cancer were obtained from public databases.Bidirectional MR analyses were performed between gut microbiota,metabolites,and colorectal cancer,respectively.Subsequently,a two-step MR was used to explore whether specific gut microbiota affect the occurrence and development of colorectal cancer through metabolites.Results The study found that the abundances of 7 gut microbiota were positively correlated with the risk of colorectal cancer:Alloprevotella,Atopobiaceae,Clostridium S felsineum,Hungatella,Microvirga,Peptococcia and Ruminococcus A;The abundances of 4 gut microbiota were negatively correlated with the risk of colorectal cancer:Paenibacillales,Prevotella buccae,Psychroserpens and Succinivibrionaceae.Through the two-step mediation analysis,it was confirmed that the ratio of Triglycerides to total lipids ratio in medium very low-density lipoprotein could reduce the impact of Clostridium S felsineum as a risk factor for the occurrence of colorectal cancer.Conclusion The results of this study confirm the causal relationship between some gut microbiota,metabolites,and colorectal cancer,and discover potential interaction chains,providing ideas for the pathogenesis and prevention of colorectal cancer.

β-hydroxy-β-methylbutyric acid (HMB) is widely applied in sports nutrition, disease prevention and other fields. However, chemical synthesis methods, limited by toxic reagents and violent reactions, can hardly meet the demands of green production. The biosynthesis method mainly utilizes enzymatic catalysis or metabolic engineering techniques for synthesis, and has the advantages of high efficiency, low cost, and sustainability. Therefore, the production of HMB by the biosynthesis method has a good application prospect. In this research, a biosynthesis-based production strategy for HMB was developed. By using L-leucine as the substrate and constructing a dual-enzyme co-expression system, we established an efficient catalytic process. At first, the enzymatic properties of L-amino acid deaminase (PvL-AAD) from Proteus vulgaris and 4-hydroxyphenylpyruvate dioxygenase (Rn4-HPPD) from Rattus norvegicus were characterized. Rn4-HPPD had low relative activity and required an acidic environment for catalysis. Based on the surface charge modification strategy of the enzyme protein, site-directed mutagenesis and combinatorial mutagenesis were conducted on 10 sites of Rn4-HPPD. A double mutant Rn4-HPPD^H18R/N302R was thus obtained, with the enzyme activities being 2.00 times and 2.39 times that of the wild type at pH 5.5 and pH 6.5, respectively. Subsequently, the expression of the two enzymes in Escherichia coli was optimized. After the optimal expression ratio of the two enzymes was determined as 1:3 and under the conditions of OD₆₀₀ of 70, pH 6.0, 35 ℃, Fe²⁺ concentration of 1.5 mmol/L, and feeding of the substrate in batches in a 5 L fermenter, the maximum yield of HMB reached 8.60 g/L. This study not only enhances the optimal pH and activity of Rn4-HPPD but also provides new approaches for the efficient microbial synthesis of HMB.
Escherichia coli/metabolism* ; Valerates/metabolism* ; Recombinant Proteins/biosynthesis* ; Animals ; Metabolic Engineering/methods* ; Rats ; Catalysis

Objective To explore the causal relationship between gut microbiota and colorectal cancer,and to investigate whether metabolites have a mediating effect through Mendelian randomization(MR)analysis.Methods Genome-wide association studies data of 473 gut microbiota,233 metabolites,and colorectal cancer were obtained from public databases.Bidirectional MR analyses were performed between gut microbiota,metabolites,and colorectal cancer,respectively.Subsequently,a two-step MR was used to explore whether specific gut microbiota affect the occurrence and development of colorectal cancer through metabolites.Results The study found that the abundances of 7 gut microbiota were positively correlated with the risk of colorectal cancer:Alloprevotella,Atopobiaceae,Clostridium S felsineum,Hungatella,Microvirga,Peptococcia and Ruminococcus A;The abundances of 4 gut microbiota were negatively correlated with the risk of colorectal cancer:Paenibacillales,Prevotella buccae,Psychroserpens and Succinivibrionaceae.Through the two-step mediation analysis,it was confirmed that the ratio of Triglycerides to total lipids ratio in medium very low-density lipoprotein could reduce the impact of Clostridium S felsineum as a risk factor for the occurrence of colorectal cancer.Conclusion The results of this study confirm the causal relationship between some gut microbiota,metabolites,and colorectal cancer,and discover potential interaction chains,providing ideas for the pathogenesis and prevention of colorectal cancer.

This study was designed to study the effect and mechanism of dehydroepiandrosterone(DHEA)on diabetic wound healing in mice.High-fat feed combined with streptozotocin was utilized to induce diabetes and full-thickness incisional wounds were made on the back.The mice were randomly divided into normal wound group(NW),diabetic wound group(DW)and DHEA intervention group(DHEA).The wounds were photographed and the wound healing rates were calculated;RT-PCR was used to detect the expression of inflammatory factors in wound tissues and wound macrophages,and the expression of Dicer1 and pentose phosphate pathway(PPP)related factors in wound macrophages.Furthermore,wound macrophages phagocytosis of apoptotic Jurkat cells were measured by flow cytometry.Data showed that the wound healing rate,the expression of inflammatory factors and the phagocytosis rate were similar between the DHEA group and the NW group(P＞0.05);compared with the DW group,the wound healing rate in the DHEA group was accelerated,the expression of TNF-α,IL-6 and IL-1β were decreased,the expression of IL-10 and TGF-β were increased,and the phagocytosis rate was increased(P＜0.01);the expression of Dicer1 in wound macrophages of the DW group was lower than that in the NW group,and the expression of PPP-related factors G6pdx,Taldo1,Pfkl,H6pd,Pgd,Aldoc1 and Tkt were increased(P＜0.01);the expression of Dicer1 between DW group and DHEA group was similar(P＞0.05),and the expression of PPP-related factors G6pdx,Taldo1,Pfkl,H6pd,Pgd,Aldoc1 and Tkt were lower in the DHEA group(P＜0.01).In conclusion,DHEA promotes diabetic wound healing by inhibiting macrophage pentose phosphate pathway activity.

Bridging therapy serves as an adjunctive treatment during chimeric antigen receptor T cell therapy(CAR-T)and is specifically im-plemented after the collection of mononuclear cells but before the subsequent infusion of CAR-T cells.This approach can mitigate the pro-gression of large B-cell lymphoma(LBCL)to a certain extent,reduce tumor burden,and facilitate the infusion of CAR-T cells.Bridging therapy includes chemotherapy,radiation therapy,and targeted therapies and ensures effective reinfusion of CAR-T cells and enhances the thera-peutic efficacy of CAR-T cells.This study systematically reviews the significance,methodologies,and characteristics of CAR-T-cell-related bridging therapy for large B-cell lymphoma to provide valuable references for its clinical application.

Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.

Robotic surgery is known as the"third technological revolution"in the field of surgery,and is an important milestone in the development of modern surgery.However,our country's innovative surgical robot industry is still in its early stages,and it is only being utilized in certain surgical fields.To explore the effectiveness of the application of do-mestic surgical robot in oral and maxillofacial surgery,the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot.The operation was successful,facial nerve function was preserved,and postoperative wound healing was good.

Objective To evaluate the application of immediate resection after interventional embolization in treating hypervascular nasal skull base tumors.Methods The clinical data of 25 patients with hypervascular nasal skull base tumors,who were treated at the Affiliated Eye ENT Hospital of Fudan University of China from December 2020 to June 2022,were retrospectively analyzed.All patients underwent tumor surgical resection immediately after interventional embolization on the same day of admission.The success rate of embolization,incidence of complications,amount of blood loss during resection,tumor resection condition and prognosis were analyzed.Results Successful immediate surgical resection after interventional embolization was accomplished in all the 25 patients.Arterial approach was used for the interventional embolization,which was successfully performed under general anesthesia(n=19)or local anesthesia(n=6).No embolization-related complications occurred.The tumor resection was successfully accomplished under nasal endoscopy,endoscopy-guided translabial-gingival crevicular incision,or under oral endoscopy.No resection-related complications occurred.The median amount of blood loss during resection was 844 mL(range of 100-2 000 mL).Conclusion For the treatment of hypervascular nasal skull base tumors,immediate surgical resection after interventional embolization is clinically safe and feasible,and this therapeutic method is worthy of clinical promotion.

Traditional open head and neck surgery often leaves permanent scars,significantly affecting appearance.The emergence of surgical robots has introduced a new era for minimally invasive surgery.However,the complex anatomy of the head and neck region,particularly the oral and maxillofacial areas,combined with the high costs associated with established systems such as the da Vinci,has limited the widespread adoption of surgical robots in this field.Recently,surgical robotic platform in China has developed rapidly,exemplified by the promise shown by the KangDuo Surgical Robot(KD-SR).Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery,its performance in complex head and neck regions remains untested.This study evaluated the feasibility,effectiveness,and safety of the newly developed KD-SR-01,comparing it with standard endoscopic systems in head and neck procedures on porcine models.We performed parotidectomy,submandibular gland resection,and neck dissection,collected baseline characteristics,perioperative data,and specifically assessed cognitive workload using the NASA-TLX.None of the robotic procedures were converted to endoscopic or open surgery.The results showed no significant difference in operation time between the two groups(P=0.126),better intraoperative bleeding control(P=0.001),and a significant reduction in cognitive workload(P<0.001)in the robotic group.In conclusion,the KD-SR-01 is feasible,effective,and safe for head and neck surgery.Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.