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.

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

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.

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.

Objective:To investigate the risk factors of pulmonary infection in patients with acute intracerebral hemorrhage based on nomogram prediction model.Methods:The clinical data of 235 patients with acute intracerebral hemorrhage admitted to Lu′an Hospital of Anhui Medical University from June 2018 to December 2021 were retrospectively analyzed. According to whether the patients were complicated with pulmonary infection, they were divided into pulmonary infection group (55 cases) and non-pulmonary infection group (180 cases). The best cut-off value of each factor was obtained through the receiver operating characteristic (ROC) curve analysis of all patients. Multivariate Cox regression analysis was used to analyze the independent risk factors of pulmonary infection in patients with acute intracerebral hemorrhage. The R software "rms" package was constructed to predict pulmonary infection in patients with acute intracerebral hemorrhage. For high-risk nomogram model, calibration curves were used for internal validation of the nomogram model, and decision curves were used to assess the predictive power of the nomogram model.Results:Patients in the pulmonary infection group were with higher age, proportion of smoking, proportion of brain ventricle bleeding, bleeding volume, length of stay, Glasgow coma scale (GCS) score, white blood cell count (WBC) and interleukin-6 (IL-6) than in the non-pulmonary infection group: (78.65 ± 5.33) years old vs. (65.41 ± 4.55) years old, 67.27% (37/55) vs. 48.89% (88/180), 49.09% (27/55) vs. 7.22% (13/180), (26.47 ± 1.41) ml vs. (18.24 ± 0.47) ml, (15.65 ± 2.49) d vs. (10.16 ± 1.64) d, (13.74 ± 1.48) points vs. (7.81 ± 1.09) points, (16.50 ± 2.40) × 10 9/L vs. (9.10 ± 2.35) × 10 9/L, (82.50 ± 21.80) ng/L vs. (57.90 ± 11.50) ng/L, with statistically significant differences ( P<0.05); the AUCs of age, bleeding volume, hospital stay, GCS score, WBC, and IL-6 were 0.743, 0.886, 0.771, 0.800, 0.829 and 0.557, respectively; the best cut-off values were 69 years old, 20 ml, 12 d, and 10 scores, 13 × 10 9/L, 66 ng/L, respectively; age (≥69 years old), smoking (yes), bleeding site (brain ventricle), bleeding volume (≥20 ml), hospital stay (≥12 d) and GCS score (<10 points) were independent risk factors for pulmonary infection in patients with acute intracerebral hemorrhage ( P<0.05); the decision curve results showed that when the risk threshold was greater than 0.15, the clinical net benefit provided by this predictive model was higher than that by a single independent risk factor, and in predicting the high risk of pulmonary infection in patients with acute intracerebral hemorrhage this predictive model could provide a significant additional net clinical benefit. Conclusions:This study constructed a nomogram model for predicting the risk of pulmonary infection in patients with acute intracerebral hemorrhage based on age, smoking history, bleeding site, bleeding volume, hospital stay and GCS score. It could provide important strategic guidance for prevention and control of this disease.

Objective:To compare the effects of auricular point intradermal needling with auricular point sticking on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy regimens. Methods:Ninety-six patients receiving platinum-based chemotherapy were randomly assigned to three groups using the random number table method,with 32 cases in each group.The control group received conventional nursing care plus 5-hydroxytryptamine receptor antagonist,and the other two groups received additional auricular point intradermal needling or sticking.For the three groups of participants,the acute and delayed vomiting and nausea severity,quality of life,and the additional antiemetic consumption rate were observed. Results:The three groups had no significant differences in the acute vomiting frequency and nausea severity and appetite(P>0.05)but had significant differences in the delayed vomiting frequency and nausea severity(P<0.05);the auricular point intradermal needling group won over the auricular point sticking group.The three groups showed significant differences in comparing the appetite in the delayed stage(P<0.05);both auricular point intradermal needling and sticking groups showed advantages over the control group(P<0.05),but no significant difference existed between the auricular point intradermal needling and sticking groups(P>0.05).There were significant differences in comparing the functional living index-emesis(FLIE)score in both acute and delayed stages among the three groups(P<0.05)and the result favored the auricular point intradermal needling group over the auricular point sticking group(P<0.05).The additional antiemetic consumption rate was higher in the control group than in the other groups(P<0.05). Conclusion:Based on the conventional nursing and 5-hydroxytryptamine receptor antagonist,adding either auricular point intradermal needling or auricular point sticking can lower the vomiting frequency and nausea severity in the delayed stage and improve appetite in patients receiving platinum-based chemotherapy regimen,but they have no notable impact on digestive symptoms in the acute stage;auricular point intradermal needling is superior to auricular point sticking in comparing the overall efficacy.Both auricular point intradermal needling and auricular point sticking can enhance the quality of life in patients undergoing chemotherapy and reduce their additional antiemetic consumption.

BACKGROUND: Men who have sex with men (MSM) have become a high risk population of HIV infection due to their risky sexual behaviors. The latent pattern of psychosocial characteristics plays an important effect in HIV-related risky behaviors among HIV-negative MSM. METHOD: Participants were recruited from Wuhan, Nanchang, and Changsha city from September 2017 to January 2018. Social support was assessed by the multidimensional scale of social support, Connor-Davidson Resilience scale-10 items for reliance, the assessment of Stigma towards Homosexuality for sexual minority stigma, the Likert subscale of nondisclosure for identity concealment, the ACE questionnaire-Kaiser-CDC for adverse childhood experience, the Centers for Epidemiological Studies Depression Scale for depression. Latent profile analysis (LPA) and multivariate regression were used to analyze the data. RESULTS: Three psychosocial characteristic patterns were revealed by the LPA. "Social support and resilience group" (SR group), "Identity concealment group" (IC group) and "Adverse childhood experience" (ACE group) were identified, respectively. In comparison with "SR group", "IC group" have a higher likelihood of one-night male partners (AOR = 2.74, 95%CI = [1.54, 4.90]), both fixed and one-night male partners (AOR = 2.01, 95%CI = [1.34, 3.01]) and HIV-unsure male partner (AOR = 2.12, 95%CI = [1.44, 3.13]). Similarly, "ACE group" were more likely having inconsistent condom use (AOR = 2.58, 95%CI = [1.41, 4.73]), and having sex with HIV-positive male partner (AOR = 4.90, 95%CI = [1.95, 12.30]) with comparison of "SR group". In addition, we further revealed that "ACE group" had a higher ratio (90.0%) of inconsistent condom use among MSM whose male partners were HIV-positive. CONCLUSIONS Six important psychosocial factors were divided into three latent pattern classes. Compared with "SR group", "IC group" and "ACE group" were more likely to engage in HIV-related risky sexual behaviors. Further research may pay more attention to "IC group" and "ACE group" for targeted intervention.
Humans ; Male ; HIV Infections/epidemiology* ; Homosexuality, Male/psychology* ; Risk Factors ; Sexual and Gender Minorities/psychology* ; Sexual Behavior/psychology*

The spread of COVID-19 has greatly threatened human health and economic growth. Angiotensin-converting enzyme 2 (ACE2) is a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). By attaching to ACE2, SARS-COV-2 reduces its expression and induces lung injury. Vitamin D can inhibit the progression of COVID-19 by inhibiting the activity of ROCK pathway, up-regulating ACE2 expression and bio-availability, and slowing down the adverse reactions caused by Ang II accumulation. This study explored a novel mechanism, i.e., vitamin D protects against COVID-19-induced injury by upregulating ACE2 expression. It provides theoretical guidance for the role of Vitamin D in the prevention and treatment of COVID-19.

【Objective】 To compare the similarities and differences of polymerized human cord hemoglobin (PolyCHb) and free hemoglobin (FHb) on partial coagulation indexes in vitro, so as to analyze the effect of PolyCHb on coagulation dysfunction. 【Methods】 Using normal saline, two concentrations of FHb and PolyCHb and 36% methemoglobin-containing PolyCHb to mix with fresh whole blood or plasma-rich plasma (PRP) in equal proportions, and incubate at 37°C for 30 minutes to detect prothrombin time (PT), activated partial thromboplastin time (APTT), coagulation factor Ⅱactivity (FⅡ∶C), coagulation factor Ⅴactivity (FⅤ∶C), coagulation factor Ⅷactivity (FⅧ∶C), coagulation factor Ⅸactivity (FⅨ∶C), von Willebrand factor (vWF) and platelet P-selectin (CD62P). 【Results】 1) NaCl group: PT(22.68±1.76) s; APTT(59.58±7.52) s; FⅡ∶C(45.91±3.27) %; FⅤ∶C(30.86±4.43) %; FⅧ∶C(41.32±12.94) %; FⅨ∶C(23.96±5.10) %; vWF (2.14±0.54) mg/L; CD62P(7.44±4.47) %. This group kept as a diluted control. 2) 2% FHb group compared with 7% FHb group: FⅧ∶C (42.16±12.31) %vs (56.64±12.22 ) % (P<0.05). No significant difference was found in other indexes (P>0.05). 3) There is no significant difference between 2% PolyCHb group and 7% PolyCHb group (P>0.05). 4) There is no significant difference between 2% FHb group and 2% PolyCHb group (P>0.05). 5) 7% FHb group compared with 7% PolyCHb group: PT(23.31±1.34)s vs (21.97±1.56)s (P<0.05); APTT(50.12±5.72)s vs (55.43±5.43)s (P<0.05); FⅧ∶C (56.64±12.22) %vs (42.37±13.00)% (P<0.05); vWF (1.41±0.30) mg/L vs (2.25±0.41) mg/L (P< 0.05). No significant difference was found in other indexes (P>0.05). 6) 7% PolyCHb group Compared with Met-PolyCHb group: APTT(55.43±5.43) s vs (46.33±4.86)s (P<0.05); FⅧ∶C (42.37±13) %vs (60.51±10.16) % (P<0.05). No significant difference was found in other indexes (P>0.05). 【Conclusion】 The effect of PolyCHb on coagulation markers is different from FHb. At the concentration of this study, PolyCHb will not cause coagulation disorders. However, if the methemoglobin (MetHb) content is too high, it will activate the intrinsic coagulation pathway.