The intestine is a complex symbiotic system, and the gut microbiota is closely related to host health. Studies have indicated that the gut microbiota influences physiological functions of the host by producing a variety of metabolites, which act as signaling molecules and substrates for metabolic reactions in the host. Dysbiosis of the gut microbiota affects the abundance of gut microbiota-derived metabolites, thereby influencing host health by disrupting signal transduction in multiple organs. Additionally, dietary compounds can shape the gut microbiota, affecting gut microbiota-derived metabolite levels and regulating host metabolism. This article introduces the methods for mining gut microbiota-derived metabolites, reviews the roles of these metabolites in metabolic diseases and related dietary interventions. Which provides a perspective on the prevention and treatment of metabolic diseases by targeting these metabolites, enriching the knowledge on the role of gut microbiota in the regulation of host metabolism.
Gastrointestinal Microbiome/physiology* ; Humans ; Dysbiosis/microbiology* ; Metabolic Diseases/metabolism* ; Diet

Objective:This study aims to explore the causal relationship between obstructive sleep apnea (OSA) and type 2 diabetes (T2D) using bidirectional Mendelian randomization (MR).Methods:The genetic data related to OSA were obtained from the FinnGen Biobank (Ncase=16, 761, Ncontrol=201, 194) in the Genome-wide association study (GWAS). Three single nucleotide polymorphism (SNP) were screened out as instrumental variable (IV) of OSA. The genetic data related to T2D were derived from a large Meta-analysis of GWAS (Ncase=62, 892, Ncontrol=596, 424), 114 SNP were selected as IV of T2D. Multiple MR methods were used for analysis and inverse variance weighted (IVW) was performed as main method. The sensitivity of MR analytic results was analyzed using MR-Egger and other methods, and the IV was evaluated using F-value statistics. Results:MR analysis showed that OSA was significantly associated with increased risk of T2D ( OR=2.016, 95% CI: 1.185-3.429, P<0.05). There was no significant relationship between T2D and OSA risk ( OR=1.030, 95% CI: 0.980-1.082, P=0.238). There was heterogeneity in both-way results (OSA?T2D, P=1.808×10 -11; T2D?OSA, P=1.729×10 -7), and no horizontal pleiotropy (OSA?T2D, P=0.477; T2D?OSA, P=0.349). IV of OSA and T2D-selected in the study were strong instrumental variables ( F statistics of OSA=20.543; F statistics of T2D=30.117). Conclusion:Our results supported that OSA was a risk factor for T2D, but T2D had no significant impact on the incidence of OSA. Blood glucose monitoring and diabetes screening in OSA patients might be beneficial to the early detection and intervention of T2D.

Background Silica nanoparticles (SiNPs) enter the human body through respiratory tract, digestive tract, and skin, causing body damage. Lung is one of the main damaged organs. Objective To observe the expressions of complement activated fragment C3a and its receptor C3aR in the lungs of mice exposed to SiNPs through respiratory tract, and to explore the involvement of C3a/C3aR in lung injury induced by SiNPs exposure. Methods The ultrastructure of SiNPs (particle size 5-20 nm) was determined under a transmission electron microscope, and the hydrodynamic diameter and surface Zeta potential of SiNPs were determined using a nanoparticle size analyzer. A total of 88 SPF C57BL/6J mice were randomly divided into five groups: a blank control group without any treatment (14 mice), a vehicle control group treated with 50 μL stroke-physiological saline solution by intratracheal instillation (14 mice), and three SiNPs exposure groups (low-dose group, medium-dose group, and high-dose group with 20 mice in each group, who were given 50 μL SiNPs suspension of 7, 21, and 35 mg·kg⁻¹ respectively and exposed once every 3 days for 5 times). The mice were anesthetized on day 1 (1-day model group) and day 15 (15-day model group) after exposure, then sacrificed after extraction of bronchoalveolar lavage fluid (BALF), and lung tissues were retained. The morphological changes of lung tissues were observed by HE staining, the expression level of C3a in BALF was detected by enzyme-linked immunosorbent assay, the deposition of C3a and C3aR in lung tissues were observed by immunohistochemistry, the protein expression level of C3aR was determined by Western blotting, and the localization and semi-quantitative detection of C3a and C3aR in lung tissues was observed by immunofluorescence. Results SiNPs agglomerated in stroke-physiological saline solution. The average hydrodynamic diameter was (185.60±7.39) nm and the absolute value of Zeta potential was (43.33±0.76) mV. The condition of mice in the 1-day model group and the 15-day model group was good, while 2 mice died in the medium-dose group of the 1-day model group due to misoperation. The autopsy results of the two mice showed congestion of the lung tissue, emphysema, and no imperfection of trachea integrity. No death was observed in other dose groups. The HE staining results showed pathological damage to the mouse lung, including alveolar wall thickening and inflammatory cell infiltration after SiNPs exposure. The pathological damage became more serious with the increase of dose. Regarding pathological changes, the 15-day model group was slightly relieved compared with the 1-day model group, but there were still pathological changes. The enzyme-linked immunosorbent assay results showed that there was no difference in the expression level of C3a between the blank control group and the vehicle control group (P＞0.05), the expression levels of C3a in the medium-dose group and the high-dose group were significantly higher than that in the vehicle control group (P<0.05). The immunohistochemistry results showed that C3a deposition was consistent with the enzyme-linked immunosorbent assay results. The Western blotting and the immunohistochemistry results showed that C3aR expression was low in the blank control group and the vehicle control group, while the expression in each dose group tended to increase with the increase of dose. The immunofluorescence results showed that the fluorescence signals of C3a and C3aR were weak in the blank control group and the vehicle control group in the 1-day model group and the 15-day model group, while the fluorescence signals in the lung tissues of mice in the SiNPs exposure groups tended to increase with the increase of dose. Conclusion The increased expressions of C3a and C3aR in complement activation may be related to lung injury induced by intratracheal instillation of SiNPs, suggesting that C3a/C3aR may be involved in lung injury induced by SiNPs exposure.

ObjectiveTo analyze the typical performance of initiating and responding behaviors of turn-taking in operational games for autistic children with low language function in special education schools and to provide a reference for intervention of turn-taking behaviors in operational games. MethodsFrom November, 2021 to January, 2022, a total of 23 autistic children with low language function (language ability ≤ three years old) in Shanghai Putuo District Qixing School were selected. Their linguistic ability was evaluated. A behavioral assessment approach was used to evaluate the behavior of initiating and responding behaviors of turn-taking in three operational games. The typical errors in initiating behaviors were summarized as difficult to initiate, untimely initiation, no response and abnormal initiation. The typical errors in responding behaviors of turn-taking in operational games were summarized as difficult to respond, untimely response, no response and abnormal response. ResultsThere was no significant differences in the performance of initiating behaviors among three types of operational games (χ² = 11.106, P = 0.196), and there were significant differences in the performance of responding behaviors among operational games (χ² = 26.256, P = 0.001). The initiating behaviors were postively correlated with word comprehension (r = 0.420, P < 0.05), word naming (r = 0.510, P < 0.05), and sentence imitation (r = 0.505, P < 0.05). The responding behaviors were postively correlated with word comprehension (r = 0.546, P < 0.01), word naming (r = 0.728, P < 0.01), sentence comprehension (r = 0.668, P < 0.01) and sentence imitation (r = 0.656, P < 0.01). ConclusionAutistic children with low language function showed different typical behaviors of initiating and responding behaviors of turn-taking in operational games. It is suggested that when designing training programs for turn-taking skills, targeted interventions should be made to address the typical types of errors in response and initiation turns, and individualized intervention programs should be designed to enhance children's communicative efficacy in play game and promote their language development and social participation.

Objective:To investigate the correlation between protein C -1641A/-1654C haplotype and coagulation disorder in Chinese Han septic patients.Methods:The genotypes of protein C gene -1641A>G (rs1799809) and -1654C>T (RS1799808) in septic patients were detected by direct sequencing, and their haplotypes were analyzed and divided into two groups according to the haplotype, -1641A/-1654C (AC) carriers and non-AC haplotype carriers. At the same time, unpaired t test or Mann-Whitney U test was used to compare the differences in coagulation/fibrinolytic parameters, including partial activated thrombin time, prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer levels, as well as APC levels between the two groups. Results:A total of 174 septic patients were included in this study, including 60 AC haplotype carriers and 114 non-AC haplotype carriers. Compared with non-AC haplotype carriers, AC haplotype carriers had significantly lower platelet counts, significantly longer partial activated thrombin time, and significantly decreased activated protein C levels. Other coagulation/fibrinolytic parameters including prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer were not significantly different between the two groups.Conclusions:In this study, the protein C-1641A/-1654C haplotype was found to lead to decreased circulating activated protein C levels decreased platelet counts, and prolonged partial activated thrombin time in septic patients. These results suggest that the protein C-1641A/-1654C haplotype may directly affect the APC level and consequently influence the coagulation disorder of sepsis.

Objective:To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice.Methods:In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group ( n=5) , vehicle control group ( n=5) , TCE group ( n=15) and TCE+CTSLi group ( n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results:The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups ( P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group ( P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group ( P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group ( P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group ( P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant ( P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group ( P<0.05) . Conclusion:CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

Objective:To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice.Methods:In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group ( n=5) , vehicle control group ( n=5) , TCE group ( n=15) and TCE+CTSLi group ( n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results:The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups ( P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group ( P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group ( P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group ( P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group ( P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant ( P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group ( P<0.05) . Conclusion:CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

Objective:To study the clinicopathological features of large B-cell lymphoma (LBCL) with IRF4 rearrangement.Methods:Seven cases of LBCL with IRF4 rearrangement collected at the First Affiliated Hospital of Nanjing Medical University from November 2018 to October 2019 were evaluated by hematoxylin and eosin staining, immunohistochemistry and fluorescence in situ hybridization detection. The relevant literature was reviewed.Results:Four tumors were located in the tonsils, 2 tumors in the lymphoid nodes and one tumor in the adenoid.The patients were 3 males and 4 females patients with a median age of 24 years (range, 6 to 39 years).Microscopically, entirely follicular pattern was present in one case, entirely diffuse pattern in 2 cases, and follicular and diffuse pattern in other 4 cases. The tumor cells were medium to large in size and showed the morphology of centroblasts or blastoid cells with irregular nuclei, brisk mitotic activity in 3 cases and starry sky in 2 cases. All of the cases were positive for CD20, PAX-5, bcl-6, and MUM1 and had a Ki-67 index>80%, while CD10 and bcl-2 were positive in 3 cases. IRF4 gene rearrangement was identified in all cases and bcl-6 gene rearrangement in 2 cases. All patients presented with localized disease with clinical stage Ⅰ or Ⅱ, except one with stage Ⅳ at presentation and a new lesion in the mediastinum developed 8 months later.Conclusions:LBCL with IRF4 rearrangement is a clinicopathologically distinct entity. The observations reveal a broader spectrum of morphology and biological behaviors. The relationship between clinical stage and prognosis needs to be determined in more cases.

Objective: To investigate the association of SNPs in TET2 gene with the susceptibility and prognosis of sepsis. Methods: Ninety-nine patients diagnosed with sepsis and 107 controls were enrolled in the study. The septic patients were further divided into survivors (56 cases) and non-survivors (43 cases) according to the outcome of 28-day hospitalization. Patients without sepsis after major surgery were enrolled as the controls. The genotypes of the five loci (rs6839705, rs7670522, rs7679673, rs7698522 and rs10010325) with high minor allele frequency in the TET2 were screened according to the existing research reports and the SNP database of the NCBI website. The five loci were detected by TaqMan probe based allelic discrimination assays using real-time polymerase chain reaction (PCR). The data were calculated for genetic association study through χ² test and Fisher’s exact probability method. Results: There was no significant difference in genotype frequencies of the five tested SNPs in TET2 gene between septic patients and controls or between survivors and non-survivors in septic patients (P > 0.05). Furthermore, the allelic frequencies of the five SNPs between septic patients and controls or between survivors and non-survivors in septic patients also had no significant difference (P > 0.05). Conclusions This study showed that the five SNPs in TET2 gene (rs6839705, rs7670522, rs7679673, rs7698522, and rs10010325) were not associated with the susceptibility and prognosis of sepsis, which needs to be further confirmed by large-sample studies.

OBJECTIVE To invest igate the immediate to middle-term outcome of operation for 22 children with first branchial cleft anomalies(FBCA). METHODS Twenty-two hospital ized cases who underwent s urgery for fi rst branchial cleft a nomalies f rom Jan. 2010 to Jan. 2017 were included in the study. Among them, 14 patients were male and the others were female. The median age at operation was 4.0 years old(11 months to 12 years old), and the weight of body was 14 kg(10 kg to 37 kg). There were 11 cases complicated with infection before operation. Eight patients had a history of incision and drainage. RESULTS Thirteen patients were diagnosed as Work Type I and the others were Type II. There were 2 cysts, 9 sinuses and 11 fistulas. All of the patients underwent surgery to remove the tract of FBCA. Based on the intraoperative anatomy, the tract ran superficial to the facial nerve in 15 cases, deep to it in 2 and passed between the branches in 5. There were no severe postoperative complications except 3 facial paralyses. At a median followup of 46 months (range from 7 to 84 months), one of the 3 patients with facial paralyses developed into normal and the other two became permanent. None of the patients had postoperative external auditory canal stenosis. There were 2 cases of recurrence who accepted a total of another three operations, and the others were free from reoperation. CONCLUSION Complete excision of the tract is the only way to cure FBCA, which has a close relationship with facial nerve. The surgical approach should be chosen according to the various types.