OBJECTIVES: To investigate the impact of hepatitis B virus (HBV) infection on oral microbiota and metabolites in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and the underlying mechanisms. METHODS: This prospective study was conducted in 47 MAFLD patients complicated with chronic hepatitis B (CHB) and 48 MAFLD patients without CHB enrolled from November, 2023 to January, 2024. Fasting tongue coating samples were collected from the patients for analyzing microbial community structures and metabolites using high-throughput 16S rDNA sequencing and non-targeted metabolomics techniques, and their associations with clinical indicators and biological pathways were explored using correlation analysis and functional annotation. RESULTS: The levels of fasting blood glucose, total cholesterol (TC), gamma-glutamyl transferase (GGT), and severity of fatty liver were all significantly lower in MAFLD+CHB group than in MAFLD group. Microbiota analysis showed that the abundances of Patescibacteria (at the phylum level), Hydrogenophaga, and Absconditabacteriales (at the genus level) were significantly increased, while the abundance of Megasphaera was decreased in MAFLD+CHB group. The differential microbiota were significantly correlated with TC, GGT and low-density lipoprotein (r=-0.68‒0.75). Metabolomics analysis revealed that 469 metabolites (including lipids and amino acids) were upregulated and 2306 (including organic oxygen-containing compounds and phenylpropanoids) were downregulated in MAFLD+CHB group, for which KEGG enrichment analysis suggested abnormal activation of the linoleic acid metabolism and glycerophospholipid metabolism pathways. Correlation analysis between microbiota and metabolites indicated that Patescibacteria and Megasphaera, which were positively correlated with lipid metabolites and negatively with fatty acid metabolites, respectively, jointly affected glycolipid metabolism and oxidative stress pathways. CONCLUSIONS Compared to patients with MAFLD alone, MAFLD patients with concurrent chronic HBV infection showed lower levels in some lipid metabolism indicators and the degree of hepatic steatosis, accompanied by alterations in oral microbiota structure and metabolic profiles. The precise mechanisms involved require further investigation to be fully elucidated.
Humans ; Lipid Metabolism ; Prospective Studies ; Microbiota ; Hepatitis B, Chronic/microbiology* ; Male ; Female ; Adult ; Fatty Liver/microbiology* ; Middle Aged ; Mouth/microbiology* ; Metabolomics

The excessive accumulation of advanced glycosylation end products(AGEs), the end products of non-enzymatic glycosylation reactions, can be involved in the pathological processes of various ocular diseases through mechanisms such as oxidative stress, inflammatory responses and apoptosis. In this paper, we systematically reviewed the key role of AGEs in diabetic keratopathy, cataract, glaucoma, age-related macular degeneration(ARMD)and diabetic retinopathy(DR). It was found that AGEs activate signalling pathways such as NADPH oxidase, MAPK and NF-κB by binding to the receptor RAGE, leading to reactive oxygen species(ROS)generation, release of inflammatory factors, and vascular endothelial dysfunction, which in turn induces delayed corneal healing, cross-linking of lens proteins, optic nerve degeneration, formation of choroidal neovascularisation(CNV), and blood-retinal barrier(BRB)disruption. For example, in diabetic keratopathy, AGEs delay wound healing via the ROS/NLRP3 inflammatory vesicle axis; in cataract, ascorbic acid-mediated cross-linking of lens proteins due to AGEs directly impairs lens transparency; and in DR, AGEs exacerbate microvascular damage by regulating vasucular endothelial growth factor(VEGF)expression and pericyte apoptosis. In addition, this article discusses the advances and limitations of AGEs detection techniques, such as the potential application of lens AGEscan fluorescence assay in screening for diabetic complications, and the need to develop tissue-specific assays for aqueous humour and vitreous. For therapeutic strategies, the research directions of inhibiting AGEs production, blocking RAGE signalling pathway and developing anti-glycosylation drugs are proposed to emphasise their clinical value in delaying disease progression. This review not only integrates the molecular mechanisms and clinical associations of AGEs in ocular diseases, but also provides a theoretical basis for targeted interventions, which is of great significance in exploring novel diagnostic and therapeutic strategies.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To investigate the clinical characteristics, postoperative complications, and risk factors for pouchitis in surgical patients with ulcerative colitis (UC).Methods:This was a retrospective observational study. The clinical data of 336 UC patients who had undergone surgical treatment at the Inflammatory Bowel Disease Center of the Department of General Surgery, Jinling Hospital Affiliated to Nanjing University Medical School from February 2014 to February 2024 were enrolled. The study patients were stratified into 2014-2019 ( n = 158) and 2020–2024 groups ( n = 178), these being the periods before and after biologics were covered for treatment of UC by national insurance in China in 2020. Clinical characteristics and surgical complications were analyzed and compared between the 2014-2019 and 2020-2024 groups. Multivariable logistic regression was performed to identify the risk factors associated with pouchitis in UC patients undergoing total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA). Results:The study cohort comprised 336 UC patients, 193 (57.4%) of whom were men. The median preoperative disease course was 48.0 months and the mean age at colectomy was 46.4±15.4 years. TPC-IPAA had been performed on 275 patients (81.8%), 129 in the 2014-2019 group and 146 in the 2020-2024 group. Sixty-one patients had undergone total or subtotal colectomy, 29 in the 2014-2019 group and 32 in the 2020-2024 group. 262 (78.0%) UC patients underwent surgery due to medical refractory. Ninety-nine (29.5%) had used biopharmaceuticals within 2 months prior to surgery, 63 (18.8%) of them having received infliximab. A smaller proportion of patients had undergone surgery for UC that was refractory to medications in the 2020–2024 group than in the 2014–2019 group (73.0% [130/178] vs. 83.5% [132/158], χ 2=5.384, P=0.020), the patients were older at colectomy (48.0±15.4 years vs. 44.6±15.2 years, t=-2.008, P=0.045), the body mass index was higher (20.2±3.1 kg/m 2 vs. 19.4±3.2 kg/m 2, t=-2.201, P=0.028), the Mayo score prior to surgery was lower ( M[ Q1, Q3]: 11.0 [9.2, 12.0 points] vs. 12.0 [11.0, 12.0) points, Z=-4.242, P=0.001), the rate of Charlson Comorbidity Index ≥ 3 scores was higher (27.0% [48/178] vs. 17.1% [27/158], χ 2=5.384, P=0.020), a greater percentage of patients had received biologics prior to surgery (41.0% [73/178) vs. 16.5% [26/158], χ 2=24.285, P<0.001), and intraoperative blood loss was greater ( M[ Q1, Q3]: 100.0 [100.0, 150.0] ml vs. 50.0 [30.0, 100.0] ml, Z=-7.054, P<0.001) despite the operation time being shorter (253.8±74.6 minutes vs. 315.2±96.8 minutes, t=6.265, P<0.001). Among the 275 patients undergoing TPC-IPAA, 95 (34.6%) had early complications (within 30 days after surgery), 20 (7.3%) of which were Clavien-Dindo Grade III–IV complications. Among these patients, 50 (18.2%) had ileus or small bowel obstruction, 11 in the 2014-2019 group and 39 in the 2020-2024 group; this difference is statistically significant (χ 2=15.225, P<0.001). Ninety-one patients (33.1%) had late complications (more than 30 days after surgery), 75 (27.3%) being pouchitis (36 in the 2014-2019 group and 39 in the 2020-2024 group); this difference is not statistically significant (χ 2=0.049, P=0.824). Five patients (1.8%) had undergone pouch excision with permanent ileostomy. Among the 61 patients who had undergone total or subtotal colectomy, 26 (42.6%) developed early postoperative complications, including 10 (16.4%) Clavien-Dindo Grade III-IV complications and one death (1.6%), the last being attributable to multiorgan dysfunction. Three patients (4.9%) had late complications; the difference in incidence of postoperative complications between the 2014-2019 and 2020-2024 groups is not statistically significant (both P>0.05). Multivariable analysis identified intraoperative blood transfusion (OR: 2.12, 95% CI: 1.19–3.75, P=0.010) and interval to stoma closure > 120 days (OR: 2.05, 95%CI: 1.16-3.62, P = 0.013) as independent risk factors for development of pouchitis in UC patients undergoing TPC-IPAA. Conclusion:Surgical treatment of UC remains safe in the biologics era. Proactive strategies to reduce intraoperative blood transfusion and achieve timely stoma closure may reduce the risk of pouchitis in UC patients undergoing TPC-IPAA.

Objective:To investigate the impact of delayed ileostomy closure (>6 months) on postoperative complications in patients with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) .Methods:Using propensity score matching. Clinical data of UC patients who underwent IPAA and subsequent ileostomy closure at Jinling Hospital from January 2014 to December 2021 were retrospectively analyzed. Patients were categorized into a routine group (2 to ≤6 months) and a delayed group (>6 months) based on the timing of ileostomy closure. A 1∶1 propensity score matching analysis was performed to compare early (≤30 days) and late (>30 days) postoperative complications between the two groups.Results:A total of 225 UC patients who underwent IPAA and ileostomy closure were included, comprising 129 males (57.3%) and 96 females (42.7%). After propensity score matching, 88 patients were included in the analysis, with 44 patients in each group. There was no significant difference in the overall incidence of early postoperative complications (11.4% vs. 15.9%, P = 0.534) or late postoperative complications (43.2% vs. 43.2%, P = 1.000) between the delayed and routine groups. Additionally, no significant differences were observed in other postoperative complications (all P > 0.05) . Conclusion:Delayed ileostomy closure following IPAA does not significantly increase the risk of postoperative complications in UC patients.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To investigate the impact of delayed ileostomy closure (>6 months) on postoperative complications in patients with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) .Methods:Using propensity score matching. Clinical data of UC patients who underwent IPAA and subsequent ileostomy closure at Jinling Hospital from January 2014 to December 2021 were retrospectively analyzed. Patients were categorized into a routine group (2 to ≤6 months) and a delayed group (>6 months) based on the timing of ileostomy closure. A 1∶1 propensity score matching analysis was performed to compare early (≤30 days) and late (>30 days) postoperative complications between the two groups.Results:A total of 225 UC patients who underwent IPAA and ileostomy closure were included, comprising 129 males (57.3%) and 96 females (42.7%). After propensity score matching, 88 patients were included in the analysis, with 44 patients in each group. There was no significant difference in the overall incidence of early postoperative complications (11.4% vs. 15.9%, P = 0.534) or late postoperative complications (43.2% vs. 43.2%, P = 1.000) between the delayed and routine groups. Additionally, no significant differences were observed in other postoperative complications (all P > 0.05) . Conclusion:Delayed ileostomy closure following IPAA does not significantly increase the risk of postoperative complications in UC patients.

Objective:To investigate the clinical characteristics, postoperative complications, and risk factors for pouchitis in surgical patients with ulcerative colitis (UC).Methods:This was a retrospective observational study. The clinical data of 336 UC patients who had undergone surgical treatment at the Inflammatory Bowel Disease Center of the Department of General Surgery, Jinling Hospital Affiliated to Nanjing University Medical School from February 2014 to February 2024 were enrolled. The study patients were stratified into 2014-2019 ( n = 158) and 2020–2024 groups ( n = 178), these being the periods before and after biologics were covered for treatment of UC by national insurance in China in 2020. Clinical characteristics and surgical complications were analyzed and compared between the 2014-2019 and 2020-2024 groups. Multivariable logistic regression was performed to identify the risk factors associated with pouchitis in UC patients undergoing total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA). Results:The study cohort comprised 336 UC patients, 193 (57.4%) of whom were men. The median preoperative disease course was 48.0 months and the mean age at colectomy was 46.4±15.4 years. TPC-IPAA had been performed on 275 patients (81.8%), 129 in the 2014-2019 group and 146 in the 2020-2024 group. Sixty-one patients had undergone total or subtotal colectomy, 29 in the 2014-2019 group and 32 in the 2020-2024 group. 262 (78.0%) UC patients underwent surgery due to medical refractory. Ninety-nine (29.5%) had used biopharmaceuticals within 2 months prior to surgery, 63 (18.8%) of them having received infliximab. A smaller proportion of patients had undergone surgery for UC that was refractory to medications in the 2020–2024 group than in the 2014–2019 group (73.0% [130/178] vs. 83.5% [132/158], χ 2=5.384, P=0.020), the patients were older at colectomy (48.0±15.4 years vs. 44.6±15.2 years, t=-2.008, P=0.045), the body mass index was higher (20.2±3.1 kg/m 2 vs. 19.4±3.2 kg/m 2, t=-2.201, P=0.028), the Mayo score prior to surgery was lower ( M[ Q1, Q3]: 11.0 [9.2, 12.0 points] vs. 12.0 [11.0, 12.0) points, Z=-4.242, P=0.001), the rate of Charlson Comorbidity Index ≥ 3 scores was higher (27.0% [48/178] vs. 17.1% [27/158], χ 2=5.384, P=0.020), a greater percentage of patients had received biologics prior to surgery (41.0% [73/178) vs. 16.5% [26/158], χ 2=24.285, P<0.001), and intraoperative blood loss was greater ( M[ Q1, Q3]: 100.0 [100.0, 150.0] ml vs. 50.0 [30.0, 100.0] ml, Z=-7.054, P<0.001) despite the operation time being shorter (253.8±74.6 minutes vs. 315.2±96.8 minutes, t=6.265, P<0.001). Among the 275 patients undergoing TPC-IPAA, 95 (34.6%) had early complications (within 30 days after surgery), 20 (7.3%) of which were Clavien-Dindo Grade III–IV complications. Among these patients, 50 (18.2%) had ileus or small bowel obstruction, 11 in the 2014-2019 group and 39 in the 2020-2024 group; this difference is statistically significant (χ 2=15.225, P<0.001). Ninety-one patients (33.1%) had late complications (more than 30 days after surgery), 75 (27.3%) being pouchitis (36 in the 2014-2019 group and 39 in the 2020-2024 group); this difference is not statistically significant (χ 2=0.049, P=0.824). Five patients (1.8%) had undergone pouch excision with permanent ileostomy. Among the 61 patients who had undergone total or subtotal colectomy, 26 (42.6%) developed early postoperative complications, including 10 (16.4%) Clavien-Dindo Grade III-IV complications and one death (1.6%), the last being attributable to multiorgan dysfunction. Three patients (4.9%) had late complications; the difference in incidence of postoperative complications between the 2014-2019 and 2020-2024 groups is not statistically significant (both P>0.05). Multivariable analysis identified intraoperative blood transfusion (OR: 2.12, 95% CI: 1.19–3.75, P=0.010) and interval to stoma closure > 120 days (OR: 2.05, 95%CI: 1.16-3.62, P = 0.013) as independent risk factors for development of pouchitis in UC patients undergoing TPC-IPAA. Conclusion:Surgical treatment of UC remains safe in the biologics era. Proactive strategies to reduce intraoperative blood transfusion and achieve timely stoma closure may reduce the risk of pouchitis in UC patients undergoing TPC-IPAA.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*