The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

OBJECTIVE: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA. METHODS: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed. RESULTS: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3^rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ²=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034). CONCLUSIONS Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.
Humans ; Carbapenems/therapeutic use* ; Pseudomonas aeruginosa ; Soft Tissue Infections/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Hematologic Diseases ; Survival Analysis

Violet root rot is one of the main root diseases in the production process of Pseudostellaria heterophylla. To clarify the pathogenic species that cause the violet root rot of P. heterophylla in Fujian province, the roots and the sclerotia with violet root rot symptoms were collected from the main producing areas of P. heterophylla(Fujian province) from 2017 to 2021, and the pathogens were isolated by tissue separation method and identified by morphology and multi-gene phylogenetic analysis. Additionally, the biological characteristics of the pathogens were studied and the fungicides were determined. The results showed that 78 strains of violet root rot were isolated from the collected root samples, which belonged to one type after preliminary morphological identification. Two represen-tative strains were selected from the pathogens for multi-gene phylogenetic analysis, and they were clustered with Helicobasidium mompa together. The suitable culture conditions for the mycelium were OA medium, 25 ℃, pH 6, and ammonium oxalate as the nitrogen source. The lethal temperature of the mycelium was 50 ℃ for 10 minutes. Moreover, 99.1% propiconazole and 98.7% azoxystrobin had the optimal bacteriostatic effect, and the concentrations with the 50% bacteriostatic rate were 16.85 and 12.24 μg·mL~(-1), respectively. On the basis of the above results, the pathogen causing violet root rot of P. heterophylla in Fujian province was H. mompa. The medium type, growth temperature, pH value, nitrogen source, etc. had significant effect on the growth of mycelium.
Plant Roots ; Phylogeny ; Temperature ; Caryophyllaceae ; Nitrogen

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

A diving decompression procedure is a specific rule that divers should follow when they ascend and get out of water. It comes from the decompression theory and algorithm and is designed for the prevention of decompression sickness. With the ， ， development of diving technology and diving medicine the decompression procedures are constantly innovated and the new ， decompression procedure can be used in diving practice after safety verification. In principle the safety verification of ， decompression procedures should be conducted on animal experiments before human experiments and the risks of ， decompression sickness and oxygen toxicity should be systematically assessed. However the assessment methods used in ， ， ， different studies differ greatly thus it is urgent to establish a standard and universal verification system. Traditionally the risk ， ， assessment of decompression sickness and oxygen toxicity is mainly carried out by observing the incidence detecting bubbles ， theoretical calculation and lung functional test. Furthermore biochemical indicators are increasingly becoming important ， ， supplements. Due to the special underwater environment the diving operation is prone to accidents. Therefore in addition to ， verifying the safety of the new decompression procedure exploring its safety decompression limit is of great significance for the formulation of emergency decompression procedures in emergency situations. The specific approach is to shorten the decompression time and assess the safety until the critical time for detecting bubbles without the occurrence of decompression ， ， sickness is found. Future studies should continue to optimize safety assessment methods explore sensitive biochemical markers ， clarify species associations and improve verification efficiency and reliability of results.

To investigate the relationship between serum uric acid to creatinine ratio (SUA/Cr) and metabolic syndrome (MS) and other indexes on physical examination population in Nantong area. Using the method of cross-sectional study, 8 148 physical examiners in the physical examination center of the Affiliated Hospital of Nantong University from January 2017 to April 2020 were used as the research objects, and the clinical data and serum biochemical indicators such as smoking and alcohol addiction, physical examination and so on were collected. According to the standard diagnosis of MS of Diabetes Society of Chinese Medical Association, the patients were grouped according to the quartile of SUA/Cr and the clinical data of each group were compared. Pearson correlation analysis and logistic regression analysis were used to explore the correlation between SUA/Cr and clinical indicators and the relationship between SUA/Cr and the risk of MS. The results showed that UA and SUA/Cr were the lowest in normal metabolism group, followed by abnormal metabolism group and the highest in MS group, The difference between the two groups was statistically significant (H=919.21 and 629.34, P<0.001). According to the SUA/Cr quartile, the population was divided into four groups. After adjusting for gender, age, smoking history and drinking history, SUA/Cr in group Q₁ was positively correlated with BMI and TG (r=0.061 and 0.080, P<0.05), but negatively correlated with HDL-C (r=-0.057, P<0.05). Multivariate logistic regression results showed that after adjusting for age, sex, smoking history and drinking history, the risk of MS for BMI, SBP, DBP, FBG, TG, HDL-C and SUA/Cr [OR (95%CI)] were: 1.44 (1.41-1.47), 1.07 (1.06-1.07), 1.10 (1.10-1.11), 1.83 (1.73-1.92), 1.89 (1.79-1.99), 0.08 (0.06-0.10) and 1.54 (1.47-1.62). Compared with SUA/Cr group Q₁, the risk of MS in group Q₂, Q₃ and Q₄ increased by 75%, 162% and 346%, respectively. In conclusion, there was an independent positive correlation between SUA/Cr and MS risk in Nantong area.
Humans ; Metabolic Syndrome/epidemiology* ; Creatinine ; Uric Acid ; Cross-Sectional Studies ; Physical Examination ; Risk Factors

Objective: To introduce a new self-developed irrigation device(SID) that does not employ a sheath or an irrigation-suction system and evaluate to its efficiency in transcanal endoscopic ear surgery (TEES) for attic cholesteatoma. Methods: 38 patients who were subjected to TEES for attic cholesteatoma between October 2019 to June 2021 were included in this study, including 17 males and 21 females with an average age of (38.6±11.9) years. SID and underwater continuous drilling were used during operation. Width of endoscope and irrigation speed were measured when SID was applied. The operating time, surgical view and complications were compared between two groups. Results: The width of the endoscope was 3.5-4.6 mm in diameter and the irrigation speed was 20-40 ml/min when SID was used. SID cleaned the lens at the tip of the endoscope and created a clear field of view during TEES. The operation time was (86.6±18.1) min. The skin of the external ear canal was found injured during operation in 3 patients, but there were no complications such as necrosis of the flap, stenosis of external ear canal, sensorineural hearing loss, facial paralysis and cerebrospinal fluid leakage. Conclusions: SID is simple and enhances the efficacy of TEES, providing a new irrigation choice in TEES for attic cholesteatoma.
Humans ; Male ; Female ; Adult ; Middle Aged ; Cholesteatoma, Middle Ear/surgery* ; Suction ; Sudden Infant Death ; Otologic Surgical Procedures ; Ear, Middle/surgery*