ObjectiveTo investigate the impact of anticentromere antibody （ACA） on the clinical features and prognosis of patients with primary biliary cholangitis （PBC） by comparing clinical classification， ursodeoxycholic acid （UDCA） response， GLOBE score， and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients. MethodsA total of 749 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients. According to their conditions on admission， the two groups were compared in terms of the distribution of clinical types， i.e.， chronic progression-type PBC， portal hypertension-type PBC， and standard jaundice/liver failure-type PBC. There were 261 patients with complete data after 1-year follow-up， among whom there were 53 patients with positive ACA and 208 with negative ACA. A statistical analysis was performed， and propensity score matching was performed based on sex and age at a ratio of 1∶2. The two groups were compared in terms of 1-year UDCA response rate， GLOBE score， and UK-PBC score before and after matching. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the ACA-negative group， the ACA-positive group had a significantly higher age （61.28±10.35 years vs 56.74±12.17 years， t=4.164， P<0.001）， a significantly higher proportion of female patients （93.9% vs 77.6%， χ²=20.221， P<0.001）， a significantly higher proportion of patients with portal hypertension （48.3% vs 27.6%， χ²=23.289， P<0.001）， and a significantly lower proportion of patients with jaundice/liver failure （24.5% vs 38.5%， χ²=10.205， P<0.001）. After 1-year follow-up， for the 261 PBC patients with complete data， there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group （41.5% vs 41.8%， P>0.05）， and there was a significant difference in the proportion of patients with a GLOBE score of >0.3 between the ACA-positive group and the ACA-negative group （92.5% vs 80.3%， χ²=3.935， P=0.047）. There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching， and there were no significant differences between the two groups in UDCA response rate， GLOBE score， and UK-PBC score （all P>0.05）. ConclusionACA-positive patients tend to have an older age， with a higher proportion of female patients or patients with portal hypertension， while there is a relatively low proportion of patients with jaundice/liver failure. Positive ACA has no significant impact on UDCA response rate， GLOBE score， and UK-PBC score.

ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective: To investigate the causal relationship between gut microbiota and polycystic ovary syndrome (PCOS) using a Mendelian randomization (MR) study, so as to provide insights into the pathogenesis of PCOS and the formulation of prevention and treatment strategies. Methods: The genetic data on gut microbiota was derived from a meta-analysis of genome-wide association studies (GWAS) involving 18 340 participants. The genetic data on PCOS was sourced from two GWAS meta-analyses in European populations, serving as the discovery set and the validation set, respectively. A two-sample MR analysis was conducted using the discovery set, with the inverse variance weighted (IVW) method as the primary approach. Sensitivity analyses employed the weighted median method, MR-Egger regression, and the MR-PRESSO test. The validation set was utilized for verification, and a meta-analysis was performed to combine the results from the two datasets. Results: Forward MR analysis results showed that nine types of gut microbiota were statistically associated with PCOS (all P<0.05). Specifically, the association of family Streptococcaceae (OR=1.442, 95%CI: 1.097-1.895), genus Actinomyces (OR=1.359, 95%CI: 1.036-1.784), genus Ruminococcaceae UCG 011 (OR=0.755, 95%CI: 0.619-0.921), genus Sellimonas (OR=0.766, 95%CI: 0.657-0.893) and genus Streptococcus with PCOS (OR=1.496, 95%CI: 1.136-1.972) remained consistent in the sensitivity analysis. Reverse MR analysis showed no evidence for the causal association between PCOS and the aforementioned five types of gut microbiota (all P>0.05). The MR analysis results of the validation set showed that there was no statistical association between the aforementioned five types of gut microbiota and PCOS (all P>0.05). However, the associations remained significant for genus Actinomyces (OR=1.226,95%CI：1.010-1.503) and genus Streptococcus (OR=1.266,95%CI：1.042-1.452) in the meta-analysis (both P<0.05). Conclusion This study provides the evidence that genus Actinomyces and genus Streptococcus are causally associated with PCOS.

ObjectiveAlveolar macrophages (AMs) are critical for maintaining the homeostasis of pulmonary microenvironment. They process surfactants to ensure alveoli patency, and also serve as the first line of immune defense against pathogen invasion. Available studies have shown that monocyte-derived AMs continuously release pro-inflammatory cytokines and chemokines, recruiting other immune cells to the damaged area during pulmonary fibrosis. These monocyte-derived AMs maintains and amplifies inflammation, playing a negative role in pulmonary fibrosis progression. Current researches have predominantly focused on the gene expression levels of AMs in pulmonary fibrosis microenvironment, with less emphasis on the function and regulation of proteins. This study aims to investigate the differentially expressed proteins (DEPs) of AMs under normal physiological conditions and after pulmonary fibrosis, in order to gain a more comprehensive understanding of the role of AMs in the progression of pulmonary fibrosis. MethodsFirstly, the construction of bleomycin-induced pulmonary fibrosis mouse models was evaluated through using measurements such as body mass, lung coefficient, lungwet-to-dry mass ratio, H&E staining and Masson staining. Subsequently, AMs from both the saline controls and the pulmonary fibrosis models (2.5×10⁵ cells per sample) were collected using FACS sorting, and protein expression profiles of these cells were obtained through label-free proteomics approach. The quality of the proteomic data was assessed by comparing our saline control proteomic data with public proteomic data of physiological AMs. Thirdly, DEPs analysis between the saline controls and the bleomycin groups was carried out using R package Prostar. Functional enrichment analyses of significantly upregulated DEPs were performed using R package Clusterprofiler for GO and KEGG pathways. Finally, the STRING database was used to explore the protein-protein interaction networks related to phagocytosis regulation, inflammatory response regulation, andI-κB/NF-κB signaling pathway. The expression levels of Tlr2 and Pycard were detected respectively by FACS and western blotting. ResultsCompared to the saline controls, mice in the bleomycin groups exhibited a lower average body mass, extensive infiltration of inflammatory cells, and deposition of collagen in the lungs. This indicates that bleomycin successfully induced pulmonary fibrosis in mouse models. The proteomic data of AMs obtained from these models was of high quality and fulfilled the research requirements. A comprehensive analysis showed that 778 proteins were upregulated in pulmonary fibrosis groups compared with control groups. Moreover, the signal pathways enriched in up-regulated DEPs were related to the I‑κB/NF‑κB pathway, inflammatory response regulation, phagocytosis regulation, TGF-β signaling, and HIF-1 pathway, indicating that AMs in pulmonary fibrosis microenvironment exerted pro-inflammatory and pro-fibrotic functions. Protein-protein interaction network analysis of the DEPs suggested that the interactions between Tlr2 and Pycard were control nodes for the pro-inflammatory phenotype of AMs, thereby contributing to pulmonary fibrosis progression. Further validation by FACS and Western blotting respectively confirmed that the expression levels of Tlr2 and Pycard in AMs were significantly increased after pulmonary fibrosis. ConclusionThis study investigates the changes in the protein expression profile of AMs in the pulmonary fibrosis microenvironment. The results show that AMs notably enhanced the activity of various pathways associated with inflammation and fibrosis, suggesting that the interaction between Tlr2 and Pycard serves as a key control node for the highly pro-inflammatory behavior of AMs.

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.