OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

Objective Mobile artificial lumbar complex(MALC)which suitable for reconstruction after subtotal lumbar resection in goats was developed,and to test stability of the complex and postoperative lumbar segmental motor function.Methods Eighteen male boer goats aged from 1 to 2 years old(weighted from 35 to 45 kg)were selected and divided into con-trol group,fusion group and non-fusion group,with 6 goats in each group.According to preoperative CT scans and MRI exami-nations of lumbar,the goat MALC was designed and performed by 3D printed for non-fusion group.Operation was performed on three groups respectively,and only vertebral body and disc were exposed in control group.In fusion group,L4 part of vertebral body and the upper and lower complete disc tissues were removed,and the lumbar spine bone plate fixation was performed with titanium mesh bone grafting.In non-fusion group,vertebral body and disc were removed in the same way,and MALC was im-planted.AP and lateral X-rays of lumbar vertebrae in goat were taken at 6 months after surgery,in order to understand whether the plant was dislocated,displaced and fractured.Biomechanical tests were performed on the specimens by mechanical instru-ment to measure range of motion(ROM)of L2,3,L,4,L4,5intervertebral space and the overall ROM of L2-5 lumbar vertebrae.Results MALC of lumbar vertebra was designed by 3D printing,and its component artificial vertebrae and upper and lower ar-tificial end plates were manufactured.The semi-spherical structure was fabricated by precision lathe using high-crosslinked polyethylene material,and the prosthesis was assembled.Postoperative AP and lateral X-rays of lumbar vertebra at 6 months showed the implant position of implant and MALC were good without displacement and dislocation.In vitro biomechanical test of lumbar vertebrae specimens:(1)There were no statistical significance in ROM of lumbar intervertebral space flexion and extension,lateral flexion and rotation on L.4 and L4,5,between non-fusion group and control group(P＞0.05),while ROM of fu-sion group was significantly reduced compared with the other two groups(P＜0.05).There were no significant difference in ROM of L2.3 intervertebral flexion and extension,lateral flexion and rotation between non-fusion group and control group(P＞0.05),while fusion group was significantly increased compared with the other two groups(P＜0.001).(2)There was no signifi-cant difference in overall lumbar ROM of L2-5(P＞0.05).Conclusion The individual MALC could restore intervertebral height of lumbar vertebra while maintaining the stability of lumbar vertebra and re-establishing motor function of lumbar space.

The population aging and the coming of the information era are accompanied with the growing incidence of spinal degenerative diseases, which result in heavy social and economic burdens. Under the guidance of the tendon-bone theory, rich experience has been accumulated in the prevention and diagnosis of spinal degenerative diseases with traditional Chinese medicine(TCM), which demonstrates unique advantages. China's government has placed people's health in the strategic position of development, providing a favorable environment for the realization of healthy aging. The Healthy China 2030 advocates special actions for healthy bones. As China is facing an important period of demographic transition, the Traditional Chinese Medicine for Bone Health Program has emerged, combining the needs of the national health strategy and the advantages of TCM. This paper discusses the background and significance of the program. According to the theory of five body constituents and the characteristics of musculoskeletal system diseases, this paper constructs a theoretical system of "tendon-meridian-muscle-bone-marrow" to explain the structure and function of the musculoskeletal system. From the holistic view of TCM, this system shows not only the structure and function of the musculoskeletal system but also the patterns of disease development and the mechanism of TCM treatment. The system facilitates the research on not only the comorbidities related to bone health but also the occurrence, development, and outcome of diseases. In the management of chronic degenerative diseases, attention should be paid to the establishment and improvement of the disease prevention and control system in addition to the disease treatment alone. Finally, this paper introduces the characteristic advantages of TCM in the whole process of prevention, diagnosis, treatment, rehabilitation, and health maintenance of spinal degenerative diseases, aiming to enrich the connotation of the tendon-bone theory, provide ideas and implementation strategies for TCM clinical practice, and ultimately achieve the effective management of the diagnosis and treatment of spinal degenerative diseases.
Humans ; Medicine, Chinese Traditional ; Spinal Diseases/prevention & control* ; Drugs, Chinese Herbal/therapeutic use* ; China ; Bone and Bones/drug effects*

OBJECTIVE: This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase (DGC) in Vibrio cholerae and how its transcription is regulated by Fur and HapR. METHODS: The roles of VCA0560 was investigated by utilizing various phenotypic assays, including colony morphological characterization, crystal violet staining, Cyclic di-GMP (c-di-GMP) quantification, and swimming motility assay. The regulation of the VCA0560 gene by Fur and HapR was analyzed by luminescence assay, electrophoretic mobility shift assay, and DNase I footprinting. RESULTS: VCA0560 gene mutation did not affect biofilm formation, motility, and c-di-GMP synthesis in V. cholerae, and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity. The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator HapR. CONCLUSION Overexpressed VCA0560 functions as an active DGC in V. cholerae, and its transcription is repressed by Fur and HapR.
Vibrio cholerae/genetics* ; Biofilms ; Quorum Sensing ; Mutation ; Gene Expression Regulation, Bacterial ; Bacterial Proteins/genetics*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.
Bacterial Proteins/metabolism* ; Bacterial Toxins/metabolism* ; Caco-2 Cells ; Clostridioides ; Clostridioides difficile/genetics* ; Humans ; Oxidoreductases/metabolism* ; Transcriptome ; Vaccines, Attenuated

Child ; Chronic Disease ; Epstein-Barr Virus Infections/complications* ; Familial Primary Pulmonary Hypertension/complications* ; Herpesvirus 4, Human ; Humans ; Persistent Infection ; Pulmonary Arterial Hypertension

Bacterial Proteins/metabolism* ; Operon/genetics* ; Phosphotransferases/metabolism* ; Quorum Sensing/genetics* ; Vibrio cholerae/genetics*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome