Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

OBJECTIVES: This study aimed to investigate the perception of dental outpatient care quality from multiple perspectives of administrators, physicians, nurses, and patients and propose nursing care quality evaluation indices that are consistent with the clinical reality to provide reference for the construction of a scientific, systematic, and comprehensive dental outpatient care quality evaluation system. METHODS: A total of 39 interviewees, including 7 administrators, 11 doctors, 11 nurses, and 10 patients, were selected for semi-structured in-depth interviews in five regionally representative tertiary-level A stomatological specialty hospitals nationwide during January-April 2024 by using a multistage sampling method. Colaizzi 7-step analysis was used to analyze and summarize the interview data. Themes were extracted on the basis of the Structure-Process-Outcome (SPO) three-dimensional quality assessment model. RESULTS: Five main themes and 15 secondary themes were extracted from three quality dimensions: structure, process, and result. The related topics of structural quality were as follows: disinfection and isolation norms, equipment and consumable management, nursing manpower ratio and nurse education structure, and emergency capability. The related topics of process quality were as follows: pre-diagnosis risk assessment, patient triage and guidance, communication and attitude, health education, humanistic care, continuous care, specialty operation, and four-hand operation. The related topics of result quality were as follows: satisfaction, adverse event management and analysis, effective complaints and disputes. CONCLUSIONS Structure quality is the foundation, process quality is the core, and result quality is the key in the evaluation of the quality of oral outpatient care. The standardization of disinfection and isolation, equipment and consumable management, allocation of reasonable nursing manpower and post capacity, implementation of high-quality nursing services, and improvement of the quality and satisfaction of medical cooperation are necessary guarantees to ensure the quality of oral outpatient care.
Humans ; Quality of Health Care ; Ambulatory Care/standards* ; Dental Care/standards* ; Outpatients

OBJECTIVES: This study aimed to construct an evaluation index system for nursing quality management in outpatient dental clinics based on the structure-process-outcome model and provide an objective standard for the evaluation of nursing quality in outpatient dental clinics. METHODS: Through literature review, multi-subject interviews, and expert meetings, the first draft of the evaluation index for nursing quality management in outpatient dental clinics was formulated. The Delphi method was adopted to select and invite 15 experts in the fields of hospital infection management, nursing management, and specialized oral care from across the country to modify the first draft. RESULTS: The positive coefficients of the experts in the two rounds of consultation were 86.7% and 92.3%, respectively. The total authority coefficients of the experts were 0.791 and 0.717, respectively. The mean scores of the importance and feasibility of the third-level indices in the two rounds of consultation were all ≥4.333; the coefficients of variation were all ≤0.150; and the Kendall's coordination coefficients were 0.308 and 0.184 respectively, with P<0.05 for all. These results indicated that the experts were motivated to participate in this study. They recognized the importance and feasibility of the overall items in this index system, and their opinions were relatively consistent. Finally, an evaluation index system, which included 3 first-level indices, 7 second-level indices, 22 third-level indices, and 69 index connotations, for nursing quality management in outpatient dental clinics was determined. The weights of the three first-level indicators were all 0.333. Patient satisfaction (0.076, outcome dimension), hand hygiene (0.061, outcome dimension), chair care ratio (0.057, structural dimension), and turnover rate (0.057, structural dimension) were the top tertiary indicators in terms of portfolio weight. CONCLUSIONS The construction method of the evaluation index system for nursing quality management in outpatient dental clinics is scientific and reliable. It can provide a reference for the evaluation of the management level of nursing quality in outpatient dental clinics and promote the continuous improvement of nursing quality in outpatient dental clinics.
Humans ; Dental Clinics ; Delphi Technique

Allergic asthma is a complex，polygenic disease characterized by chronic inflammation and airway hyperresponsiveness. Fungus and dust mites are the most important inhaled allergens of allergic asthma，and often exist in the form of mixed allergens. In recent years，genetic studies have shown that several genes are associated with allergic asthma attacks. This article reviews the studies on the genes related to allergic asthma caused by dust mites and fungus，such as a disintegrin and metalloproteinase 33（ADAM33），interleukin-4（IL-4），glycoprotein A repetitions predominant（GARP），toll like receptor 3（TLR3），mannose-binding lectin 2（MBL2），chemokine（C-C motif）ligand 17（CCL17）and other genes .

Objective:To explore the expression of family with sequence similarity 83 member A (FAM83A) in colorectal cancer, and the effect of FAM83A knockdown on the proliferation of colorectal cancer cells and the related mechanism.Methods:The expression of FAM83A in the tissues of 102 patients with colorectal cancer and its adjacent tissues was detected by immunohistochemistry. HCT116 cells were divided into experimental group and control group. The experimental group cells were transfected with FAM83A-siRNA plasmid, and the control group cells were transfected with MOCK-siRNA plasmid. The mRNA content of FAM83A in each group was detected by fluorescence quantitative PCR. The expressions of FAM83A, P13K, p-AKT and p-mTOR in each group were detected by Western blot. CCK8 assay and clonogenesis assay were used to detect cell proliferation.Results:The positive rate of FAM83A in colorectal cancer patients was 88.23% (90 cases /102 cases), and the expression rate of FAM83A in paracancer tissues was 10.78% (11 cases /102 cases). The expression rate of Fam83a in colorectal cancer tissues was significantly higher than that in paracancer tissues, with statistical significance ( P<0.001). After siRNA transfection, the mRNA expression levels of FAM83A in HCT116 cells of the experimental group and control group were 1.23±0.20 and 0.43±0.12, respectively, and the protein expression levels of FAM83A were 1.19±0.11 and 0.23±0.08, respectively. The expression levels of P13K were 1.21±0.17 and 0.28±0.09, the expression levels of p-AKT were 1.35±0.23 and 0.57±0.18, and the expression levels of p-mTOR were 1.48±0.20 and 1.05±0.14. The expression of P13K, p-Akt and p-mTOR was down-regulated (all P<0.05). The absorbance of HCT116 cells in the experimental group and the control group was 1.09±0.22 and 2.21±0.27, respectively. The cloning rate of HCT116 cells in the experimental group and the control group was 21.6%±2.4% and 62.7%±4.1%, respectively. The proliferation ability of HCT116 cells in the experimental group decreased significantly ( P<0.05) . Conclusions:The expression of FAM83A is significantly increased in colorectal cancer tissues, which may be related to the malignant degree of colorectal cancer. FAM83A affects the proliferation of colorectal cancer cells through the P13K/AKT/mTOR signaling pathway.

Objective To analyze the characteristics of work-related musculoskeletal disorders (WMSDs) among sonographers in Guangdong Province, and to explore the disease pattern of the cases. Methods A total of 512 sonographers from 31 hospitals in Guangdong Province were selected as the research subjects using stratified cluster sampling method. The prevalence of WMSDs in the past year was investigated using the Musculoskeletal Disorders Questionnaire, and the characteristics of WMSDs were analyzed. Latent class analysis was used to identify the disease pattern of WMSDs. Results The overall prevalence of WMSDs was 94.3%. The top five affected body parts were right shoulder, neck, right hand/wrist, lower back and right forearm/elbow, with the prevalence of 80.3%, 75.4%, 61.1%, 55.5% and 45.3%, respectively. The prevalence of WMSDs was higher on the right side for the shoulder, hand/wrist, forearm/elbow, hip/leg and knee compared with the left side (80.3% vs 31.3%, 61.1% vs 13.9%, 45.3% vs 10.0%, 17.4% vs 8.6%, 13.1% vs 8.4%, all P<0.05). The prevalence of WMSDs increased with work years, as well the prevalence of WMSDs in the top five affected body parts among the sonographers (all P<0.05). However, there were no statistical differences in prevalence of WMSDs between general hospitals and maternal and child health hospitals, tertiary hospitals and non-tertiary hospitals, Pearl River Delta hospitals and non-Pearl River Delta hospitals; there was also no statistical difference between different genders and age groups of the sonographers (all P>0.05). The best-fit latent disease pattern for sonographers WMSDs comprised three categories： symptom of neck-right shoulder, symptom of neck-lower back-right shoulder-right elbow-right hand/wrist, and symptom of multi-parts above the knees, with the latent probabilities of 0.438, 0.427 and 0.135, respectively. Conclusion The prevalence of WMSDs in sonographers is extremely high, with a dose-effect relationship with work years. The most common affected parts are neck, lower back and right shoulder, right hand/wrist, and right forearm/elbow. The prevalence of WMSDs in the right side of limb was higher than that in the left. WMSDs primarily occur in multiple parts simultaneously. The most common symptoms occur in the neck-right shoulder and neck-lower back-right shoulder-right elbow-right hand/wrist.

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9), the third-generation genome editing tool, has been favored because of its high efficiency and clear system composition. In this technology, the introduced double-strand breaks (DSBs) are mainly repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR) pathways. The high-fidelity HDR pathway is used for genome modification, which can introduce artificially controllable insertions, deletions, or substitutions carried by the donor templates. Although high-level knock-out can be easily achieved by NHEJ, accurate HDR-mediated knock-in remains a technical challenge. In most circumstances, although both alleles are broken by endonucleases, only one can be repaired by HDR, and the other one is usually recombined by NHEJ. For gene function studies or disease model establishment, biallelic editing to generate homozygous cell lines and homozygotes is needed to ensure consistent phenotypes. Thus, there is an urgent need for an efficient biallelic editing system. Here, we developed three pairs of integrated selection systems, where each of the two selection cassettes contained one drug-screening gene and one fluorescent marker. Flanked by homologous arms containing the mutated sequences, the selection cassettes were integrated into the target site, mediated by CRISPR/Cas9-induced HDR. Positively targeted cell clones were massively enriched by fluorescent microscopy after screening for drug resistance. We tested this novel method on the amyloid precursor protein (APP) and presenilin 1 (PSEN1) loci and demonstrated up to 82.0% biallelic editing efficiency after optimization. Our results indicate that this strategy can provide a new efficient approach for biallelic editing and lay a foundation for establishment of an easier and more efficient disease model.
Alleles ; CRISPR-Cas Systems ; DNA End-Joining Repair ; Gene Editing/methods* ; Recombinational DNA Repair

Objective:To evaluate the positive rate of the bronchodilation test (BDT) in asthmatic children with normal forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC) and FEV 1/FVC, so as to improve the recognition of the importance of the BDT test in asthmatic children with normal FEV 1, FVC and FEV 1/FVC. Methods:Children aged 5-14 who were diagnosed with asthma in the outpatient clinic of Shandong Provincial Hospital Affiliated to Shandong University from September 2018 to August 2019 and willing to receive pulmonary function and BDT examinations were enrolled.Data of pulmonary function of children with normal FEV 1, FVC and FEV 1/FVC were collected to analyze the rate of positive BDT results and the status of small airway function. Results:A total of 1 631 asthmatic children with normal FEV 1, FVC and FEV 1/FVC were enrolled in this study, including 1 414 children with normal pulmonary function and 217 children with small airway dysfunction.Fifteen minutes after the bronchodilator was inhaled, 127 children (87 males and 40 females) showed positive BDT results, accounting for 7.8%.Among these children, 62 cases (28.6%) with co-existing small airway dysfunction showed positive BDT results.The improvement rate of FEV 1 was 8.0% to 11.9% in 132 cases (8.1%). The FEV 1 before bronchodilator inhalation accounted for (98.5±10.3)% of the predicted value.Fifteen minutes after terbutaline sulfate inhalation, the improvement rate was 13.5% (12.5%, 16.2%). The improvement rates of forced expiratory flow at 50% of FVC exhaled (FEF 50, r=-0.339, P<0.01), forced expiratory flow at 75% of forced vital capacity exhaled (FEF 75, r=-0.400, P<0.01), maximum mid-expiratory flow(MMEF, r=-0.375, P<0.01) were negatively correlated with their baseline values.The improvement rate of FEV 1 was not associated with its baseline value ( r=-0.128, P=0.153), but negatively correlated with the baseline value of MMEF ( r=-0.231, P<0.01). Conclusions:BDT results are positive in some asthmatic children with normal FEV 1, FVC and FEV 1/FVC.It is recommended that BDT testing should be conducted as much as possible in the diagnosis and follow-up of children with typical or atypical asthma.In this way, the diagnosis can be confirmed and the current optimal results can be obtained.Meanwhile, small airway function testing is helpful for comprehensive assessment of asthma and its control level.