Objective To develop a nomogram diagnostic model to differentiate peripheral small cell lung cancer(PSCLC)from peripheral lung adenocarcinoma(PADC)using clinical and multi spiral computed tomography features.Methods A retrospective analysis was conducted on the CT characteristics and clinical presentations of 50 PSCLC and 100 PADC.Univariate and multivariate logistic regression analyses were employed to identify significant features.A nomogram was constructed to quantify the influencing factors.The efficacy and clinical applicability of the model were assessed using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Smoking,neuron-specific enolase(NSE),smooth margin,spindle/branching shape,and lymphadenopathy were independent risk factors for PSCLC(P＜0.05),whereas rough margin and lobulation sign were independent risk factors for PADC(P＜0.05).The nomogram model demonstrated high diagnostic efficacy,and the calibration curve exhibited a good degree of calibration(Brier=0.079).The DCA indicated that the nomogram model possesses substantial clinical utility.Conclusion The nomogram model developed based on six indicators,including smoking,NSE≥17 ng/mL,margin characteristics,spindle/branching shape,lobulation sign,and lymphadenopathy can well distinguish PSCLC from PADC.

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Objective:To observe the characteristics of brain functional activity in patients with chronic non-specific low back pain(CNLBP)and to explore the potential mechanism of brain functional remodeling in acupuncture treatment based on resting-state fMRI.Method:The 22 patients with CNLBP were included as the CNLBP group,and 22 healthy subjects(HCs)were included as the HCs group.The visual analogue scale(VAS)for pain,Oswestry disability index(ODI),Japanese Orthopedic Association(JOA)score for lumbar spine were collected before and after acu-puncture treatment in the CNLBP group.Resting-state fMRI data were acquired for all participants.The frac-tional amplitude of low frequency fluctuation(fALFF)values of the different brain regions in CNLBP patients before treatment compared with the HCs group were extracted and correlated with the differences in VAS,ODI,and JOA scores.Result:Acupuncture treatment significantly improved the VAS,ODI,and JOA scores in the CNLBP group(P＜0.001);Before treatment,the CNLBP group showed higher fALFF values in the right orbital middle frontal gy-rus,right anterior cingulate gyrus,left anterior cingulate gyrus and left precuneus compared to the HCs group,while lower fALFF values were observed in the right precentral gyrus/right postcentral gyrus,left precentral gy-rus/left postcentral gyrus,right thalamus,right postcentral gyrus/precentral gyrus,and left thalamus.After treat-ment,the CNLBP group exhibited increased fALFF values in the right precentral gyrus/postcentral gyrus,left precentral gyrus/postcentral gyrus,and left middle temporal gyrus,and decreased fALFF values in the left me-dial superior frontal gyrus,right precuneus/left precuneus compared to pre-treatment.Additionally,pre-treatment fALFF value in the right orbital part of the middle frontal gyrus,right anterior cingulate gyrus and left anteri-or cingulate gyrus in the CNLBP group was negatively correlated with the changes in VAS scores(r=-0.699,P=0.000).Conclusion:Acupuncture treatment can significantly improve pain intensity and lumbar spinal dysfunction in CNLBP.CNLBP has multiple abnormalities in brain functional activities related to pain regulation pathways and the default mode network(DMN),and acupuncture treatment can restore most of these abnormal brain ac-tivities;the characteristic of brain functional activity in the right orbital part of the middle frontal gyrus,right anterior cingulate gyrus and left anterior cingulate gyrus before CNLBP treatment is related to the difference in VAS score,providing a potential imaging biomarker for predicting treatment efficacy.

Objective:To observe the characteristics of brain functional activity in patients with chronic non-specific low back pain(CNLBP)and to explore the potential mechanism of brain functional remodeling in acupuncture treatment based on resting-state fMRI.Method:The 22 patients with CNLBP were included as the CNLBP group,and 22 healthy subjects(HCs)were included as the HCs group.The visual analogue scale(VAS)for pain,Oswestry disability index(ODI),Japanese Orthopedic Association(JOA)score for lumbar spine were collected before and after acu-puncture treatment in the CNLBP group.Resting-state fMRI data were acquired for all participants.The frac-tional amplitude of low frequency fluctuation(fALFF)values of the different brain regions in CNLBP patients before treatment compared with the HCs group were extracted and correlated with the differences in VAS,ODI,and JOA scores.Result:Acupuncture treatment significantly improved the VAS,ODI,and JOA scores in the CNLBP group(P＜0.001);Before treatment,the CNLBP group showed higher fALFF values in the right orbital middle frontal gy-rus,right anterior cingulate gyrus,left anterior cingulate gyrus and left precuneus compared to the HCs group,while lower fALFF values were observed in the right precentral gyrus/right postcentral gyrus,left precentral gy-rus/left postcentral gyrus,right thalamus,right postcentral gyrus/precentral gyrus,and left thalamus.After treat-ment,the CNLBP group exhibited increased fALFF values in the right precentral gyrus/postcentral gyrus,left precentral gyrus/postcentral gyrus,and left middle temporal gyrus,and decreased fALFF values in the left me-dial superior frontal gyrus,right precuneus/left precuneus compared to pre-treatment.Additionally,pre-treatment fALFF value in the right orbital part of the middle frontal gyrus,right anterior cingulate gyrus and left anteri-or cingulate gyrus in the CNLBP group was negatively correlated with the changes in VAS scores(r=-0.699,P=0.000).Conclusion:Acupuncture treatment can significantly improve pain intensity and lumbar spinal dysfunction in CNLBP.CNLBP has multiple abnormalities in brain functional activities related to pain regulation pathways and the default mode network(DMN),and acupuncture treatment can restore most of these abnormal brain ac-tivities;the characteristic of brain functional activity in the right orbital part of the middle frontal gyrus,right anterior cingulate gyrus and left anterior cingulate gyrus before CNLBP treatment is related to the difference in VAS score,providing a potential imaging biomarker for predicting treatment efficacy.

Objective To develop a nomogram diagnostic model to differentiate peripheral small cell lung cancer(PSCLC)from peripheral lung adenocarcinoma(PADC)using clinical and multi spiral computed tomography features.Methods A retrospective analysis was conducted on the CT characteristics and clinical presentations of 50 PSCLC and 100 PADC.Univariate and multivariate logistic regression analyses were employed to identify significant features.A nomogram was constructed to quantify the influencing factors.The efficacy and clinical applicability of the model were assessed using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Smoking,neuron-specific enolase(NSE),smooth margin,spindle/branching shape,and lymphadenopathy were independent risk factors for PSCLC(P＜0.05),whereas rough margin and lobulation sign were independent risk factors for PADC(P＜0.05).The nomogram model demonstrated high diagnostic efficacy,and the calibration curve exhibited a good degree of calibration(Brier=0.079).The DCA indicated that the nomogram model possesses substantial clinical utility.Conclusion The nomogram model developed based on six indicators,including smoking,NSE≥17 ng/mL,margin characteristics,spindle/branching shape,lobulation sign,and lymphadenopathy can well distinguish PSCLC from PADC.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.
Animals ; Zebrafish ; Melatonin/pharmacology* ; Lipid Metabolism/drug effects* ; Disease Models, Animal ; Rotenone/pharmacology* ; Sleep Wake Disorders/metabolism* ; Parkinson Disease/metabolism* ; Motor Activity/drug effects* ; Sleep/drug effects*

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O₂) or hypoxia condition (1%O₂). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×10⁶/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×10⁶/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD₃₁], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD₃₁ showed that, the expressions of VEGFA and CD₃₁ in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD₃₁ in BMSC-exo group and CD₃₁ in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD₃₁ in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.
Rats ; Female ; Humans ; Animals ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism* ; Vascular Endothelial Growth Factor A ; Exosomes/metabolism* ; Uterine Diseases/therapy* ; Collagen ; Hypoxia/therapy* ; Fibrosis ; Mesenchymal Stem Cells/metabolism* ; Oxygen

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.
Humans ; Hospitals ; Life Style ; Sleep