Juvenile idiopathic arthritis (JIA) is the most common condition of chronic rheumatic disease in children. JIA is an autoimmune or autoinflammatory disease, with unclear mechanism and limited treatment efficacy. Recent studies have found a number of alterations in gut microbiota and its metabolites in children with JIA, which are related to the development and progression of JIA. This review focuses on the influence of the gut microbiota and its metabolites on immune function and the intestinal mucosal barrier and discuss the key role of the gut-joint axis in the pathogenesis of JIA and emerging treatment methods based on gut microbiota and its metabolites. This review could help elucidate the pathogenesis of JIA and identify the potential therapeutic targets for the prevention and treatment of JIA.
Humans ; Arthritis, Juvenile/physiopathology* ; Gastrointestinal Microbiome/physiology* ; Child ; Intestinal Mucosa

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ² test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ²=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ²=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.
Infant ; Female ; Male ; Humans ; Child ; Retrospective Studies ; China/epidemiology* ; Hospitalization ; Community-Acquired Infections/therapy* ; Hospitals, Pediatric ; Pneumonia/therapy*

BACKGROUND: In recent years, visual quality has been extensively investigated in various conditions. In this community-based population study, we analyzed the effects of aging, refraction, and Lens Opacification Classification System III (LOCSIII) score on retinal imaging quality in healthy Chinese adults. METHODS: This cross-sectional study was conducted on sub-group subjects from The Handan Eye Study between October 2012 and January 2013. Healthy subjects over 30-years-old with logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) less than 0 were included. Retinal image quality was measured by optical quality analysis system (OQAS) and recorded as modulation transfer function cutoff frequency (MTFcutoff), OQAS value (OV) 100%, OV20%, OV9%, Strehl ratio (SR), and objective scatter index (OSI). The correlation between age, spherical equivalent refraction (SE), LOCSIII score, and optical quality parameters were investigated by multivariate analysis. RESULTS: Among 1108 verified subjects, 690 subjects (1380 eyes) met the inclusion criteria. Their age ranged from 30 to 76 years, SE ranged from -4.75 to 2.75 D. They were divided into five age groups (30-39, 40-49, 50-59, 60-69, and ≥70 years) for further analysis. After multivariate analysis by mixed-effect linear model, SR (t =  -3.03, P = 0.002), OV20% (t = -2.39, P = 0.017), and OV9% (t = -3.16, P = 0.001) significantly decreased with the increasing age, whereas logMAR BCVA (t = 4.42, P < 0.001) and OSI (t = 4.46, P < 0.001) significantly increased with age. As SE increased, SR (t = 2.74, P = 0.01), OV20% (t = 2.31, P = 0.02), and OV9% (t = 2.79, P = 0.005) significantly elevated, and OSI (t = -3.38, P < 0.001) significantly decreased. With the increase in cortical opacity score, all optical quality parameters except for SR significantly decreased, including MTFcutoff (t = -2.78, P = 0.01), OV100% (t = -2.78, P = 0.005), OV20% (t = -2.60, P = 0.009), and OV9% (t = -2.05, P = 0.040). As posterior sub capsular opacity score increased, MTFcutoff (t = -2.40, P = 0.02) and OV100% (t = -2.40, P = 0.01) significantly decreased, while OSI (t = 7.56, P < 0.001) significantly increased. CONCLUSIONS In healthy Chinese adult population, optical quality-related parameters significantly decrease with the increasing age, and OSI significantly increases with age. In normal BCVA subjects, optical quality is significantly impacted by cortical and posterior sub capsular opacity rather than by nuclear opacity.

Purpose: This study aimed to investigate the potential systemic antitumor effects of stereotactic ablativeradiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods: Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor;irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grewto the touchable size, mice were randomly divided into eight treatment groups. These groupsreceived normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not tothe primary tumor. The further tumor growth/regression of mice were followed andobserved. Results: For the single 15 Gy modality, tumor growth delay could only be observed at the primarytumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primaryand secondary tumor growth could be observed, indicated an abscopal effect wasinduced. Mechanism analysis suggested that programmed death-ligand 1 expressionincreased with SABR was counteract by additional apatinib therapy. Furthermore, whenapatinib was combined with SABR, the composition of immune cells could be changed.More importantly, this two-pronged approach evoked tumor antigen–specific immune responsesand the mice were resistant to another tumor rechallenge, finally, long-term survivalwas improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib,which was effective in eliciting an abscopal effect induced by SABR.

Objective To investigate the status of suicidal behaviors and suicidal ideation among HIV positive patients in Guangzhou, and to explore its relevant psycho-social factors. Methods We conducted a cross-sectional survey of HIV positive adult patients in six districts of Guangzhou to collect social-demographic characteristics, HIV infection time, suicidal ideation, suicidal behaviors and psycho-social factors. Use suicidal ideation and suicidal behaviors as the dependent variables to conduct the univariate analysis and multivariate Logistic regression analysis. Results Of the 464 subjects,5.2% and 17.4% of them had suicidal behaviors and suicidal ideation. Analysis showed that the infection route, depression, anxiety, social discrimination, self-discrimination were correlated with the suicidal behaviors(all P<0.05), while age, health status, spouse infection, depression, anxiety and social support, social discrimination, self-discrimination were correlated with the suicidal ideation(all P<0.05). Multivariate Logistic regression model showed that depression and self-discrimination were associated with suicidal behaviors(all P<0.05),depression and social discrimination were associated with suicidal ideation (all P<0.05). Conclusions HIV-positive adult patients in Guangzhou have a high incidence of suicidal ideation and behaviors. Psychological counseling, risk assessment and timely treatment related to depression, social discrimination self-discrimination and early antiviral treatment should be targeted in HIV-positive adult patients.

Background: Neural respiratory drive (NRD) using diaphragm electromyography through an invasive transesophageal multi-electrode catheter can be used as a feasible clinical physiological parameter in patients with chronic obstructive pulmonary disease (COPD) to provide useful information on the treatment response. However, it remains unknown whether the surface diaphragm electromyogram (EMGdi) could be used to identify the deterioration of clinical symptoms and to predict the necessity of hospitalization in acute exacerbation of COPD (AECOPD) patients. Methods: COPD patients visiting the outpatient department due to acute exacerbation were enrolled in this study. All patients who were subjected to EMGdi and classical parameters such as spirometry parameters, arterial blood gas analysis, COPD assessment test (CAT) score, and the modified early warning score (MEWS) in outpatient department, would be treated effectively in the outpatient or inpatient settings according to the Global Initiative for Chronic Obstructive Lung Disease guideline. When the acute exacerbation of the patients was managed, all the examination above would be repeated. Results: We compared the relationships of admission-to-discharge changes (Δ) in the normalized value of the EMGdi, including the change of the percentage of maximal EMGdi (ΔEMGdi%max) and the change of the ratio of minute ventilation to the percentage of maximal EMGdi (ΔVE/EMGdi%max) with the changes of classical parameters. There was a significant positive association between ΔEMGdi%max and ΔCAT, ΔPaCO, and ΔpH. The change (Δ) of EMGdi%max was negatively correlated with ΔPaO/FiOin the course of the treatment of AECOPD. Compared with the classical parameters including forced expiratory volume in 1 s, MEWS, PaO/FiO, the EMGdi%max (odds ratio 1.143, 95% confidence interval 1.004-1.300) has a higher sensitivity when detecting the early exacerbation and enables to predict the admission of hospital in the whole cohort. Conclusions The changes of surface EMGdi parameters had a direct correlation with classical measures in the whole cohort of AECOPD. The measurement of NRD by surface EMGdi represents a practical physiological biomarker, which may be helpful in detecting patients who should be hospitalized timely.
Diaphragm ; physiopathology ; Electromyography ; methods ; Forced Expiratory Volume ; physiology ; Hospitalization ; Humans ; Pulmonary Disease, Chronic Obstructive ; metabolism ; physiopathology ; Spirometry ; Vital Capacity ; physiology