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OBJECTIVE: To investigate the distribution and activation of B-cell subpopulations in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) and to analyze their correlation with disease remission. METHODS: Peripheral blood samples were collected from 23 adult healthy controls and 58 RA patients, 31 of whom were treated with JAKis and assessed during a 24-month follow-up. The number of peripheral B-cell subpopulations (including naive B cells, nonswitched memory B (NSMB) cells, switched memory B cells, and double-negative B cells), their activation, and phosphorylation of SYK and AKT upon B-cell receptor (BCR) stimulation in each population were analyzed by flow cytometry. RESULTS: Compared with that in healthy controls, the frequency of NSMB cells was significantly lower in new-onset untreated RA patients. However, expression of CD40, CD80, CD95, CD21low and pAKT significantly increased in these NSMB cells. Additionally, the number of NSMB cells correlated negatively with DAS28-ESR and IgG and IgA levels in these patients; expression of CD80, CD95 and CD21low on NSMB cells correlated positively with DAS28-ESR and IgG and IgA levels. After treatment with JAKis, the serum IgG concentration significantly decreased in RA patients in remission, but CD40, CD95 and pAKT levels in NSMB cells significantly decreased. CONCLUSION: RA patients present different B-cell subpopulations, in which the frequency of NSMB cells is negatively associated with disease activity. However, treatment with JAKis can inhibit activation of NSMB cells, restore the balance of kinase phosphorylation, and facilitate disease remission in RA patients.

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As an important commercial form of vanadium, vanadium pentoxide (V2O5) is widely used in various modern industries, and its environmental impacts and ecotoxicity have been extensively studied. In this research, the ecotoxicity of V2O5 to earthworms (Eisenia fetida) in soil was tested by exposure to V2O5 at a series of doses, and biochemical response indices, such as the superoxide dismutase (SOD) and catalase (CAT) enzyme activity and malondialdehyde (MDA) content, were analysed to determine the mechanism by which antioxidant enzymes respond to V2O5 exposure. The bioaccumulation factor (BAF) of vanadium pentoxide in the earthworms and soil was also measured to explore the bioaccumulation process of V2O5 in the test period. The results showed that the acute and subchronic lethal toxicity values of V2O5 towards E. fetida were 21.96 mg/kg (LC50, 14 days) and 6.28 mg/kg (LC10, 28 days), respectively. For the antioxidant enzymes, SOD and CAT were synchronously induced or inhibited within the time period, and the enzyme activity had a dose-effect relationship with the V2O5 concentration. MDA analysis indicated that lipid peroxidation in earthworms mainly occurred at the early stage and was eliminated slowly in the later stage during the test time. In addition, the BAFs were much less than 1, which indicated that V2O5 did not easily accumulate in earthworms, and the BAF was positively correlated with the exposure time and negatively linearly correlated with the V2O5 concentration in the soil. These results indicated that the bioconcentration and metabolic mechanism of V2O5 in earthworms differed with the different exposure concentrations, and bioaccumulation became balanced after 14-28 days in earthworms exposed to a relatively lower dose of V2O5. The analysis of the integrated biomarker response (IBR) index indicated that the trends of IBR values were positively related to the changing V2O5 concentration, and the IBR index could reflect the organism's sensitivity to the external stimulus of V2O5. The toxicity of V2O5 is mainly caused by V5+, which is also an important factor in formulating guidelines regarding vanadium levels in soil, and the test earthworm species (Eisenia fetida) is a sensitive biological indicator for risk assessments of vanadium oxidation in the soil.

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Pentachlorophenol (PCP) has been widely used as an insecticide for killing oncomelania (the intermediate host of schistosome) in China and leads to severe environmental contamination. Poyang Lake, as the largest freshwater lake and bird habitat in China, was once a schistosomiasis epidemic area. In this study, the concentrations of PCP in water and aquatic products from Poyang Lake were determined and analyzed, and then the human health ambient water quality criteria (AWQC) was derived based on native parameters of Poyang Lake basin. Finally, a comprehensive analysis of the health risks of drinking water and different types of aquatic products consumption was carried out. The results showed that PCP concentrations were ranged from 0.01 to 0.43 µg/L in surface water and 3.90 to 85.95 µg/kg in aquatic products. Due to the carcinogenicity of PCP, the human health AWQC for PCP are 0.02 µg/L for consumption of water and organisms and 0.03 µg/L for consumption of organisms only. Deterministic and probabilistic risk analysis indicated that the non-carcinogenic risk of PCP were acceptable in Poyang Lake, while the carcinogenic risk cannot be ignored. The health risks of PCP caused by aquatic products consumption were higher than that by drinking water. The percentages of acceptable risk for the population in Poyang Lake Basin were 99.95% at acceptable level of 10-4. Based on the sensitivity analysis, the impact of PCP concentrations on health risk values ranged from 53 to 82%. The study provided valuable information for regional water quality criteria development and water quality assessment.

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Acute lung injury (ALI) is a serious complication in clinical settings. This study aimed to elucidate the immune molecular mechanisms underlying ALI by bioinformatics analysis. Human ALI and six ALI mouse model datasets were collected. Immune cell infiltration between the ALI samples and non-ALI controls was estimated using the ssGSEA algorithm. Least absolute shrinkage and selection operator (LASSO) regression analysis and Wilcoxon test were performed to obtain the significantly different immune cell infiltration types. Immune feature genes were screened by differential analysis and the weighted correlation network analysis (WGCNA) algorithm. Functional enrichment was then performed and candidate hub biomarkers were identified. Finally, the receiver operator characteristic curve (ROC) analysis was used to predict their diagnostic performances. Three significantly different immune cell types (B cells, CD4 T cells, and CD8 T cells) were identified between the ALI samples and controls. A total of 13 immune feature genes were obtained by WGCNA and differential analysis and found to be significantly associated with immune functions and lung diseases. Four hub genes, including CD180, CD4, CD74, and MCL1 were identified using cytoHubba and were shown to have good specificity and sensitivity for the diagnosis of ALI. Correlation analysis suggested that CD4 was positively associated with T cells, whereas MCL1 was negatively correlated with B and T cells. We found that CD180, CD4, CD74, and MCL1 can serve as specific immune biomarkers for ALI. MCL1-B cell, MCL1-T cell, and CD4-T cell axes may be involved in the progression of ALI.

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Endolymphatic hydrops is a characteristic pathological manifestation of Meniere's disease (MD) that has been previously associated with autoimmunity. Interest in the circulating immune complex (CIC) has increased due to its reported role in the occurrence of MD. The present study aimed to investigate the potential value of serum CIC concentration in the diagnosis of MD and the therapeutic potential of cyclophosphamide (CTX) for the treatment of MD. In the present study, guinea pigs were immunized with isologous crude inner ear antigens to establish an autoimmune MD model. Pure tone audiometry, Vestibular-evoked myogenic potential test, electrocochleography test and auditory brainstem response was applied in this study for assessing the severity of MD in guinea pigs. ELISA was applied to measure CIC, tumor necrosis factor α (TNF-α) and heat shock protein 70 (HSP70) expression levels in the serum samples of different groups of patients. Western blotting was applied to detect the protein expression of HSP70 in inner ear tissues in guinea pigs. Hematoxylin and eosin staining was applied to visualize the spiral ganglions in spiral ganglions models. CIC expression in the inner ear was detected by immunohistochemistry. In vivo experiments were performed to confirm the therapeutic effects of CTX in MD. Serum concentrations of CIC, TNF-α and HSP70 were found to be significantly higher in patients with MD, which were also associated with increases in hearing classification and the severity of endolymphatic hydrops. Using a guinea pig MD model, ELISA results revealed significantly increased serum CIC, TNF-α and HSP70 concentrations compared with those in the control group. ABR results showed that the thresholds in the CTX group were notably decreased compared with that in the dexamethasone group, whereas CIC concentrations in the serum were reduced following dexamethasone and CTX treatments compared with those after saline treatment. In the inner ear tissues, the CIC concentration in CTX group was lower than that in the dexamethasone group. Similarly, reductions in HSP70 and TNF-α concentrations was also observed in a similar manner. Immunohistochemistry staining found notably lower CIC deposition in the inner ear tissues following CTX treatment than that in dexamethasone group. Taken together, higher CIC expression can be used as a biomarker for MD diagnosis. The efficacy of CTX in MD was found to be higher compared with that in dexamethasone, which may be associated with the effective inhibition of CIC, HSP70 and TNF-α generation.

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Phenol is widely used in the production of insulation and thermal insulation materials, adhesives, perfumes, coatings for food containers, paints, and pharmaceutical production, and is also widely detected in the aquatic environment. Long-term exposure to phenol can elicit adverse effects, such as skin burn, liver and central system damage. Here, phenol concentrations in the water and aquatic products of Poyang Lake were investigated. Human health risks from phenol to adults and adolescents were also assessed based on local population exposure parameters. The exposure concentration range of phenol in the studied water and aquatic products was not detected (ND)-556.26 ng·L-1 and 11.98-255.51 µg·kg-1, respectively. Human health risk based on drinking water in different areas ranged from 3.80×10-7-8.46×10-5. Higher human health risks from drinking water was detected in the southern area of Poyang Lake and at the confluence of the Yangtze River to the north. Health risks caused by different types of aquatic products ranges 2.65×10-5-1.47×10-4. In particular, human health risks from the consumption of yellow catfish and catfish are an order of magnitude higher than for other aquatic products. Probabilistic risk assessment was also conducted through Monte Carlo simulation to analyze the health risk to the population in the Poyang Lake Basin and assess its sensitivity of different exposure parameters. The 95th percentile health risk of drinking water and aquatic product consumption in the Poyang Lake Basin was calculated as being acceptable. Overall, the concentrations of phenol had the greatest impact on the calculated health risk values. This study provides valuable information for phenol risk management in the Poyang Lake basin.

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BACKGROUND: Glycogen storage disease (GSD) type Ib is an autosomal recessive disease caused by defects of glucose-6-phosphate transporter (G6PT), encoded by the SLC37A4 gene. To date, over 100 mutations have been revealed in the SLC37A4 gene. GSD-Ib patients manifest a metabolic phenotype of impaired blood glucose homeostasis and also carry the additional complications of neutropenia and myeloid dysfunction. METHODS: Here, we present two daughters with an initial diagnosis of gout in a Chinese consanguineous family. Whole-exome sequencing was performed to identify the mutations. The mechanism of leukocytopenia was investigated. RESULTS: Whole-exome sequencing analysis of the proband identified a novel homozygous p.P119L mutation in SLC37A4, leading to a diagnosis of GSD-Ib. We found that the potential pathogenic p.P119L mutation leads to an unusual phenotype characterized by gout at onset, and GSD-Ib arising from this variant also manifests multiple metabolic abnormalities, leukocytopenia, and anemia, but no hepatomegaly. The leukocytes from the proband showed increased mRNA levels of sXBP-1, BIP, and CHOP genes in the unfolded protein response pathway, and enhanced Bax mRNA and caspase-3 activity, which might contribute to leukocytopenia. CONCLUSION: Our findings broaden the variation spectrum of SLC37A4 and suggest no strict genotype-phenotype correlations in GSD-Ib patients.

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Perfluorooctane sulfonate (PFOS) is a synthetic substance with a great number of applications. However, it persists in the environment and is potentially toxic to organisms. Although China has been the main manufacturer and consumer for PFOS, the national pollution level and potential risk of this chemical are yet to be determined. This study aimed to provide an overview of PFOS contamination in surface and drinking water across China and to assess the potential ecological and health risks. Available monitoring data for PFOS in surface and drinking water were evaluated. PFOS was found to be ubiquitous in China, but the overall level of contamination was low compared with that in other countries. The southeast coastal area of China, with major PFOS-related companies, was characterized by relatively high PFOS exposure concentrations. The most sensitive effects was screened and applied to assess the ecological risk using the joint probability curve method. The probability of exceeding the growth and development toxicity for 5% of aquatic species was 0.65% in Chinese surface waters, while the highest probability of 0.90% was in Tai Lake in east China. Considering the average daily dose (ADD) for the Chinese population, the health risk posed by PFOS through drinking water ranged from 1.31 × 10-4 to 13.91. Besides the relatively high health risk existed in east China, most health risks in China were acceptable.

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BACKGROUND: One-lung ventilation (OLV) is becoming an essential component of thoracic anesthesia. The two principal devices used for OLV are a double-lumen tube (DLT) and a bronchial blocker (BB). We hypothesized that the use of a BB with the disconnection technique would improve the quality of lung collapse in video-assisted thoracoscopic surgery (VATS). METHODS: Seventy-five patients undergoing scheduled VATS were enrolled in this study and were randomly divided into two groups: a left-sided DLT group (Group D) and a BB with the disconnection technique group (Group B). OLV was initiated when the surgeon performed the skin incision. In Group D, the left channel of the DLT was opened to the air. In Group B, the lung was deflated via the disconnection technique, thus opening the breathing circuit to the air fifteen seconds after opening the pleura. The mean arterial pressure (MAP) and heart rate (HR) during induction; the quality of lung collapse 1 and 10 minutes after pleural opening; the time required for complete lung collapse; the correct placement of the device; and the number of patients suffering from a sore throat after surgery were recorded. RESULTS: Compared with the use of the DLT, the use of the BB with the disconnection technique was associated with a similar quality of lung collapse, a comparable required time for total lung collapse (P>0.05, respectively), a lower incidence of sore throat both when leaving the PACU and 24 hours after surgery (34.2% vs. 13.5%, 15.8% vs. 5.4%, P<0.05, respectively) and fewer hemodynamic fluctuations after intubation both one and ten minutes after pleural opening. CONCLUSIONS: The use of a BB with the disconnection technique in VATS offers an effective method for improving the quality of lung collapse and reducing postoperative sore throat.

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The popularity of e-commerce has impacted traditional retail business. Farmer cooperatives running green agri-food pick-your-own (PYO) farms are facing the choice of whether or not to adopt online channels. PYO operation refers to consumers picking and purchasing the agri-food growing on a farm, and due to it being environmentally-friendly, healthy, and popular, it has been widely adopted by many farm cooperatives. This paper aims to discuss the practicality of introducing online channels to already established PYO farms in the green agri-food supply chain (GASC), who can personally take charge of the online channel or transfer it to one online retailer. Firstly, we constructed the demand functions of green agri-food by putting consumer utility, the freshness of agri-food, and transportation cost into consideration. Secondly, five decision models are built to characterize five operation modes, namely pure PYO mode, self-operated dual-channel mode, decentralized dual-channel mode, centralized dual-channel mode, and contractual cooperation mode. Furthermore, by taking price, demand, and profit with different modes into consideration, we are able to explore the introduction of online channels and green brand construction. Finally, numerical analysis is performed. We found that: (1) introducing an online channel is preferable strategy since the profit of the farmer cooperative in pure PYO mode is always less than the profit of a farmer cooperative in non-self-operated dual-channel modes; (2) the decision of self-operating an online channel is related to the fixed cost of creating a new online channel and the green food brand effect of online channel, and it is the optimal mode in some cases, while the contractual cooperation mode is the optimal mode in the remaining cases; and (3) the green food brand effect of online channels is does not necessarily improve with scale, and the initial freshness has a positive relationship to the profit, demand, and price of farmer cooperatives and online retailers.

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Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor protein and highly expressed in myeloid cells. Our previous study demonstrates a critical protective effect of CARD9 in the development of colitis-associated colon cancer. Nevertheless, the effect of CARD9 in lung cancer remains unclear. Here, using a mouse Lewis lung cancer model, we found the tumor burden of CARD9-/- mice was much heavier than that in wild-type (WT) mice. More myeloid-derived suppressor cells (MDSCs) were accumulated and less cytotoxicity T lymphocyte was found in tumor tissues of CARD9-/- mice, compared to WT mice. Depleting MDSCs using anti-Gr1 antibody can significantly decrease tumor burden in CARD9-/- mice. Furthermore, the noncanonical nuclear factor-kappaB (NF-κB) pathway was activated in CARD9-/- mice-derived MDSCs. Deficiency of CARD9 enhanced expression of indoleamine 2,3-dioxygenase (IDO) in MDSCs via noncanonical NF-κB pathway. Moreover, correlations between CARD9 expressions and MDSCs relative genes (IDO, iNOS-2 and arginase 1 [ARG-1]) were further confirmed in tumor tissues from lung cancer patients. Taken together, we showed a CARD9-NF-κB-IDO pathway in MDSCs which can inhibit the suppressive function of MDSCs and prevent lung cancer development.

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OBJECTIVE: To investigate the social support level and its influencial factors in patients with systemic lupus erythematosus (SLE), and to develop the management strategies for chronic disease.
 Methods: Patients with SLE were investigated by Social Support Rating Scale (SSRS), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), 36-Item Short-Form Health Survey (SF-36) and Visual Analogue Scale (VAS) of fatigue. The demographic and clinical data of SLE patients were recorded. SLE disease activity and damage severity were assessed by SLE Disease Activity Index (SLEDAI) and SLE Damage Index (SDI), respectively. Influencial factors for social support were analyzed.
 Results: A total of 246 patients were included. Social support scores for these patients were 40.76±7.93 and the scores showed no significant difference with the national norm (P>0.05). Patients who were younger than 18, single, unemployed or damaged by disease showed lower level of social support (P<0.05). Compared with the high social support group, patients in the low social support group experienced more severe depression or anxiety, and scored lower on mental component summary scale (vitality, social functioning, emotional role and mental health perception) and physical role of SF-36 (P<0.05).
 Conclusion: Social support levels for patients with SLE are closely related to the quality of life, and influenced by age, marital status, professional condition, and disease damage. Health education for patients and their families should be strengthened in chronic disease management to enhance social support and finally, improve their quality of life.

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RATIONALE: Relapsing polychondritis (RP) is a rare autoimmune-related disease and may be associated with other autoimmune diseases. PATIENT CONCERNS: Here we reported a case of RP patients with mixed-type AIHA. The patient was diagnosed with RP in March 2008 which was treated and the patient was in stable condition. Laboratory data revealed progressive decrease in hemoglobin during her hospitalization due to pulmonary infection in 2016. Positive Coombs' test and moderate titer of anti-cold agglutinin was detected. DIAGNOSIS: Mixed-type AIHA was diagnosed as a comorbidity in this case given the circumstance that her RP was stable and low-dose oral corticosteroids was enough to maintain remission. INTERVENTIONS: The patient was treated with intravenous immunoglobulin and steroids. OUTCOMES: The patient's body temperature dropped and hemoglobin levels rose in 2 weeks. LESSONS: Reports of RP patients with autoimmune hemolytic anemia (AIHA) are extremely rare and cases with the mixed-type AIHA has not been reported. Here we describe a case of RP with mixed-type AIHA which was considered as a comorbidity rather than a complication.

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Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors, including colorectal cancer (CRC). The crosstalk between carcinoma- associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment promotes tumor development and confers chemoresistance. In this study, we further investigated the underlying tumor-promoting roles of CAFs and the molecular mediators involved in these processes. Methods: The AOM/DSS-induced colitis-associated cancer (CAC) mouse model was established, and RNA sequencing was performed. Small interfering RNA (siRNA) sequences were used to knock down H19. Cell apoptosis was measured by flow cytometry. SW480 cells with H19 stably knocked down were used to establish a xenograft model. The indicated protein levels in xenograft tumor tissues were confirmed by immunohistochemistry assay, and cell apoptosis was analyzed by TUNEL apoptosis assay. RNA-FISH and immunofluorescence assays were performed to assess the expression of H19 in tumor stroma and cancer nests. The AldeRed ALDH detection assay was performed to detect intracellular aldehyde dehydrogenase (ALDH) enzyme activity. Isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking and Western blotting. Results: H19 was highly expressed in the tumor tissues of CAC mice compared with the expression in normal colon tissues. The up-regulation of H19 was also confirmed in CRC patient samples at different tumor node metastasis (TNM) stages. Moreover, H19 was associated with the stemness of colorectal cancer stem cells (CSCs) in CRC specimens. H19 promoted the stemness of CSCs and increased the frequency of tumor-initiating cells. RNA-FISH showed higher expression of H19 in tumor stroma than in cancer nests. Of note, H19 was enriched in CAF-derived conditioned medium and exosomes, which in turn promoted the stemness of CSCs and the chemoresistance of CRC cells in vitro and in vivo. Furthermore, H19 activated the ß-catenin pathway via acting as a competing endogenous RNA sponge for miR-141 in CRC, while miR-141 significantly inhibited the stemness of CRC cells. Conclusion: CAFs promote the stemness and chemoresistance of CRC by transferring exosomal H19. H19 activated the ß-catenin pathway via acting as a competing endogenous RNA sponge for miR-141, while miR-141 inhibited the stemness of CRC cells. Our findings indicate that H19 expressed by CAFs of the colorectal tumor stroma contributes to tumor development and chemoresistance.

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It is known that the quality of life (QOL) and psychological status of patients with systemic lupus erythematosus (SLE) are severely impaired. However, a few reports have assessed the QOL and psychological status in relatives of these patients. This study aimed to assess the QOL and psychological status in relatives of patients with SLE and their impact on patients. A total of 104 patient-relative dyads were evaluated using a 36-Item Short-Form Survey (SF-36), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Social Support Rating Scale (SSRS). Relatives of patients with SLE exhibited an impaired QOL compared with the general population (69.59 ± 22.78 vs 78.18 ± 15.88, P < 0.001) and suffered from depression (5.8 ± 5.4) and anxiety (5.8 ± 6.0). GAD-7 of relatives was positively correlated with GAD-7 of patients (r = 0.210, P < 0.05). Patients reported a lower global SF-36 score when their relatives had lower global SF-36 scores (50.13 ± 19.18 vs 58.44 ± 19.67, P < 0.05) and significantly higher SSRS when their relatives had lower PHQ-9 (41.9 ± 8.7 vs 36.3 ± 6.2, P < 0.01) or GAD-7 scores (42.8 ± 7.4 vs 36.7 ± 6.6, P < 0.01). The QOL and psychological status in relatives of patients with SLE were adversely impaired. Associations exist between the QOL and psychological status of relatives and patients with SLE. Therefore, both patients and their relatives should be taken into account when making management decisions.

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Our previous studies showed that low frequency magnetic fields (LF-MF) suppressed tumor growth and influenced the function of immune system. Nevertheless the mechanisms behind the effect of LF-MF still remain to be elucidated. In this study, Tumor- bearing mice subcutaneously inoculated with Lewis lung cancer cells were exposed to a LF-MF (0.4T, 7.5 Hz) for 35 days and Survival rate, tumor growth and the tumor markers were measured. Results showed that tumor growth was obviously inhibited with a prolonged survival of tumor- bearing mice by LF-MF exposure. In vitro experiments, LF-MF was found to induce cell growth arrest, cell senescence and inhibit iron metabolism of lung cancer cells. Moreover, LF-MF stabilized p53 protein via inhibiting cell iron metabolism and the stabilized p53 protein enhanced miR-34a transcription. Furthermore, increased expression of miR-34a induced cell proliferation inhibition, cell cycle arrest and cell senescence of lung cancer cells by targeting E2F1/E2F3. We also detected the relevant indicator in tumor tissue such as the iron content, the level of miR-34a and related protein, corresponding results were obtained. Taken together, these observations imply that LF-MF suppressed lung cancer via inhibiting cell iron metabolism, stabilizing p53 protein and activation P53- miR-34a-E2F1/E2F3 pathway.

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