OBJECTIVE To investigate the effects of calcitriol on sepsis-induced immunosuppression and its potential mechanism. METHODS A sepsis-induced immunosuppression mice model was established using cecal ligation and puncture （CLP）. The 7-day survival rate， serum levels of tumor necrosis factor- α （TNF- α）， interleukin-6 （IL-6）， and IL-1β were determined in sham operation group， CLP group and calcitriol group （1 μg/kg）； the morphological changes of lung tissue in mice were observed. Lipopolysaccharide （LPS） tolerance macrophage models （representing sepsis-induced immunosuppression） were established using mice macrophage cell line RAW264.7 cells. The levels of TNF-α and IL-6 in cell supernatants as well as mRNA expressions of IL-1β， nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， IL-18 and caspase-1 were assessed in culture medium group， LPS group， LPS tolerance group， and calcitriol （5 μmol/L） group. The following parameters were measured： propidium iodide （PI）-positive cell ratio， caspase-1 activity， lactate dehydrogenase （LDH） release， and Ca2+ levels. RESULTS Compared with CLP group， 7-day survival rate and serum levels of TNF-α， IL-6 and IL-1β were increased significantly in calcitriol group （P＜0.05）. Additionally， pulmonary tissue damage was markedly attenuated in calcitriol group. Compared with LPS tolerance group， the levels of TNF-α and IL-6 in cell supernatants， mRNA expressions of IL- 1β， NLRP3， IL-18 and caspase-1， PI-positive cell ratio， caspase-1 activity， LDH release， and Ca2+ levels were all increased significantly in calcitriol group （P＜0.05）. CONCLUSIONS Calcitriol can reverse sepsis-induced immunosuppression， and the mechanism of action may be E-mail：yarfwy@163.com achieved by the binding of calcitriol to vitamin D receptor，which promotes the release of Ca2+ from the endoplasmic reticulum， thereby driving the NLRP3/caspase-1-mediated pyroptosis pathway.

Objective To explore the influencing factors of liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease(MAFLD)complicated with chronic hepatitis B(CHB),and to find clinically convenient predictive parameters for assessing liver fibrosis risk.Methods A retrospective analysis was conducted on 221 cases of MAFLD with CHB diagnosed and treated at the Second Hospital of Lanzhou University between January 2015 and August 2022.Patients were divided into low-risk(FIB-4<1.30,n=84),medium-risk(1.30≤FIB-4≤2.67,n=94)and high-risk(FIB-4>2.67,n=43)liver fibrosis groups based on the Fibrosis-4(FIB-4)index.General clinical data,laboratory indicators and composite indicators were compared among the three groups.Variables were screened using forward stepwise regression,and binary logistic regression analysis was performed to determine independent predictors of liver fibrosis.A prediction model was constructed and evaluated using receiver operating characteristic(ROC)curve analysis.Results Age,AST and Triglyceride-glucose index(TyG)were independent risk factors for liver fibrosis in patients with MAFLD combined with CHB,while platelet-to-lymphocyte ratio(PLR)was an independent protective factor(all P<0.05).ROC curve analysis showed that the area under the curve(AUC)for age,AST,TyG,PLR,age-AST and AST-TyG in predicting liver fibrosis were 0.668,0.764,0.680,0.738,0.856 and 0.805,respectively.At the optimal cut-off values,the sensitivities were 86.0%,67.4%,93.0%,62.8%,86.0%and 79.1%,and the specificities were 43.3%,82.0%,51.7%,86.0%,71.3%and 70.2%.Conclusion Age,AST,TyG and PLR are influencing factors of liver fibrosis in MAFLD combined with CHB patients.The parameters established based on these factors may predict the risk of liver fibrosis,and combined prediction can improve predictive efficacy.

OBJECTIVE To explore the improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis （RA） rats by regulating neutrophil extracellular traps （NETs）. METHODS Establishment of rat RA model using bovine type Ⅱ collagen and Freund’s complete adjuvant. The model rats were randomly divided into model group and low-dose， middle-dose and high-dose groups （55， 110， 220 mg/kg） of petroleum ether extract of S. divaricata； the normal group without modeling was also established， with 10 rats in each group. Each group was given corresponding drugs or constant volume of 2% Tween-80 solution intragastrically， once a day， for consecutive 28 days. The toe swelling degree in rats was observed， and the arthritis index （AI） was scored. The serum levels of interleukin-1β （IL-1β）， IL-10， IL-17， tumor necrosis factor-α （TNF-α）， 25-hydroxyvitamin D3 [25（OH）D3]， myeloperoxidase （MPO）， neutrophil elastase （NE） and NETs in rats were detected. The histopathological changes in ankle joint were observed. The expression of citrullinated histone H3 （CitH3） in ankle joint as well as the expressions of cytochrome P450 24A1 （CYP24A1）， cytochrome P450 27B1 （CYP27B1），vitamin D receptor （VDR） and peptidyl arginine deiminase 4 疾病。E-mail：zhongyao626@126.com （PAD4） in synovium were all determined. RESULTS Compared with the model group， the toe swelling degree and AI score in the middle-dose and high-dose groups of petroleum ether extract of S. divaricata decreased significantly from day 14 to day 28 after administration （P＜0.05 or P＜0.01）. The serum levels of IL-1β， IL-17， TNF-α， MPO， NE and NETs decreased significantly， while the levels of IL-10 and 25（OH）D3 increased significantly （P＜0.05 or P＜0.01）. The widened ankle joint space and the improved structure were found； the expression of CitH3 in ankle joint， and the expressions of CYP24A1 and PAD4 in synovium were down-regulated significantly， while the expressions of CYP27B1 and VDR were up-regulated significantly in synovium （P＜0.05 or P＜0.01）. CONCLUSIONS The petroleum ether extract of S. divaricata may inhibit the production of NETs and improve the symptoms of RA by regulating the vitamin D system.

5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.

Objective: To make a postural transfer belt for patients with cervical spinal cord injury, to reduce and prevent the corresponding nursing problems with traditional methods of transfer Methods: 44 patients with cervical spinal cord injury admitted to the ward from January to June 2017 were selected as the control group by traditional methods of postural metastasis, and 48 patients with cervical spinal cord injury admitted to the ward from July to December 2017 were selected as the observation group by using self-made transfer belt. Results: Number of the skin injury caused by transfer in observation group was 0 cases, in control group was four cases, and there was significant difference (χ²=1.91, P=0.049). Falls occur due to metastasis: there were 0 cases in the observation group and five cases in the control group, there was significant difference (χ²=2.39, P=0.026). The number of caregivers in the observation group decreased on average (1.21±0.08), and the number of caregivers in the control group decreased on average (0.86±0.09). The differences between the two groups are statistically significant (t=2.905, P=0.005). The results of the investigation on the escorts in the observation group showed that 46 (95.8%) people believed that the transfer belt was convenient for patients. 47 people believed that the transfer belt was safer and more labor-saving to use, accounting for 97.9%, and 47 people believed that the transfer belt would continue to be used when they went home, who occupied 97.9%. Conclusion The self-made transfer belt is convenient for the caregivers to carry the patients with cervical spinal cord injury, which effectively prevents the occurrence of skin injury, falls and other nursing problems, and improves the quality and experience of the caregivers. This technology is worthwhile to spread.

OBJECTIVETo investigate the mechanisms underlying the ability ofheparin-treated dendritic cells (DCs) to promote Th0 to Th1 differentiation in chronic hepatitis B (CHB).

METHODSPeripheral blood mononuclear cells (PBMCs) were isolated from CHB patients and cultured in RPMI-1640 with recombinant GM-CSF and IL-4 with or without heparin to obtain DCs for study. The levels of Toll-like receptors (TLRs) on the DCs were measured using FACS and qPCR techniques.DC subsets with high expression of TLRs were selected for analysis of functional changes by treatment with the corresponding TLR-siRNA. The CD4+ T cell subpopulation was purified from peripheral blood by Dynal immunomagnetic beads, and then the production of IL-12 by DCs in the presence of poly(I:C) or R848 and ofIFN and IL-4 by Th cells co-cultured with DCs was evaluated by ELISA. The t-test was used for statistical analysis.

RESULTSTLR3 expression, and not expression of TLR 7 or TLR8,was significantly increased in heparin-treated DCs as compared to levels detected in the DCs without heparin treatment (t =2.849,P less than 0.05;t =3.027,P less than 0.05). The level of IL-12 produced by heparin-treated DCs stimulated with poly(I:C) was obviously higher than that produced by DCs without heparin treatment and stimulated with poly(I: C) (t =8.68,P less than 0.01) or with R848 (t =19.01,P less than 0.01). However, the IL-12 production by TLR3-siRNA transfected-DCs was significantly reduced (t =31.49, P less than 0.01).When Th cells from allogenic patients with CHB were co-cultured with the TLR3-siRNA transfectedDCs, the frequency ofCD4+ IFN+ cells was significantly reduced (1.64+/-0.57% vs.6.31+/-0.88%,P less than 0.01),as was the capability of Thl to generate IFNg (t =20.83,Pless than 0.01).

CONCLUSIONHeparin may have up-regulated the TLR3 expression level of DCs, and sequentially promoted Th0 to Th1 differentiation.

CD4-Positive T-Lymphocytes ; cytology ; Cell Differentiation ; Coculture Techniques ; Dendritic Cells ; cytology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Heparin ; pharmacology ; Hepatitis B, Chronic ; immunology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; pharmacology ; Monocytes ; cytology ; Recombinant Proteins ; pharmacology ; Toll-Like Receptor 3 ; metabolism

Objective To investigate the demand of health management of psychiatric patients primary caregivers after discharge, and to provide references for the health management of patients after discharge. Methods A self-designed questionnaire was used.One hundred and eighty two primary caregivers of patients to be discharged in psychiatric department were enrolled.Results 96.15% of caregivers had demands of health management for patients after discharge.In the content of management, the highest score was relapse prevention related knowledge (4.75 ±0.23), the lowest score was the vocational skills training (2.74 ±0.47).The highest demand of health management mode of patients after discharge from hospital was telephone follow-up, totally 158 caregivers (86.81%), followed by medical personnel on-site guidance, totally 139 caregivers (76.37%).In the management of frequency, most of the caregivers selected telephone and SMS follow-up once per half a month, or medical personnel on-site guidance once per two months;or designated medical expert consultants once per month. In the management period, 3 to 6 months after discharge was the mainly choice.Conclusions The main caregivers of patients after discharge from hospital has strong demand of health management.The hospital should establish reasonable health management service system according to the needs and wishes of patients, and carry out targeted content rich, diverse forms, a specific number of health management services, to improve the patient’ s family function, promote the recovery of social function of patients, to reduce the relapse rate and disabled rate.

Objective To explore the effect of oxymatrine o n the airway inflammation and the cytokine production in asthmatic mice. Methods Forty BALB/c mice were divided into four groups in cluding a control group (group A), an asthmatic model group (group B), a dexamet hasone treatment group (group C) and a oxymatrine treatment group (group D). Ast hma mouse models in group B, group C and group D were prepared by injecting oval bumin (OVA) into the abdominal cavity and inhalation of aerosol. Group C were in jected dexamethasone, and group D recceived oxymatrine on day 15 to 22 .The numb er of EOS and the concentration of IL-4 and IL-5 and IFN-? in th e mouse bronchoalveolar lavage fluids (BALF) were detected. Results Oxymatrine could significantly reduce the mumber of EOS and the concentration of IL-4 and IL-5, and increase the level of IFN-? in the BALF of asthmatic mice. Significant difference was fo und between group D and group A or B(P0.05). Conclusion Oxymatrine can remarkably reduce the mumber of i nflammation cells in the BALF, and influence the level of cytokines so as to imp rove airway inflammation in the patients with asthma.