Objective To systematically review and synthesize the psychological experience of kinesiophobia in patients with cardiac rehabilitation.Methods PubMed,Web of science,Journals@Ovid,Embase,CINAHL,PsycINFO,Cochrane Library,CNKI,SinoMed,WanFang Database,Vip Database,American Heart Association,European Society of Cardiology and American Association of Cardiovascular and Pulmonary Rehabilitation were searched to collect qualitative research on the psychological experience of cardiac rehabilitation patients with kinesiophobia.The retrieval time was from the establishment of the databases to Jun 2023.The literature was evaluated using the Australian JBI Quality Evaluation Criteria for Qualitative Research in Evidence-based Health Care Centres(2016),and the results were consolidated using an aggregative integration approach.Results A total of 45 results were extracted from 14 studies.Similar results were summarized into 10 groups,and 3 integrated results were synthesized as followed.Kinesiophobia was influenced by many factors;kinesiophobia affects the life experience of patients;strategies to reduce the level of kinesiophobia.Conclusion Nurses should pay more attention to psychological experience of kinesiophobia,and take the corresponding intervention measures to help patients overcome the psychological barriers of kinesiophobia,perfect personalized exercise programs,and improve the level of physical activity.

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective:To compare the clinical efficacy of different guidelines recommending the dosage of paricalcitol in the treatment of maintenance hemodialysis (MHD) with secondary hyperparathyroidism (SHPT).Methods:The clinical data of 150 patients with MHD combined with SHPT in the First Affiliated Hospital of Xinjiang Medical University from January 2021 to January 2022 were retrospectively analyzed. Among them, 75 patients were treated with the recommended dose of paricalcitol according to European guidelines (European guidelines group), and the starting dose was blood intact parathyroid hormone (iPTH) (ng/L)/80 μg; 75 patients were treated with the recommended dose of paricalcitol according to American guidelines (American guidelines group), and the starting dose was 0.04 μg/kg. The blood calcium, blood phosphorus, creatinine and urea nitrogen before treatment and 1, 3 months after treatment were measured, and the calcium phosphorus product was calculated. The serum alkaline phosphatase (ALP) and iPTH before treatment and 3, 6 months after treatment were measured. The adverse reactions (nausea, vomiting and gastrointestinal discomfort) during the treatment were recorded.Results:There were no statistical difference in the indexes before treatment between two groups ( P>0.05). The blood calcium, blood phosphorus and calcium phosphorus product 1 and 3 months after treatment in American guidelines group were significantly lower than those in European guidelines group, 1 month after treatment: (2.40 ± 0.15) mmol/L vs. (2.53 ± 0.23) mmol/L, (1.70 ± 0.15) mmol/L vs. (2.00 ± 0.30) mmol/L and (4.08 ± 0.42) mmol 2/L 2 vs. (5.06 ± 0.47) mmol 2/L 2, 3 months after treatment: (2.37 ± 0.14) mmol/L vs. (2.50 ± 0.25) mmol/L, (1.65 ± 0.13) mmol/L vs. (1.98 ± 0.27) mmol/L and (3.91 ± 0.40) mmol 2/L 2 vs. (4.95 ± 0.45) mmol 2/L 2, and there were statistical differences ( P<0.01). There were no statistical difference in creatinine and urea nitrogen 1 and 3 months after treatment between two groups ( P>0.05). There was no statistical difference in ALP 3 and 6 months after treatment between two groups ( P>0.05); the iPTH 3 and 6 months after treatment in American guidelines group was significantly lower than that in European guidelines group: (348.20 ± 21.50) ng/L vs. (451.65 ± 28.48) ng/L and (252.64 ± 21.64) ng/L vs. (340.48 ± 19.85) ng/L, and there were statistical differences ( P<0.01). There was no statistical difference in incidence of adverse reactions between two groups ( P>0.05). Conclusions:For patients with MHD combined with SHPT, the recommended dosage of paricalcitol in the American guidelines can significantly improve calcium and phosphorus levels and parathyroid function, without affecting renal function or increasing the incidence of adverse reactions.

Objective:To observe the effects of three different blood purification modes on nutritional status and insulin resistance in patients with end-stage diabetes nephropathy (DN).Methods:From January 2019 to January 2022, 150 patients with end-stage DN admitted to the First Affiliated Hospital of Xinjiang Medical University were retrospectively selected. All patients were divided into three groups according the treatment methods, the group A was treated with high-throughput hemodialysis, the group B was treated with sequential hemodialysis, the group C was treated with hemodialysis combined with hemoperfusion, with 50 patients in each group. After 3 months of treatment with different blood purification modes, the nutritional status, insulin resistance, inflammatory factors and adverse reactions of the patients in the three groups were evaluated.Results:After treatment, the levels of serum prealbumin (PA) and albumin (ALB) in the group C were higher than those in the group A and group B: (328.19 ± 34.82) mg/L vs. (241.87 ± 23.75), (246.35 ± 24.06) mg/L; (36.82 ± 9.51) g/L vs. (30.07 ± 8.73), (29.54 ± 8.14) g/L, there were statistical differences ( P<0.05). After treatment, the levels of fasting insulin (FINS), fasting blood glucose (FBG) and homeostatic model assessment insulin resistance index (HOMA-IR) in the group C were lower than those in the group A and group B: (6.82 ± 1.46) mU/L vs. (8.79 ± 1.1), (8.34 ± 1.08) mU/L; (7.57 ± 1.13) mmol/L vs. (9.51 ± 1.25), (9.28 ± 1.21) mmol/L; 2.29 ± 0.75 vs. 4.11 ± 0.84, 3.81 ± 0.79, there were statistical differences ( P<0.05). After treatment, the levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) in the group C were lower than those in the group A and group B: (9.28 ± 2.96) μg/L vs. (16.34 ± 3.13), (17.52 ± 4.08) μg/L; (5.17 ± 1.1) mg/L vs. (7.81 ± 1.25), (7.36 ± 1.21)mg/L; (36.06 ± 4.7) ng/L vs. (42.07 ± 5.84), (43.23 ± 5.79) ng/L, there were statistical differences ( P<0.05). After treatment, the rate of adverse reactions in the group A, group B and group C was 20.00%(10/50), 16.00%(8/50), 4.00%(2/50), there was statistical difference ( χ2 = 6.31, P = 0.043). Conclusions:Compared with high-throughput hemodialysis and sequential hemodialysis, hemodialysis combined with hemoperfusion can effectively improve the nutritional status of patients, reduce their blood sugar level and insulin resistance, reduce their micro inflammatory state, and reduce adverse reactions.

Objective:To investigate the effect of continuous renal replacement therapy(CRRT)by series double tank on serum soluble transferrin receptor(sTfR),human macrophage chemotactic protein-1(MCP-1)level and survival quality in uremic patients with chronic renal failure.Methods:A total of 96 uremia patients with chronic renal failure underwent hemodialysis in the First Affiliated Hospital of Xinjiang Medical University from April 2022 to April 2023 were selected,and they were randomly divided into single tank group(single tank of CRRT continuous blood purification)and series double tank group(series double tank of CRRT continuous blood purification),with 48 patients in each group.The serum sTfR and MCP-1 levels of patients in two groups were measured before treatment,and 2 months,half a year and 1 year after treatment,and the relieved degree of skin pruritus after treatment was judged.The white blood cell(WBC)levels and the scores of acute physiological and chronic health evaluation II(APACHEII)scale of two groups were recorded before and 72h after treatment,respectively.The Chinese version of the European Five Dimension Scale(CEQ-5D-3L)was used to assess the quality of life of patients before and after treatment.Results:There was no significant difference in serum sTfR levels between the two groups(P>0.05).At 2 months,half a year and 1 year after treatment,the serum sTfR levels in the series double tank group were respectively lower than those of the single tank group,with statistically significant differences(t=5.089,18.410,41.306,P<0.05).There was no significant difference in serum MCP-1 level before treatment between two groups(P>0.05).At 2 months,half a year and 1 year after treatment,the MCP-1 levels in the series double tank group were respectively lower those in the single tank group,with statistically significant differences(t=8.554,8.019,10.744,P<0.05).The degree of existing skin pruritus of two groups were improved after treatment,however,the relieved degree of the single tank group was significantly lower than that of the series double tank group,with statistically significant difference(x2=8.540,P<0.05).The differences of WBC and APACHEII scores before treatment between the two groups were not statistically significant(P>0.05).At 72h after treatment,the WBC and APACHEII scores of two groups decreased,and the improvement degrees of them of the series double tank group were better than those of the single tank group,with statistically significant differences(t=5.549,14.781,P<0.05).The difference of serum CEQ-5D-3L scores before treatment between the two groups was not significant(P>0.05).At each time point of 2 months,half a year and 1 year after treatment,the total scores of the health description system standard of the series double tank group were significantly lower than those of the single tank group,and the visual analogue scale(VAS)scores of the series double tank group were significantly higher than those of the single tank group(t the total score of t he health description system standard=4.744,5.103,9.418,t VAS score=3.375,2.866,3.126,P<0.05),respectively.Conclusion:The series double tank CRRT can effectively reduce the serum sTfR and MCP-1 levels in uremia patients with chronic renal failure,and relieve the skin pruritus,and improve the survival quality,and effectively reduce the WBC level,and improve APACHEII score and blood routine.

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 10⁵ and 10³ respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.
Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza A Virus, H3N2 Subtype/genetics* ; Mice, Inbred BALB C ; Mice ; Influenza Vaccines/genetics* ; Hemagglutinin Glycoproteins, Influenza Virus/genetics* ; Humans ; Antibodies, Viral/blood* ; Antigens, Viral/genetics* ; Immunoglobulin G/immunology* ; Female ; Orthomyxoviridae Infections/prevention & control* ; HEK293 Cells

Objective:To assess the effectiveness of a model created using clinical features and preoperative chest CT imaging features in predicting the chronic obstructive pulmonary disease (COPD) among patients diagnosed with lung cancer.Methods:A retrospective analysis was conducted on clinical (age, gender, smoking history, smoking index, etc.) and imaging (lesion size, location, density, lobulation sign, etc.) data from 444 lung cancer patients confirmed by pathology at the Second Affiliated Hospital of Naval Medical University between June 2014 and March 2021. These patients were randomly divided into a training set (310 patients) and an internal test set (134 patients) using a 7∶3 ratio through the random function in Python. Based on the results of pulmonary function tests, the patients were further categorized into two groups: lung cancer combined with COPD and lung cancer non-COPD. Initially, univariate analysis was performed to identify statistically significant differences in clinical characteristics between the two groups. The variables showing significance were then included in the logistic regression analysis to determine the independent factors predicting lung cancer combined with COPD, thereby constructing the clinical model. The image features underwent a filtering process using the minimum absolute value convergence and selection operator. The reliability of these features was assessed through leave-P groups-out cross-validation repeated five times. Subsequently, a radiological model was developed. Finally, a combined model was established by combining the radiological signature with the clinical features. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were plotted to evaluate the predictive capability and clinical applicability of the model. The area under the curve (AUC) for each model in predicting lung cancer combined with COPD was compared using the DeLong test.Results:In the training set, there were 182 cases in the lung cancer combined with COPD group and 128 cases in the lung cancer non-COPD group. The combined model demonstrated an AUC of 0.89 for predicting lung cancer combined with COPD, while the clinical model achieved an AUC of 0.82 and the radiological model had an AUC of 0.85. In the test set, there were 78 cases in the lung cancer combined with COPD group and 56 cases in the lung cancer non-COPD group. The combined model yielded an AUC of 0.85 for predicting lung cancer combined with COPD, compared to 0.77 for the clinical model and 0.83 for the radiological model. The difference in AUC between the radiological model and the clinical model was not statistically significant ( Z=1.40, P=0.163). However, there were statistically significant differences in the AUC values between the combined model and the clinical model ( Z=-4.01, P=0.010), as well as between the combined model and the radiological model ( Z=-2.57, P<0.001). DCA showed the maximum net benifit of the combined model. Conclusion:The developed synthetic diagnostic combined model, incorporating both radiological signature and clinical features, demonstrates the ability to predict COPD in patients with lung cancer.

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1^mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.
Animals ; Swine ; African Swine Fever Virus/metabolism* ; Membrane Proteins/metabolism* ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction/genetics*