ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 （TRPV1） and bitter taste receptor 14 （TAS2R14） in the lung tissue of the rat model of cold asthma. MethodSeventy SD rats were randomized into 7 groups： normal， model， Shegan Mahuangtang， pungent Chinese herbs， bitter Chinese herbs （6.43 g·kg^-1）， dexamethasone （0.5 g·kg^-1）， and Guilong Kechuanning （10 g·kg^-1）. The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin （OVA） and aluminium hydroxide in the limbs， combined with 2% OVA atomization and cold （2-4 ℃） stimulation. The rats were treated with corresponding drugs by gavage and atomization， and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation， airway inflammation and cell proliferation were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and Masson staining of the lung tissue. The levels of interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， thymic stromal lymphopoietin （TSLP）， and transforming growth factor-β₁ （TGF-β₁） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1， TAS2R14， phospholipase Cβ₂ （PLCβ₂）， B-cell lymphoma-2 （Bcl-2）， and α-smooth muscle actin （α-SMA） in the lung tissue was determined by Western blot. ResultCompared with the normal group， the model group showed decreased water intake， food intake， and body weight， increased airway inflammatory cell infiltration， goblet cell proliferation， tissue fibrosis and collagen deposition， elevated levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， upregulated expression of TRPV1， PLCβ₂， and α-SMA， and downregulated expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. Compared with model group， Shecgan Mahuangtang， pungent Chinese herbs， and bitter Chinese herbs increased the water intake， food intake， and body weight， reduced the inflammatory cell infiltration and goblet cell proliferation， alleviated tissue fibrosis and collagen deposition， lowered the levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， downregulated the expression of TRPV1， PLCβ₂， and α-SMA， and upregulated the expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation， downregulate the expression of TRPV1， PLCβ₂， and α-SMA， and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover， bitter Chinese herbs outperformed pungent Chinese herbs， and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14.

Objective:We genetically modified our non-replicating vaccinia virus NTV to improve its immunogenicity.Methods:We constructed NTV-modified strain NTV-ΔF1L-C7L by homologous recombination of vaccinia virus based on CRISPR-Cas9 technology by inserting the C7L gene while deleting the F1L gene. The recombinant virus NTV-ΔF1L-C7L was then immunized with 10 7 PFU in BALB/c mice, and the levels of humoral and cellular immunity induced by NTV-ΔF1L-C7L were detected by ELISA and ELISpot method, respectively, and the levels of neutralizing antibodies were determined by the phage-reduced neutralization assay. Results:The PCR and western- blot identification proved that the F1L gene of the constructed NTV-modified strain NTV-ΔF1L-C7L was missing, while the C7L gene was inserted back in the region, and the C7L gene could be expressed normally, indicating that the recombinant virus was constructed correctly. After immunization of mice with NTV-ΔF1L-C7L, ELISA result showed that the recombinant virus NTV-ΔF1L-C7L induced a higher level of IgG antibody than NTV; ELISpot result also showed that the recombinant virus was able to induce a higher level of IFN-γ; and the result of plaque reduction neutralization test showed that the recombinant virus was able to induce a higher level of IFN-γ antibody than that of NTV.Conclusions:We correctly constructed the NTV gene-modified strain NTV-ΔF1L-C7L, which induced stronger humoral and cellular immunity compared with NTV, and provided reference data for the research and development of replacement products for smallpox or monkeypox vaccines.

Background: and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

Objective:Through the study of the cell biological characteristics and virulence in mice in vivo of three non-replicating vaccinia virus modified strains to provide reference for the development of smallpox/monkeypox vaccine replacement products.Methods:Replicating vaccinia virus Tiantan strain VTT and non-replicating Tiantan Vaccinia Strain NTV were studied in BHK-21/CEF and its modified strains NTV-C7L, NTV-△F1L-C7L, NTV-K1L were amplified, purified, and identified by Western blotting. The virulence and diffusivity of each strain in cells were evaluated by immune-plaque assay. The replication dynamics curves were used to compare the replication differences between the strains, and the weight loss was observed by intranasal route in the mouse model to compare the virulence levels of the viruses.Results:In this study, Western blotting result proved that the amplified and purified vaccinia virus strains were correct. Immunophagocytosis and replication kinetics showed that the replication capacity of the three NTV modified strains in CEF was similar to that of NTV. The diffusion ability and replication ability between Vero cells were improved, but the replication multiple was less than 100 times. The replication level of MRC-5 was significantly enhanced compared with that of NTV, and the replication ratio of NTV-C7L was more than 20000 times. The virulence in mice showed that the body weight of the three NTV modified strains had no statistical significance compared with that of NTV.Conclusions:The three NTV modified strains recovered their replication ability in human MRC-5 cells, but their virulence in mice was similar to that of NTV, which provided the preliminary conditions for being candidate strains of smallpox/monkeypox vaccine replacement products.

Objective:To investigate the risk factors of moderate to severe cancer-related fatigue (CRF) in patients undergoing chemotherapy of prostate cancer, and to construct a nomogram model to predict the occurrence of CRF.Methods:Using the case data questionnaire, Brief Fatigue Inventory, Social Support Rating Scale and International Prostate Symptom Scores, 724 patients of prostate cancer treated by chemotherapy in Shanghai Tenth People′s Hospital from August 2016 to June 2021 were selected and were treated with 1∶1 ratio, and the indexes of the moderate and severe CRF group (216 cases) and the non-moderate and severe CRF group (216 cases) were compared. According to the ratio of 7∶3, the envelope method was used to divide into training set and validation set. The independent risk factors of moderate and severe CRF were explored by univariate analysis and multivariate Logistic regression analysis, and the risk prediction model was established and the nomogram model was constructed. The C-index and area under ROC curve were used to verify the prediction effect of the model.Results:Multivariate Logistic regression analysis showed that BMI ranged from 24.0 to 27.9 kg/m 2 ( OR=1.733), BMI≥28.0 kg/m 2 ( OR=3.126), neutropenia occurred during chemotherapy ( OR=1.747), chemotherapy course >6 months ( OR=1.893), moderate social support level ( OR=1.244), low social support level ( OR=2.434), mild urinary tract symptoms ( OR=1.264), moderate urinary tract symptoms ( OR=3.371) and severe urinary tract symptoms ( OR=5.297) were independent risk factors for moderate and severe CRF. The nomogram model constructed according to the above risk factors was internally verified by the training set and the validation set, and its C-index was 0.854 and 0.741 respectively. The area under ROC curve training set was 0.823, and the validation set was 0.733. Conclusions:The nomogram model can effectively predict the occurrence of moderate to severe CRF in patients with prostate cancer undergoing chemotherapy.

Objective:To explore the mediating role of social support between mindfulness and perceived pressure in young and middle-aged patients with inflammatory bowel disease (IBD) .Methods:From January to September 2021, the convenient sampling method was adopted to select 350 patients with inflammatory bowel disease who were treated in 5 ClassⅢ Grade A hospitals in Shanghai. The general information questionnaire, Mindful Attention Awareness Scale (MAAS) , Social Support Ratings Scale (SSRS) and Chinese Perceived Stress Scale (CPSS) were used for survey. Pearson correlation analysis was used to test the correlation between variables. AMOS 22.0 was used to establish the structural equation model, the maximum likelihood method was used to fit and modify the data and the Bootstrap method was used to test the mediation effect. A total of 350 questionnaires were distributed in this study and 324 valid questionnaires were recovered, with an effective recovery rate of 92.57%.Results:The total score of perceived stress in young and middle-aged IBD patients was (27.81±3.86) . Social support, mindfulness and perceived stress were negatively correlated ( r=-0.306, -0.220, P<0.01) . Social support played a partial mediating role between mindfulness and perceived stress, accounting for 55.13% of the total effect. Conclusions:The perceived stress level of young and middle-aged IBD patients is relatively high, which is not optimistic. Mindfulness affects perceived stress in young and middle-aged IBD patients through social support. Clinical workers need to pay attention to condition of mindfulness and social support of patients and take targeted psychological interventions to reduce their perceived stress.

Background/Aims: This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniforms were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B.vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Objective:To investigate the effect of slow intravenous infusion of low-dose mannitol on the hemodynamics of patients after cardiopulmonary bypass.Methods:Prospective, continuous inclusion of 62 patients after cardiac surgery under cardiopulmonary bypass. By random number method, they were divided into normal treatment group(group C) with 29 cases and mannitol treatment group(group M) with 33 cases. Group C was treated according to the postoperative routine treatment measures. On the basis of conventional treatment, group M received intravenous infusion of 20% mannitol injection 0.25 g/kg at 1、8、24 hours after operation, and the intravenous infusion time was 60 minutes each time. According to the hemodynamic changes during the two groups of treatment, the effect of slow intravenous infusion of low-dose mannitol on patients after cardiopulmonary bypass under cardiopulmonary bypass was analyzed.Results:In group M, CI and SVI were significantly increased after use of mannitol than before, with statistical significance( P<0.01). SVRI showed a downward trend, and the changes were statistically significant after use of mannitol( P<0.01). PAWP increased first and then decreased after operation, and the changes were statistically significant after mannitol use than before( P<0.05). RAP and MPAP had no significant changes after the first use of mannitol, but the changes after the latter two use mannitol were statistically significant than before( P<0.05). Repeated-measurement data analysis of variance was performed on the hemodynamic parameters of each group, and the results were all P<0.01. Conclusion:Postoperative slow intravenous infusion of low-dose mannitol optimizes hemodynamic status, increases stroke volume, reduces cardiac preload, improves systemic and pulmonary circulation resistance, and promotes recovery of postoperative cardiopulmonary function.

Objective:To study the cell morphological changes and related molecular mechanisms of non-replicating vaccinia virus NTV infection with human cells and to provide a scientific basis for the further optimization, transformation and application of NTV vectors.Methods:HeLa cells were infected with vaccinia virus Tiantan strain VTT and non-replicating vaccinia virus NTV, and the morphological changes of cells were observed. Then cells were harvested, and rRNA break levels were detected by electrophoresis and the molecular signals associated with apoptosis were detected by Western blotting, and the pathways and mechanisms of NTV-induced early apoptosis were preliminarily determined.Results:In this study, in terms of cell morphology, it was observed that cells infected with NTV were able to have cell rounding, wrinkles and other lesions at an earlier time compared with VTT. DAPI staining showed that NTV-infected nuclei exhibited high chromatin aggregation, marginalization, and disintegration over time. The rRNA fracture level test result indicate that rRNA has been broken and degraded after 16 hours of NTV infection. The Western blotting test result showed that the molecular signals of PARP, caspase-3 and caspase-9 that were stronger than in normal cells could be detected in NTV-infected HeLa cells, but there was no significant increase in caspase-8, while the result of VTT were the opposite of those in NTV.Conclusions:NTV can induce apoptosis in the early stage and provide a theoretical basis for the modification of vaccinia vectors.

Objective:To explore the depression of patients with systemic lupus erythematosus (SLE) during the coronavirus disease 2019 (COVID-19) pandemic.Methods:Patients with SLE and healthy subjects(control group) from August 16, 2020 to September 2, 2020 in Urumqi, Xinjiang were collected. The depression and sleep quality were assessed by Self rating Depression Scale (SDS) and Pittsburgh sleep quality index (PSQI). The nonparametric data were represented by median (quartile spacing), and the rank sum test was used to compare the continuous variables between the two groups. Pearson correlation test was used for continuous variables, and Spearman correlation test was used for rank variables or classified variables. Statistical product and service solutions.Results:The prevalence rate of depression in the SLE group (41.9%) was significantly higher than that in healthy control group (32.1%). The difference was statistically significant ( χ2= 10.312, P<0.01). The prevalence rate of poor sleep in the SLE group (31.8%) was significantly higher than that in healthy control group (21.6%). The difference was statistically significant( χ2=3.885, P=0.049). The total score of VAS ( OR=1.366, P<0.01) , PSQI( OR=1.198, P<0.01) were the risk factor of depression in patients with SLE. Conclusion:SLE patients have a higher prevalence of depression during pandemic quarantinee-period, pain and poor sleep quality are risk factors. We need to pay attention to the psychological status of SLE patients.