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Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.
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Objective:To evaluate the efficacy and safety of small incision surgery combined with multi-point skin fixation in the treatment of axillary osmidrosis.Methods:104 patients with axillary osmidrosis who were treated in the dermatology department of the Third Hospital of Changsha from January 2017 to December 2020 were retrospectively analyzed. They were divided into the observation group (56 cases) and the control group (48 cases). Both groups were treated with small incision pruning combined with porous drainage. On this basis, the observation group was treated with multi-point skin fixation gauze compression bandage, while the control group was treated with conventional gauze stacking compression bandage. The efficacy, satisfaction, postoperative wound healing time and complication rate of the two groups were compared.Results:The effective rate of the observation group and the control group were 96.43%(54/56) and 95.83%(46/48) respectively, with no significant difference ( P>0.05). Compared with preoperative, the Visual Analogue Scale (VAS) score of patients in the two groups was significantly lower after operation, and the difference was statistically significant (both P<0.05). The satisfaction of patients in the observation group was higher than that in the control group [(4.05±1.15)points vs (3.19±1.00)points], and the difference was statistically significant ( t=4.10, P<0.05). The wound healing time in the observation group was shorter than that in the control group, and the incidence of complications was lower than that in the control group, with statistically significant difference (all P<0.05). Conclusions:Small incision surgery combined with multi-point skin fixation for the treatment of axillary osmidrosis has good curative effect, short postoperative wound healing time and fewer complications, and improved patient satisfaction, which can be popularized in clinical application.
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Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.
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The endocrine disruptor chemicals (EDCs) are ubiquitous in the environment, and it has raised wide public concern because of the dangers of EDCs for living organisms and the environment. In order to comparatively study the effects of EDCs [17-α-ethinylestradiol (EE2), Bisphenol A (BPA) and Nonylphenol (NP)] on the expression of estrogen receptors (ERs: erα, erß1, and erß2) at mRNA and protein level, total 520 adult Tanichthys albonubes were exposed to E2, EE2, BPA and NP with three concentrations respectively: EE2 (1, 5, 25 ng/l), NP (10, 50, 250 µg/l), BPA (100, 500, 2,500 µg/l) for 28 days, E2 (2, 20, 200 ng/l) being as the positive control. After treatment, the brain, eye, gill, heart, liver, gut, kidney, muscle, testis, and ovary were collected, following by the real-time quantitative PCR (RT-qPCR) and western blot methods to detect the expression levels of erα, erß1, and erß2 in T.albonubes at mRNA and protein level. Our results showed that high expression of terα (t means T.albonubes), terß1, and terß2 were detected in liver, while terß1 and terß2 mainly expressed in the liver, intestine, kidney, muscle and testis. EE2, BPA, and NP treatment all up-regulated the expression of terα, terß1, and terß2 in the brain, liver, and testis, but with some variations. Similar to mRNA level, both TERα and TERß were up-regulated by all the EE2, BPA, and NP treatment with dose-dependent effect. In conclusion, the responses of ERs of T.albonubes to the EDCs present measurability and susceptibility, which make it possible for T. albonubes to be an efficient biomarker to monitor and evaluate the pollution of endocrine disrupting chemicals in water environment.
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Beginning in late 2020, the emergence and spread of multiple variant SARS-CoV-2 strains harboring mutations which may enable immune escape necessitates the rapid evaluation of second generation COVID-19 vaccines, with the goal of inducing optimized immune responses that are broadly protective. Here we demonstrate in a mouse immunogenicity study that two doses of a modified B.1.351 spike (S)-Trimer vaccine (B.1.351 S-Trimer) candidate can induce strong humoral immune responses that can broadly neutralize both the original SARS-CoV-2 strain (Wuhan-Hu-1) and Variants of Concern (VOCs), including the UK variant (B.1.1.7), South African variant (B.1.351) and Brazil variant (P.1). Furthermore, while immunization with two doses (prime-boost) of Prototype S-Trimer vaccine (based on the original SARS-CoV-2 strain) induced lower levels of cross-reactive neutralization against the B.1.351 variant, a third dose (booster) administered with either Prototype S-Trimer or B.1.351 S-Trimer was able to increase neutralizing antibody titers against B.1.351 to levels comparable to neutralizing antibody titers against the original strain elicited by two doses of Prototype S-Trimer.
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Objective To evaluate the efficacy and adverse reactions of platinum-based combined chemotherapeutical regimens in treating relapsed or refractory non-Hodgkin lymphoma(NHL).Methods The clinical data of 68 patients with relapsed or refractory NHL treated with platinum-based combined chemotherapeutical regimens in the Affiliated Tumor Hospital of Guangxi Medical University from January 2008 to December 2014 were retrospectively analyzed.The curative effect of related regimens,adverse reactions and related influence factors were analyzed.Results Sixty-eight cases received 283 cycles of chemotherapy.In all cases,11 cases(16.18 %) achieved the complete response(CR),31 cases(45.59 %) achieved the partial response(PR),the overall response rate(ORR) was 61.76%;the median progression-free survival(PFS) was 6.51 months(95%CI:4.97-8.04 months).ORR and PFS in the cases of stage Ⅱ-Ⅲ,IPI score 0-2 and receiving only one chemotherapeutical regimen were superior to those in the cases of corresponding subgroup(P<0.05);ORR and PFS had no statistical difference between the B cells lymphoma and Tcells lymphoma(P>0.05).The medion PFS in the combined R group was 11.16 months,which was longer than 5.84 months in the non-combined R group(P =0.004).The major adverse events (stage Ⅱ-Ⅲ) included leukopenia (41.18 %),thrombocytopenia (27.94%),hemoglobin decrease(11.76%),vomiting(8.82%) and diarrhea(1.47%).Conclusion The platinum-based combined chemotherapeutical regimens are effective with good safety in the treatment of relapsed or refractory NHL.
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Objective:To illuminate a method for establishment of a cost-efficient atopic dermatitis (AD) mouse model by topical application of ovalbumin (OVA),super-antigen staphylococcal enterotoxin B (SEB),and calcipotriene ointment (CO) on the back of BALB/c mice.Methods:Experimental mice were topically treated with OVA/SEB or OVA/SEB/CO every other day during 15 days of induction.Clinical alterations on the skin area were monitored every other day.Epidermal thickness were measured by reflectance confocal microscope (RCM) before harvest.Inflammatory cells in skin biopsies were marked by hematoxylin-eosin (HE) staining.Blood sample and skin biopsies were measured by ELISA and quantitative real-time PCR to detect the expression of IL-2,IL-4,IL-31,interferon (IFN)-γ,tumor necrosis factor (TNF)-α pruritus-associated nerve growth factor (NGF),and serum IgE.Results:Human AD-like cutaneous local inflammatory reaction was characterized by the accumulation of inflammatory cells,increased epidermal thickness and serum IgE levels as well as Th1 cell-associated cytokines (IFN-γ,TNF-α),Th2 cell-associated cytokines (IL-4,IL-31),and NGF in the OVA/SEB/CO group compared with that in the normal control group or the OVA/ SEB group.Conclusion:OVA/SEB/CO can induce an AD-like mouse model with lower economic and time consumption.
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Objective To evaluate the clinical efficacy and safety of combined ozone hydrotherapy for the treatment of atopic dermatitis(AD). Methods A total of 60 patients with moderate or severe AD aged from 6 to 65 years were enrolled, and randomly and equally divided into a test group and a control group. Both the two groups were treated with oral levocetirizine capsules 5 mg once a day, topical tacrolimus ointment twice a day, and topical moisturizers. The test group was additionally treated with ozone hydrotherapy 3- 5 times every week. The treatment lasted 2 weeks. The severity scoring of atopic dermatitis (SCORAD) score, visual analog scale (VAS) score, dermatology life quality index (DLQI) or children′s dermatology life quality index (CDLQI) score were assessed before and after the treatment, and compared between the two groups. Enzyme?linked immunosorbent assay(ELISA) was performed to measure the levels of interleukin?4(IL?4)and nerve growth factor(NGF)in peripheral blood from the patients before and after the treatment. Results After 2?week treatment, the SCORAD scores, VAS scores and DLQI/CDLQI scores significantly decreased from 42.13 ± 16.03, 7.14 ± 2.12 and 14.92 ± 5.94 before the treatment to 27.3 ± 11.01, 2.23 ± 1.31 and 9.69 ± 4.17 respectively in the test group(all P0.05). Conclusion Combined ozone hydrotherapy can effectively and safely improve the condition of patients with AD, likely by decreasing the levels of IL?4 in peripheral blood.
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OBJECTIVE:To observe the effect of Maren pills combined with lactulose preventing opioid-induced constipation (OIC) in patients with cancer pain. METHODS:281 cases of advanced cancer pain were selected and divided into Maren pills group,lactulose group and drug combination group. 3 groups were given opioid to relieve pain,and additionally received Maren pills,lactulose or drug combination(lactulose for 3 d and then Maren pills for 3 d instead,repeated in the same way)to treatment OIC prophylactically. The constipation conditions of 3 groups were observed and recorded at 2,4 and 6 weeks after the therapy. And then the data were analyzed statistically. RESULTS:The regular doses of Maren pills and lactulose alone or combination had prevention effect on OIC. Drug combination showed better long-term prevention effect;there were statistically significant difference in constipation conditions between grug combination group and other 2 groups after 4 and 6 weeks of therapy (P<0.05 or P<0.01). CONCLUSIONS:Maren pills combined with lactulose are obvious benefit for constipation prevention and relief in cancer pain patients who use opioid for a long time.