Objective To investigate the protective effect of sappanone A(SA)against high-fat diet-induced myocardial lipotoxicity through ferroptosis in rats.Methods Sixteen healthy male rats were equally divided into the normal diet(NCD)and model groups(n=8).Another 40 healthy male rats were equally divided into the high-fat diet(HFD),high-fat diet+normal saline(HFD+saline),high-fat diet+low-dose SA(HFD+10 mg/kg SA),high-fat diet+medium-dose SA(HFD+20 mg/kg SA),and high-fat diet+high-dose SA(HFD+40 mg/kg SA)groups(n=8).Ultrasonography detected the changes in cardiac systolic function in the rats.Changes of myocardial hypertrophy,myocardial fibrosis,and myocardial cell apoptosis were evaluated by HE,Masson,Sirius red,and TUNEL staining.Differen-tially expressed genes in the myocardium of the HFD+20 mg/kg SA and HFD groups were analyzed by transcriptome sequencing.The SA signaling pathway was analyzed using the Kyoto Encyclopedia of Genes and Genomes.Results Compared with the NCD group,the model group had significantly increased left ventricular wall thickness,cross-sectional area of the myocardium,percentage of myocardial fibrosis,myocardial collagen deposition,and apoptosis,and significantly reduced short-axis shortening rate(all P＜0.05).Compared with the HFD group,the SA treatment groups has significantly reduced left ventricular wall thickness,cross-sectional area of the myocardium,percentage of myocardial fibrosis,myocardial collagen deposition,and apoptosis,and significantly increased short-axis shortening rate(all P＜0.05).Transcriptome sequencing revealed that ferroptosis was the most abundant pathway.Conclusion High-fat diet can induce myocardial lipotoxicity,and SA has a protective effect against myocardial lipotoxicity through ferroptosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

Objective:To investigate the effect of compound matrine injection on morphine tolerance in mice with lung cancer in situ and the expressions of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp).Methods:A mouse model of lung cancer in situ and morphine tolerance mode was established. The mice were injected with gradient concentration of compound matrine. The pain thresholds under different conditions were measured by thermal radiation tail-flick method. The mRNA level of MDR1 was tested by reverse transcription polymerase chain reaction (RT-PCR) and the protein level of P-gp was detected by western blot. The DNA binding activity of cyclophosphoadenosine response element binding protein (CREB) to the promoter of MDR1 gene was detected by electrophoretic mobility shift assay (EMSA).Results:The maximum analgesic percentage (MPE) of the mice in the morphine group was (85.21±6.53)% on the 8th day, and decreased to (38.45±5.52)% and (28.14±4.52)% on the 10th and 12th day, respectively, which indicated the morphine tolerance of mice with lung cancer in situ.The MPE of the mice in the group treated with morphine and compound matrine injection (300 mg/kg) was (79.34±6.50)% on the 8th day, and decreased to (62.16±5.53)% and (40.20±4.50)% on the 10th and 12th day, respectively.The results of RT-PCR assay showed that the relative expression levels of MDR1 mRNA in the brain tissues of mice in the morphine group, saline group, morphine combined with compound matrine injection (300 mg/kg) group and compound matrine injection (200 mg/kg) group were 2.33±0.79, 1.04±0.38, 1.37±0.38, and 1.43±0.53, respectively. There were statistically significant differences between the morphine group and the normal saline group, the morphine group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). There was no significant difference between the normal saline group and the compound matrine injection (200 mg/kg) group ( P=0.05). The results of western blot showed that the relative expression levels of P-gp protein in the brain tissue of mice in the morphine group, saline group, and morphine combined with compound matrine injection (300 mg/kg) group were 1.86±0.40, 1.00±0.23, and 1.27±0.27, respectively. The expression of P-gp protein in the morphine group was significantly higher than those of the normal saline group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). The DNA-binding activity of CREB in the saline group was (0.23±0.07) Pu, significantly lower than (0.89±0.23) Pu of morphine combined with naloxone group and (0.80±0.23) Pu of morphine group ( P<0.05). While the CREB DNA binding activity of morphine combined with compound matrine injection (300 mg/kg) group was (0.79±0.21) Pu, implicated that compound matrine had marginal effect on the DNA-binding activity of CREB ( P>0.05). Conclusion:Compound matrine injection can significantly improve morphine tolerance and drug resistance of lung cancer through inhibiting the upregulations of MDR1 and P-gp induced by morphine.

Objective:To investigate the effect of compound matrine injection on morphine tolerance in mice with lung cancer in situ and the expressions of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp).Methods:A mouse model of lung cancer in situ and morphine tolerance mode was established. The mice were injected with gradient concentration of compound matrine. The pain thresholds under different conditions were measured by thermal radiation tail-flick method. The mRNA level of MDR1 was tested by reverse transcription polymerase chain reaction (RT-PCR) and the protein level of P-gp was detected by western blot. The DNA binding activity of cyclophosphoadenosine response element binding protein (CREB) to the promoter of MDR1 gene was detected by electrophoretic mobility shift assay (EMSA).Results:The maximum analgesic percentage (MPE) of the mice in the morphine group was (85.21±6.53)% on the 8th day, and decreased to (38.45±5.52)% and (28.14±4.52)% on the 10th and 12th day, respectively, which indicated the morphine tolerance of mice with lung cancer in situ.The MPE of the mice in the group treated with morphine and compound matrine injection (300 mg/kg) was (79.34±6.50)% on the 8th day, and decreased to (62.16±5.53)% and (40.20±4.50)% on the 10th and 12th day, respectively.The results of RT-PCR assay showed that the relative expression levels of MDR1 mRNA in the brain tissues of mice in the morphine group, saline group, morphine combined with compound matrine injection (300 mg/kg) group and compound matrine injection (200 mg/kg) group were 2.33±0.79, 1.04±0.38, 1.37±0.38, and 1.43±0.53, respectively. There were statistically significant differences between the morphine group and the normal saline group, the morphine group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). There was no significant difference between the normal saline group and the compound matrine injection (200 mg/kg) group ( P=0.05). The results of western blot showed that the relative expression levels of P-gp protein in the brain tissue of mice in the morphine group, saline group, and morphine combined with compound matrine injection (300 mg/kg) group were 1.86±0.40, 1.00±0.23, and 1.27±0.27, respectively. The expression of P-gp protein in the morphine group was significantly higher than those of the normal saline group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). The DNA-binding activity of CREB in the saline group was (0.23±0.07) Pu, significantly lower than (0.89±0.23) Pu of morphine combined with naloxone group and (0.80±0.23) Pu of morphine group ( P<0.05). While the CREB DNA binding activity of morphine combined with compound matrine injection (300 mg/kg) group was (0.79±0.21) Pu, implicated that compound matrine had marginal effect on the DNA-binding activity of CREB ( P>0.05). Conclusion:Compound matrine injection can significantly improve morphine tolerance and drug resistance of lung cancer through inhibiting the upregulations of MDR1 and P-gp induced by morphine.

Objective: To know condom use negotiation with clients and regular sex partners and condom use in female sex workers (FSWs), and provide reference for the development of comprehensive HIV/AIDS intervention for FSWs. Methods: The cross sectional survey was conducted in Jianshui county and Mengzi county in Honghe Hani and Yi autonomous prefecture. A total of 476 FSWs aged 16 years and above were recruited from entertainment venues, and the information about their demographic characteristics, condom use negotiation and condom use were collected by using questionnaires. Logistic regression model was used to analyze related factors of condom use after negotiation between FSWs and clients unwilling use condom. Results: A total of 852 FSWs who aged (24.29±8.44) years old participated in the survey. In past month, 499 FSWs had negotiation for condom use with unwilling clients (58.6%, 499/852), after negotiation, 441 FSWs (88.4%, 441/499) had consistent condom use in each sex with the clients. In the past one month, 99 FSWs had negotiation for unwilling use condom with regular sex partners (14.4%, 99/687), after negotiation, 54 FSWs (54.5%, 54/99) had consistent condom use in each sex with regular sex partners. Among the FSWs, 266 (53.3%, 266/499) reported that they could say "It is a mandatory requirement" to persuade clients who were unwilling to use condom. 97(19.4%, 97/499) reported that they could say "There is risk for infection" to persuade clients who were unwilling to use condoms. 115 (23.1%,115/499) reported that they could say "It is a mandatory requirement" and "there is risk for infection" to persuade their unwilling clients to use condoms. 21 (4.2%, 21/499) reported that they used other strategies. 22 (4.4%, 22/499) felt that it was difficult to persuade clients to use condoms. Multivariate logistic regression analysis showed that compared with FSWs who felt difficult in persuading clients to use condoms, FSWs who felt moderate difficulty were more likely to have consistent condom use after negotiation (OR=4.00, 95%CI: 1.55-10.32) and FSWs who felt easy in persuading clients to use condoms were also more likely to have consistent condom use (OR=30.17, 95%CI: 3.22-282.44). Compared with FSWs used other strategies to persuade their clients to use condoms, FSWs who said it was a mandatory requirement were more likely to have consistent condom use after negotiation (OR=4.44, 95%CI: 1.41-14.01) and FSWs who said it was a mandatory requirement and there was risk for infection were also more likely to have consistent condom use (OR=5.52, 95%CI: 1.55-19.73). Conclusions Negotiation for condom use increased the rate of condom use in FSWs in sex with clients who were unwilling to use condom. The negotiation strategy of "It is a mandatory requirement" would promote condom use in FSWs in sex with clients who were unwilling to use condom. Besides, the negotiation strategy of saying "there is risk for infection" had additional effects.

Objective To improve the recognition of therapy-related acute myeloid leukemia (t-AML). Methods One patient who was diagnosed as AML with inv (16) following treatment of Hodgkin lymphoma (HL) was reported. The pathomechanism, diagnosis, treatments and prognosis of t-AML were systematically studied by reviewing a series of literature. Results A 36-year-old female with a history of HL 2 years ago was diagnosed t-AML. Karyotype analysis demonstrated inv (16) and the fusion gene of CBFβ/MYH11 was positive by polymerase chain reaction (PCR). The fusion gene of CBFβ/MYH11 was still positive after receiving 3 courses of chemotherapy. The leukemia reached completely molecular biological remission after receiving haploidentical peripheral blood stem cell transplantation. The patient has now survived 1.5 years with leukemia free and in a good performance. Conclusions The t-AML is difficult to treat, but it is heterogeneous. Cytogenetics and molecular biology have important implications for the prognosis of t-AML. Currently, allogeneic hematopoietic stem cell transplantation is the only effective way to cure t-AML.

Objective To study the regulation of Withaferin A on apoptosis-related proteins in lung squamous cell carcinoma and its effect on cell epithelial-mesenchymal transition.Methods Lung squamous cell carcinoma cell line SK-MES-1 were cultured in vitro.The SK-MES-1 cells were treated with the final mass concentration of 0 (control),5,10,20,and 40 μg/ml for 28 h,and the general morphology and shedding of the cells were observed under phase contrast microscope;MTT assay was used for detection of cell viability;flow cytometry was used for detection of apoptosis;immunofluorescence and real-time fluorescent polymerase chain reaction (RT-PCR) was used for detection of apoptosis-related proteins and genes bcl-2 and bax,and expression of the epithelial marker E-cadherin and the interstitial marker Vimentin.Results Different concentrations (0,5,10,20,40 μg/ml) of Withaferin A inhibited the activity of SK-MES-1 cells with cell viability of 0.62±0.05,0.42±0.04,and 0.33±0.06,0.21±0.03,0.17±0.04,respectively,which suggesting that this inhibition was related to the concentration of Withaferin A (F =386.505,P =0.005).After treatment with SK-MES-1 cells for 24 h at different concentrations (0,5,10,20,40 μg/ml) of Withaferin A,the apoptosis rates of each group were (0.180±0.011) ％,(0.310±0.013) ％,(0.500±0.021) ％,(0.540±0.018) ％,and (0.410± 0.027) ％,which suggesting that Withaferin A rarely caused apoptosis,mostly necrotic cells (F =1 065.78,P =0.124).In SK-MES-1 cells treated with different concentrations of Withaferin A for 24 h,the results of immunofluorescence showed that the expression of Vimentin was decreased in the experimental group at a concentration of 20 μg/ml compared with the control group,and the fluorescence intensity was lower than that of the control group,but the fluorescence intensity of E-cadherin was higher than that of the control group;the intensity did not change significantly in the experimental group with the other concentrations.While the expression levels of bax and bcl-2 proteins in the control group and the experimental group did not change significantly.RT-PCR results showed that the mRNA expression of E-cadherin (6.7±0.6 and 6.4±0.9) in the experimental group at a concentration of 20 and 40 μg/ml was significandy higher than that in the control group (4.2±1.0),and the difference was statistically significant (both P ＜ 0.05),and the mRNA expression of Vimentin (4.7±0.5 and 4.7±0.5) was significantly lower than that in the control group (7.2±0.7),and the difference was statistically significant (both P ＜ 0.05).Conclusion Withaferin A can inhibit the growth of lung squamous cell carcinoma cells and inhibit the process of epithelial-mesenchymal transition,but it has no obvious relationship with apoptosis and apoptosis-related proteins.

Objective To discuss the effect of grade repositioning designed by our team on preventing the development of pressure ulcers in ICU patients and its influence on nursing workload of repositioning. Methods Eligible patients admitted to ICU were randomly divided into control group (traditional repositioning,219 cases)and experimental group(grade repositioning,230 cases).The patients in control group was routinely repositioned every 2 hours;the patients in experimental group was classified as"A""B""C"three levels according to Braden Scores and catecholamine scores,and their repositioning frequency was 1 hour,2 hours and 4 hours respectively.Number of pressure ulcers and nursing workload of repositioning were observed and compared between the two groups. Results At last,the data analysis was included in 201 patients in control group and 220 patients in experimental group.There was no significant difference in the rate of pressure ulcer occurrence between the experimental group(0)and the control group[0.1%(2/201)](P>0.05).But the rate of skin redness occurrence was significant less in the experimental group than in the control group[1.36%(3/220)vs.11.44%(23/201), χ2=13.20,P<0.05]. The mean repositioning times for each patient in the experimental group was significantly less than the control group[(7.22±1.81)times/day vs.(11.38±1.23)times/day],and turn over time was(42.09±1.68)min and(66.35±1.83)min which was also significantly different(t=6.563, 5.210, P<0.05). Conclusion Grade repositioning could effectively prevent critically illed patients from the occurrence of pressure ulcers,while reducing the overall nursing workload of repositioning in an ICU.

Objective: To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation. Results: The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively]. Conclusion The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.

Objective To investigate the distribution characteristics of bone marrow(BM)cell morphological results and their role in the etiological diagnosis of blood diseases,and to understand the characteristics of hematological diseases spectrum in this ar-ea.Methods The BM puncture specimens in 372 cases of hematological diseases in our hospital from March 2012 to April 2014 were performed the Wright-Giemsa staining and cytochemical staining.The cell morphology and cytochemical staining were ob-served by microscope,which was combined with the related clinical data for obtaining the morphological report.Results Among 372 cases,368 cases were diagnosed with hematological diseases,which were dominated by 3 kinds of main type,leukemia(95/372), hyperplasia anemia(36/372)and iron-deficiency anemia (26/372).In 82 cases of anemia,hyperplasia anemia(36/82),iron-deficiency anemia (26/82)and megaloblastic anemia (11/82)were predominant.Conclusion The BM morphological examination is one of im-portant measures for the etiological diagnosis in hematological diseases.The analysis on the diseases spectrum is conducive to guide the diagnosis and treatment in clinic.