ObjectiveTo study the pathway of cis-dichlorodiamineplatinum (DDP) inhibiting the synthesis of steroid hormones in mice, and to observe the intervention effect of dehydroepiandrosterone (DHEA).MethodsSixty adult ICR mice were randomly divided into three groups: control group, DDP modeling group, and DHEA group, with 10 male and 10 female mice in each group. The DDP modeling group mice were intraperitoneally injected with DDP solution at a dose of 2.5 mg·kg^-1·d^-1, once every 3 days, a total of 7 times. On the same day of modeling, the control group mice were injected with an equal amount of physiological saline intraperitoneally. The DEHA treatment group mice were treated with DDP and given a dose of 8.3 mg·kg^-1·d ^-1 of DHEA by gavage for 21 consecutive days. The changes of fatigue indexes of mice were observed by open field, grip and rod rotation tests. The morphology changes of adrenal gland, testicular and ovarian tissue were observed by pathological section and HE staining. The levels of serum steroid hormones were detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The mRNA and protein expression levels of the related genes of the hypothalamus, hypophysis, adrenal, testis and ovary were tested by real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting.ResultsCompared with control group, both male and female mice in DDP modeling group were significantly losing weight (P＜0.05), their abilities in horizontal movement and vertical movement decreased (all P＜0.05), and the stay time and grip also significantly decreased (all P＜0.05) in female mice. Indexes of fatigue were improved after DHEA supplement (all P＜0.05). In the DDP modeling group, the arrangement of spermatogenic cells at all levels in the testicular tissue was disordered and the testicular interstitial edema was observed, and a large number of primordial follicles in the ovarian tissue were activated, the number of atresia follicles increased, and the number of granulosa cells in the follicles decreased; while in the DHEA group, the damaged phenotype of testicles and ovaries was significantly improved. Compared with control group, the levels of serum testosterone and dihydrotestosterone in both male and female DDP modeling mice significantly decreased (P＜0.01), the pregnenolone was down-regulated but corticosterone was up-regulated significantly (P＜0.05) in male mice, the corticosterone was down-regulated significantly (P＜0.05) in female mice. Compared with the DDP group, after DHEA supplement, the pregnenolone in male mice and the progesterone in female mice increased significantly (P＜0.05), but the pregnenolone in female mice and the progesterone in male mice decreased significantly (P＜0.05). Compared with control group, the expression levels of Cyp21a1 and Cyp11a1 genes in the adrenal gland and Gnrh gene in the hypothalamus of male and female mice in the DDP modeling group significantly decreased (all P＜0.05); the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, and Lhr genes in the ovaries, Crh, Pomc, and Lhb genes in the hypothalamus, pituitary, and pituitary of female mice significantly decreased (all P＜0.05); the expression levels of Star gene and StAR protein in the testicles of male mice, as well as Fshb and Lhb genes in the pituitary gland, were significantly down-regulated (all P＜0.05). After DHEA supplement, compared with the DDP modeling group, the mRNA expression levels of Cyp17a1 in the adrenal gland of male mice and Cyp17a1, Lhr and Fshr genes in testis were down-regulated significantly (P＜0.05); the expression level of Cyp11a1 gene in the adrenal gland of female mice was also decreased (P＜0.05); while the expression levels of Hsd3b2 gene in the adrenal gland, Star, Cyp11a1, Hsd3b2 and Lhr gene in the ovary, and Lhb gene in the pituitary gland were all up-regulated ( P＜0.05).ConclusionThe function of hypothalamus-pituitary-adrenal/gonadal axis was inhibited by DDP intermittent injection, especially in female. Supplementation of DHEA can help regulate the homeostasis of steroid hormone levels.

OBJECTIVE To prov ide reference for improving the participation mechanism of stakeholders in the process of medical insurance negotiation for oncology drug in China. METHODS Based on the stakeholder theory ，combined with literature research，case analysis （taking the review of reimbursement of Bentuximab as an example ）and other methods ，analysis and research were conducted on the Canadian oncology drug review process and the participation mechanism and role of stakeholders. The suggestions were put forward for our country. RESULTS & CONCLUSIONS Canadian oncology drug reimbursement review process was composed of four stages ：the pre-submission planning stage ，the formal submission stage of application，the review stage，and the stage of forming reimbursement recommendations. As the role of stakeholders ，drug manufacturers ，patient representative advisory group ， clinical review expert advisory groups and provincial advisory groups participated in the reimbursement review process of oncology drug by providing suggestions and feedback to CADTH. The participation of stakeholders had improved the transparency of the review of oncology drugs in Canada and made the reimbursement results of oncology drugs more scientific ，reasonable and accurate. In China ，it is recommended to define rights ，responsibilities and interests as well as the participation mechanism of stakeholders in the medical insurance negotiation process ，attach importance to the role of patients in the medical insurance negotiation process of oncology drug ，improve information disclosure and increase the transparency of the negotiation mechanism and process so as to increase the participation of stakeholders.

OBJECTIVE To compare the effect between drug donation model and national drug negotiated model on drug sales，and to provide reference for pharmaceutical enterprises to optimize their business strategies . METHODS Based on medical insurance statistics and settlement data of city A in Jiangsu province from 2013 to 2018，trastuzumab was selected as the representative drug . The sales and utilization of trastuzumab were compared during the implementation of the two models . At the same time ，the changes of medication behavior of some patients were analyzed . RESULTS After the implementation of drug donation model ，sales volume and turnover of trastuzumab increase by 193.87% and 155.71% in that year compared with the previous year ，and then the growth trend became stable ；after including the national negotiated drug list ，the number of users of trastuzumab in the year increased by 87.68% compared with the previous year ，and the sales volume increased by 48.06%；turnover increased by 22.81% even though the unit price decreased significantly . Both models could improve drug sales ，and the results of multiple linear regression also proved that different models had a significant impact on the consumption sum of trastuzumab in patients. CONCLUSIONS Under the condition that the unit price level of drugs is approximately the same ，both drug donation model and national drug negotiated model can increase the sales volume and expand the coverage of drugs . The latter reduces the drug threshold of patients ，and plays a positive role in improving the drug accessibility of patients and the sales and development of enterprises.

OBJECTIVE：To eval uate the effectiveness ，safety and economy of chimeric antigen receptor T cells （CAR-T） therapy for the treatment of B-lymphoblastic hematologic malignancy ，and to provide evidence-based reference for clinical decision. METHODS：Rapid health technology assessment （HTA）was adopted. PubMed ，Embase，Cochrane Library ，CNKI，Wanfang databases and foreign HTA official websites were systematically searched during the inception-Mar. 20th，2021. After inclusion ， data extraction and quality evaluation of literatures according to the inclusion and exclusion criteria ，descriptive analysis was performed for the effectiveness ，safety and economy of CAR-T therapy for the treatment of B-lymphoblastic hematologic malignancy. RESULTS ：A total of 2 HTA reports ，5 systematic reviews/Meta-analysis ，and 5 economics studies were included. In terms of effectiveness ，CAR-T therapy showed good efficacy in the treatment of B-lymphoblastic hematologic malignancy ；overall remission rate （ORR）of CAR-T therapy in the treatment of acute lymphoblastic leukemia was more than 63.5％，and the complete remission rate （CR）was 77.1％（95％CI：62.8％-87.1％）；ORR of CAR-T therapy in the treatment of chronic lymphoblastic leukemia was 70.0％（95％CI：53.0％-80.0％），and the CR was 25.5％（95％CI：13.9％-42.1％）；ORR of CAR-T therapy in the treatment of B-cell lymphoma was more than 44.4％. In terms of safety ，the incidence of cytokine release syndrome was more than 20％ during the treatment of CAR-T therapy ，and 1/3 or more （9％ believed in some studies ）patients suffered from neurotoxicity ； the incidence of infection was 12.2％-33.3％，and the incidence of graft-versus-host disease was 23.4％（95％CI：8.6％-49.8％）. In terms of economy ，most of the included studies believed that CAR-T therapy possessed economic advantages ，which were the results of evaluation in developed countries such as the United States and Japan. CONCLUSIONS ：CAR-T，as a new product of treatment for hematological malignancy ，shows good effectiveness and low level of ADR ，which is basically controllable ；its economy needs to be further evaluated by relevant researches combined with domestic reality.

For improving epitope immunogenicity and achieving the co-immunization, late protein 1 (L1) of HPV type 16 (HPV16L1) was selected as the vector to carry the dominant epitope of Toxoplasma gondii because of the shared common population between Toxoplasma gondii and human papillomavirus (HPV). RSepitope-HPV16L1 (RSepitope fused at the "N-terminus" of HPV16L1) and HPV16L1-RSepitope (RSepitope fused at the "C-terminus" of HPV16L1) chimeras were constructed. After transfection of COS-7 cells with the recombinants, Western blot, RT-PCR, and immunofluorescence experiments confirmed that RSepitope-HPV16L1 could successfully express the corresponding mRNA and protein of RSepitope and HPV16L1, but the HPV16L1-RSepitope construct could not. A "prime-boost" immunization program was applied in mice to further evaluate the immune response elicited by the constructs, and the RSepitope-HPV16L1 immunization group produced the most significantly increased humoral and cellular immune responses (the highest RSepitope-specific IgG antibody level and the highest IFN-γ production, respectively), in which both elevated Th1 and Th2 immune responses were obtained. Moreover, the advantage of HPV16L1 as an epitope carrier was remarkable for RSepitope-HPV16L1, which induced a more prominent immunological response than RSepitope alone (without fusion with HPV16L1). Our research indicated that the N-terminus of HPV16L1 could be a better insertion site for enhancing target epitope immunogenicity, and our study offers a design for epitope vaccine of reasonable combination.
Animals ; Antibody Formation ; Epitopes ; Immunization ; Mice ; Mice, Inbred BALB C ; Toxoplasma ; Vaccination ; Vaccines, DNA

Objective:To explore the influencing factors of uterine myometrial and parauterine venous plexus reflux during transvaginal four-dimensional contrast-enhanced hysterosalpingography, which will help reduce and avoid the occurrence of reflux and improve the accuracy of diagnosis.Methods:A total of 306 infertile patients who underwent transvaginal four-dimensional contrast-enhanced hysterosalpingograph from June 2016 to June 2017 in the Third Affiliated Hospital of Guangzhou Medical University were retrospectively enrolled. The ultrasonographic characteristics were reviewed and the correlations between reflux and endometrial thickness, days after menstruation, intrauterine operation history and patency of fallopian tube were analyzed.Results:The incidence of countercurrent during four-dimensional contrast-enhanced hysterosalpingography was 14.71%. The chi-square test showed that the endometrial thickness and the days after menstruation had statistically significant effects on the incidence of reflux ( P=0.031 and <0.001, respectively). There were no statistically significant effects of intrauterine operation history and patency of the fallopian tube on the incidence of reflux ( P=0.610, 0.137). Logistic regression analysis showed that the incidence of reflux was associated with endometrial thickness ( B=-1.171, P<0.001) and the days after menstruation ( B=0.439, P=0.015). Conclusions:Transvaginal ultrasound measurement of endometrial thickness before angiography and selection of appropriate examination time according to the menstrual cycle can effectively reduce the incidence of reflux, and adverse reactions, and improve the accuracy of four-dimensional contrast-enhanced hysterosalpingography.

Cardiac magnetic resonance (CMR) imaging provides accurate anatomic information and advanced soft contrast, making it the reference standard for assessing cardiac volumes and systolic function. In this review, we summarize the recent advances in CMR sequences. New technical development has widened the use of CMR imaging beyond the simple characterization of myocardial scars and assessment of contractility. These novel CMR sequences offer comprehensive assessments of coronary plaque characterization, myocardial fiber orientation, and even metabolic activity, and they can be readily applied in clinical settings. CMR imaging is able to provide new insights into understanding the pathophysiologic process of underlying cardiac disease, and it can help physicians choose the best treatment strategies. Although several limitations, including the high cost and time-consuming process, have limited the widespread clinical use of CMR imaging so far, recent advances in software and hardware technologies have made the future more promising.
Cardiac Volume ; Cardiology ; Cicatrix ; Heart Diseases ; Magnetic Resonance Imaging

Cardiac magnetic resonance (CMR) imaging provides accurate anatomic information and advanced soft contrast, making it the reference standard for assessing cardiac volumes and systolic function. In this review, we summarize the recent advances in CMR sequences. New technical development has widened the use of CMR imaging beyond the simple characterization of myocardial scars and assessment of contractility. These novel CMR sequences offer comprehensive assessments of coronary plaque characterization, myocardial fiber orientation, and even metabolic activity, and they can be readily applied in clinical settings. CMR imaging is able to provide new insights into understanding the pathophysiologic process of underlying cardiac disease, and it can help physicians choose the best treatment strategies. Although several limitations, including the high cost and time-consuming process, have limited the widespread clinical use of CMR imaging so far, recent advances in software and hardware technologies have made the future more promising.

Objective: To explore the prescription rules in treating liver cirrhosis's based on poison phlegm blood stasis and deficiency. Method: Clinical data of patients, who had been diagnosed with liver cirrhosis, was gathered. The data had been extracted, transformed and loaded through data integration and remittance, then, the data was analyzed by data classification, association, clustering and other large data analysis methods. Results: The prescription rules based on poison phlegm blood stasis and deficiency showed that according to medication frequency, detoxification drugs commonly used ArtemisiacapillarisThunb, Coptis chinensis Franch, Forsythia suspensa, Hedyotis diffusa Willd, and Scutellaria baicalensis Georgi, eliminating phlegm drugs commonly used Semen Coicis, Citrus aurantium L, Pinellia ternate, Pericarpium Citri Reticulatae and Trichosanthes kirilowii Maxim, removeing blood stasis drugs commonly used Radix Salviae Miltiorrhiae, Radix Curcumae, Rhizoma Curcumae, Herba Lycopi and Pollen Typhae, reinforcing deficiency drugs commonly used Poria, Carapax Trionycis, Rhizoma Atractylodis Macrocephalae, Radix Astragali seu Hedysari and Radix Codonopsis (Radix Pseudostellariae) . The selection of herbal medicine for poison in traditional Chinese medicine (TCM) is not only cold in property, bitter in flavor, but also converges to liver, gallbladder, spleen and stomach channel.The selection of herbal medicine for phlegm in TCM is not only warm in property, pungent in flavor, but also converges to spleen and lung channel. The selection of herbal medicine for blood stasis in TCM is not only cold in property, bitter in flavor, but also converges to liver, heart and spleen channel. The selection of herbal medicine for deficiency in TCM is not only mild in property, sweet in flavor, but also converges to spleen, liver and kidney channel. Conclusion: The syndrome differentiation and treatment of liver cirrhosis in Liver Institute of Hubei Provincial Hospital of Traditional Chinese are mainly based on poison phlegm blood stasis and deficiency.