Objective To explore the effects of total flavonoids from portulaca against liver fibrosis in rats by detecting TGF-β1 gene and protein expressions. Methods A total of 48 SD rats were randomly divided into normal control, model control, glucyrrhizin aqueous,and total flavonoids groups,with 12 rats in each group. Except those in the normal control group, rats in other groups were intraperitoneally injected with 2 mL · kg-1 · d-1 carbon tetrachloride to induce liver fibrosis. Rats in glucyrrhizin aqueous group and total flavonoids ones were intragastrically administered with 15. 75 mg · kg-1 of glycyrrhizin aqueous solution or 35. 6 mg·kg-1 of total flavonoids aqueous solution,respectively. The normal and model control groups were administered with equal volume of aqueous solution. Thirty days later,rats were sacrificed by anesthesia. Livers were obtained to detect TGF-β1 gene and protein expressions by RT-PCR and Western-Blot. Results Relative gene expression of TGF-β1 in the normal control,model control,glucyrrhizin aqueous and flavonoids groups was 0. 725±0. 130,7. 493±1. 410,3. 016±1. 240,and 2. 668±1. 150,respectively. Total flavonoids from portulaca significantly reduced the gene (P<0. 01) and protein (P<0. 01) expressions of TGF-β1 . Conclusion Efficacy of total flavonoids from portulaca in treating hepatic fibrosis may be related to decreased TGF-β1 expression in rats.

Objective:To evaluate the diagnostic value of serum prostate-specific antigen (PSA) levels and multi-parameter magnetic resonance imaging (mpMRI) in patients with granulomatous prostatitis after intravesical Bacillus Calmette-Guérin (BCG) therapy.Methods:The medical records of eight patients with pathologically proven granulomatous prostatitis in Shandong Provincial Hospital Affiliated to Shandong University from January, 2015 to June, 2020, were enrolled and analyzed in this retrospective study. All 8 patients (ages 47-76, mean 63.6) underwent pelvic mpMRI and serum tPSA levels before TURBT, which showed the results of tPSA, f/t and mpMRI were normal before TURBT (0.45-3.62 ng/ml, 0.20-0.51 and normal signal intensities on T1WI and T2WI, respectively). All patients underwent intravesical BCG therapy after post-TURBT 4-6-weeks’ intravesical gemcitabine therapy as a result of pathologically proven middle and high risk NMIBC via cystoscopy.Results:The results of tPSA levels in all 8 patients were elevated after intravesical BCG therapy after 9-15 months (mean 10.5 months), with 4 patients above 4 (6.77-12.89)ng/ml and 4 patients within the normal ranges(2.02-2.68)ng/ml, and f/t levels decreased to lower than 0.16 (0.09-0.15)in all patients. The mpMRI abnormal signals in all patients were all located in the peripheral zone of prostate. All nodular lesions of prostate mpMRI showed lower signal intensity (SI) on T2WI, higher SI on DWI and lower SI on ADC after BCG therapy. All patients underwent prostate biopsy for abnormal signal on prostate mpMRI. The biopsy pathologic results of all patients were granulomatous prostatitis.Conclusions:When elevated PSA and abnormal signals on prostate mpMRI after intravesical BCG therapy occurred, prostate biopsy may not be required for secondary granulomatous prostatitis patients with non-muscle invasive bladder cancer in combination of clinical history.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Allergic rhinitis is a common allergic disease in children.Its pathogenesis is complex and it is difficult to achieve radi-cal cure or effective and stable long-term treatment goals.Chinese medicine has obvious advantages in preventing and treating allergic rhinitis in children due to its wide range of targets,long-lasting effects and few adverse reactions.This paper proposes that the onset of allergic rhinitis is mostly caused by the dysfunction of the lung,spleen and kidney,the external wind triggering the latent wind,and the combination of the two winds.A staged prevention and treatment strategy of Chinese medicine should be adopted,which includes dispersing external wind,suppressing latent wind,and promoting lung-qi and clearing nasal orifice during the attack period to treat its symptoms,and preventing external wind,calming down latent wind,and regulating and tonifying the lung,spleen,and kidney during the remission period to treat its root cause;meanwhile,attention should be paid to avoiding the adverse effects of congenital endowment factors and the induction of acquired environmental factors,strengthening the body's health to protect against the evil wind,preventing the transformation of existing diseases and the recurrence of allergic rhinitis in children at all stages.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.