Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To explore the cognition and use experience of residents based on technical acceptance model, and provide decision-making information and reference for the promotion and optimization construction of the smart ward.Methods:Based on the technical acceptance model, the research team made cognitive and experience evaluation questionnaire of hospitalization patients of the smart wards and evaluated its reliability. By adopting cross-sectional research methods, 368 patients who were hospitalized in the smart wards of the 10 leading clinical specialty in"136" Xingyi Project in Shanxi Province were selected as research objects from January to April 2022. The cognitive and experience evaluation questionnaire of hospitalization patients of the smart wards were used to conduct investigations and research.Results:Among 368 patients, male 148 cases, female 220 cases, aged 18 to 70 years old. The overall Cronbach α coefficient of the questionnaire was 0.887, which had a good degree of reliability. In the cognition and experience evaluation of the smart wards, the five dimensions of perception of usefulness, perception of ease of use, perception safety, attitude and willingness to use were (4.76 ± 0.38),(4.75 ± 0.46), (4.75 ± 0.46), (4.72 ± 0.19), (4.73 ± 0.55), (4.77 ± 0.27) points respectively, the proportion of "very agreed" was 80.16% (295/368); the overall satisfaction of the smart wards scored (4.76 ± 0.35) points, the proportion of "very satisfied" was 79.35% (292/368). Conclusions:The application of the smart ward in the nursing work of inpatients will help optimize the patients′ medical service experience and improve the satisfaction of hospitalization.

Objective:To improve the quality standard of Xiaoer Shenzhu Jianpi Pills.Methods:The microscopic identification method was used to qualitatively identify Hordei Fructus Germinatus.TLC was used to qualitatively i-dentify of Atractylodis Macrocephalae Rhizoma,Glycyrrhizae Radix Et Rhizoma,Citri Reticulatae Pericapium.HPLC was adopted to determine the contents of hesperidin and ammonium glycyrrhizinate.Results:The microscop-ic identification of Hordei Fructus Germinatus had strong specificity and high viewing rate.The TLC identification spots of Atractylodis Macrocephalae Rhizoma,Glycyrrhizae Radix Et Rhizoma,Citri Reticulatae Pericapium were clear,with good separation and durability.The linear ranges of hesperidin and ammonium glycyrrhizinate were 0.060 0-1.501 0 μg and 0.020 1-0.502 2 μg,respectively(r≥0.999 8).The average recoveries(n=9)were 99％,96％and RSDs were 2.8％and 1.8％.The RSDs of precision,stability and repeatability of the two components were less than 3.0％.Conclusion:The newly established quality standard increases the quality control research of microscopic identification,thin layer chromatography and content determination.The experimental method is accurate and reliable,simple and fast,and has good applicability.It can be used for the quality control and evaluation of Xiaoer Shenzhu Jianpi Pills.

The increasing incidence of chronic kidney disease (CKD) has become a major global public health problem. Hypertension and CKD can cause and effect each other and often coexist. Controlling blood pressure is one of the core tasks in the treatment of CKD. Over the past 10 years, many large clinical studies have provided evidence-based medical evidence for the updating and revision of hypertension management guidelines, but there remains controversies in targets of blood pressure in hypertensive patients with CKD. Personalized and evidence-based management is the key to achieve effective control of blood pressure and slow the progression of CKD. This review will summary the epidemiological status of hypertensive patients with CKD and the progress related to the targets of controlling blood pressure in CKD.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Objective:To study the effects of Zuogui Pills on the expressions of miR-133b-3p and RhoA in osteoclasts of postmenopausal osteoporosis rats; To discuss its potential mechanism.Methods:SD female rats were randomly divided into normal group, model group, sham-operation group, and Zuogui Pills group using a random number table method, with 6 rats in each group. The model group and Zuogui Pills group were treated with oophorectomy to construct a rat model of osteoporosis. Zuogui Pills group was orally administered with Zuogui Pills decoction at a concentration of 10 g/kg for 12 consecutive weeks. Colorimetric method was used to measure the serum calcium and phosphorus levels of rats, and ELISA method was used to detect ALP levels. Bone density meter was used to measure the bone density of the femurs of rats in each group. The osteoclast of each group were cultured, and the expressions of RANKL and RUNX2 protein were detected by Western blot. MiRNA sequencing and differential expression analysis were performed on bone tissues of rats. Osteoclasts were treated with miR-133b-3p mimic and its negative control. The cell proliferation activity of osteoclasts was detected by cell counting kit-8 (CCK-8). The osteoclast differentiation activity was detected by the tartrate-resistant acid phosphatase staining. The dual-luciferase reporter assay was used to detect the relationship between miR-133b-3p and RhoA. The "rescue" experiment of miR-133b-3p mimic and RhoA co-expression were used to study the molecular regulatory mechanism of Zuogui Pills on osteoclast activity.Results:Compared with the model group, the bone mineral density of Zuogui Pills group significantly increased ( P<0.05, P<0.01), the levels of calcium and phosphorus in serum increased, the level of alkaline phosphatase ALP decreased ( P<0.05), the expression of RANKL protein decreased, and the expression of RUNX2 protein increased. Sequencing results showed that rno-miR-133b-3p was down-regulated in osteoclasts of postmenopausa osteoporosis rats treated with Zuogui Pills with the maximum difference ( P<0.01). Q-PCR results showed that the expression of miR-133b-3p in osteoclasts of Zuogui Pills group was significantly lower than that of the model group. The upregulation of miR-133b-3p could significantly promote the cell proliferation and differentiation of osteoclasts. RhoA overexpression could reverse the excessive proliferation and differentiation of osteoclasts caused by miR-133b-3p overexpression. Conclusions:RhoA is the target gene regulated by miR-133b-3p. Zuogui Pills can inhibit the activity of osteoclasts by regulating miR-133b-3p/RhoA axis, relieving the symptoms of osteoporosis.

【Objective】 To evaluate the value of platelet-to-lymphocyte ratio (PLR) in the prognosis of prostate cancer. 【Methods】 Relevant studies were searched in CNKI, Wanfang, CBM, VIP, PubMed, Web of Science, Cochrane Library and Embase databases from inception to Dec.2021. The literature was screeded, data were extracted, and the quality was evaluated according to the inclusion and exclusion criteria. A meta-analysis by using the hazard risk (HR) and 95% confidence interval (CI) was adopted to assess the prognostic value of PLR. The data were analyzed with STATA 16.0 software. 【Results】 A total of 10 studies were included, involving 1 802 patients. For patients with high level of PLR, the overall survival (OS) (HR=1.70, 95%CI:1.25-2.30, P=0.001) and disease-free survival (DFS)(HR=1.44, 95%CI:1.15-1.81, P=0.002) were significantly shorter. 【Conclusion】 PLR is an independent risk factor affecting the long-term prognosis of prostate cancer patients. Pretreatment detection of PLR is meaningful in determining the prognosis.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

Myeloid-derived suppressor cells (MDSCs) are a group of immature and heterogeneous cells that can inhibit T cell function. In pathological conditions such as tumors, infections, and chronic inflammation, the large expansion of MDSCs is involved in processes of immune escape, immune tolerance and inflammatory reactions. MDSCs are also crucial in the pathophysiology of hepatitis B virus (HBV) infection, however, their activation, differentiation, and function during HBV infection are still unclear. This article reviews the general characteristics and roles of MDSCs in HBV infection, as well as related drug therapies, in order to provide information for further research on the related mechanism and potential targeted treatment.

The human biorhythm is closely related to the blood pressure level and the effect of the antihypertensive treatment of hypertension. The human circadian biorhythm changes the therapeutic effect of antihypertensive drugs by affecting the pharmacokinetics and pharmacodynamics; at the same time, following the human blood pressure rhythm in the treatment of hypertension can reduce the risk of target organ damage and cardiovascular and cerebrovascular events. Therefore, in the treatment of hypertension, the administration time and drug dosage should be adjusted according to the pharmacochronology to obtain the best curative effect and minimal side effects, and reduce the occurrence of adverse reactions and complications.