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1.
Acta Pharmaceutica Sinica ; (12): 36-45, 2022.
Article in Chinese | WPRIM | ID: wpr-913166

ABSTRACT

At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.

2.
Article in Chinese | WPRIM | ID: wpr-907371

ABSTRACT

Patients with chronic kidney dysfunction (CKD) have abnormal coagulation function and impaired drug metabolism, resulting in increased bleeding risk and decreased drug clearance. Therefore, while receiving treatment, the prognosis of ischemic stroke patients with CKD is different from that of ischemic stroke patients without CKD. For patients with CKD who need anticoagulant treatment, the use of new anticoagulants without renal metabolism can achieve the same anticoagulant effect as warfarin, and the risk of bleeding is lower. When using antiplatelet drugs, due to the increased risk of bleeding in ischemic stroke patients with CKD, the clinical benefits and bleeding risk should be carefully weighed. Although CKD is not an absolute contraindication of intravenous thrombolysis or endovascular treatment in patients with acute ischemic stroke, attention should be paid to the influence of CKD on the increased risk of death in patients with ischemic stroke after treatment.

3.
Journal of Clinical Hepatology ; (12): 2338-2342, 2021.
Article in Chinese | WPRIM | ID: wpr-904944

ABSTRACT

Objective To investigate the mechanism of Fuzheng Huayu(FZHY) decoction in the treatment of liver cancer based on network pharmacology. Methods TCMSP, BATMAN, and Drugbank databases were searched for the main chemical components and corresponding targets of FZHY, and STRING database was used to perform a PPI network analysis. Cytoscape software was used to establish a drug-disease network model and perform a network analysis, and R language was used to perform GO and KEGG enrichment analysis of targets. Results A total of 192 intersection genes between FZHY and liver cancer and 95 potential compounds were screened out, among which quercetin and luteolin were the active components with an important regulatory role. INS, IL-6, and EGFR were the key targets for the potential effect of FZHY. The GO enrichment analysis showed the involvement in various biological processes such as response to drug and response to oxygen level, and the KEGG enrichment analysis showed the involvement in the signaling pathways including apoptosis and tumor necrosis factor signaling pathways. Conclusion Based on the method of network pharmacology, this study reveals the mechanism of action of multiple targets and targets of FZHY in the treatment of liver cancer, which provides a theoretical basis for clinical and basic scientific research.

4.
Journal of Clinical Hepatology ; (12): 2338-2342, 2021.
Article in Chinese | WPRIM | ID: wpr-904894

ABSTRACT

Objective To investigate the mechanism of Fuzheng Huayu(FZHY) decoction in the treatment of liver cancer based on network pharmacology. Methods TCMSP, BATMAN, and Drugbank databases were searched for the main chemical components and corresponding targets of FZHY, and STRING database was used to perform a PPI network analysis. Cytoscape software was used to establish a drug-disease network model and perform a network analysis, and R language was used to perform GO and KEGG enrichment analysis of targets. Results A total of 192 intersection genes between FZHY and liver cancer and 95 potential compounds were screened out, among which quercetin and luteolin were the active components with an important regulatory role. INS, IL-6, and EGFR were the key targets for the potential effect of FZHY. The GO enrichment analysis showed the involvement in various biological processes such as response to drug and response to oxygen level, and the KEGG enrichment analysis showed the involvement in the signaling pathways including apoptosis and tumor necrosis factor signaling pathways. Conclusion Based on the method of network pharmacology, this study reveals the mechanism of action of multiple targets and targets of FZHY in the treatment of liver cancer, which provides a theoretical basis for clinical and basic scientific research.

5.
China Occupational Medicine ; (6): 481-487, 2021.
Article in Chinese | WPRIM | ID: wpr-923074

ABSTRACT

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.

6.
Chinese Medical Journal ; (24): 2666-2674, 2021.
Article in English | WPRIM | ID: wpr-921171

ABSTRACT

BACKGROUND@#Intravenous thrombolysis (IVT) is an effective way for treating acute ischemic stroke (AIS). However, its effects have not been established among AIS patients with unclear stroke symptoms or with stroke onset for >4.5 h.@*METHODS@#We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Google Scholar databases for randomized controlled trials that compared IVT (IVT group) and placebo or usual care (control group [CG]) in AIS patients with disease onset for >4.5 h. The outcomes of interest included the favorable functional outcome (defined as modified Rankin Scale [mRS] scores 0-1) at 90 days, the functional independence (defined as mRS scores 0-2) at 90 days, proportion of patients with symptomatic intracerebral hemorrhage (sICH) and death at 90 days. We assessed the risk of bias using the Cochrane tool. Pre-specified subgroup analyses were performed by age (≤70 years or >70 years), National Institute of Health Stroke Scale (NIHSS, ≤10 or >10) and time window (4.5-9.0 h or >9.0 h).@*RESULTS@#Four trials involving 848 patients were eligible. The risk of bias of included trials was low. Patients in the IVT group were more likely to achieve favorable functional outcomes (45.8% vs. 36.7%; OR 1.48, 95% CI 1.12-1.96) and functional independence (63.8% vs. 55.7%; OR 1.43, 95% CI 1.08-1.90) at 90 days, but had higher risk of sICH (3.0% vs. 0.5%; OR 5.28, 95% CI 1.35-20.68) at 90 days than those in the CG. No significant difference in death at 90 days was found between the two groups (7.0% vs. 4.1%; OR 1.80; 95% CI 0.97-3.34).@*CONCLUSIONS@#Use of IVT in patients with extended time window may improve their functional outcomes at 90 days, although IVT may induce increased risk of sICH. Care of these patients should well balance the potential benefits and harms of IVT.


Subject(s)
Administration, Intravenous , Aged , Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Humans , Ischemic Stroke , Stroke/drug therapy , Thrombolytic Therapy , Treatment Outcome
7.
Chinese Medical Journal ; (24): 2438-2446, 2021.
Article in English | WPRIM | ID: wpr-921152

ABSTRACT

BACKGROUND@#Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19.@*METHODS@#Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders.@*RESULTS@#The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities.@*CONCLUSIONS@#Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.


Subject(s)
COVID-19 , China/epidemiology , Cities , Humans , SARS-CoV-2
8.
Article in Chinese | WPRIM | ID: wpr-911707

ABSTRACT

Sixty general practitioners of in-service training undertaking rotation in gastroenterology department of Qingdao Municipal Hospital from July 2017 to July 2019 were randomized assigned in trial group ( n=30) and control group ( n=30). The problem-oriented mode was applied in trial group and conventional mode was applied in control group for teaching of two typical digestive diseases (upper gastrointestinal bleeding and acute pancreatitis). The formative evaluation and questionnaire survey were used to compare the teaching effects and the results of evaluation were compared with χ 2 test by SPSS 17.0 between two groups. The excellent and good rates of evaluation for the clinical psychological quality, clinical reasoning ability, doctor-patient communication ability and practice-based learning and improvement ability in trial group were significantly higher than those in the control group(χ2=7.38, P=0.03; χ2=12.96, P<0.01; χ2=23.33, P<0.01; χ2=16.14, P<0.01). Questionnaire survey showed more satisfaction towards teaching method in trial group was higher than that in control group(χ2=12.86, P<0.01); and the clinical reasoning ability, learning initiative and self-confidence in trial group were improved more markedly than those in control group(χ2=8.26, P=0.02; χ2=19.48, P<0.01; χ2=21.46, P<0.01). The problem-oriented clinical thinking teaching model demonstrates good effects on clinical comprehensive ability for general practitioners of in-service training during gastroenterology rotation, which is worth further promotion.

9.
Article in Chinese | WPRIM | ID: wpr-888119

ABSTRACT

The present study aimed to explore the effect of Erxian Decoction on proteomics of osteoblasts stimulated by hydrogen peroxide(H_2O_2) and its protective mechanism with the H_2O_2-induced cell model of oxidative stress. The primary osteoblasts were cultured from the skulls of newborn rats(within 24 hours) and divided into a control group, a model group, a Fosamax group, and an Erxian Decoction group. Blank serum was added in the control group and model group, and the drug-containing serum was added correspondingly to the remaining two groups. After 45 hours, H_2O_(2 )stimulation was conducted for three hours except for the control group, followed by protein extraction. Nano-LC-LTQ-Orbitrap system was used for protein detection, Protein Discovery for protein identification, and SIEVE for quantitative and qualitative analysis. Furthermore, following the blocking of PI3 K signaling pathway by LY294002(10 μmol·L~(-1)), a control group, a model group, an LY294002 group, an Erxian Decoction group, and an Erxian Decoction + LY294002 group were set up to observe the effect of Erxian Decoction on cell proliferation, alkaline phosphatase(ALP) activity, and the relative expression of BMP-2, OPG, p-Akt, p-FoxO1 of osteoblasts stimulated by H_2O_2 under LY294002 intervention. The results revealed that 78 differential proteins were discovered between the Erxian Decoction group and model group, which were involved in the regulation of PI3 K/Akt, glucagon, estrogen, insulin, and other signaling pathways. LY294002 blunted the promoting effect of Erxian Decoction on osteoblast proliferation and significantly down-regulated the expression of OPG and p-FoxO1, whereas its down-regulation on the expression of BMP-2 and p-Akt was not significant. Both LY294002 and Erxian Decoction increased the ALP activity of osteoblasts, which may be related to the cell state and the cell differentiation. The above results suggest that Erxian Decoction can protect osteoblasts stimulated by H_2O_2, with the PI3 K/Akt signaling pathway as one of the internal mechanisms.


Subject(s)
Animals , Drugs, Chinese Herbal , Hydrogen Peroxide , Osteoblasts/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proteomics , Proto-Oncogene Proteins c-akt/metabolism , Rats , Signal Transduction
10.
Acta Pharmaceutica Sinica ; (12): 2567-2572, 2021.
Article in Chinese | WPRIM | ID: wpr-886963

ABSTRACT

The cyanuric chloride linkers have been used for cyclizing polypeptide, but not used for α-conotoxin, the peptides with rich disulfide bonds and more amino acid residues. In this study, cyclic peptides c[A10L]PnIA-1-4 were synthesized efficiently by lysine assisted cyanuric chloride linkers with 28.92%-52.00% yields. The activity evaluation showed that the IC50 values of c[A10L]PnIA-1 against α7 and α3β2 nAChR subtypes were 5 and 7 times higher than [A10L]PnIA respectively, and the subtype selectivity was maintained. The results of circular dichroism show that this cyclization method had no significant effect on its secondary structure. Compared with the commonly used head-to-tail cyclization in conotoxin cyclization, this method has the advantages of rapid reaction and high yield, which is expected to be further applied to the cyclization study of various α-conotoxins.

11.
Article in Chinese | WPRIM | ID: wpr-882857

ABSTRACT

Objective:To understand the present situation of the construction of standardized asthma clinic for children in China, to explore the problems existing in the process of construction, and to promote the healthy development of standardized clinic construction.Methods:The process and current situation of the construction of standar-dized asthma clinics for children in China were reviewed and investigated, and the practical significance of the China Children′s Asthma Action Plan (CCAAP) in the construction of standardized asthma clinics for children was explored.Results:(1)By December 2020, 1 289 standardized asthma clinics for children and 135 regional demonstration centers had been built; 56 training sessions had been held, with a total of 2 560 doctors and 650 nurses trained, covering 2 560 hospitals across the country; and 4 518 patient education sessions were held.Online publicity covers a total of 1 million person-times, with an annual average of 1.33 million patients.(2)CCAAP improved the quality control level of standardized asthma clinic and promoted the standardized management of children.Conclusions:Through process optimization, professional evaluation, individual health education and real-time disease monitoring, standardized asthma clinic for children with asthma can effectively enhance asthma management awareness of children and their parents, improve disease awareness, and promote better control of asthma.It is an effective management model of asthma in children at present, and it is worthy of clinical promotion.CCAAP plays a good role in the construction of standardized outpatient clinic for asthma in children.The construction of standardized asthma clinic for children in China has achieved remarkable results, and the development trend is good in the future.

12.
Article in Chinese | WPRIM | ID: wpr-882851

ABSTRACT

The incidence of allergic diseases, including bronchial asthma, atopic dermatitis, allergic rhinitis and food allergies, is increasing year by year.Recently, more and more studies have been conducted to explore the relationship between intestinal microecology and allergic diseases, which indicated that the influence of intestinal flora on the immune system is one of the important mechanisms.This article was based on the immune status and microecology.This article reviewed and explored the important role and mechanism changes of intestinal flora in the early life in terms of the occurrence and development of allergic diseases, and the research progress in the application of probiotics in allergic diseases, aiming to further understand the relationship between intestinal microecology and children allergy and provide new ideas for the prevention and treatment of allergic diseases.

13.
China Occupational Medicine ; (6): 59-64, 2021.
Article in Chinese | WPRIM | ID: wpr-881970

ABSTRACT

OBJECTIVE: To explore the effects of combined exposure to low-level benzene derivatives and noise on hearing loss of workers. METHODS: A total of 216 employees from nine wood furniture factories and four printing factories were selected as research subjects by typical sampling method. Those without exposure to occupational hazardous factors were set as the control group, those exposed to noise alone were set as the noise group, and those exposed to benzene derivatives and noise were set as the combined exposure group. The normalization of equivalent continuous A-weighted sound pressure level to a nominal 8 hours working day(L_(EX,8 h)) and the exposure concentration of time weighted average(C_(TWA)) of benzene, toluene, xylene, ethylbenzene in the workplace air of the three groups were detected, and the hearing threshold of 0.5-8.0 kHz in both ears of the research subjects were measured by pure tone audiometry. RESULTS: No benzene was detected in the workplace air of the combined exposure group, and the C_(TWA) of toluene, xylene and ethylbenzene were all lower than the occupational exposure limits. The L_(EX,8 h) of the noise group and combined exposure group were all higher than that of the control group [(85.6±2.5) vs(68.7±4.4) dB(A),(84.3±3.1) vs(68.7±4.4) dB(A), all P<0.05], while the L_(EX,8 h) of the noise group was higher than that of the combined exposure group [(85.6±2.5) vs(84.3±3.1) dB(A), P<0.05]. Compared with the control group, the individual frequency hearing thresholds, average hearing threshold of speech frequency and average hearing threshold of high frequency in both ears in the noise group and the combined exposure group were increased(all P<0.05), and the detection rates of speech frequency hearing loss and high frequency hearing loss were increased(all P<0.02). The hearing thresholds of right ear of 0.5, 1.0 kHz and left ear of 0.5 kHz were increased in the combined exposure group(all P<0.05), and the detection rate of speech frequency hearing loss was increased(16.7% vs 40.8%, P<0.02), when compared with the noise group. Multivariate logistic regression analysis results showed that the risk of speech frequency hearing loss and high frequency hearing loss in the combined exposure group were higher than that in the control group and the noise group(all P<0.05), after excluding the influence of confounding factors such as education level and smoking.CONCLUSION: The combined exposure to low-level benzene derivatives and noise may have a synergistic effect on the hearing loss in workers.

14.
Article in English | WPRIM | ID: wpr-881062

ABSTRACT

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg

15.
Article in English | WPRIM | ID: wpr-881058

ABSTRACT

This study was to investigate the protective effect of paeoniflorin (PF) on hydrogen peroxide-induced injury. Firstly, "SMILES" of PF was searched in Pubchem and further was used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Injury-related molecules were obtained from GeenCards database, and the predicted targets of PF for injury treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, and the KEGG analysis was conducted in Webgestalt. Then, cell viability and cytotoxicity assay were established by CCK8 assay. Also, the experimental cells were allocated to control, model (200 μmol·L

16.
Article in Chinese | WPRIM | ID: wpr-879280

ABSTRACT

To explore the focus and trends in real-world studies in Chinese through knowledge mapping method, databases CNKI, VIP, Wanfang and Sinomed were retrieved, with 1 757 relevant articles published before September 30rd, 2020 finally included, whose bibliographical records were imported into NoteExpress to avoid duplication and check relativity. VOSviewer, a bibliometric analysis tool, was used to analyze their development. It was found that real-world studies have mainly taken shape after 2010, in which traditional Chinese medicine research plays an important role.


Subject(s)
Bibliometrics , China , Databases, Factual , Publications
17.
Yonsei Medical Journal ; : 29-40, 2021.
Article in English | WPRIM | ID: wpr-875605

ABSTRACT

Purpose@#The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. @*Materials and Methods@#A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. @*Results@#Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. @*Conclusion@#LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

18.
Article in Chinese | WPRIM | ID: wpr-873696

ABSTRACT

@#Adherence to reporting guidelines contributes to report methodology and outcomes of research distinctly and transparently. There are some checklists with specific study types related to surgery on the EQUATOR Network’s website. However, the IDEAL framework focuses on stepwise evaluation of surgical innovation through all stages with some key elements, which those existing guidelines may not mention. This likely results in the inaccuracy in reporting in studies attempting to follow the IDEAL recommendations and suggests a pressing need for IDEAL reporting guidelines. Considering these limitations, the IDEAL developed the IDEAL reporting guidelines between October 2018 and May 2019. The paper aimed to provide interpretation of IDEAL reporting guideline, and promote its understanding and use among Chinese researchers.

19.
Article in Chinese | WPRIM | ID: wpr-873611

ABSTRACT

@#Surgical innovation is an important part of surgical research and practice. The evaluation of surgical innovation through the stages is similar to those for drug development, but with important differences. The Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) Framework and Recommendations represent a new paradigm for the evaluation of surgical intervention and devices which was developed in 2009. The IDEAL is a five-stage framework involving the nature stages of surgical innovation, together with recommendations for surgical research pathway. The Framework and Recommendations were updated and published in 2019, which added a pre-IDEAL stage if necessary. The updated IDEAL also underlines the purpose, key question and ethical issues for each stage. In the first paper of IDEAL Framework and Recommendations series, we conducted a comprehensive introduction of IDEAL (e.g. the development, updates and application of IDEAL) to promote the dissemination and application of IDEAL in China.

20.
Journal of Breast Cancer ; : 460-483, 2020.
Article in English | WPRIM | ID: wpr-898967

ABSTRACT

We aimed to explore what kind of endocrine treatments are optimal for hormone receptorpositive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

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