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简介：AbstractIncreasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.

简介：AbstractThe maternal-fetal interface is a key barrier to protect the fetus from infection. Toll-like receptors (TLRs) at the maternal-fetal interface are involved in antiviral responses. TLRs are expressed in both maternal decidua and fetal trophoblasts. Virus-induced activation of TLR signaling pathways triggers the release of interferon-related antiviral molecules and other inflammatory cytokines and/or chemokines by the host innate immune system, which may disrupt immune tolerance at the maternal-fetal interface and lead to pregnancy complications. In this review, we summarize the state of knowledge on the most common viral infections during pregnancy, antiviral TLR responses at the maternal-fetal interface, and TLR-associated pregnancy complications.

简介：AbstractAntiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID-19 during the pandemic of this disease. We need to answer the following questions: do we still need to use rigorously designed randomized controlled clinical trials (RCTs)? Or, will it be enough if we use loosened criteria, observational studies or even retrospective case series and case reports? The answer is "No, we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents." In this article, we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID-19, and found that among the reports on monotherapies, only remdesivir, and among combined antiviral agents, only the combined regimen with interferon-β1b, lopinavir-ritonavir and ribavirin were effective and safe based on evidences from RCTs. The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID-19, especially at larger doses. Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed, discussed and emphasized from the specific requirements and considerations of antiviral therapies. We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.

简介：AbstractBiologic drugs have been increasingly used in the treatment of psoriasis and are especially favorable for severe, recalcitrant, and special-type cases. Therefore, appropriate, effective, and safe use of biologic drugs has drawn attention from dermatologists. For this purpose, Chinese experts majoring in psoriasis analyzed domestic and international research data, summarized current clinical experiences, investigated features of Chinese patients with psoriasis, and finally formulated the present consensus, which provides detailed guidances to clinicians in terms of the principles and methods of the application of biologics, the efficacy and safety profile, patient screening and monitoring, main adverse events and corresponding solutions, and precautions for special patient populations.

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简介：AbstractPeriodontitis is one of the most prevalent epidemics affecting human health and life recently, and exploration of the pathogenesis and treatment of periodontitis has been valued by scholars. In recent years, sclerostin, a new factor on bone resorption and reconstruction caused by inflammation and mechanical stimulation, has been a research hotspot. This article summarizes the researches on sclerostin in periodontitis development in recent years. Among them, sclerostin has been shown to be a critical negative regulator of bone formation, thereby inhibiting bone remodeling in periodontitis development, and is closely associated with tooth movement. Besides, evidence indicates that the removal of sclerostin seems to reasonably protect the alveolar bone from resorption. Regulation of sclerostin expression is a novel, promising treatment for periodontitis and addresses several complications seen with traditional therapies; accordingly, many drugs with similar mechanisms have emerged. Moreover, the application prospect of sclerostin in periodontal therapy combined with orthodontic treatment is another promising approach. There are also a lot of drugs that regulate sclerostin. Anti-sclerostin antibody (Scl-Ab) is the most direct one that inhibits bone resorption caused by sclerostin. At present, drugs that inhibit the expression of sclerostin have been applied to the treatment of diseases such as multiple myeloma and osteoporosis. Therefore, the application of sclerostin in the oral field is just around the corner, which provides a new therapeutic bone regulation strategy in oral and general health.

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简介：AbstractGastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.

简介：AbstractImportance:Irradiation treatment for pediatric patients with neuroblastoma represents a major challenge due to the pediatric dose limits for critical structures and the necessity of sufficient dose coverage of the clinical target volume for local control.Objective:To investigate dosimetric differences between tomotherapy (TOMO) and volumetric-modulated arc therapy (VMAT) as retroperitoneal radiotherapy for children with neuroblastoma.Methods:Eight patients who received retroperitoneal radiotherapy for neuroblastoma were selected for comparison of TOMO and VMAT treatment plans. The Dmin, Dmax, Dmean, D95, D2, and D98 of planning target volume (PTV), conformity index (CI), heterogeneity index (HI), and organs at risk (OARs) parameters were compared. Delivery machine unit (MU) and image-guide radiotherapy solution results were also compared.Results:All patients received a cumulative dose of 19.5 Gy to the PTV. VMAT showed higher CI (0.93 ± 0.02), compared with TOMO (0.87 ± 0.03, P < 0.001). Notably, the average PTV HI was significantly better using TOMO (1.05 ± 0.01) than VMAT (1.08 ± 0.02, P = 0.003). Compared with VMAT, the Dmin, D95, and D98 all exhibited increases in TOMO; Dmax variation was less than 1% in TOMO. The D0.1cc for the spinal cord and D2cc for the small intestine were better in TOMO in terms of OARs. However, TOMO had more MUs and required a longer delivery time.Interpretation:Both planning techniques are capable of producing high-quality treatment plans. TOMO is superior for PTV coverage, but inferior for CI. TOMO requires extra treatment time; its cost is greater than the cost of VMAT.

简介：AbstractBackground:After the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China.Methods:Blood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR.Results:In total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95% CI: 1.57–4.44) and individuals from Liangshan, Dehong, and Lincang (aOR= 2.04, 95% CI: 1.26–3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong.Conclusions:Overall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.

简介：AbstractBackground:Super-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs.Methods:We retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging.Results:Seventeen SRs were included with LV ejection fraction increased from 33.0 ± 4.6% to 59.3 ± 6.3%. The intrinsic QRS duration after super-response was 148.8 ± 30.0 ms, significantly shorter than baseline (174.8 ± 11.9 ms, P = 0.004, t = -3.379) but longer than BIV-paced level (135.5 ± 16.7 ms, P = 0.042, t = 2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1 ± 16.5° vs. 19.8 ± 8.1°, P < 0.001, t= 5.726; phase histogram bandwidth (PHB), 171.7 ± 64.2° vs. 60.5 ± 22.9°, P < 0.001, t= 5.376) but was inferior to BIV-paced synchrony (PSD, 19.8 ± 8.1° vs. 15.2 ± 6.4°, P = 0.005, t = 3.414; PHB, 60.5 ± 22.9° vs. 46.0 ± 16.3°, P = 0.009, t = 3.136).Conclusions:SRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.

简介：AbstractCOVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.

简介：AbstractThe pathophysiology of twin-to-twin transfusion syndrome (TTTS) is complex, and its understanding has evolved along with the evolution and revolution of fetal diagnostic and therapeutic techniques. Over the last few decades, several therapeutic interventions have been researched for improving the outcomes in TTTS. We present a summary of the current protocols for surveillance, diagnosis, and staging of TTTS in monochorionic pregnancies. We also describe in detail the technique for treatment of TTTS by endoscopic laser photocoagulation.

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简介：AbstractBackground:At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.Methods:The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.Discussion:The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.Trial registration:ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

简介：摘要A 65-year-old man visited a primary care hospital with a continued fever of 38°C for 3 days. As his fever did not improve until 8 days after, he was admitted into another acute care hospital, where his respiratory condition rapidly worsened. Therefore, the patient was transferred to our hospital. On the day of transfer (day 1) he was started on mechanical ventilation. COVID-19 was diagnosed using a polymerase chain reaction assay 6 days after admission (day 6). The rehabilitation therapy was begun on day 6. The initial rehabilitation programs focused on positioning and postural drainage. The patient was extubated on day 19 and he began standing and stepping on the same day. Gait exercises began on day 22, and endurance training was initiated on day 28. The patient was discharged from our hospital on day 34 as he met the physical function milestones. One month after discharge, the Medical Research Council sum score and Barthel Index had each improved; therefore, muscle strength and daily activities had returned to normal. It was assumed that mobilization should be performed as soon as possible after the end of sedation during the acute phase of severe COVID-19 infection in patients receiving mechanical ventilation.

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简介：AbstractFrom December 31st, 2019, a novel highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, reaching at present the dimension of a pandemic. In addition to damaging the lungs, SARS-CoV-2 may also damage the heart and this is corroborated by the evidence that cardiovascular comorbidities are associated with a higher mortality and poor clinical outcomes in patient infected by the virus. During the infection myocardial injury, myocarditis and arrhythmias have also been reported, but the pathophysiological mechanisms of these complications are yet to be understood. Great attention is also being posed on the potential beneficial/harmful role of angiotensin converting enzyme (ACE) inhibitors, as far as the virus binds to ACE2 to infect cells, but evidences lack. Furthermore, SARS-CoV-2 can also affect the aspect of acute coronary syndromes, not only because these two distinct pathological entities share pathogenic aspects (such as the systemic inflammatory state and cytokine release), but also and above all for the consequences that the need to contain the infection has on the management of cardiological urgencies. The aim of this review was therefore to summarize the relationship between the virus and the cardiovascular system.

简介：AbstractSingle-domain antibodies have the characteristics of small molecular weight, strong tissue penetration, and high affinity, and are widely used to construct molecular probes for disease diagnosis and treatment. This article reviews molecular imaging studies including positron emission tomography (PET), single-photon emission computed tomography/computed tomography (CT), PET/CT, and fluorescent imaging of molecular probes composed of single-domain antibodies against eight esophageal squamous cell carcinoma biological targets. These 8 targets are highly expressed on the membrane of esophageal squamous cell carcinoma cells and include epidermal growth factor receptor, human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2, chemokine receptor 4, chemokine receptor 7, and carcinoembryonic antigen. The current problems and solutions are also discussed to provide a reference for future design of molecular imaging probes targeting esophageal squamous cell carcinoma.