A novel dual-activatable ultrasensitive chemiluminescent probe for mercury (II) monitoring: From rational design to multiple application.

Real-time optical sensing of mercury has been developed rapidly in recent years but remains challenging such as bearing background interference. Herein, a Hg2+ and base dual-activatable ultrasensitive chemiluminescent probe CL-Hg based on benzothiazole-phenoxyl-dioxetane with profits of excitation light-free and minimal interference is presented. The photophysical properties study and sensing performance verified CL-Hg is coupled with unique advantages of long-term detection (more than 400 min), ultrahigh sensitivity (LOD = 0.52 nM), and high specificity to Hg2+, and visualization detection by the paper-based test strips. More importantly, CL-Hg showed the qualitative and quantitative detection capability for Hg2+ with great recyclability in real samples of water, seafood, and beverages, holding great potential for on-site monitoring of Hg2+ levels in the actual samples. To our knowledge, this is the first work achieving the detection of Hg2+ by chemiluminescence. Overall, the Hg2+-activated visualization platform offers a practical method for detecting Hg2+ in various application scenarios.

Comparative Study on the Efficacy of Precise Radiotherapy in Lymphatic Drainage Area of Esophageal Cancer between Preventive Radiation and Invasive Field Radiation.

To investigate the efficacy of precise radiation therapy for lymphatic drainage area prevention (ENI) and invasive field irradiation (IFI) in patients with esophageal cancer undergoing radical radiotherapy. A retrospective analysis was conducted on 96 esophageal cancer patients admitted to our hospital from March 2018 to March 2021 who underwent radical radiotherapy. Among them, 48 patients who received precise radiation therapy to prevent radiation in the lymphatic drainage area were included in the ENI group, and 48 patients who received field irradiation were included in the IFI group. Compare and analyze the total clinical response rate, local control rate within 3 years after treatment, survival rate, and incidence of adverse reactions after radiotherapy between two groups of patients. There was no statistically significant difference in the total clinical response rate between the ENI group and the IFI group after radiotherapy (P > .05). There was no statistically significant difference in local control rate and survival rate between the ENI group and the IFI group within 3 years of treatment (P > .05). The incidence of postoperative complications in the ENI group was significantly higher than that in the IFI group, with a statistically significant difference (P < .05). When giving radical radiotherapy to esophageal cancer patients, the clinical total effective rate, survival rate, and local control rate of involving field irradiation are equivalent to the preventive radiation effect of precise radiotherapy for lymphatic drainage area. Besides, involving field irradiation can reduce the incidence of adverse reactions in patients after radiotherapy, which has high clinical value.

The Dawn of a New Era: Tumor-Targeting Boron Agents for Neutron Capture Therapy.

Cancer is widely recognized as one of the most devastating diseases, necessitating the development of intelligent diagnostic techniques, targeted treatments, and early prognosis evaluation to ensure effective and personalized therapy. Conventional treatments, unfortunately, suffer from limitations and an increased risk of severe complications. In light of these challenges, boron neutron capture therapy (BNCT) has emerged as a promising approach for cancer treatment with unprecedented precision to selectively eliminate tumor cells. The distinctive and promising characteristics of BNCT hold the potential to revolutionize the field of oncology. However, the clinical application and advancement of BNCT technology face significant hindrance due to the inherent flaws and limited availability of current clinical drugs, which pose substantial obstacles to the practical implementation and continued progress of BNCT. Consequently, there is an urgent need to develop efficient boron agents with higher boron content and specific tumor-targeting properties. Researchers aim to address this need by integrating tumor-targeting strategies with BNCT, with the ultimate goal of establishing BNCT as an effective, readily available, and cutting-edge treatment modality for cancer. This review delves into the recent advancements in integrating tumor-targeting strategies with BNCT, focusing on the progress made in developing boron agents specifically designed for BNCT. By exploring the current state of BNCT and emphasizing the prospects of tumor-targeting boron agents, this review provides a comprehensive overview of the advancements in BNCT and highlights its potential as a transformative treatment option for cancer.

Surgical site infection following open lobectomy in patients with lung cancer: A prospective study.

OBJECTIVE: To assess the incidence and risk factors of surgical site infection after open pulmonary lobectomy and to quantify their clinical and economic burden. METHODS: A prospective nested case-control study was performed on patients with lung cancer who underwent open lobectomy in the lung cancer center of West China Hospital from January 2017 to December 2019. Demographic, clinical data and medical costs were recorded. Logistic regression was used to evaluate risk factors associated with surgical site infection. A Mann-Whitney U test was carried out to evaluate the differences in medical costs. RESULTS: A total of 1395 patients were eligible, and the surgical site infection incidence was 13.47% (188/1395). Of the 188 instances of surgical site infection, 171 (90.96%) were classified as organ/space infection, 8 (4.25%) as superficial incisional infection and 9 (4.79%) as deep incisional infection. The patients with surgical site infection had significantly higher mortality (3.19% vs. 0.41%, p < 0.001), higher median medical cost (90774.95 yuan vs. 63079.38 yuan, p < 0.001), and longer postoperative length of stay (15 days vs. 9 days, p < 0.001). Multivariate logistic regression analysis indicated that age (odds ratio (OR) = 1.560, p = 0.007), respiratory failure (OR = 5.984, p = 0.0012), American Society of Anesthesiologists score (OR = 1.584, p = 0.005), operating time (OR = 1.950, p < 0.001), and operation team (OR = 1.864, p < 0.001) were independent risk factors for surgical site infection. CONCLUSIONS: The high incidence of surgical site infection indicates that postoperative infections remain a significant clinical burden in patients who underwent open lobectomy. Identifying risk factors timely through prospective surveillance may assist clinical decisions against surgical site infection.

Multi-Model Strategies for Prevention of Infection Caused by Certain Multi-Drug Resistant Organisms in A Rehabilitation Unit: A Semi-Experimental Study.

Objective: To assess the effectiveness of multi-model strategies on healthcare-associated infections (HAIs) caused by multi-drug resistant organisms (MDROs) in rehabilitation units. Methods: A semi-experimental study was conducted in a rehabilitation unit with 181 beds from January 2021 to December 2022 in a teaching hospital with 4300 beds in China. In 2021, many basic prevention and control measures were conducted routinely. Based on the basic measures, strengthening multi-model strategies for the prevention and control of MDROs was pursued year-round since 1 January 2022. Results: A total of 6206 patients were enrolled during the study period. The incidence density of HAIs caused by MDROs decreased from 1.22 (95% CI, 0.96~1.54) cases/1000 patient-days in the pre-intervention period to 0.70 (95% CI, 0.50~0.95) cases/1000 patient-days (p = 0.004). Similarly, the incidence of HAIs in the intervention period was 50.85% lower than that in the pre-intervention period (2.02 (95% CI, 1.50~2.72) vs. 4.11 (95% CI, 3.45-4.85) cases/100 patients, p < 0.001). The rate of MDROs isolated from the environment decreased by 30.00%, although the difference was not statistically significant (p = 0.259). Conclusion: Multi-model strategies can reduce the incidence of HAIs and HAIs caused by certain MDROs in the rehabilitation unit.

Analysis of risk factors associated with healthcare-associated carbapenem-resistant Klebsiella pneumoniae infection in a large general hospital: a case-case-control study.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a major public health threat in the world. To inform the prevention and control of CRKP infection in hospitals, this study analyzed the factors associated with CRKP infection and resistance to carbapenems in K. pneumoniae. This case-case-control study was carried out in a large general hospital in China from January 2016 to December 2018, comprising 494 hospitalized patients infected with CRKP (case group 1) and 2429 hospitalized patients infected with carbapenem-susceptible K. pneumoniae (CSKP, case group 2). We selected control groups from hospitalized patients without K. pneumoniae infections for the two case groups separately, with a 1:3 case-control ratio, to analyze the risk factors of the two case groups using the conditional logistic regression. Multivariate analysis showed that the risk factors of CRKP infection were intensive care unit (ICU) admission (odds ratio [OR], 6.85; 95% confidence interval [CI], 4.90-9.58; P < 0.001), respiratory failure (OR, 1.93; 95% CI, 1.34-2.77; P < 0.001), age-adjusted Charlson comorbidity index (aCCI; OR, 1.08; 95% CI, 1.02-1.15; P = 0.007), admission from the Emergency (OR, 1.37; 95% CI, 1.02-1.85; P = 0.036), and imipenem use (OR, 1.80; 95% CI, 1.30-2.49; P < 0.001). Among the aforementioned five risk factors, aCCI (OR, 1.09; 95% CI, 1.06-1.13; P < 0.001) was also identified as a risk factor of CSKP infections in multivariate analysis. The risk factors for resistance to carbapenems in K. pneumoniae were ICU admission, respiratory failure, admission from the Emergency, and imipenem use.

Effect of daily chlorhexidine bathing on reducing infections caused by multidrug-resistant organisms in intensive care unit patients: A semiexperimental study with parallel controls.

OBJECTIVE: To assess the effectiveness of daily bathing by chlorhexidine bathing on multidrug-resistant organisms in ICU, especially on carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Enterobacteriaceae (CRE). METHODS: Semiexperimental study which employed both precontrols and a parallel control was conducted. In the intervention period (from July 1 to December 31, 2016), strengthened infection control measures and daily bathing with 2% CHG-impregnated wipes once daily was performed in the ICU. Fifty-seven non-ICU wards with the occurrence of multidrug-resistant organisms (MDRO) infections during the same time were selected as parallel control group (only CHG bathing was not performed). The net effect of the 2% CHG daily bathing was evaluated by the difference in difference (DID) model. RESULTS: The DID model analysis showed that CHG bathing reduced the incidence of CRAB- and CRPA-caused infections in ICU by 1.56 and 2.15 cases/1000 patient days, and bathing of every 19 patients (95CI% 13 to 41) and 39 patients (95CI% 24 to 110) were able to prevent one case of HAIs of total MDROs and CRPA, respectively. However, CHG bathing showed no effect on MRSA, VRE, and CRE (p > 0.05). CONCLUSION: Daily bathing with 2% CHG-impregnated wipes can reduce HAIs caused by CRAB and CRPA, while it is not effective for the prevalence of infections caused by MRSA, VRE, and CRE.

Extracting Chinese events with a joint label space model.

The task of event extraction consists of three subtasks namely entity recognition, trigger identification and argument role classification. Recent work tackles these subtasks jointly with the method of multi-task learning for better extraction performance. Despite being effective, existing attempts typically treat labels of event subtasks as uninformative and independent one-hot vectors, ignoring the potential loss of useful label information, thereby making it difficult for these models to incorporate interactive features on the label level. In this paper, we propose a joint label space framework to improve Chinese event extraction. Specifically, the model converts labels of all subtasks into a dense matrix, giving each Chinese character a shared label distribution via an incrementally refined attention mechanism. Then the learned label embeddings are also used as the weight of the output layer for each subtask, hence adjusted along with model training. In addition, we incorporate the word lexicon into the character representation in a soft probabilistic manner, hence alleviating the impact of word segmentation errors. Extensive experiments on Chinese and English benchmarks demonstrate that our model outperforms state-of-the-art methods.

The effect of a full-time infection control nursing service in the prevention of multidrug-resistant organism in the orthopedic ward.

BACKGROUND: Our aim was to evaluate the effect of setting up a full-time infection control nursing service on reducing the prevalence of multidrug-resistant organism (MDRO) in the orthopedic ward. METHODS: From January 2015 to March 2019, routine prevention and control measures were taken for patients infected/colonized with MDRO in this ward, which was set as the pre-intervention period. The intervention period was from April 2019 to June 2021. The study was designed to evaluate whether the establishment of a full-time infection control nursing service could reduce the positive density of MDRO in the hospital by using an interrupted time-series model of a quasi experimental study. RESULTS: There were 11,759 patients during pre-intervention period and 8142 patients during intervention period. The total number of MDRO isolated before intervention was 177, of which 145 were obtained in hospital and 32 were brought in from outside hospital. The total number of MDRO isolated after intervention was 47, of which 29 were obtained in hospital and 18 were brought in from outside hospital. Before intervention, the positive density of MDRO in the orthopedic ward showed an increasing trend (ß1 = 0.02, P = 0.003). After intervention, the positive density of MDRO showed a downward trend (ß3 = - 0.05, P = 0.018). CONCLUSIONS: The establishment of the full-time infection control nursing service in the orthopedic ward can effectively reduce the nosocomial prevalence of MDRO.

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients.

OBJECTIVE: To investigate the efficacy of bevacizumab, paclitaxel and carboplatin in the treatment of ovarian cancer (OC) and the impact on patients' prognosis. METHODS: A total of 90 patients with OC treated at our institution were enrolled in this retrospective analysis. Among them, 30 patients treated with bevacizumab plus paclitaxel and carboplatin regimen were classified as an observation group (OG), and 60 other patients who received paclitaxel and carboplatin were assigned as a control group (CG). The changes of carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA) and carcinoembryonic antigen 242 (CA242) were observed before and after treatment in both groups. The clinical efficacy was observed, and the patients were followed up for 3 years to observe their survival and the adverse effects. Independent factors affecting patient's prognosis were evaluated by Cox regression analysis. RESULTS: After treatment, the objective remission rate and disease control rate were markedly higher in the OG than those in the CG (P<0.05). The serum CA199, CEA and CA242 levels of patients in the OG were dramatically lower than those in the CG after chemotherapy (P<0.05). There was no statistically significant difference in the incidence of leukopenia, hemoglobin reduction, neutropenia, gastrointestinal reactions, abnormal renal function and abnormal liver function between the two groups (P>0.05). Cox regression analysis identified that the degree of differentiation, International Federation of Gynecology and Obstetrics stage, CA199 and treatment regimen were independent factors affecting the prognosis of patients (P<0.05). CONCLUSION: Combined treatment of bevacizumab plus paclitaxel and carboplatin improved the treatment outcome and reduced the levels of CA199, CEA and CA242 in OC without increasing the incidence of adverse events.

Factors for Visual Acuity Improvement After Anti-VEGF Treatment of Wet Age-Related Macular Degeneration in China: 12 Months Follow up.

Purpose: To evaluate the treatment solutions and effectiveness of intravitreal ranibizumab (RBZ) or conbercept in patients with wet age-related macular degeneration (wAMD) in a real-life setting in China. Methods: The medical records of 368 patients with wAMD who started RBZ or conbercept treatment between 1 May 2014 and 30 April 2018 were evaluated. All patients were defined on fundus angiography at baseline to determine the subtype of AMD (PCV or CNV). We report visual acuity (VA) and central retinal thickness (CRT) measurements at baseline and 12 months. Results: The average number of anti-VEGF injections was 2.1 ± 1.2. The BCVA improvement of these two groups was similar with a difference of 1.00 letter (95% CI: -1.4~3.4, p = 0.8505). At the end of the study, a BCVA increase of at least 5 letters was determined to be a satisfactory efficacy endpoint. Several factors were related to the possible improvement in the satisfactory efficacy endpoint, including female sex (OR 2.07, 95% CI 1.22~3.51), number of injections (OR 1.40, 95% CI 1.12~1.75) and VA change at the first month (OR 13.75, 95% CI 7.41~25.51). Additionally, some factors were related to the possible reduction in the satisfactory efficacy endpoint, including diabetes (OR 0.27, 95% CI 0.10~0.73) and disease history (OR 0.75, 95% CI 0.57~0.98). Conclusion: Our study demonstrates that anti-VEGF drugs can effectively improve BCVA and reduce CRT in AMD patients. Sex, number of injections, VA change at the first month, diabetes and disease history are the most important factors affecting visual acuity.

Correction: A transition-based neural framework for Chinese information extraction.

[This corrects the article DOI: 10.1371/journal.pone.0235796.].

Long-term trends and regional variations of hypertension incidence in China: a prospective cohort study from the China Health and Nutrition Survey, 1991-2015.

OBJECTIVE: The aim is to explore the trends of hypertension incidence and regional variations in China from 1991 to 2015. DESIGN: A dynamic prospective cohort study. SETTING: China Health and Nutrition Survey 1991-2015. PARTICIPANTS: 12 952 Chinese adults aged 18+ years. PRIMARY OUTCOME MEASURES: Incident hypertension from 1993 to 2015. RESULTS: Age-standardised hypertension incidence increased from 40.8 per 1000 person-years (95% CI 38.3 to 43.4) between 1993 and 1997 to 48.6 (95% CI 46.1 to 51.0) between 2011 and 2015. The increasing trends were further supported by results from subsequent extended Cox proportional hazard model. In addition, results from the modelling analysis showed that individuals in eastern, central and northeastern China had greater risks of hypertension occurrence in comparison with their counterparts in western China. CONCLUSION: Hypertension incidence increased during the study period. The growth called for more attention on the health education and health promotion of individuals with great risks.

Handwashing Sink Contamination and Carbapenem-resistant Klebsiella Infection in the Intensive Care Unit: A Prospective Multicenter Study.

BACKGROUND: Handwashing sinks can become contaminated by carbapenem-resistant Klebsiella (CRK), including carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Klebsiella oxytoca (CRKO), but whether they are major sources of CRK infections remains unknown. METHODS: We performed a prospective multicenter study in 16 intensive care units (ICUs) (9 general and 7 neonatal) at 11 hospitals. All sinks at these locations were sampled to screen CRK. All CRK clinical isolates recovered between 2 weeks before and 3 months after sampling in ICUs with CRK-positive sinks or other participating ICUs at the same hospital were collected. Whole-genome sequencing of all isolates was performed. Isolates of the same sequence type (ST) were assigned to clones by calling single-nucleotide polymorphisms. RESULTS: Among 158 sinks sampled, 6 CRKP and 6 CRKO were recovered from 12 sinks in 7 ICUs, corresponding to a 7.6% CRK contamination rate. Twenty-eight clinical isolates were collected, and all were CRKP. The 34 CRKP isolates belonged to 7 STs, including ST789 (n = 14, all had blaNDM-5); ST11 (n = 12, 5 belonged to KL64 and 7 to KL47, all had blaKPC-2); ST709 (n = 4, all had blaNDM-5); and ST16, ST20, ST1027, and ST2407 (n = 1 each). One particular ST789 clone caused an outbreak and contaminated a sink. ST11_KL47 sink isolates were likely the source of a cluster of clinical isolates. Two ST11_KL64 isolates belonged to a common clone but were from 2 hospitals. CONCLUSIONS: Contaminated sinks were not the major source of CRK in our local settings. ST789 blaNDM-5-carrying CRKP might represent an emerging lineage causing neonatal infections.

Contamination of SARS-CoV-2 in patient surroundings and on personal protective equipment in a non-ICU isolation ward for COVID-19 patients with prolonged PCR positive status.

OBJECTIVES: We performed an environmental sampling study to investigate the environmental contamination of SARS-CoV-2 by COVID-19 patients with prolonged PCR positive status of clinical samples. METHODS: We sampled the air from rooms for nine COVID-19 patients with illness or positive PCR > 30 days, before and after nasopharyngeal/oropharyngeal swabbing and before and after nebulization treatment. We also sampled patients' surroundings and healthcare workers' personal protection equipment (PPE) in a non-ICU ward. SARS-CoV-2 was detected by PCR. RESULTS: Eighty-eight samples were collected from high-touch surfaces and floors in patient rooms and toilets, with only the bedsheets of two patients and one toilet positive for SARS-CoV-2. All air samples (n = 34) were negative for SARS-CoV-2. Fifty-five samples collected from PPE were all negative. CONCLUSION: Contamination of near-patient surroundings was uncommon for COVID-19 patients with prolonged PCR positive status if environmental cleaning/disinfection were performed rigorously. Airborne transmission of SARS-CoV-2 was unlikely in these non-ICU settings.

Risk factor for intestinal carriage of carbapenem-resistant Acinetobacter baumannii and the impact on subsequent infection among patients in an intensive care unit: an observational study.

OBJECTIVES: To assess the incidence and the impact of carbapenem-resistant Acinetobacter baumannii (CRAB) intestinal carriage on subsequent CRAB infection and to study risk factors of acquiring CRAB intestinal carriage among patients in intensive care unit (ICU). DESIGN: Observational study including a case-control study and a retrospective cohort study. SETTING: A 50-bed general ICU of a university hospital, China. METHODS: From May 2017 to April 2018, an observational study was conducted in a 50-bed general ICU of a university hospital in China. Rectal swabs were collected from ICU patients on admission and thereafter weekly. A case-control study was performed to analyse risk factors of the acquisition of CRAB intestinal carriage in ICU using multiple logistic regression. A retrospective cohort study was performed to address whether intestinal CRAB carriage could lead to an increased likelihood of subsequent CRAB infection using subdistribution hazard model regarding death in the ICU as a competing risk event. RESULTS: CRAB intestinal carriage was detected in 6.87% (66/961; 95% CI 5.27% to 8.47%) of patients on ICU admission, whereas 11.97% (115/961; 95% CI 9.91% to 14.02%) of patients acquired CRAB intestinal carriage during the ICU stay. Pancreatitis (OR 2.16, 95% CI 1.28 to 3.67), haematological disease (OR 2.26, 95% CI 1.42 to 3.58), gastric tube feeding (OR 3.35, 95% CI 2.03 to 5.51) and use of carbapenems (OR 1.84, 95% CI 1.11 to 3.07) were independent risk factors for acquiring CRAB intestinal carriage. The incidence of subsequent CRAB infection was 2.24-fold in patients with CRAB intestinal carriage compared with that in patients without (95% CI 1.48 to 3.39, p<0.001). CONCLUSION: More patients acquired CRAB intestinal carriage during their ICU stay than had on admission. Severity of illness, acute pancreatitis, tube feeding and use of carbapenems were independent risk factors of acquisition of CRAB intestinal carriage. Patients with CRAB intestinal carriage are more likely to develop CRAB infection.

A transition-based neural framework for Chinese information extraction.

Chinese information extraction is traditionally performed in the process of word segmentation, entity recognition, relation extraction and event detection. This pipelined approach suffers from two limitations: 1) It is prone to introduce propagated errors from upstream tasks to subsequent applications; 2) Mutual benefits of cross-task dependencies are hard to be introduced in non-overlapping models. To address these two challenges, we propose a novel transition-based model that jointly performs entity recognition, relation extraction and event detection as a single task. In addition, we incorporate subword-level information into character sequence with the use of a hybrid lattice structure, removing the reliance of external word tokenizers. Results on standard ACE benchmarks show the benefits of the proposed joint model and lattice network, which gives the best result in the literature.

Asymptomatic COVID-19 Patients Can Contaminate Their Surroundings: an Environment Sampling Study.

The contamination of patients' surroundings by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. We sampled the surroundings and the air of six negative-pressure non-intensive care unit (non-ICU) rooms in a designated isolation ward in Chengdu, China, that were occupied by 13 laboratory-confirmed coronavirus disease 2019 (COVID-19) patients who had returned from overseas travel, including 2 asymptomatic patients. A total of 44 of 112 (39.3%) surface samples were positive for SARS-CoV-2 as detected by real-time PCR, suggesting extensive contamination, although all of the air samples were negative. In particular, in a single room occupied by an asymptomatic patient, four sites were SARS-CoV-2 positive, highlighting that asymptomatic COVID-19 patients do contaminate their surroundings and impose risks for others with close contact. Placement of COVID-19 patients in rooms with negative pressure may bring a false feeling of safety, and the importance of rigorous environment cleaning should be emphasized.IMPORTANCE Although it has been well recognized that the virus SARS-CoV-2, the causative agent of COVID-19, can be acquired by exposure to fomites, surprisingly, the contamination of patients' surroundings by SARS-CoV-2 is largely unknown, as there have been few studies. We performed an environmental sampling study for 13 laboratory-confirmed COVID-19 patients and found extensive contamination of patients' surroundings. In particular, we found that asymptomatic COVID-19 patients contaminated their surroundings and therefore imposed risks for other people. Environment cleaning should be emphasized in negative-pressure rooms. The findings may be useful to guide infection control practice to protect health care workers.

Adjuvant breast inversely planned intensity-modulated radiotherapy with simultaneous integrated boost for early stage breast cancer : Results from a phase II trial.

PURPOSE: To report early toxicity and 5­year clinical outcomes of adjuvant breast inversely planned intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB) after breast-conserving surgery for early stage breast cancer patients. PATIENTS AND METHODS: In all, 467 patients including 406 invasive breast cancer and 61 ductal carcinoma in situ (DCIS) were enrolled in a single institutional phase II trial. All patients underwent IMRT-SIB treatment to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical bed were 45 and 60 Gy, respectively, delivered in 25 fractions over 5 weeks. The grade of maximum acute skin toxicity during treatment was recorded. Lung toxicity was noted within 6 months and patient-reported cosmetic outcomes were recorded at the 12 month follow-up after the end of radiotherapy. Clinical outcomes were assessed during follow-up. RESULTS: Median follow-up time was 5.46 years. Median age was 46 years old (range 22-70 years old). No patient with DCIS had a local recurrence or distant metastasis. Among 406 patients with invasive breast cancer, the unadjusted 5­year actuarial rate of locoregional control was 98.7% (95% confidence interval [CI] 97.5-100), and distant metastasis-free survival 98.7% (95% CI 97.4-100), respectively. Acute skin toxicity was recorded at grade 0-1 in 76.5% of patients, and grade 2 in 23.5% of patients. None of these patients had grade 3 or more than grade 3 skin toxicity. Grade 1 pneumonitis was found in 25.3% of patients. Assessment of patient reported cosmetic outcomes at the 12 month follow-up showed good or excellent outcome in 86.5% of cases. CONCLUSIONS: The use of inversely planned IMRT-SIB as part of breast-conserving therapy results in optimal 5­year tumor control and minor early toxicities.

Molecularly targeted therapy and immunotherapy for hormone receptor­positive/human epidermal growth factor receptor 2­negative advanced breast cancer (Review).

The advent of targeted therapy for hormone receptor­positive/human epidermal growth factor receptor 2­negative advanced breast cancer (HR+/HER2­ aBC) provides a novel therapeutic approach other than endocrine therapy. One targeted signaling pathway and three immune­checkpoints have been demonstrated to be in association with tumor proliferation and growth in HR+/HER2­ aBC. A number of phosphoinositide 3­kinase/AKT/mammalian target of rapamycin signaling pathway inhibitors demonstrate clinical activity against this tumor subtype. The CDK4/6 inhibitors as a single agent or in combination with endocrine therapy have produced promising tumor response with acceptable toxicity in patients with HR+/HER2­ aBC. Programmed death 1/programmed death ligand 1 (PD1/PD­L1) and cytotoxic T lymphocyte antigen­4 inhibitors can also produce an antitumor immune response, which provides a proof­of­principle for the initial utilization of immunotherapy in breast cancer. The aim of the present review was to discuss the mechanisms of action, clinical efficacy and safety profiles of all the targeted biological therapies and immunotherapies that have been approved or are currently under evaluation for HR+/HER2­ aBC.