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Background: Triple-negative breast cancer (TNBC) is associated with a dismal prognosis. Immune checkpoint inhibitors have shown promising antitumor activity in neoadjuvant settings. This single-arm, phase II trial aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy as the neoadjuvant therapy (NAT) in early TNBC., Methods: Patients received eight cycles of camrelizumab plus nonplatinum-based chemotherapy. The primary endpoint was total pathological complete response (pCR). Secondary endpoints included the breast pathological complete response (bpCR), adverse events (AEs). Multiomics biomarkers were assessed as exploratory objective., Results: Twenty of 23 TNBC patients receiving NAT underwent surgery, with the total pCR rate of 65% (13/20) and bpCR rate of 70% (14/20). Grade ≥3 treatment-related AEs were observed in 14 (60.9%) patients, with the most common AE being neutropenia (65.2%). Tumor immune microenvironment was analyzed between pCR and non-pCR samples before and after the NAT. Gene expression profiling showed a higher immune infiltration in pCR patients than non-pCR patients in pre-NAT samples. Through establishment of a predictive model for the NAT efficacy, TAP1 and IRF4 were identified as the potential predictive biomarkers for response to the NAT. Gene set enrichment analysis revealed the glycolysis and hypoxia pathways were significantly activated in non-pCR patients before the NAT, and this hypoxia was aggravated after the NAT., Conclusion: Camrelizumab plus nonplatinum-based chemotherapy shows a promising pCR rate in early-stage TNBC, with an acceptable safety profile. TAP1 and IRF4 may serve as potential predictive biomarkers for response to the NAT. Aggravated hypoxia and activated glycolysis after the NAT may be associated with the treatment resistance., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Empathy is an ability to fully understand and feel the mental states of others. We emphasize that empathy is elicited by the transmission of pain, fear, and sensory information. In clinical studies, impaired empathy has been observed in most psychiatric conditions. However, the precise impairment mechanism of the network systems on the pathogenesis of empathy impairment in psychiatric disorders is still unclear. Multiple lines of evidence suggest that disturbances in the excitatory/inhibitory balance in neurologic disorders are key to empathetic impairment in psychiatric disorders. Therefore, we here describe the roles played by the anterior cingulate cortex- and medial prefrontal cortex-dependent neural circuits and their impairments in psychiatric disorders, including anxiety, depression, and autism. In addition, we review recent studies on the role of microglia in neural network excitation/inhibition imbalance, which contributes to a better understanding of the neural network excitation/inhibition imbalance and may open up innovative psychiatric therapies., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Various tenofovir (TFV) prodrugs have been developed by introducing masking groups to the hydroxyls of the monophosphonate group to enhance intestinal absorption efficiency and therapeutic effects. However, the reported TFV prodrugs have drawbacks such as low bioavailability, systemic toxicity caused by their breakdown in non-targeted tissues, and potential low intracellular conversion efficiency. In the present study, we developed a class of TFV monobenzyl ester phosphonoamidate prodrugs without substitutions on the benzene ring. Compared with previous TFV prodrugs, compounds 3a and 3b developed in the present study showed higher anti-hepatitis B virus activity, stronger stability and higher levels of intrahepatic enrichment of the metabolic product (TFV), indicating the potential of these compounds as novel prodrugs with high efficiency and low systemic toxicity for the treatment of hepatitis B., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Many species living in groups can perform prosocial behaviors via voluntarily helping others with or without benefits for themselves. To provide a better understanding of the neural basis of such prosocial behaviors, we adapted a preference lever-switching task in which mice can prevent harm to others by switching from using a lever that causes shocks to a conspecific one that does not. We found the harm avoidance behavior was mediated by self-experience and visual and social contact but not by gender or familiarity. By combining single-unit recordings and analysis of neural trajectory decoding, we demonstrated the dynamics of anterior cingulate cortex (ACC) neural activity changes synchronously with the harm avoidance performance of mice. In addition, ACC neurons projected to the mediodorsal thalamus (MDL) to modulate the harm avoidance behavior. Optogenetic activation of the ACC-MDL circuit during non-preferred lever pressing (nPLP) and inhibition of this circuit during preferred lever pressing (PLP) both resulted in the loss of harm avoidance ability. This study revealed the ACC-MDL circuit modulates prosocial behavior to avoid harm to conspecifics and may shed light on the treatment of neuropsychiatric disorders with dysfunction of prosocial behavior., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that is associated with long-lasting memories of traumatic experiences. Extinction and discrimination of fear memory have become therapeutic targets for PTSD. Newly developed optogenetics and advanced in vivo imaging techniques have provided unprecedented spatiotemporal tools to characterize the activity, connectivity, and functionality of specific cell types in complicated neuronal circuits. The use of such tools has offered mechanistic insights into the exquisite organization of the circuitry underlying the extinction and discrimination of fear memory. This review focuses on the acquisition of more detailed, comprehensive, and integrated neural circuits to understand how the brain regulates the extinction and discrimination of fear memory. A future challenge is to translate these researches into effective therapeutic treatment for PTSD from the perspective of precise regulation of the neural circuits associated with the extinction and discrimination of fear memories.

Animals need discriminating auditory fear memory (DAFM) to survive, but the related neural circuits of DAFM remain largely unknown. Our study shows that DAFM depends on acetylcholine (ACh) signal in the auditory cortex (ACx), which is projected from the nucleus basalis (NB). At the encoding stage, optogenetic inhibition of cholinergic projections of NB-ACx obfuscates distinct tone-responsive neurons of ACx recognizing from fear-paired tone to fear-unpaired tone signals, while simultaneously regulating the neuronal activity and reactivation of basal lateral amygdala (BLA) engram cells at the retrieval stage. This NB ACh -ACx-BLA neural circuit for the modulation of DAFM is especially dependent on the nicotinic ACh receptor (nAChR). A nAChR antagonist reduces DAFM and diminishes the increased magnitude of ACx tone-responsive neuronal activity during the encoding stage. Our data suggest a critical role of NB ACh -ACx-BLA neural circuit in DAFM: manipulation of the NB cholinergic projection to the ACx via nAChR during the encoding stage affects the activation of ACx tone-responsive neuron clusters and the BLA engram cells during the retrieval stage, thus modulating the DAFM., (© 2023. The Author(s).)

Rural settlements are the spatial carriers of rural multifunctionality, and various issues related to livability are the main manifestations and causes of unbalanced and insufficient rural development. In the new era, it is imperative to promote the livability of rural settlements with the implementation of rural revitalization. However, compared with urban settlements, there are still fewer studies on the livability of rural settlements, especially those in disaster-prone areas; thus, this paper takes the upper reaches of the Minjiang River as the study area. It adopts GIS spatial analysis and the model of minimum cumulative resistance, etc., to conduct a livability evaluation and construct an optimization model by innovatively taking five aspects into account including site security and resource endowment. The results show that: (1) The overall livability of the region is relatively good, and the main factors affecting the livability are site security and economic affluence; (2) The location of rural settlements was highly livability-oriented, and the area of rural settlements in the moderate- and high-livability zones accounted for more than 90%; and (3) The key to improving the livability of rural settlements lies in the construction of development synergy, disaster management, cultural preservation and industrial upgrading, and thus, four types of settlement livability enhancement are proposed. The research results provide theoretical support for the construction of livable villages in the upper reaches of the Minjiang River and similar mountainous areas.

Mountainous areas are susceptible to disasters; the frequent occurrence of disasters drives the changes in ecosystem service value (ESV) and also brings certain ecological risk, which further increases the incidence of disasters. However, few scholars have investigated the spatiotemporal correlation between the ESV of disaster-prone mountainous areas and ecological risk index (ERI) with basin as the unit. This paper aims to clarify the spatial relationship between ESV and ERI under the changes of land use. Taking the upper reaches of the Minjiang River as the study area, the authors collected the land use data of 2000-2020, estimated ESV by the value equivalent factor per unit area method, and constructed the ERI. On this basis, the relationship between ESV and ERI was investigated in details. The results show the following: (1) From 2000 to 2020, the total ESV exhibited a fluctuating upward trend. The spatial distribution of ESV was greatly affected by slope and altitude; an important reason for the rising ESV in the study area is the increase of forest area and water area. (2) The upper reaches of the Minjiang River had a generally low ERI and relatively good overall ecoenvironment. After 2010, however, the ecological risk continued to rise. Most of the strongly high risk areas are areas with frequent human activities, such as low-altitude areas and river banks. (3) There is a spatial correlation and coupling between ESV and ERI in the study area; i.e., the strongly high ESV areas generally had a low ecological risk. The correlation intensified with the elapse of time. The changes in the service value of regional ecosystems driven by unreasonable land use will have a great impact on the ecoenvironment. By clarifying the spatiotemporal relationship between ESV and ERI, this research provides theoretical basis and data support to the formulation of ecoenvironmental restoration and protection plans for the upper reaches of the Minjiang River and to the coordinated development between society, economy, and ecoenvironment in the region., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Linsen Duan et al.)

The reference intensity ratio (RIR) method, using X-ray diffraction (XRD), is considered one most of the rapid and convenient approaches for phase quantification in multi-phase mixture, in which nanocrystals are commonly contained in a mixture and cause a broadening of the diffraction peak, while another broadening factor, instrumental broadening, does not attract enough attention in related quantitative analysis. Despite the specimen consisting of 50 wt.% TiO 2 nanomaterials (nano-TiO 2 ) and 50 wt.% microscale ZnO powder, the nano-TiO 2 quantitative result changes from 56.53% to 43.33% that occur as a variation of instrumental broadening are caused by divergence slit adjustment. This deviation could be accounted through a mathematical model that involves instrumental broadening. The research in this paper might provide a useful guide for developing an approach to measure accuracy quantification in unknown multi-phase mixtures.

Research on the poverty risk caused by geological disasters in disaster-prone areas is a useful exploration to coordinate social economic development with disaster prevention and reduction, and is of great significance to the regional sustainable development. Based on statistical data and spatial data, this paper takes Sichuan Province as the typical research area. Remote sensing and geographic information technology are used to study the poverty risk caused by disasters based on the quantitative evaluation of geological disasters risk and regional development level. The spatial differentiation characteristics of poverty risk caused by disasters are explored on the 1 km × 1 km grid scale. The results indicate that (1) the overall risk of geological disasters in Sichuan Province is relatively high, with high and relatively high risk areas accounting for more than 40% and low and relatively low risk areas accounting for less than 30%. The risks in Mountain and Ravine Areas are significantly higher than other areas. (2) The regional development level in Sichuan Province is relatively high, but with significant spatial differences. The development level of high-altitude areas and remote mountainous areas is quite different from that of the Chengdu Plain in the middle Sichuan Province. The uneven development in the east, middle, and west is a prominent problem. (3) The poverty risk caused by disasters is high, and the spatial pattern presents a characteristic of "high in the west and low in the east" with high positive spatial correlation. High-High Cluster Areas are mainly distributed in western and southwestern Sichuan. Low-Low Outlier Areas are mainly distributed in Chengdu Plain and Hilly Areas of Sichuan Basin. High-Low Outlier and Low-High Outlier Areas occupy a relatively small percentage with scattered distribution. This paper provides some theoretical support for policy formulation and management of coordinated development of regional socioeconomic and ecological environment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Mitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate MHI's efficacy and safety in sentinel lymph node biopsy (SLNB)., Methods: The trial was conducted across seven hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and technetium-99m (99mTc) during the surgery. Sentinel node detection rates were compared between MHI and 99mTc to evaluate non-inferiority and concordance. Non-inferiority was valid if the lower limit of the 95% CI of sentinel node relative detection rate difference was ≥-5%., Results: SLN relative detection rate of MHI was 97.31% (362/372). Of the SLNs, 79.69% (871/1093) were co-detected by both tracers. Of the patients, 4.13% (16/387) had adverse events and recovered during the follow-up., Conclusions: MHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB., Clinical Trial Registration: http://www.chinadrugtrials.org.cn, CTR20192435., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XW declared a shared affiliation with the authors CW and YSW to the handling editor at the time of review., (Copyright © 2022 Jiao, Yang, Chen, Wang, Jin, Zhao, Gao, Wang, Li, Zhao, Wu, Fan, Wang, Liu, Wang and Wu.)

The carbon sequestration function of the ecosystem is one of the most important functions of ecosystem service, and it of great significance to study the spatio-temporal differentiation of carbon storage for promoting regional sustainable development. Ecosystems on the Western Sichuan Plateau are highly variable, but its spatio-temporal differentiation and driving factors are not yet clear. In this study, on the basis of land use monitoring data, meteorological and demographic data interpreted from Landsat remote sensing image, and through GIS analysis tools, the carbon storage module of InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) model was used to estimate carbon storage and geodetector was used to detect the driving factors of carbon storage spatial differentiation. The results show that: (1) The carbon storage increased to 1.2455 × 10 10 t from 1.2438 × 10 10 t in the past 20 years, the ecosystem developed in a healthy way overall. (2) Carbon storage show High-High and Low-Low aggregation characteristics, but the area decreased by 1481.81 km 2 and 311.11 km 2 respectively, and the spatial cluster effect gradually weakened. (3) HAI is the leading factor causing the spatio-temporal differentiation of regional carbon storage, followed by temperature and NDVI; the interaction between factors significantly enhances the spatial differentiation of carbon storage, indicating that the change of carbon storage is the result of the joint action of natural and socioeconomic factors. The results of the study provide some theoretical basis for the development of differentiated ecological regulation models and strategies, and help to promote high-quality regional development., (© 2022. The Author(s).)

Purpose: To investigate the efficacy and safety of pyrotinib in treating patients with human epidermal growth factor receptor type 2 (HER2)-positive breast cancers with brain metastasis., Patients and Methods: This is a multicenter retrospective study, and the HER2-positive breast cancer patients with brain metastasis were studied. The enrolled patients were given pyrotinib 400 mg orally once per day for 21 days as one cycle, and evaluated every two cycles. All relevant data were detected for final assessments including medical history, clinical examination, histopathology, immunohistochemistry, radiographic imaging, treatment outcome, and adverse events., Results: Forty-two female patients in total were enrolled in this study. The objective response rate (ORR) and disease control rate (DCR) of central nervous system (CNS), were found in 20 of 42 (47.6%) and in 39 of 42 (92.8%), respectively, while for extra-CNS, the respective ORR and DCR were in 9 of 38 (23.6%) and in 36 of 38 (94.7%), respectively. The compounded ORR and DCR were seen in 17 of 42 (40.4%) and in 39 of 42 (92.8%), respectively. The improvement rate of craniocerebral symptoms after treatment was (19/19) 100% and the median duration was 15 months. The median effective time of brain metastases and other metastases was 43 and 50 days. The median follow-up time was 22 months (interquartile range, 16.0-24.3 months). The median time for progression in brain metastasis was 16.6 months. The median time to progress for our group patients was 11.1 months. Sixteen patients (36%) with adverse reactions were recorded in the study., Conclusion: Pyrotinib combined with chemotherapy/radiotherapy or alone showed significantly greater local control rates and progression free survival (PFS), with manageable toxicity for patients with HER2-positive breast cancer with brain metastases, and further follow-up will provide an overall survival (OS) data., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The olfactory dysfunction can signal and act as a potential biomarker of preclinical AD. However, the precise regulatory mechanism of olfactory function on the neural pathogenesis of AD is still unclear. The impairment of neural networks in olfaction system has been shown to be tightly associated with AD. As key brain regions of the olfactory system, the olfactory bulb (OB) and the piriform cortex (PCx) have a profound influence on the olfactory function. Therefore, this review will explore the mechanism of olfactory dysfunction in preclinical AD in the perspective of abnormal neural networks in the OB and PCx and their associated brain regions, especially from two aspects of aberrant oscillations and synaptic plasticity damages, which help better understand the underlying mechanism of olfactory neural network damages related to AD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: With the improvement of the efficacy of neoadjuvant therapy (NAT) that is guided by molecular subtypes, the rate of pathologically node-negative disease after NAT (ypN0) is increasing for HER2 positive (HER2+) and triple-negative (TN) breast cancer patients. The necessity of axillary surgery for patients with high ypN0 has been questioned. This study aimed to identify patients among HER2+ and TN breast cancer with low risk for axillary metastases after NAT, and, perhaps, they are suitable for selective elimination of axillary surgery staging., Methods: From January 2010 to August 2018, 865 breast cancer patients who underwent NAT were included in this retrospective clinical study, and 184 patients (21.3%,184/865) suffered from TN and HER2+ breast cancer and received full-course NAT. The correlation among clinicopathological characteristics of HER2+ and TN breast cancer and ypN0 were analyzed., Results: Among the 184 HER2+ and TN breast cancer patients, tumor staging, lymph node staging and Ki-67 before NAT, clinically node-negative disease after NAT (ycN0), and breast radiologic and pathologic complete response (bpCR) were correlated with ypN0 (P<0.05). Lymph node staging before NAT (OR =0.363, P<0.001), ycN0 (OR =4.995, P<0.001) and bpCR (OR =11.285, P<0.001) were the independent effects of ypN0. The ypN0 rate after NAT in cN0/1 patients with bpCR and ycN0 (97.6%, 40/41) was significantly higher than that in cN2/3 patients (62.5%, 10/16) (P<0.001). Among the 37 patients with initial nodal ultrasonography showing cN0 disease, 17 of 17 (100.0%) with and 18 of 20 (90.0%) without bpCR had no evidence of residual nodal disease (P=0.178). Among the 42 patients with cN1 to ycN0, 23 of 24 (95.8%) with and 10 of 18 (55.6%) without bpCR had no evidence of residual nodal disease (P<0.001). Patients without bpCR had a relative risk for nodal residual metastases of 10.560 (95% CI: 2.720-41.003; P<0.001) compared with those with bpCR in cN1 group., Conclusions: In terms of HER2+ and TN breast cancer patients, clinical lymph node staging before NAT, ycN0 and bpCR were the independent predictors of ypN0. bpCR was highly correlated with nodal status after NAT. The risk of axillary lymph nodes residual metastases after NAT in the patients of bpCR with cN0 and cN1 to ycN0 was less than 5%, thus making it possible to selectively avoid axillary surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-573). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Background: Asthma is a prevailing respiratory disease among children, characterized by allergic airway inflammation, airway remodeling, and airway hyperresponsiveness. Although it is well-known that long non-coding RNAs (lncRNAs) are linked to a variety of human diseases and well-documented, very few studies explore its role in asthma. In this study, we investigate the effects of lncRNA PVT1 on the promotion of airway inflammation and its associated mechanisms., Methods and Materials: Human small airway epithelial cells (HSAECs) with PVT1 overexpressed or knocked down were constructed, and platelet activating factor (PAF) was used to treat HSAECs to mimic the pathological process of asthma in vitro. The expressions of prostaglandin E2 (PGE2), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of PKC, MyD88, and NF-ĸB were measured by Western blot. Monolayer permeability of HSAECs was also compared within different groups. Luciferase reporter gene assay was employed to detect the targeting relationship between PVT1 and miR-149., Results: The knockdown of PVT1 attenuated the levels of inflammatory factors induced by PAF and destruction of cell-barrier function. The overexpression of PVT1 facilitated the pathological development. Additionally, miR-149 was identified as a target microRNA of PVT1, and the overexpression of miR-149 could reverse the effects of PVT1 on PAF-induced HSAECs., Conclusion: These findings suggest that PVT1 may represent a novel potential target for treatment of asthma., (© 2020 Wiley Periodicals LLC.)

The hippocampal CA3 contributes to spatial working memory (SWM), but which stage of SWM the CA3 neurons act on and whether the lateralization of CA3 function occurs in SWM is also unknown. Here, we reveal increased neural activity in both sample and choice phases of SWM. Left CA3 (LCA3) neurons show higher sensitivity in the choice phase during the correct versus error trials compared with right CA3 (RCA3) neurons. LCA3 initiates firing prior to RCA3 in the choice phase. Optogenetic suppression of pyramidal neurons in LCA3 disrupts SWM only in the choice phase. Furthermore, we discover that parvalbumin (PV) neurons, rather than cholinergic neurons in the medial septum (DB were cholinergic neurons), can project directly to unilateral CA3. Selective suppression of PV neurons in the MS projecting to LCA3 impairs SWM. The findings suggest that MS PV -LCA3 projection plays a crucial role in manipulating the lateralization of LCA3 in the retrieval of SWM.

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) ( χ (2)=0.030, P =0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ (2)=0.037, P =0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) ( χ (2)=6.811, P =0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) ( χ (2)=2.929, P =0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ (2)=1.045, P =0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] ( P =0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % ( P =0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

Purpose: This study aims to determine the optimal time to perform sentinel lymph node biopsy (SLNB) for patients with clinically node-negative (cN 0 ) disease following neoadjuvant chemotherapy (NAC)., Method: From April 2008 to April 2018, 592 patients with breast cancer underwent after NAC were included in this study. Patients with cN 0 before and ycN 0 disease after NAC received SLNB and axillary lymph node dissection (ALND) in case of positive sentinel lymph nodes (SLNs). For patients with clinically node-positive (cN + ) disease, the axillary surgery is based on the doctor's decision., Result: In general, 17.6% (104/592) of patients achieved total pathologic complete response (pCR), which was 6.9%, 33.3%, 32.3% and 15.3%, respectively, among patients with hormone receptor (HR) positive/ human epidermal growth factor receptor-2 (HER-2) negative (HR+/HER2-) subtype, triple-negative (TN) subtype, HER-2 positive (HER2+) subtype with and without targeted therapy (p < 0.001). Among the 525 cN + patients, the axillary nodal pCR (apCR) rate was 34.5%, and the apCR rate was significantly higher in patients with HER2+ (58.6% with and 28.2% without targeted therapy respectively) and TN subtype (53.2%) than that in patients with HR+/HER2-subtype (21.2%, p < 0.001). Among the 67 cN 0 patients, the positive rate of SLNs was 19.4% (13/67), which was 28.1% (9/32), 13.3% (2/15) and 10.0% (2/20), respectively, among patients with HR+/HER2-, TN and HER2 + subtypes., Conclusion: The pCR rates were significantly related to molecular subtype. Combining the apCR rates in different molecular subtypes of cN + patients and the excellent locoregional control of AOSOG Z0011 and AMAROS trials in cN 0 patients, it would be preferable to perform SLNB prior to NAC for cN 0 patients with HR+/HER2- subtype, and SLNB after NAC for those cN 0 patients with TN and HER2+ subtype to increase the chance of avoiding ALND. Among cN 0 patients, TN and HER2 + subtypes would benefit more from axillary de-escalating surgery after NAC than HR+/HER2- subtype.

Objective: To investigate the clinical features and treatment in patients of marginal zone lymphoma (MZL)with monoclonal immunoglobulin (McIg)., Methods: The clinical data of MZL patients with McIg, including 3 cases diagnosed and treated in Beijing Anzhen Hospital from Jan 2007 to Dec 2014 were retrospectively studied, meanwhile 36 patients searched from literatures were reviewed., Results: Of a total of 39 patients, the ratio of male and female was 1.05∶1 with an average age of 65.1± 12.3 years old. 28 cases (71.8%)were with mucosa associated lymphoid tissue lymphomas (MALTL), 9 cases (23.1% )with nodal marginal zone lymphoma, and 2 cases (5.1%)with splenic marginal zone lymphoma. Nine cases (23.1% )were in the early stage, 30 cases (76.9%)in the advanced stage. The common initial symptom was non-mass lesions (65.5%), such as skin purpura, peripheral neuropathy; 13 patients (33.3% )were accompanied by autoimmune phenomenon, and most were with Sjogren's syndrome. Among MALTL patients, the common primary lesion was in non- gastrointestinal tract (17 cases, 60.7%). Most of patients with McIg were one with McIgM (82.0%); the others with McIgA, Mcκ-light chain, McIgG and double McIg. The level of plasma McIgM was (25.55±21.31)g/L, which was higher in advanced stage patients than in early stage ones [(29.85±20.60)g/Lvs (3.23±2.95)g/L,P= 0.008]. The complete remission (CR)rate was 56.0% and the overall response rate (ORR)92.0%, respectively in 30 patients treated by chemotherapy. At a median follow- up of 10 months, the 3- year progression free survival and the 3-year overall survival were 44.7% and 76.5%, respectively. The rates of ORR and CR in the patients received rituximab- included regimen were seemly better than those without rituximab one (100.0%vs 78.6%, 63.6%vs 50.0%;P>0.05), but no statistic differences were found. The CR rate in patients with McIgM was significantly higher than that with non- McIgM (P=0.026). The plasma McIgM level decreased after chemotherapy (P=0.002)., Conclusion: The MZL with McIg, perhaps a kind of unique subtype, usually occurred in 60 years or older patients. It was often diagnosed in patients of advanced stage and susceptible to autoimmune phenomenon. MALTL in non- gastrointestinal tract was more prone to find McIg. In MZL patients with McIg, McIgM was more common and other McIg rare. Rituximab-included regimen produced a better therapeutic response.

Objective: The aim of this study was to determine the impact of routinely performed internal mammary sentinel lymph node biopsy (IM-SLNB) on the staging and treatment, and to analyze the success rate, complications and learning curve., Methods: All patients with biopsy-proven breast cancer who underwent sentinel lymph node biopsy between 2012 and 2014 were included in a prospective analysis. Internal mammary sentinel lymph node biopsy (IM-SLNB) was performed in all patients with IM-SLN visualized on preoperative lymphoscintigraphy and/or detected by intraoperative gamma probe detection. The adjuvant treatment plan was adjusted according to the current guidelines., Results: In a total of 349 patients, 249 patients (71.1%) showed internal mammary drainage. IM-SLNB was performed in 153 patients with internal mammary drainage, with a success rate of IM-SLNB of 97.4% (149/153). Pleural lesion and internal mammary artery bleeding were found in 7.2% and 5.2% patients, respectively. In 8.1% of patients (12/149) the IM-SLN was tumor positive. In the group of patients who underwent IM-SLNB, lymph node staging was changed in 8.1% of patients, and IMLNs radiotherapy was guided by these results, however, systemic treatment was changed in only 0.7% of the patients., Conclusions: IM-SLNB has a high successful rate and good safety. Identification of internal mammary metastases through IM-SLNB may provide more accurate staging and guide the tailored internal mammary radiotherapy., Trial Registration: ClinicalTrials. gov, NCT01642511.

Male breast cancer (MBC) is considered as a rare disease that accounts for less than 1% of all breast cancers, and its treatment has been based on the evidence available from female breast cancer. Axillary sentinel lymph node biopsy (SLNB) is now regarded as the standard of care for both female and male patients without clinical and imaging evidence of axillary lymph node metastases, while internal mammary SLNB has rarely been performed. Internal mammary chain metastasis is an independent prognostic predictor. Internal mammary SLNB should be performed to complete nodal staging and guide adjuvant therapy in MBC patients with preoperative lymphoscintigraphic internal mammary chain drainage. We report both axillary and internal mammary SLNB in two cases with MBC. Internal mammary sentinel lymph node did contain metastasis in one case.

Objective: To evaluate the accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy (NAC) with three-dimensional (3D) reconstruction technique., Methods: This was a prospective study. The data of 61 patients with pathologically proven solitary invasive ductal carcinoma (IIA-IIIC) who had received 6 to 8 cycles of NAC from July 2010 to August 2013 was analyzed. All the patients were female, aging from 31 to 70 years with a median of 49 years. Breast specimen after surgery was prepared with part-mount sub-serial section, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of pathological and MRI residual tumors was reconstructed with 3D-DOCTOR software. The longest diameter, maximum cross-section area and volume of the residual tumors determined using 3D MRI were compared with 3D pathological findings, and the associations between MRI and pathology were analyzed by Spearman rank correlation and Bland-Altman analysis., Results: The longest diameter, maximum cross-section area and volume of the residual tumors after NAC measured by MRI and pathology was highly correlated (r=0.942, 0.941, 0.903, all P=0.00). MRI appears to underestimate pathology in the longest diameter, maximum cross-section area, but slightly overestimate in volume, and two methods had a good consistence (MD=0.3 cm, 95% CI: -1.43 to 1.9 cm; MD=1.39 cm², 95% CI: -9.55 to 12.34 cm²; MD=-0.433 cm³, 95% CI: -7.065 to 6.199 cm³)., Conclusion: 3D MRI reconstruction after NAC could accurately detects the residual tumors after neoadjuvant chemotherapy, and contribute to select patients who received breast conserving therapy after NAC with tumor downstaging.

Background: The main purpose of the study reported here was to validate the clinical value of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram that predicts non-sentinel lymph node (SLN) metastasis in SLN-positive patients with breast cancer., Methods: Data on 1,576 patients who received sentinel lymph node biopsy (SLNB) at the Shandong Cancer Hospital from December 2001 to March 2014 were collected in this study, and data on 509 patients with positive SLN were analyzed to evaluate the risk factors for non-SLN metastasis. The MSKCC nomogram was used to estimate the probability of non-SLN metastasis and was compared with actual probability after grouping into deciles. A receiver-operating characteristic (ROC) curve was drawn and predictive accuracy was assessed by calculating the area under the ROC curve., Results: Tumor size, histological grade, lymphovascular invasion, multifocality, number of positive SLNs, and number of negative SLNs were correlated with non-SLN metastasis (P<0.05) by univariate analysis. However, multivariate analysis showed that tumor size (P=0.039), histological grade (P=0.043), lymphovascular invasion (P=0.001), number of positive SLNs (P=0.001), and number of negative SLNs (P=0.000) were identified as independent predictors for non-SLN metastasis. The trend of actual probability in various decile groups was comparable to the predicted probability. The area under the ROC curve was 0.722. Patients with predictive values lower than 10% (97/492, 19.7%) had a frequency of non-SLN metastasis of 17.5% (17/97)., Conclusion: The MSKCC nomogram can provide an accurate prediction of the probability of non-SLN metastasis, and offers a reference basis about axillary lymph node dissection. Axillary lymph node dissection could be avoided in patients with predictive values lower than 10%.

The design and fabrication of functional nanocomposites is an active area of research because composite particles have significantly improved physical and chemical properties over those of their single-component counterparts. Traditionally, chemical pretreatments of the components were used to enhance their physicochemical or chemical interactions. Here, we propose a novel approach to taking advantage of the beauty of thermodynamics. A series of functional materials, including graphene nanosheets, carbon nanotubes, noble metals, magnetic materials, conducting polymers, attapulgite, and etc. were incorporated with polystyrene particles by a thermodynamic driving force. This unique approach is facile and versatile and shows the considerable significance of developments in both scientific methodology and particle engineering.

Using 1-octyl-3-methylimidazolium hexafluorophosphate ([C(8)MIM][PF(6)]) ionic liquid as extraction solvent, organophosphorus pesticides (OPPs) (parathion, phoxim, phorate and chlorpyifos) in water were determined by dispersive liquid-liquid microextraction (DLLME) combined with high-performance liquid chromatography (HPLC). The extraction procedure was induced by the formation of cloudy solution, which was composed of fine drops of [C(8)MIM][PF(6)] dispersed entirely into sample solution with the help of disperser solvent (methanol). Parameters including extraction solvent and its volume, disperser solvent and its volume, extraction time, centrifugal time, salt addition, extraction temperature and sample pH were investigated and optimized. Under the optimized conditions, up to 200-fold enrichment factor of analytes and acceptable extraction recovery (>70%) were obtained. The calibration curves were linear in the concentration range of 10.5-1045.0 microg L(-1) for parathion, 10.2-1020.0 microg L(-1) for phoxim, 54.5-1089.0 microg L(-1) for phorate and 27.2-1089.0 microg L(-1) for chlorpyifos, respectively. The limits of detection calculated at a signal-to-noise ratio of 3 were in the range of 0.1-5.0 microg L(-1). The relative standard deviations for seven replicate experiments at 200 microg L(-1) concentration level were less than 4.7%. The proposed method was applied to the analysis of four different sources water samples (tap, well, rain and Yellow River water) and the relative recoveries of spiked water samples are 99.9-115.4%, 101.8-113.7% and 87.3-117.6% at three different concentration levels of 75, 200 and 1000 microg L(-1), respectively.