Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

As one of the common traumatic diseases in clinical practice,peripheral nerve injury(PIN)often causes nerve pain,abnormal reflexes,autonomic disorders,and even sensorimotor disorders due to the slow regeneration rate after injury,which seriously affects body function.Even as the gold standard of treatment,autologous nerve transplantation has limitations such as limited donor area and donor injury,which greatly limits its clinical application effect.Therefore,the preparation of ar-tificial nerve grafts suitable for clinical practice has become the future development trend of peripheral nerve injury treatment,and the repair of injury defects and the promotion of nerve regeneration have also become research hotspots in tissue engineer-ing and regenerative medicine.In recent years,extensive research has been carried out on nerve guidance conduits(NGCs)in the field of nerve regeneration and repair,in which scaffold materials and intemal fillers have also become the focus of research as the core elements of neural catheters,and a series of achievements have been made in the application of new materials,em-bedding stem cells/precursor cells,and developing trophic factors and drug-loaded sustained-release systems.Therefore,this paper focuses on the application progress of hydrogel and its related derivative materials in the field of peripheral nerve injury repair,and provides new ideas for promoting the related research of tissue engineering and clinical medicine.

Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.
Humans ; Adult ; Hepatitis B, Chronic/complications* ; Retrospective Studies ; Cross-Sectional Studies ; Hepatitis B e Antigens ; DNA, Viral ; Antiviral Agents/therapeutic use* ; Hepatitis B virus/genetics* ; Demography

Aim To investigate the mechanism and search for potential biomarkers of ovalbumin ( OVA ) -induced asthma in mice base on lipidomics. Methods A BALB/c mouse model of asthma was prepared by OVA. TNF-α, IL-4, IL-10, IFN-γ levels in BALF and IgE level in serum were measured by ELISA. The inflammatory changes in mouse lung tissue were observed using HE staining. Lipid mediators ( LMs) in lung tissue and serum were quantified with UPLC-MS/ MS strategy. Results IgE level in serum and TNF-α, IFN-γ levels in BALF were higher (P <0.05) of asthmatic mice.Typical inflammatory manifestations were seen in lung tissue of asthmatic mice. A total of 57 lipid mediators were quantified with UPLC-MRM. LMs metabolic profiles differed significantly in serum and lung tissue between asthmatic and normal mice, 17 significantly different LMs were found in lung tissue and 6 LMs were found in serum, and the differential metabolites were produced through the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 oxidase (P450) metabolic pathways. Conclusions OVA-induced allergic asthma can cause disorder of lip-id mediators, LMs and cytokines are involved in the occurrence and development of asthma. The differential LMs have potential research value as biomarkers for the development of allergic asthma.

Male ; Humans ; Germ-Line Mutation ; Prostatic Neoplasms/genetics* ; BRCA2 Protein/genetics* ; Genetic Predisposition to Disease

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 μmol·L^-1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Atractyloside/pharmacology* ; Cyclophilin D ; Male ; Matrix Metalloproteinases ; Mice ; Mitochondrial Membrane Transport Proteins/metabolism* ; Mitochondrial Permeability Transition Pore ; RNA, Messenger ; Rats

With continuous introduction of relevant national policies on famous classical formulas, the research of famous classical formulas is popular all over the country. Different from other new drugs, in the research and development process of famous classical formulas, substance benchmark is earlier than the product, suggesting that the research and development of substance benchmark is of great significance. Based on previous work of the authors, content of substance benchmark of famous classical formulas was analyzed, which was included in the document The Management Regulation of Simplified Registration and Approval over Chinese Herbal Medicine Compound Preparations of Ancient Famous Classical Formulas released by the National Medical Products Administration in May 2018. In this paper, the significance of substance benchmark development was described, a five-stage of research strategy was proposed, covering the prescription textual research and historical evolution, the collection and quality evaluation of medicinal materials, the processing method and quality evaluation of decoction pieces, the preparation and quality research of substance benchmark, the drafting and formulating of quality standard over substance benchmark. At the same time, some suggestions were put forward to the feasibility of compound preparations development over famous classical formulas, the implementation difficulty of resource evaluation over Chinese medicinal materials, and the irrationality on the quality correlation of Chinese medicinal materials. All of these are expected to provide reference and enlightenment for the development and policy officially landed over ancient famous classical formulas.

To explore the way of prenatal echocardiography in the diagnosis of fetal double aortic arch . Methods T he data of fetuses diagnosed as double aortic arch in 6 prenatal centers in Hunan in echocardiograms performed at 20－36 weeks of gestation from 2013 to 2018 were reviewed . T he characteristics of echocardiographic with double aortic arch , and the associated malformations were observed ,the clinical outcome were analyzed . Results T he main echocardiographic features of the double aortic arch were three‐vessel‐tracheal view s ,which showed a bifurcation of the ascending aorta and a ring consisted of aortic right and left arch . From this retrospective analysis , 29 double aortic arches were identified ,which 8 cases ( 28% ) combined with cardiac defect and extracardiac abnormalities , 1 case with 22q11 deletion . Among them ,5 cases were confirmed by autopsy ,24 cases were diagnosed by computed tomography angiography ( 8 cases were confirmed by operation ) . Conclusions Systematic prenatal echocardiography in the diagnosis of fetal double aortic arch has significant clinical value in the cliagnose of double aortic arch ,w hether it is associated with other malformations and is important for assessing fetal prognosis .

OBJECTIVETo establish the association between the geometric anatomical characteristics of the patients and the corresponding three-dimensional (3D) dose distribution of radiotherapy plan via feed-forward back-propagation neural network for clinical prediction of the plan dosimetric features.

METHODSA total of 25 fixed 13-field clinical prostate cancer intensity-modulated radiation therapy (IMRT)/stereotactic body radiation therapy (SBRT) plans were collected with a prescribed dose of 50 Gy. With the distance from each voxel to the planned target volume (PTV) boundary, the distance from each voxel to each organ-at-risk (OAR), and the volume of PTV as the geometric anatomical characteristics of the patients, the voxel deposition dose was used as the plan dosimetric feature. A neural network was used to construct the correlation model between the selected input features and output dose distribution, and the model was trained with 20 randomly selected cases and verified in 5 cases.

RESULTSThe constructed model showed a small model training error, small dose differences among the verification samples, and produced accurate prediction results. In the model training, the point-to-point mean dose difference (hereinafter dose difference) of the 3D dose distribution was no greater than 0.0919∓3.6726 Gy, and the average of the relative volume values corresponding to the fixed dose sequence in the DVH (hereinafter DVH difference) did not exceed 1.7%. The dose differences among the 5 samples for validation was 0.1634∓10.5246 Gy with percent dose differences within 2.5% and DVH differences within 3%. The 3D dose distribution showed that the dose difference was small with reasonable predicted dose distribution. This model showed better performances for dose distribution prediction for bladder and rectum than for the femoral heads.

CONCLUSIONWe established the relationships between the geometric anatomical characteristics of the patients and the corresponding planning 3D dose distribution via feed-forward back-propagation neural network in patients receiving IMRT/SBRT for the same tumor site. The proposed model provides individualized quality standards for automatic plan quality control.

OBJECTIVE: To assess the performance of a whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating thymic carcinoma from lymphoma, and compare it with that of a commonly used hot-spot region-of-interest (ROI)-based ADC measurement. MATERIALS AND METHODS: Diffusion weighted imaging data of 15 patients with thymic carcinoma and 13 patients with lymphoma were retrospectively collected and processed with a mono-exponential model. ADC measurements were performed by using a histogram-based and hot-spot-ROI-based approach. In the histogram-based approach, the following parameters were generated: mean ADC (ADCmean), median ADC (ADCmedian), 10th and 90th percentile of ADC (ADC10 and ADC90), kurtosis, and skewness. The difference in ADCs between thymic carcinoma and lymphoma was compared using a t test. Receiver operating characteristic analyses were conducted to determine and compare the differentiating performance of ADCs. RESULTS: Lymphoma demonstrated significantly lower ADCmean, ADCmedian, ADC10, ADC90, and hot-spot-ROI-based mean ADC than those found in thymic carcinoma (all p values < 0.05). There were no differences found in the kurtosis (p = 0.412) and skewness (p = 0.273). The ADC10 demonstrated optimal differentiating performance (cut-off value, 0.403 × 10−3 mm2/s; area under the receiver operating characteristic curve [AUC], 0.977; sensitivity, 92.3%; specificity, 93.3%), followed by the ADCmean, ADCmedian, ADC90, and hot-spot-ROI-based mean ADC. The AUC of ADC10 was significantly higher than that of the hot spot ROI based ADC (0.977 vs. 0.797, p = 0.036). CONCLUSION: Compared with the commonly used hot spot ROI based ADC measurement, a histogram analysis of ADC maps can improve the differentiating performance between thymic carcinoma and lymphoma.
Area Under Curve ; Diffusion* ; Humans ; Lymphoma* ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Thymoma*