Search

The aim of this prospective study was to compare the diagnostic accuracy of oral contrast-enhanced transabdominal ultrasound imaging (OCTU) with that of contrast-enhanced computed tomography (CT) for the pre-operative tumor staging of gastric cancer, with post-operative pathology as the standard. We included 108 cases of gastric cancer with simultaneous OCTU and enhanced CT pre-operative tumor staging diagnoses. Results were compared with post-operative pathology based on the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging guidelines for gastric cancer. The accuracy of each tumor stage was obtained by comparing OCTU and enhanced CT diagnoses with post-operative pathology. The McNemar test was used to compare the overall accuracy of the two methods. There was no statistical difference in accuracy between OCTU (72.2%) and enhanced CT (75.9%, p = 0.644) for overall pre-operative tumor staging diagnosis. For stages T1 to T4, the accuracy rates of OCTU were 84.2%, 81.8%, 69.4% and 65.5%, respectively, and those for enhanced CT were 52.6%, 72.7%, 87.8% and 72.4%, respectively. OCTU is comparable to enhanced CT in the preoperative overall T-stage diagnosis of gastric cancer.

Background Qizhi Xiangfu Pills (QXPs) are a traditional Chinese medicine (TCM) used clinically for qi stagnation and blood stasis. The current quality control of QXPs in the ministry standards and the reported literature is minimal, and requires improvement. Objective This study aimed to analyze and determine the active ingredients in QXPs for its overall evaluation. Methods In this study, a quantitative analysis of multi-components by a single marker (QAMS) method was established to simultaneously determine caryophyllene oxide, cyperotundone, ligustilide, and α-cyperone in QXPs by GC. Moreover, the GC fingerprints of 22 batches of samples were also established, and the common peaks were initially identified by GC–MS, then classified in various dimensions using chemometric methods, and the main markers causing the discrepancies between groups were analyzed by orthogonal partial least-squares discrimination analysis (OPLS-DA). Results Compared with an internal standard method (ISM), the determination results obtained by QAMS had no significant difference. Twenty-two common peaks were distinguished in the fingerprint of 22 batches of QXPs, 17 of which were identified, and the similarity of the fingerprints was greater than 0.898. The 22 batches of QXPs were roughly divided into 3 categories, and 12 main markers causing the discrepancies were discovered. Conclusion The established QAMS method combined with the GC fingerprint and chemometrics is convenient and feasible, which helps to improve the quality evaluation of QXPs and provides a demonstration for the related study of compound preparations and single herbs. Highlights QAMS combined with a GC fingerprint and chemometrics method was established to evaluate the quality of QXPs for the first time.

Background: Hypopharynx reconstruction after hypopharyngectomy is still a great challenge. Perfusion decellularization is for extracellular matrix (ECM) scaffolding and had been used in organ reconstruction. Our study aimed to prepare an acellular, natural, three-dimensional (3D) biological hypopharynx with vascular pedicle scaffold as the substitute materials to reconstruct hypopharynx. Result: Scanning electron microscope (SEM) and immuno showed that the decellularized hypopharynx with vascular pedicle scaffold retained intact native anatomical ECM structure. Myoblasts were observed on the recellularized scaffolds with bone marrow mesenchyml stem cells (BMSCs) induced by 5-azacytidine implanted in the rabbit greater omentum by immunohistochemical analysis. conclusion: the decellularized hypopharynx with vascular pedicle scaffold prepared by detergent perfusion in our study has an potential to be an alternative material to pharynx reconstruction.

Backgrounds: Since human epidermal growth factor receptor 2 (HER2)-positive breast cancers may have different HER2/CEP17 ratios and HER2 copy numbers, outcomes of HER2-positive breast cancer patients treated with anti-HER2 neoadjuvant chemotherapy (NACT) may be different. The aim of this study is to explore the relationship between different groups of HER2 fluorescence in situ hybridization (FISH) positive patterns and response to anti-HER2 NACT. Methods: 513 HER2-positive invasive breast cancers who received anti-HER2 NACT in Fudan University Shanghai Cancer Center, during January 2015 to September 2020, were collected. According to FISH results, 513 patients were divided into three groups. Group A: HER2/CEP17 < 2.0 and HER2 average copy number ≥6.0; Group B: HER2/CEP17≥2.0 and HER2 average copy number ≥4.0 and < 6.0; Group C: HER2/CEP17≥2.0 and HER2 average copy number ≥6.0. Clinicopathological characteristics and pathological complete response(pCR) rates of three groups were analyzed. Results: All 513 patients were treated with anti-HER2 NACT. The anti-HER2 treatment included trastuzumab in 463 (90.3%) patients, trastuzumab plus pertuzumab in 21 (4.1%) patients, trastuzumab plus lapatinib in 3 (0.6%) patients, and trastuzumab plus pyrotinib in 1 (0.2%) patient. 25 (4.9%) cases were unblinded in clinical trials, who were treated either with trastuzumab plus pertuzumab or with trastuzumab plus pyrotinib. Among 513 patients, 237 cases (46.2%)were luminal B (hormone receptor positive and HER2 positive) and 276 cases (53.8%) were hormone receptor negative and HER2 overexpressed (HER2 overexpression type). According to IHC results, cases with HER2 1+,2+ and 3+ were 8 (1.6%), 123 (24.0%) and 382(74.5%), respectively. Among them, 0.0%, 25.2%, and 48.7% achieved pCR (p Citation Format: Hong Lv, Qian-Ming Bai, Yin Liu, Zhong-Hua Wang, Ruo-Hong Shui, Hong-Fen Lu, Xiao-Li Xu, Bao-Hua Yu, Xiao-Yu Tu, Rui Bi, Yu-Fan Cheng, Xiao-Yan Zhou, Zhi-Min Shao, Wen-Tao Yang. Response to anti-HER2 neoadjuvant chemotherapy in invasive breast cancers with different HER2 FISH-positive patterns [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-11.

Background Chenxiang Huaqi tablets (CXHQTs) are a traditional Chinese medicine (TCM) commonly used to treat stomach-related diseases. Currently, the ministerial standards do not provide detailed guidance and regulations on the content determination of CXHQTs, and the reported studies only use individual active components as indicators for determining effective ingredients. Objective The present study aimed to propose a methodology for quality control of CXHQTs based on high-performance liquid chromatography (HPLC) fingerprinting combined with the quantitative analysis of multi-components by single marker (QAMS) method. Methods HPLC method was used to determine seven active ingredients and performed fingerprint analysis of CXHQTs. To further process chemometric assessment, technical analysis-model including similarity analysis (SA), hierarchical clustering analysis (HCA), principal components analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) was set up to differentiate and classify the 20 batches of samples. Results After comparing the results of QAMS method with the external standard method (ESM), we found there is no significant difference. Besides, the fingerprint of CXHQT was also established. Conclusion HPLC fingerprint combined with the QAMS could be an efficient and selective analysis technique to achieve a qualitative and quantitative evaluation of executing quality processes.

Scutellariae Radix(SR), derived from the dried root of Scutellaria baicalensis in the family Lamiaceae, commonly serves as Chinese medicinal material. Affected by producing areas, growing years, and harvesting periods, the quality of SR fluctuates in the market. However, baicalin≥9% in SR required in the Chinese Pharmacopoeia(2020 edition) can only determine the qualified SR but cannot identify high-quality SR. To improve the quality control methods of SR, the present study analyzed the accumulation of metabolites in SR of different growth years by plant metabolomics, and identified 28 metabolites increasing with growth years(1-3 years). Subsequently, 14 main metabolites were quantitatively analyzed by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry(UPLC-QQQ-MS). Among them, baicalin, wogonoside, baicalein, and wogonin with high content and good activity were selected as the index components of SR for quality evaluation. A high-performance liquid chromatography(HPLC) method was established to determine the content of four index components in 32 batches of SR from different producing areas, harvesting perio-ds, and growth years. The results showed that the growth years could greatly affect the content of index components. The total content of four index components in 2-year SR was the highest, followed by the 3-/4-year SR and 1-year SR. Based on HPLC data and verification results by enterprises, baicalin ≥12.0%, wogonoside ≥2.3%, baicalein ≥0.1%, and wogonin ≥0.03% were proposed as the evaluation criteria for the high-quality SR. The findings of this study are expected to provide a basis for improving the quality of SR.

Introduction Heat shock protein 90 (Hsp90) is one of the most critical chaperones amenable to mediating the folding and maturation of more than 300 client proteins. In normal cells, Hsp90 chaperone cycle is required for regulating multiple cellular processes to maintain homeostasis. However, extremely overexpressed Hsp90 in neoplastic cells results in the dysregulation of client proteins, many of which are indispensable to the accumulation of cancer hallmarks, such as infinite proliferation and increased invasiveness. Consequently, modulation of Hsp90 activity has been considered as a potential strategy for cancer treatment. Areas covered This review recapitulated recent patents' progress in the development of Hsp90 inhibitors with potent antitumor activities during 2013 to present. Besides, the structural-activity relationships of the patented inhibitors and their structural similarity were also discussed. Expert opinion Hsp90, as an anticancer target, has been investigated for several decades. The first generation of Hsp90 inhibitors exhibited potent antitumor activities in preclinical trials but were trapped in different phases of clinical trials. The second generation of Hsp90 inhibitors has been identified with increased specificity and security through structure modification. Moreover, these inhibitors may offer opportunities for studies of Hsp90 chaperone and development of Hsp90 inhibition therapy.

Modulation of protein fate decision and protein homeostasis plays a significant role in altering the protein level, which acts as an orientation to develop drugs with new mechanisms. The molecular chaperones exert significant biological functions on modulation of protein fate decision and protein homeostasis under constantly changing environmental conditions through extensive protein–protein interactions (PPIs) with their client proteins. With the help of molecular chaperone machinery, the processes of protein folding, trafficking, quality control and degradation of client proteins could be arranged properly. The core members of molecular chaperones, including heat shock proteins (HSPs) family and their co-chaperones, are emerging as potential drug targets since they are involved in numerous disease conditions. Development of small molecule modulators targeting not only chaperones themselves but also the PPIs among chaperones, co-chaperones and clients is attracting more and more attention. These modulators are widely used as chemical tools to study chaperone networks as well as potential drug candidates for a broader set of diseases. Here, we reviewed the key checkpoints of molecular chaperone machinery HSPs as well as their co-chaperones to discuss the small molecules targeting on them for modulation of protein fate decision., Graphical abstract This review summarizes the current states on modulation of molecular chaperone by small molecules, focusing on the protein fate decision by comprehensive strategies and different mechanisms.Image 1

Sepsis has long been a major health problem worldwide. It threatens the lives of hospitalized patients and has been one of the leading causes of death in hospitalized patients over the past decades. BRD4 has been regarded as a potential target for sepsis therapy, for its critical role in the transcriptional expression of NF-κB pathway-dependent inflammatory factors. In this study, compound 1 was obtained through virtual screening, and candidate compound 27 was obtained through several rounds of iterative SAR analysis. 27 decreased LPS-induced NO production and expression of the pro-inflammatory factors IL-6, IL-1β and TNF-α. In vivo, 27 effectively protected mice from LPS-induced sepsis, increased survival rate and decreased the level of pro-inflammatory factors in serum. Collectively, we reported here 27, a BRD4 inhibitor with a new scaffold, as a potential candidate for the treatment of sepsis.

Bo-Yue Han,1–3,* Xiao-Li Xu,3,4,* Xiu-Zhi Zhu,1–3,* Xiang-Chen Han,1–3 Xin Hu,2,3 Hong Ling1,3 1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China; 2Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Hu; Hong Ling, Tel +86 18017317652; +86 18017312656, Email xinhufd@163.com; linghong98@aliyun.comBackground: Mammary Paget’s disease (PD) is a rare type of breast cancer. Most cases of PD are presented with underlying ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IDC). This study aimed to investigate the clinicopathological characteristics and survival outcomes of PD patients.Materials and Methods: A total of 406 patients diagnosed with PD with IDC/DCIS at Fudan University Shanghai Cancer Center (FUSCC) were recruited as the PD group, 1218 patients diagnosed with IDC/DCIS alone during the same period were selected as the non-PD group, and the clinicopathological results of these two groups were compared. The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the clinicopathological features between PD and non-PD patients for validation.Results: Compared with the non-PD group, the PD group was much more likely to have larger (≥2 cm: 43.1% vs 35.5%, P < 0.001), less hormone receptor (HR)-positive (68.5% vs 26.6%, P < 0.001), more human epidermal growth factor receptor-2 (HER-2)-positive (70.7% vs 27.5%, P < 0.001) and higher Ki-67 proportion (51.5% vs 42.5%, P < 0.001) tumors. The HER-2 overexpression subtype accounted for the largest proportion in the PD-IDC group and the lowest proportion in the non-PD-IDC group (54% vs 8%, P < 0.01). Moreover, the PD group had significantly worse disease-free survival (DFS) than the non-PD group (5-year DFS: 91.8% vs 97.3%, P = 0.001), and the SEER database showed a similar trend. Univariate and multivariate Cox regression analyses demonstrated that PD was an independent poor-risk factor. Our matched study showed that the PD group had worse survival than the non-PD group after excluding age, HR, HER-2, tumor size and lymph node status.Conclusion: PD with IDC/DCIS is associated with more aggressive tumor characteristics and worse survival outcomes. More than half of PD breast cancers are HER-2 overexpression subtype. PD is an independent poor-risk factor for breast cancer survival.Keywords: breast cancer, mammary Paget’s disease, clinicopathological characteristic, survival, prognosis, molecular subtype

Background and Objectives: Glomerular C4d deposits are associated the severity and outcomes of IgA nephropathy. Whether this holds true in immunoglobulin A vasculitis (IgAV) is not known. The main objective of the study was to analyze the prognostic value of glomerular C4d immunolabelling on kidney impairment in adults with IgAV.Design, Setting, Participants, Measurements: This retrospective cohort study included 120 adults with IgAV and a kidney biopsy performed between 1995 and 2018 in two French university hospital centers. All paraffin-embedded biopsies were reassessed according to Oxford classification. Immunofluorescence for C4d was performed in all cases. For analysis, patients were grouped according to positivity for C4d in the glomerular area. The main outcome was a composite endpoint of 50% increase in 24 h-proteinuria, or eGFR decrease by 50%, or kidney replacement therapy.Results: The median follow-up was 28.3 months. Twenty-three patients met the composite endpoint, 12 for kidney replacement therapy, 6 for an eGFR decrease >50% and 5 for a >50% increase in proteinuria. At time of biopsy, the median proteinuria was 1.9 g/24 h and the median eGFR 73.5 mL/min/1.73 m2. Among the 102 patients evaluable for C4d, 24 were positive on >30% glomeruli, mainly with a parieto-mesangial pattern. In this group, the initial proteinuria was more frequently nephrotic than in the C4d– group (60% vs. 33%, P = 0.039). Mesangial hypercellularity was more frequent in the C4d+ group (42% vs. 13%; P = 0.006) whereas macroscopic hematuria was more frequent in the C4d– group (18% vs. 0%; P = 0.03). After a median follow-up of 28 months, kidney survival did not differ according to C4d status.Conclusion: In a population of adult IgAV patients, glomerular positivity for C4d was associated with the severity of the kidney disease at presentation, but not with subsequent renal function deterioration.

The nucleic acid-based technique has been widely utilized in many fields including for on-site detection. However, traditional molecular detection techniques encounter limitations like relying on instruments, time consuming or complex operation, and cannot meet the demands of on-site testing. In this study, a rapid DNA extraction method (RDEM), recombinase aided amplification (RAA), and chemical heating packet (CHP) are integrated and termed as RRC platform for on-site detection of nucleic acid. For demonstration purposes, SHZD32-1 (a new transgenic soybean line from China) was detected using the novel platform to demonstrate its feasibility and capability for on-site detection. Using the RDEM, high-quality DNA appropriate for molecular detection was quickly extracted in 3–5 min. The heat energy generated by CHP was met the temperature requirements of RAA. Using the RRC platform, the whole detection process can be accomplished within only 30 min, and the results can be visually detected with glasses under blue light. No special or expensive instrument was needed for the detection process. This study provides a novel approach for on-site detection of nucleic acids besides providing valuable insight on related future research.

Stimulator of interferon genes (STING) is an adaptor protein that induces the secretion of type I interferons and proinflammatory cytokines and is triggered by cytosolic DNA of pathogen and host origins. Given that STING is a mediator in the immune system, pharmacological modulation of STING has shown viable therapeutic effects for pathogen infection, cancer, and inflammatory diseases. In the past decade, the substantial development in this field has encouraged the discovery of STING modulators. Here, we will summarize the current understanding of STING structure, survey the status quo of STING modulators, compare established bioassay methods, review the chemical structures and bioactivities of agonists and inhibitors, and propose suggestions and insights for the future exploitation of STING modulators.

A fault diagnosis method for rolling bearing based on ensemble empirical mode decomposition (EEMD) sample entropy and probabilistic neural network (PNN) is proposed for non-steady and non-linear signals. First, the rolling bearing signals are decomposed into intrinsic mode function (IMF) using EEMD. Then, the kurtosis of each component is calculated. Five components with large kurtosis are selected and the sample entropy is extracted to form the feature vectors. Finally, the feature vectors are input to the PNN for fault diagnosis. The method is used to classify the type of the rolling bearing fault. The results show that the accuracy of fault diagnosis of the proposed method is 100%, which proves the effectiveness of the proposed method.