Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.
Humans ; Kidney Neoplasms/pathology* ; Carcinoma, Renal Cell/pathology* ; Diagnosis, Differential ; Angiomyolipoma/diagnosis* ; Biomarkers, Tumor/metabolism* ; Leukemia, Myeloid, Acute/diagnosis* ; Membrane Glycoproteins

OBJECTIVE: To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma. METHODS: Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified. RESULTS: 44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013). CONCLUSION CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.
Histones ; Humans ; Multiple Myeloma/genetics* ; Neoplasm Recurrence, Local ; Oligopeptides/therapeutic use* ; Prognosis ; Receptors, CXCR4

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Biomarkers ; Carcinoma, Hepatocellular ; Golgi Apparatus ; Humans ; Liver Cirrhosis ; Liver Neoplasms

OBJECTIVE：To establish quantitative e valuation system of the prophylactic use of antibiotics in orthopedic type Ⅰ incision surgery ，and to provide reference for evaluating the rational prevention use of antibiotics in this type surgery scientifically. METHODS：Based on the Guidelines of Clinical Use of Antimicrobial Agents （2015 edition），drug instructions ，related guidelines and references ，experts from relevant departments jointly discussed and formulated the evaluation criteria for the rationality of the use of antibiotics in type Ⅰ incision in orthopedic surgery. AHP method was used to assign the weights for various indexes of evaluation criteria ；TOPSIS method was used to retrospectively analyze and evaluate the rationality of 120 cases of type Ⅰ incision surgery from 3 orthopedic departments in Peking University People ’s Hospital during Sept. 1st-30th，2019. RESULTS ：Established evaluation system included 4 primary indicators （medication indication ，usage and dosage ，medication timing ，other factors ）and 12 secondary indicators. Among the secondary indicators ，indications，drug selection and timing of preoperative administration were the most important （weights were 0.209，0.140，0.117）. Among 120 cases，30.83％ of drug use were reasonable ，47.50％ were basically reasonable and 21.67％ were unreasonable. Evaluation results obtained by AHP-TOPSIS were consistent with the actual situation. CONCLUSIONS ：The rationality evaluation method of prophylactic use of antibiotics in type Ⅰ incision surgery based on AHP-TOPSIS method can quantitatively evaluate the rationality of drug use by combining multiple indicators. The method is feasible ，operable，and the evaluation results can be quantified ，which has a wide range of application.

Aim To investigate the effect of Li-Zhong-Tang (LZT) in the treatment of gastric ulcer (GU) with pattern of spleen-stomach vacuity cold in rats based on Raf/MEK/ERK signaling pathway and the underlying molecular mechanism. Methods SD rats were randomly divided into normal group, GU model group, esomeprazole (ESO) group, LZT low dose and high dose groups. The morphological changes of gastric mucosa were observed by naked eyes and HE staining. The activities of gastric acid and pepsin were measured. The contents of prostaglandin E

To investigate the absorptive characteristics of Inula cappa extract based on the rat everted intestinal sac method . Nine representative ingredients in I. cappa extract were selected as the study objects. An UPLC-MS/MS method was established to determine and detect their cumulative absorption amount for expounding the absorptive characteristics of ingredients in different intestinal sections. According to the results， the transport mechanism of 8 compounds showed passive diffusion by the reverted gut sac method. And scopolin was actively transported in the intestine. The best absorption site of chlorogenic acid was duodenum. The best absorption site of cryptochlorogenic acid， 1，3--dicaffeoylquinic acid， luteolin-7-glucoside and 3，4--dicaffeoylquinic acid were jejunum. The best absorption site of neochlorogenic acid， scopolin， 4，5--dicaffeoylquinic acid and 3，5--dicaffeoylquinic acid was ileum. The absorption of all the compounds was affected by pH and bile. All of the nine ingredients in I. cappa extract could be absorbed in intestines， but with differences in the absorption rate， the best absorptive site and mechanism， indicating that the intestinal absorption of I. cappa extract was selective.
Animals ; Chromatography, High Pressure Liquid ; Intestinal Absorption ; Intestines ; drug effects ; Inula ; chemistry ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

OBJECTIVETo evaluate the role of microparticle (MP) derived from acute promyelocytic leukemia (APL) cells and tissue factor (TF) carried by the MP in hypercoagulable state, and the effect of treatment with cytotoxic chemotherapy/differentiating agents on procoagulant activity (PCA) of these MP.

METHODSBone marrow mononuclear cells (BMMNC) were extracted from 5 APL patients and 5 sex- and age- matched patients with iron deficiency anemia as controls. The cells were cultured in vitro for 48 h, then MP-rich culture medium and MP-free culture medium were harvested and MP was further obtained from certain volume of MP-rich culture medium. Subsequently, TF expression on MP was measured by ELISA. PCA of MP-rich culture medium or MP-free culture medium was assessed with thrombin generation assay. The role of TF on MP-related PCA was evaluated using anti-human TF antibody. In addition, APL cells were treated with all-trans retinoic acid (ATRA), arsenic trioxide (ATO) or daunorubicin (DNR) for 48 h, then MP-rich culture medium were harvested and the PCA was determined.

RESULTSNo TF expression was found in the MP released from bone marrow MNC in control group, whereas the obvious TF expression was found in the MP originated from BMMNC of APL. MP from both APL and control BM-MNC had obvious PCA. However, compared with the MP derived from control MNC, the MP from APL BM-MNC induced significantly higher PCA. TF played a crucial role in the PCA of APL BM-MNC derived MP, while played no role in that of MP from control MNCs. DNR-treating APL BM-MNC resulted in an increase in the PCA of MP, whereas ATO or ATRA exposure lead to exactly the opposite results.

CONCLUSIONMP derived from APL BM-MNC posseses obvious PCA. TF plays a crucial role in the MP-related PCA. The PCA of MP increases after treating APL BM-MNC with chemotherapy agent DNR and decreases following exposure of APL BM-MNC to differentiating agents ATRA or ATO.

OBJECTIVETo determine whether additional Chinese medicine (CM) could prolong survival and improve the quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC) compared with Western medicine (WM) alone.

METHODSThis was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage III-IV NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network (NCCN) guidelines. In the integrative medicine (IM) group, individualized CM (Chinese patent medicines and injections) and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months.

RESULTSThe median survival was 16.60 months in the IM group and 13.13 months in the WM group (P<0.01). The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group (P<0.05). The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course (P<0.05).

CONCLUSIONSAdditional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio- and chemotherapy may be attenuated as CM is used in combination with conventional treatments.

Objective To study the relationship between basal ganglia ischemic stroke (BGIS) and paroxysmal atrial fibrillation (PAF) due to abnormal vagus nerve tension.Methods A total of 1483 elderly ischemic stroke patients who underwent head CT or MRI in our hospital from January 2013 to December 2014 were divided into BGIS group (n=1045) and non-BGIS group (n=438).Their heart rate variability and frequency parameters (SDNN,RMSSD,PNNS0) were recorded.The LF/HF ratio was analyzed.Results The incidence of PAF was significantly lower in ＜69 years old patients of BGIS group than in those of non-BGIS group (P＜0.05) and was significantly higher in ≥70 years old patients of BGIS group than in those of non-BGIS group (P＜0.05).The incidence of ischemic stroke with PAF was significantly higher in BGIS group than in nonBGIS group (56.8％ vs 41.0％,P=0.031).The incidence of PAF was significantly higher in ＞79 years old patients of BGIS group than in those of non-BGIS group (P＜0.05).The incidence of AF increased with the increasing age of ischemic patients between the two groups.The SDNN,RMSSD,PNN50 were significantly higher while the LF/HF ratio was significantly lower in nonPAF patients of BGIS group than in those of non-BGIS group (P＜0.05).Conclusion The incidence of BGIS shows a tendency to increase.PAF is prone to occur in BGIS patients.The vagus nerve tension is increased in BGIS patients with PAF.

Aim To analyze the main components of effective fractions of Inula cappa in rat plasma with UHPLC/Q-TOF/MS technology and serum pharmacochemistry theory.Methods After gavage administration with Inula cappa extracts,blood was collected from abdominal aorta,and the protein in plasma sample was precipitated by methanol.Eclipse Plus C18 RRHD (2.1 mm × 100 mm,1.8 μm) was used,with 0.1％ formic acid agueous solution (A)-0.1％ formic acid and acetonitrile (B) as the mobile phase for gradient elution,and the flow rate was 0.3 mL ·min-1 Detected at negative ion mode,and with the help of Metabolite Tools software from Bruker Corporation,components in plasma were defined.Results A total of 16 compounds were identified,including 9 prototypes and 7 metabolites.Main metabolites were isomerization,methylation,glucuronidation and recombination of caffeoylquinic acid.Conclusions Therefore,our study has comprehensively expounded Inula cappa extracts' constituents migrating to rat plasma,and provided a reference for further studies for in vivo metabolic process and effective material base of Inula cappa.