Purpose To evaluate the subclassifications of pT2 diseases in tumor-nodes-metastases ( TNM) staging system for prostate cancer. Methods A retrospective analysis of the medical records of patients who underwent radical prostatectomy ( RP) with the diag-nosis of clinically localized PCa was conducted. Any preoperative therapies, in terms of active surveillance, hormone therapy or radia-tion were exclusion criteria. The RP specimens were completely embedded and histopathologically evaluated for extraprostatic exten-sion, seminal vesicle invasion and staged according to the 2002/2010 TNM staging criteria. Results Using current 2002/2010 TNM staging criteria, in all, 15 cases of the tumors were pT2, 10 cases were pT3a, and 5 cases were pT3a. When subclassification of pT2, 2 cases of the tumors were pT2a, 13 cases of the tumors were pT2c, and none was identified as a pathological T2b tumor. Conclusion The results of the present study suggest that the pathological substaging criteria of organ-confined prostate cancer via methods used in the current 2002/2010 TNM staging system may not be appropriate. Efforts should be made to upgrade the current TNM staging system for prostate cancer.

Tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 has significantly improved the survival and prognosis of patients with chronic myeloid leukemia (CML). However, long-term treatment with TKI has caused many problems like adverse drug reactions, decreasing the quality of patients' life and increasing financial burden. Therefore, whether CML patients can successfully stop taking TKI after reaching a certain therapeutic standard has become a matter of concern. At present, treatment-free remission (TFR) has already become a new target for CML therapy. Several clinical trials have confirmed the feasibility and safety of TFR in specific patient populations, and TFR is now incorporated into clinical guidelines. This paper reviews the main reasons for CML patients' pursuit of TFR and the possible mechanisms of TFR.

Objective To explore the clinical characteristics of acute calculous cholecystitis in over 80 years old patients.Methods A retrospective study was made on the clinical data of 71 cases diagnosed as acute calculous cholecystitis and receiving surgical treatment from Sep 2006 to Sep 2016.Patients were divided into three groups:Early LC group (25 patients),PTGD group (29 patients),the staged LC group (17 patients) after PTGD.Results There was statistically significant difference in the gallbladder wall thickness,operation time and blood loss between the two LC groups.There was no statistically significant difference between the two LC groups in other baseline data and hospital stay,hospital cost,rate of postoperational complication,rate of conversion to open procedure between the two LC groups.There was statistically significant difference between the early LC group and PTGD group in the baseline data.Logistic regression analysis indicated that the TG13 grade was an important influence factor for treatment selection of PTGD (OR=3.957,P=0.015,95％CI:1.30-12.043).Conclusion Laparoscopic cholecystectomy was safe for good risk over 80 years old patients.For poor risk patients,PTGD is recommended before a LC attempt.

Schizophrenia (SCZ) is a kind of devastating and common neuropsychiatric disorder, and its etiology remains to be determined. Dizocilpine MK-801 animal models, which can cover the major endophenotypes of SCZ, are widely used in the study of SCZ. In this paper, the research status is reviewed about the pathogenic mechanism, modeling method, behavioral characteristics of MK-801 animal models of SCZ in recent years in order to provide some possible ideas for the study of SCZ.

Objective:To investigate the current status of hospitalized neonatal death of different gestational ages in Shaanxi Province.Methods:All neonatal deaths in six hospitals in Shaanxi Province from 2016 to 2020 were retrospectively analyzed, and the differences in perinatal complications, the causes of death, and the age at death were compared using Chi-square (or Fisher's exact ) test. Results:(1) Totally, 220 488 neonates were delivered in the obstetric department of the six hospitals during the study period; 71 782 out of them were admitted to the neonatal department. While 424 neonatal death was reported, giving the total hospitalized neonates mortality rate of 5.5‰ (394/71 782), which included 152 deaths of transferred patients ( n=9 103, 16.7‰), 226 premature (53.3%), 196 term (46.2%), and two post-term infants (0.5%). (2) Among mothers of dead neonates, 73.6% were found to have at least one perinatal complication. The most common one was fetal distress (146 cases, 34.4%), followed by gestational diabetes mellitus (113 cases, 26.7%), amniotic fluid abnormalities ( n=73, 17.2%), maternal infectious diseases ( n=71, 16.8%), and hypertensive disorders in pregnancy (HDP) ( n=52, 12.3%). The lower the gestational age, the higher the proportion of multiple pregnancies and assisted reproduction technology applied (Fisher exact test, P<0.05). On the contrary, the higher the gestational age, the higher the cesarean section rate ( χ 2=26.69, P<0.001). HDP was more likely to occur in the gestational age of 28-31 +6 and 32-34 +6 weeks ( χ 2=37.16, P<0.001), and amniotic fluid abnormalities were more likely to occur in those over 37 weeks ( χ 2=27.47, P<0.001). (3) The five leading causes of neonatal death were neonatal respiratory distress syndrome (NRDS, n=100, 23.6%), neonatal asphyxia ( n=88, 20.8%), maternal infectious diseases ( n=80, 18.9%), and birth defects ( n=54, 12.7%), and pulmonary hemorrhage ( n=22, 5.2%). The first three causes of death in term and post-term infants were neonatal asphyxia ( n=65, 32.8%), birth defects ( n=42, 21.2%), and infectious diseases ( n=26, 13.1%). NRDS ( n=83, 36.7%), infectious diseases ( n=54, 23.9%), and neonatal asphyxia ( n=23, 10.2%) were the three leading causes of death of premature babies. (4) Out of the 326 (76.9%) neonatal deaths within seven days after birth, 162 (38.2%) died within 24 h after birth and 164 cases (38.7%) between one to seven days after birth. Conclusions:Most neonatal deaths occurred among preterm ones and within seven days after birth, whose mothers suffered perinatal complications. The causes of neonatal death vary among different gestational age groups.

We expressed and prepared the recombinant fusion protein sTNFRII-gAD consisted of soluble TNF receptor II and the globular domain of adiponectin by Adenovirus Vector System in mammalian BHK21c022 cells. First we used the adenovirus vector containing EGFP gene (rAd5-EGFP) to infect BHK21c022 cells at different MOI (from 0 to 1 000), and then evaluated their transduction efficiency and cytotoxicity. Similarly, we constructed the replication-deficient adenovirus type 5-sTNFRII-gAD (rAd5-sTNFRII-gAD). We collected the supernatants for Western blotting to determine the optimal MOI by comparing the expression levels of sTNFRII-gAD fusion protein, 48 h after the BHK21c022 cells were infected by rAd5-sTNFRII-gAD at different MOIs (from 0 to 1 000). Then, we chose rAd5-sTNFRII-gAD at MOI 100 to infect five bottles of BHK21c022 cells in 100 mL of serum-free chemically defined media 100 mL, harvested the supernatant every 48 h for 6 times, and condense and purify sTNFRII-gAD fusion protein by ammonium sulfate salt-out and size-exclusion chromatography, respectively. Finally, we analyzed anti-TNFalpha activity of sTNFRII-gAD fusion protein on L929 cells in vitro. The results showed that the number of BHK21c022 cells expressing EGFP protein was increased significantly with the increase of MOI. However, some cells died at MOI of 1 000 while there was no significant cytotoxicity at MOI from 0 to 100. Western blotting analysis showed that the more adenoviruses, the higher expression of sTNFRII-gAD fusion protein in the supernatant with the highest expression at MOI 1 000. We successfully obtained about 11 mg bioactive and purified sTNFRII-gAD fusion protein at last. The in vitro assay demonstrated that the sTNFRII-gAD fusion protein was potent to antagonize TNFalpha's cytotoxicity to L929 cells. Put together, we established a recombinant adenovirus vector/BHK21 cell expression system, characteristic of the efficient serum-free culture and easy scaling-up.
Adenoviridae ; genetics ; metabolism ; Adiponectin ; biosynthesis ; genetics ; Animals ; Cell Line ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Receptors, Tumor Necrosis Factor, Type II ; biosynthesis ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics

With the continuous development of bioinformatics technology and precision medicine, genetic mechanism investigations of genetic diseases including cleft lip and palate (CLP) have been getting more and more attention. Researchers have focused on the coding sequence of the genome and successfully found many CLP causative mutations, but there still remain some unsolved questions. In recent years, researchers′ vision has gradually shifted to non-protein coding region of the genome. This article reviews several coding sequence mutations, non-protein coding variants and their genetic mechanisms discovered in CLP researches.

Objective To explore the correlation between neutrophil-to-lymphocyte ratio(NLR)and Behcet's disease(BD)activity.Methods A total of 103 BD patients were divided into the low activity group(0-4,61 cases)and the high activity group(5-11,42 cases)according to electronic medical record-based disease activity index(EMRAI)score.The white blood cell(WBC),neutrophil(NEU),lymphocyte(LY),platelet(PLT),red blood cell(RBC),hemoglobin(Hb),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),IgG,IgA,IgM,complement C3 and C4 were detected.NLR and platelet-to-lymphocyte ratio(PLR)were calculated.The correlation between NLR,PLR and ESR,CRP,EMRAI were analyzed.Logistic regression was used to analyze the influencing factors of BD disease activity.Receiver operating characteristic(ROC)curve was drawn to evaluate the effectiveness of NLR in judging BD disease activity.Results WBC,NEU,PLT,ESR,CRP,NLR,PLR,complement C3 and C4 in patients were higher in the high activity group than those in the low activity group(P＜0.05),and there were no significant differences in other indexes(P＞0.05).NLR was positively correlated with ESR,CRP and EMRAI in the whole group,while PLR was positively correlated with ESR,CRP and EMRAI in the whole group(P＜0.05).Logistic regression analysis showed that high NLR was a risk factor for BD disease activity(OR=1.511,95%CI:1.080-2.113,P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of NLR in evaluating BD disease activity was 0.706(95%CI:0.603-0.809).Conclusion NLR is effective in judging the disease activity of BD patients,and can be used as a biological index to evaluate the disease activity of BD.

Objective:To investigate the expression of four cancer stem cell (CSC) markers (EpCAM, CD133, CD90 and CD24) in hepatocellular carcinoma tissues and peripheral blood circulating tumor cells (CTC),their value in the prognosis of patients with hepatocellular carcinoma.Methods:A total of 50 hepatocellular carcinoma tissues and 29 peripheral blood sample from 50 patients with hepatocellular cancer treated in Zhongshan Hospital Fudan University from October 2013 to September 2014 were collected and analyzed by flow cytometry or qRT-PCR to examine the expression of EpCAM, CD133, CD90 and CD24. The clinical data of patients were collected, including tumor size, tumor number, satellite lesions, vascular invasion, Edmondson stage, BCLC stage and liver cirrhosis, etc. The correlation between the expression of four markers in hepatocellular carcinoma tissues and CTC with the clinical data and survival time of patients were compared.Results:The positive expression rates of EpCAM, CD133, CD90 and CD24 in hepatocellular carcinoma tissues were 66% (33/50), 18% (9/50), 60% (30/50) and 56% (28/50); the positive expression rates in CTC were 55% (16/29), 38% (11/29), 31% (9/29) and 59% (17/29). CD90 expression in hepatocellular carcinoma tissue was positively correlated with the occurrence HCC liver cirrhosis ( P<0.05), while CD133 expression was negatively correlated with the 5-year survival rate of patients ( P<0.05). The expression of EpCAM and CD24 in peripheral blood CTC were closely related to the patient′s Edmondson stage ( P<0.05). The survival time of patients with CD133 positive expression in hepatocellular carcinoma tissue was lower than those without CD133 expression ( P<0.05); the survival rate of patients with EpCAM expressed in either tissue or peripheral blood CTC was lower than that of patients with EpCAM double negative expression ( P<0.05). The survival rate of patients with CD90 negative in HCC tissue and positive in peripheral blood was lower than that in patients with double negative/double positive in tissue and peripheral blood or patients positive in hepatocellular carcinoma tissue and negative in peripheral blood ( P<0.01). Conclusion:Different expression characteristics of four markers in cancer tissues and peripheral blood CTC might provide useful information about predicting prognosis of hepatocellular carcinoma. The expression of CD133 in tissues can be used as an important survival predictor of hepatocellular carcinoma patients. The differential expression of cancer markers in tissue samples and blood samples can provide more clinical prognostic information.

OBJECTIVETo investigate the effects of total flavonoids from astragalus complanatus (FAC) on paraquat poisoning-induced pulmonary fibrosis in rats.

METHODSThe rats were divided into six groups randomly: control group, paraquat group, prednisolone group and FAC low-dose, middle-dose, high-dose group. Pulmonary fibrosis model was replicated by intratracheal injection of paraquat. In the mext day,the rats were treated by intragastric administration once a day. After 28 days, the rats were sacrificed. The lung index and the levels of HYP and T-AOC were measured, and the pathologic changes of the lung tissue were obtained by HE staining. The levels of TGF-β, Smad2, α-SMA protein were analyzed by Western blot.

RESULTSFAC improved the activity of T-AOC in serum and reduced pulmonary index and the content of HYP as well (P<0.05 or P<0.01), the alveolitis and fibrosis extent were attenuated. The expression of Smad2 significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.45±0.12 and 0.30±0.05) as compared with that of the PQ group (0.85±0.34) (P<0.05). The expression of α-SMA significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.35±0.07 and 0.32±0.10) as compared with that of the PQ group (0.45±0.08) (P<0.05). The expression of TGF-β significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.35±0.04, 0.27±0.05 and 0.18±0.04)as compared with that of the PQ group (0.63±0.11) (P<0.05).

CONCLUSIONFAC can alleviate PQ-induced pulmonary fibrosis in rats through inhibiting TGF-β/Smad signaling pathway.

Actins ; metabolism ; Animals ; Astragalus Plant ; chemistry ; Flavonoids ; pharmacology ; Lung ; pathology ; Paraquat ; poisoning ; Phytochemicals ; pharmacology ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; Rats ; Smad2 Protein ; metabolism ; Transforming Growth Factor beta ; metabolism