Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

OBJECTIVE: To observe the effect of Tiaoqi Jieyu (regulating qi and relieving depression) acupuncture on the clinical symptoms of treatment-resistant depression (TRD), and to explore the relationship between the acupuncture pain sensitivity and symptom's improvement. METHODS: A total of 78 patients with TRD were randomly divided into an observation group (39 cases, 3 cases dropped off) and a control group (39 cases, 4 cases dropped off). The patients in the control group were treated with medications according to the treatment plan of psychiatrists (at least one medication was 5-hydroxytryptamine reuptake inhibitor). On the basis of the control group, the patients in the observation group were treated with Tiaoqi Jieyu acupuncture, and Baihui (GV 20), Yintang (GV 24⁺), Yanglingquan (GB 34), Taichong (LR 3), Hegu (LI 4), Neiguan (PC 6), Yinlingquan (SP 9) and Zusanli (ST 36), etc. were selected. The acupuncture was given three times a week. Both groups were treated for 8 weeks. After 8-week treatment, the response rate of Hamilton depression scale-24 (HAMD-24) score after was evaluated in the two groups. The scores of HAMD-24 and Hamilton anxiety scale (HAMA) were compared between the two groups before treatment, after 4, 8-week treatment and 12 weeks after treatment (follow-up). After the first treatment and 8-week treatment, the visual analogue scale (VAS) score in the observation group was evaluated, and the correlation between VAS score after the first treatment and HAMD-24 score before treatment, between VAS score after the first treatment and the course of disease in the observation group was analyzed, and the correlation between difference of VAS after 8-week treatment and after the first treatment and difference of HAMD-24 score before treatment and after 8-week treatment was analyzed. RESULTS: After 8-week treatment, the response rate of HAMD-24 score in the observation group was 52.8% (19/36), higher than 17.1% (6/35) in the control group (P<0.001). Compared before treatment, the scores of HAMD-24 and HAMA in the two groups were decreased after 4-week treatment, 8-week treatment and in follow-up (P<0.05), and those in the observation group were superior to the control group (P<0.05). After 8-week treatment, the acupuncture pain VAS score in the observation group was (5.28±2.13) points, which was higher than (3.33±1.62) points after the first treatment (P<0.001). There was a negative correlation between VAS score after the first treatment and HAMD-24 score before treatment in the observation group (r =-0.486, P=0.003); there was no correlation between acupuncture pain VAS score after the first treatment and the course of disease in the observation group (P>0.05). After 8-week treatment, there was a positive correlation between the difference of VAS score and the difference of HAMD-24 score in the observation group (r =0.514, P=0.001). CONCLUSION Tiaoqi Jieyu acupuncture could improve the depression and anxiety in patients with TRD, and the symptom's improvement is related to the recovery of acupuncture pain sensitivity.
Humans ; Depression/therapy* ; Treatment Outcome ; Acupuncture Therapy ; Acupuncture Points ; Pain

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.
Humans ; Organoids/pathology* ; Cell Culture Techniques ; Colorectal Neoplasms/pathology* ; Tumor Microenvironment

OBJECTIVES: To investigate the effect of two kinds of fermented food, noni juice and natto, on blood glucose and lipids in induced diabetic mice. METHODS: Female (ICR) mice were induced into diabetes by an injection of alloxan (55 mg/kg, i. v.). After 72 hours, those mice whose fasting blood glucose levels were over 12.00 mmol/L and urine sugar was strongly positive (+ + +) were regarded as diabetical model and were randomly divided into three groups (=10):diabetical model (DM) group, noni juice (NJ) group and natto (NT) group. Another ten normal female ICR mice were taken as normal control (NC) group. The mice in NJ and NT groups were gavaged with noni juice (25.0 ml/kg) and natto (0.6 g/kg) respectively. The other two groups were given normal saline (25.0 ml/kg). Continuous gavage administration was given for 30 days, the water-drinking volume and food-intake were recorded. After 1.5 h of the last administration, the glucose tolerance of mice was measured. Finally, the changes in glycated serum protein(GSP), insulin(Ins) and blood lipids of blood samples of mice, taken from the femoral artery, were determined. RESULTS: Compared to the NC group, the water-drinking amount and food-intake, GSP and total cholesterol (TC), triglyceride(TG) and low density lipoprotein (LDL) in DM group were increased significantly (<0.01), while glucose tolerance, Ins and high density lipoprotein (HDL) were decreased significantly (<0.01). However, when it came to DM group, NJ and NT could significantly (<0.01 or <0.05) reduce, GSP, TG and LDL, meanwhile improve glucose tolerance, Ins and HDL (<0. 01). CONCLUSIONS Both noni juice and natto could reduce the blood glucose levels in induced diabetical mice and improve blood lipids, which suggested that they may have certain application value in prevention and treatment of diabetic mellitus.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; blood ; Female ; Fermented Foods ; Fruit and Vegetable Juices ; Lipids ; blood ; Mice ; Mice, Inbred ICR ; Random Allocation

OBJECTIVETo analyze the phenotype, genotype and function in four Chinese pedigrees with inherited dysfibrinogenemia.

METHODSRouting tests including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), reptilase time (RT), the activities of antithrombin (AT), protein C (PC) and protein S (PS) were detected in four pedigrees. The activity and antigen of plasma fibrinogen were analyzed by Clauss and immunoturbidimetry methods, respectively. The molecular weight of fibrinogen of four probands was assessed by Western blot. The function of abnormal fibrinogen was evaluated by fibrinogen clottability, fibrinogen dynamic polymerization and fibrinolysis velocity, respectively. The sequences of all the exons and exon-intron boundaries of the three fibrinogen genes were amplified by PCR and analyzed by direct sequencing.

RESULTSFour probands had prolonged TT and RT, reduced plasma fibrinogen activity levels and normal antigen levels. The assays of Western blot showed no abnormal molecular weight of fibrinogen. Function tests revealed reduced fibrinogen clottability, delayed and decreased fibrinogen dynamic polymerization and reduced fibrinolysis velocity. Aα chain Arg16His and Arg16Cys mutations were identified in the four probands, respectively.

CONCLUSIONThe four probands with dysfibrinogenemia were caused by the mutations of Aα chain Arg16His or Arg16Cys. Mutation of the fibrinogen induced dysfunction of plasma fibrinogen.

Adult ; Afibrinogenemia ; blood ; genetics ; Blood Coagulation Tests ; Female ; Fibrinogen ; genetics ; Fibrinogens, Abnormal ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Pedigree ; Phenotype ; Thrombin Time

OBJECTIVETo analyze the phenotype and genotype in three Chinese pedigrees with inherited dysfibrinogenemia.

METHODSLaboratory tests including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), reptilase time (RT), and the activities of antithrombin (AT:C), protein C (PC:C) and protein S(PS:C) were detected in three pedigrees. The activity and antigen of plasma fibrinogen (Fg) were analyzed by Clauss and immunoturbidimetry methods, respectively. The Fg of three probands was assessed by Western blot and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The sequences of all the exons and exon-intron boundaries of the three Fg genes FGA, GFB and FGG were amplified by PCR and analyzed by direct sequencing.

RESULTSThree probands had normal APTT, PT, PC:C, PS:C and AT:C, but prolonged TT and RT. The activity levels of the 3 probands's plasma Fg were reduced, but antigen levels were normal. Western blot and SDS-PAGE showed no abnormal molecular weight of Fg. The 3 heterozygous mutations of γ Arg275His, Aα Pro18Leu and Aα Arg16Cys were identified in the 3 probands, respectively.

CONCLUSIONThe three probands with dysfibrinogenemia were caused by the mutations of γ Arg275His, Aα Pro18Leu and Aα Arg16Cys, respectively. Both Aα Pro18Leu and Aα Arg16Cys were first reported in Chinese population.

Adult ; Afibrinogenemia ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Female ; Fibrinogen ; genetics ; Genotype ; Humans ; Middle Aged ; Mutation, Missense ; Pedigree ; Phenotype

OBJECTIVETo investigate the clinical phenotype, genotype and molecular mechanism of recurrent venous thrombosis in two Chinese pedigrees with type I antithrombin (AT) deficiency.

METHODSThe routine coagulation screening tests were detected, thrombin generation tests was performed to evaluate the hypercoagulation. Anticardiolipin antibody (ACA) and lupus anticoagulant (LA) were detected with enzyme-linked immunosorbent assay (ELISA) and diluted viper venom time assay (DVVT), respectively. The activities of protein C, protein S and AT (PC:A, PS:A, AT:A) were tested with chromogenic substrate assay or clotting method. The antigen of AT (AT:Ag) was performed with immunoturbidimetry methods. Western blot was used to analyze the molecular weight (MW) and the plasma levels of AT:Ag. All 7 exons and the flanking sequences were amplified by PCR. The mutation of AT gene and thrombophilia associated gene polymorphisms were analyzed by direct DNA sequencing. The expression plasmid of Ala404Asp mutant was constructed with site-directed mutagenesis method based on the wild-type (WT) AT cDNA contained in pcDNA 3.1 vector, and transiently expression of AT WT and the Ala404Asp mutant was performed using HEK293T cells. Cultured supernatant and cell lysates were collected and measured for AT:Ag by ELISA and Western blot.

RESULTSThe results of routine coagulation tests in two probands were normal, thrombin generation tests indicated that proband 1 presented hypercoagulable state with 2.8 and 1.5 times higher of the endogenous thrombin potential (ETP) and peak height compared with that of normal, respectively. The levels of PC:A, PS:A, ACA and LA were normal. AT:A in proband 1 and proband 2 were 45% and 32%, and AT:Ag were almost half of the normal (121 mg/L and 158 mg/L), respectively. The results of Western blot showed that both probands' plasma levels of AT:Ag were lower than the normal pooled plasma and MW was normal. Two heterozygous mutations of g.3291C→T(Thr98Ile), g.13863C > A(Ala404Asp) were identified in the probands, respectively. No proband had venous thrombosis associated gene polymorphisms. Expression in vitro showed that AT:Ag in culture media and lysates of Ala404Asp are 4.8% and 60.6% of that of WT, respectively.

CONCLUSIONThr98Ile and Ala404Asp mutation of AT gene significantly correlate with recurrent venous thrombosis in the two probands, respectively. Ala404Asp has not been described before. The mutant Ala404Asp protein can not be expressed due to impaired secretion and increased intracellular degradation, resulting in type I AT deficiency.

Adult ; DNA Mutational Analysis ; Female ; Fibrin ; deficiency ; genetics ; Humans ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Venous Thrombosis ; genetics

Event-related potential (ERP) studies report that early components P120, N170 and VPP are associated with face processing. Several lines of evidence suggest that VPP is the positive counterpart of N170, and they are generated by the same brain sources. However, whether P120 has a negative counterpart and the relations among these early components (i.e. P120, N170, VPP) remain unclear. In this study, the scalp electroencephalogram was recorded when the subjects passively viewed different stimuli, and ERP was calculated. The synchronization of electroencephalography signals between fronto-central and bilateral occipitotemporal sites was evaluated, and independent component analysis was employed to seek the face-sensitive independent components and their corresponding sources. We found that P120 had the negative counterpart, i.e., VN120; moreover, VN120-VPP and P120-N170 complexes were generated by the same sources located in fusiform gyrus, which reflected the same sequential neural activities of face processing.
Adolescent ; Brain ; physiology ; Electroencephalography ; Evoked Potentials ; physiology ; Face ; Female ; Humans ; Male ; Pattern Recognition, Visual ; physiology ; Perception ; physiology ; Sensation ; physiology ; Young Adult

OBJECTIVETo evaluate the brain pathological changes following exdogenous neural stem cells (NSCs) intraventricular transplantation in neonatal rats with periventricular leukomalacia (PVL), and to explore the feasibility of NSCs transplantation for the treatment of PVL in premature infants.

METHODSNSCs were prepared from E14 embryonic rat brain. Two-day-old neonatal rats were randomly divided into six groups: PVL, PVL+culture medium, PVL+NSCs, sham operation, sham operation+culture medium, and sham operation+NSCs (18-21 rats each group). Intraventricular transplantation of exdogenous NSCs was performed 72 hrs after PVL induction or sham operation. The cerebral pathological evaluation was undertaken by light microscopy 7, 14 and 21 days after transplantation.

RESULTSThe pathological changes in the cerebral white matter were gradually improved with the prolonged time after transplantation. After 21 days of transplantation, 50% of the cerebral white matter showed mild pathological changes and 50% of that showed severe pathological changes, with neuronal pathological scores of 1.28+/-0.86, in the untreated PVL group. In the PVL+NSCs group, 30% of normal white matter, 40% of mild and 30% of severe pathological changes in the white matter were observed, with neuronal pathological scores of 0.32+/-0.16, 21 days after transplantation. There were very significant differences in both of pathological changes in the cerebral white matter and neuronal pathological scores between the PVL and PVL+NSCs groups (x2=10.7, P<0.01; F=29.664, P<0.01).

CONCLUSIONSIntraventricular transplantation of exdogenous NSCs can apparently improve cerebral white matter damage. It is suggested that intraventricular transplantation of NSCs is of a great potential feasibility for the treatment of PVL in premature infants.

Animals ; Animals, Newborn ; Brain ; pathology ; Female ; Humans ; Infant, Newborn ; Leukomalacia, Periventricular ; pathology ; therapy ; Neurons ; cytology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stem Cell Transplantation

Coronary Angiography ; Coronary Vessel Anomalies ; diagnostic imaging ; therapy ; Embolization, Therapeutic ; methods ; Fistula ; congenital ; diagnostic imaging ; therapy ; Heart Ventricles ; abnormalities ; diagnostic imaging ; Humans ; Male ; Middle Aged