Objective To investigate the effect and mechnism of betaine(BET)in reversing chemotherapy resistance in prostate cancer(PCa)by inhibiting ATP-binding cassette subfamily B member 1(ABCB1).Methods The PCa chemotherapy-sensitive C4-2B cells were cultured,and the TaxR cells resistant to docetaxel(DTX)were established by gradient increase the concentration of DTX.The drug resistance of C4-2B and TaxR cells against DTX was assessed using CCK-8 and the colony formation experiment.Western blotting and qRT-PCR were used to detect ABCB1 expression.The TaxR cells were divided into:(1)Control group,negative control group(NC),siABCB1-1 group(transfected with siABCB1-1),and siABCB1-2 group(transfected with siABCB1-2).Western blotting was used to detect the effect of small interfering RNA on silencing ABCB1,and CCK-8 was used to detect the differences in DTX resistance between each group.(2)Different concentrations of BET(0,100,200,400,600,800 mmol/L)groups.These groups were subjected to CCK-8 to detect cell viability,and Western blotting was used to detect the protein expression of ABCB1.(3)Control group,DTX group(20 nmol/L DTX),BET group(200 mmol/L BET),and DTX+BET group(20 nmol/L DTX+200 mmol/L BET),flow cytometry was used to detect apoptosis rate and cell cycle,and Western blotting to detect the protein expression of apoptosis-related proteins(Bcl2,BAX,c-caspase-3).(4)Control group,BET group(200 mmol/L BET),wortmannin(WM)group(100 μmol/L WM),and BET+WM group(200 mmol/L BET+100 μmol/L WM).Western blotting was used to detect the protein expression of PI3K,Akt,and ABCB1.(5)Control group,BET group(200 mmol/L BET),and BAY group(10 μmol/L BAY),BAY+BET group(200 mmol/L BET+10 μmol/L BAY).Western blotting was used to detect the protein expression of NF-κB p65,p-ikBα and ABCB1.Network pharmacology combined with transcriptome sequencing was used to predict the possible pathways for BET to reverse chemotherapy resistance.Results Compared with C4-2B cells,TaxR cells showed significantly increased resistance to DTX(P<0.01),and high expression of ABCB1(P<0.01).After silencing ABCB1 with siRNA,TaxR cells'resistance to DTX was significantly inhibited(P<0.01).The inhibition rate of TaxR cells treated with 200 mmol/L BET was less than 20%,and it significantly decreased the expression of ABCB1 protein in TaxR cells(P<0.05).Compared with control group,the combination of 200 mmol/L BET and 20 nmol/L DTX resulted in higher apoptosis rate and higher S stage cell ratio,lower expression of Bcl-2 protein and higher expression of BAX and c-caspase-3 proteins than the two drugs used alone(P<0.05).Compared with control group,the combination of 200 mmol/L BET and 100 μmol/L WM significantly down-regulated the protein expression of PI3K,Akt and ABCB1(P<0.01).The combination of 200 mmol/L BET and 10 μmol/L BAY significantly down-regulated the protein expression of NF-κB p65,p-ikBα and ABCB1(P<0.01).Conclusion BET may reverse TaxR cells'chemotherapy resistance by down-regulating ABCB1 expression through the PI3K/Akt/NF-κB signaling pathway.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.
Humans ; HEK293 Cells ; Sincalide ; China ; Amanita ; Death, Sudden

Aim To study the neuroprotective effect of rhubarb extract on MCAO model rats and explore its mechanism of action. Methods Forty-five SPF male Sprague-Dawley rats were randomly divided into sham group, MCAO group, and MCAO + rhubarb group. MCAO model was prepared by silk plug method, and rhubarb extract was administered at a concentration of 200 mg · kg

Objective: To compare the clinical features, ultrasonic imaging manifestations and therapeutic evaluations between elderly onset rheumatoid arthritis (EORA) and EORA with osteoarthritis (OA). Methods: Eighty-eight patients with rheumatoid arthritis were divided into two groups: group EORA (n=36) and group EORA+OA (n=52). The onset age of all patients was 60 years or older. General conditions, joint involvement distribution, ultrasonic manifestations and disease activity scores (DAS28-3) of patients in the two groups were analyzed. The χ² test/Fisher's exact probability test and the Student's t test/Mann-Whitney U test were used to analyze data. Results: There was no significant difference in the proportion of male and female patients and erythrocyte sedimentation rate (ESR) between the two groups (P>0.05). The onset age of patients in group EORA+OA [(68±4) years old] was higher than that in group EORA [(65±4) years old], and the difference was statistically significant (t=-3.465, P=0.001). Duration of the disease and body mass index in group EORA+OA were significantly higher respectively than those in group EORA. Joint involvement in the two groups was mainly found in shoulder, wrist, Metacarpophalangeal joint (MCP)2, MCP3, proximal inter-phalangeal joint (PIP)2, PIP3, PIP4, and knee joint (34.7%-86.5%). The percentage of MCP2[36.5%(38/104), 70.8%(51/72); χ²=20.02, P<0.01], MCP3[33.7%(35/104), 59.7%(43/72); χ²=11.72, P=0.001], MCP4[4.8%(5/104), 22.2%(16/72); χ²=12.28, P<0.01], PIP2[69.2%(72/104), 83.3%(60/72); χ²=4.51, P=0.034] and PIP3[53.8%(56/104), 70.8%(51/72); χ²=5.15, P=0.023] in the EORA+OA group was lower while the percentage of MCP1, DIP 2, DIP3, DIP4 and knee joints were higher than that in the EORA group (P<0.05). In group EORA+OA, the synovial thickness of the wrist joints [(4.2±0.5) mm] and knee joints [(7.7±0.8) mm] were significantly thicker than those in group EORA [(3.2±0.9) mm; (6.3±0.8) mm, t=-5.82, P<0.01; t=-7.22, P<0.01]; The proportion (70.0%) of level 2 and 3 of patients' wrist joint synovium pannus blood flow and knee joint synovium pannus in group EORA+OA were increased than group EORA (51.9%; 52.3%), the difference between the two groups was statistically significant (χ²=4.64, P=0.031; χ²=4.43, P=0.035). There was no significant difference in DAS28-3 scores between the two groups before patients received treatment. After 2 weeks and 12 weeks of glucocorticoid treatment, DAS28-3 scores in group EORA [3.62(2.88, 4.03); 2.35(2.26, 2.62) points] were significantly lower than group EORA+OA [5.01(4.68, 5.26); 3.38(2.28, 3.83) points] (Z=-7.766, P<0.01; Z=-3.461, P<0.01). Conclusion Compared with patients of EORA alone, patients of EORA with OA have more obvious joint symptoms, MCP1, DIP and knee joint are susceptible to the co-involvement among them, longer duration of disease, and were prone to synovial hyperplasia and pannus flow formation. The therapeutic effects of glucocorticoid on joint inflammation in patients of EORA alone are superior to those patients of EORA with OA.

Objective Idiopathic pulmonary fibrosis, the fibrosis score (i.e., the combined extent of reticulation and honeycombing) is associated with worse survival. The aim of this study was to identify high-resolution computed tomography (HRCT) patterns and patient characteristics that could predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD). Methods We retrospectively analyzed 130 patients with newly diagnosed RA-ILD from 2011 to 2017 at Shanxi People's Hospital. The Pearson correlation analysis was used for the correlation between the fibrosis score and the worse survival of RA-ILD, and Using Cox regression analysis was used to identify the associations with mortality. A value of P less than 0.05 was considered statistically significant. Results During a median follow-up of 65 months, 32/130 (24.6％) patients died. Univariate analysis identified 6 significant poor prognostic factors: lower baseline ％ predicted forced vital capacity [HR=0.97, 95％CI(0.94, 0.99);P=0.008], total interstitial disease score [HR=1.06, 95％CI(1.03, 1.08);P<0.01], reticulation score [HR=1.07, 95％CI (1.04, 1.09); P<0.01], traction bronchiectasis score [HR=2.04, 95％CI (1.21, 3.40);P=0.008], fibrosis score [HR=1.07, 95％CI (1.01, 1.13);P<0.01], and definite UIP pattern [HR=4.18, 95％CI (1.40, 12.51); P=0.010]. Fibrosis score remained to be an independent significant poor prognostic factor of survival on bivariate analysis [HR=8.136, 95％CI (2.87, 28.35); P=0.001]. Patients with a fibrosis score>20％ had high mortality. Conclusion This study has shown that fibrosis score is strongly associated with worse survival in RA-ILD, and patients with fibrosis score>20％ have a 8.136-fold increased risk of mortality.

Notopterol, isoimperatorin, volatile oil and extract （water and ethanol) were used as the research objects in this study to investigate the effects of different softening method, slice thickness and drying methods on the quality of Notopterygii Rhizoma et Radix slices, and the experimental data were analyzed by homogeneous distance evaluation method. The results showed that different softening, cutting and drying processes could affect the content of five components in Notopterygii Rhizoma et Radix incisum. The best processing technology of Notopterygii Rhizoma et Radix slices was as follows: non-medicinal parts were removed; mildewed and rot as well as moth-eaten parts were removed; washed by the flowing drinking water; stacked in the drug pool; moistening method was used for softening, where 1/8 volume of water was sprayed for every 1 kg of herbs every 2 h; upper part of herbs covered with clean and moist cotton, and cut into thick slices (2-4 mm) after 12 h moistening until appropriate softness, then received blast drying for 4 h at 50 ℃, and turned over for 2 times during the drying. The process is practical and provides the experimental basis for the standardization of the processing of Notopterygii Rhizoma et Radix, with great significance to improve the quality of Notopterygii Rhizoma et Radix slices.

Study on the standardization of Chinese materia medica is an important action for modernization and globalization for traditional Chinese medicine. Standardization on the processing of Chinese herbal pieces is an important part in the study on standardization of Chinese materia medica, so it is of great significance to establish the technical processing standards of Angelicae Sinensis Radix pieces for improving its quality. In this study, single factor experiment was designed to optimize the softening, cutting and drying processes of Angelicae Sinensis Radix. With ferulic acid, Angelicae Sinensis Radix polysaccharide, volatile oil and extracts (water and ethanol) content as the quality index, the effects of different softening, cutting and drying processes on the contents of the five components in Angelicae Sinensis Radix were analyzed, and the normalized distance evaluation method was used to analyze the experimental data. The results showed that the content of five components in Angelicae Sinensis Radix was affected by different softening methods and drying temperature, but the thickness of slice had little effect on the content. The best preparation process for Angelicae Sinensis Radix was as follows: Non-medicinal parts were removed; mildewed and rot as well as moth-eaten parts were removed; washed by the flowing drinking water; stacked in the drug pool; moistening method was used for softening, where 125 mL water was sprayed for every 1 kg of herbs every 2.5 h; upper part of herbs covered with clean and moist cotton, and cut into thin slices (1-2 mm) after 15 h moistening until appropriate softness, with disk thickness of 1-2 cm, then received blast drying for 6 h at 55 ℃, and turned over for 2 times during the drying.

BACKGROUND: The stress distribution is different between implants and natural teeth, and the biomechanical characters of implant-natural tooth supported fixed partial dentures need to be explored.OBJECTIVE: To analyze the distributions of stress and strain on the implant interface and natural tooth ligaments by loading a vertical force to a single implant crown, natural tooth crown and a implant-natural tooth supported fixed partial denture.METHODS: Two male healthy Beagle dogs were selected, and their right mandibular first molars were exacted under general anesthesia. Three months later, a 3.3 mm×10 mm RN ITI implant was implanted into the defect region of each dog. The dogs were killed under anesthesia after another 3 months to remove the mandible. One dog was restored by a single implant and natural tooth crown, and the other was restored by the implant-natural tooth supported fixed partial dentures. The specimens were fixed to the load device after embedded with self caring acrylic resin, and the strain gauges were pasted to the cortical bone around the implant and natural tooth neck. The vertical force was loaded to the implant, natural tooth and fixed denture with 40, 60, 80,120, and 160 N.RESULTS AND CONCLUSION: When the force was loaded to the implant of combined denture, the implant stress of combined denture was less than that of the single implant repair, and partial force was loaded on natural teeth; when the force was loaded to the natural tooth of combined denture, the stress to the natural tooth of combined denture was less than that of the single natural tooth repair. When the force was loaded to the natural tooth of combined denture, the stress was assumed by the whole prostheses. However, the stress was almost assumed by the implant when the force was loaded to the implant of combined denture. That is to say, it is feasible to use the implant-natural tooth supported fixed partial dentures.

OBJECTIVETo identify the candidate chromosomal region for congenital preauricular fistula (CPF) through analysis of an affected Chinese family.

METHODSConventional linkage analysis using short tandem repeats (STR) markers was performed to investigate three chromosomal regions 8q11.1-q13.3, 1q32-q34.3 and 14q31.1-q31.3.

RESULTSNone of 16 STRs could attain a LOD score of more than -2.0 (theta=0). Therefore, the three regions were all excluded as the candidate region for the disease.

CONCLUSIONCPF features high genetic heterogeneity. The family may have a causative gene elsewhere. Whole-genome-based study is needed to identify its genetic etiology.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Craniofacial Abnormalities ; genetics ; Female ; Humans ; Lod Score ; Male ; Microsatellite Repeats ; Pedigree

BACKGROUND:Studies have demonstrated that implantation of pile and different amount of residual tooth can change the stress distribution patterns of the tooth dentin within the residual root, and have an effect on the fracture mode of post-core restoration. OBJECTIVE:To evaluate the effects of the different amount of residual tooth on the fracture mode under oblique loading conditions in fiber pile composite resin core ful crown restoration. METHODS:Forty single rooted premolars extracted from orthodontic patients were divided into four groups after root canal preparation and filing. The plane going through buccal and lingual enamel cementum border midpoint and perpendicular to the long axis of the tooth was taken as the reference plane, so that the remaining amount of the tooth were 0, 1, 2, 3 mm. Fiber pile composite resin core metal ful restoration was conducted. After the repair, the oblique loading at 45° and at the rate of 1 mm/min was conducted. Fracture mode and load-displacement curve when root fracture occurred were recorded. RESULTS AND CONCLUSION:The tooth neck fracture usualy occurred in the 0 mm group, and central root fracture usualy occurred in the remaining three groups. There was a significant difference in the total fracture mode between 0 mm group and the remaining three groups (P < 0.05). There was no significant difference in the total fracture mode between 1, 2 and 3 mm groups (P> 0.05). In oblique loading conditions, when the remaining tooth structure was smal, the prosthesis was prone to have dental neck fracture. Fiber posts played a protective role in the tooth root, but the clinical probability of failure increased. The fracture mode was changed with the increase of residual tooth amount, transferring from the neck edge to the root. These results demonstrate that we must retain more tooth tissue from the crown in the restoration of residual root with fiber post-core crown.