Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

Objective To make classification and segment measurement for the cases with tibiofibular and ankle fractures in parachuting landing, and investigate main classification types of parachuting fractures and fracture segments of high risk.Methods A total of 56 fracture cases in parachuting landing were collected, and the tibiofibula and ankle fractures were classified according to AO-OTA or Lauge-Hansen classification standards respectively based on their digital X-ray images. The medium plane between talus and tibia joint planes in ankle joint was defined as the reference plane. The highest and lowest injury points of tibia and fibula were marked respectively, and the fracture segment was defined between the highest and lowest point for statistical analysis.Results For tibiofibular and ankle fracture cases in parachuting landing, fracture at both tibia and fibula accounted for 80.4%. The major classification of tibiofibula fracture was 42-D/5.2 (45.8%) and 42-D/5.1 (16.7%). The major classification for ankle fracture was pronation-external rotation (PER, 59.4%) and supination-external rotation (SER, 37.5%). When tibiofibular and ankle fracture cases in parachuting landing occurred, the fracture segment of the tibia was mainly from 57 to 143 mm above the reference plane and from 6 mm below the reference plane to 24 mm above the reference plane, while the fracture segment of the fibula was 4-45 mm and 74-83 mm above the reference plane. Injury risks of all above segments were higher than 50%.Conclusions For protection of lower limbs in parachuting landing, the fracture at both tibia and fibula should be highly noticed. The ankle motion of PER and SER should be especially restricted in parachuting ankle protection.

Objective To study effects of backpack gravity center position on kinetics and kinematics of lower-extremity joints in parachuting landing and evaluate the injuries. Methods Seven participants performed parachuting landing with backpack gravity center on three positions: low-back (position 1), upper-back (position 2) and abdomen (position 3). Results The peak vertical ground reaction force (GRF) with backpack on position 2 was significantly lower than that on position 1. The joint moment on sagittal plane of the hip with backpack on position 2 was significantly higher than that on position 1 and position 3. The joint energy absorption of the hip with backpack on position 2 was significantly higher than that on position 1. The angular displacement of the hip on sagittal plane with backpack on position 2 was significantly higher than that on position 1 and was significantly lower than that on position 3. The angular velocity of the hip on sagittal plane with backpack on position 2 was significantly lower than that on position 3. Conclusions Different positions of backpack gravity center could significantly influence kinetic and kinematic parameters of the hip. Backpack gravity center on upper-back position could decrease the lower-extremity injuries. The results can provide evidences for evaluating backpack gravity center and decreasing injuries in parachuting landing.

Objective To study the relationship between pulsatile tinnitus and temporal bone pneumatization grade. Methods Through the in vitro experiment, the generation and transmission pathways of the venous sound were simulated. The sound signals at the position of eardrum were recorded and analyzed. Results In case of cortical plate dehiscence, the high pressure and pulse-synchronous venous sounds were received at eardrum. The highest sound pressure occurred in the normal pneumatization case. In case of cortical plate intactness, the non-pulsatile venous sounds with pressure close to the background control sound were received at eardrum. Temporal bone air cells (TBAC) with different pneumatization grades would transmit venous sound in different frequency ranges. Conclusions Normal pneumatization TBAC exhibited the highest amplification on venous sound, while hypopneumatization TBAC exhibited the lowest amplification on venous sound. The pneumatization grade of TBAC is neither the sufficient nor essential condition of pathogenic venous sound, while the cortical plate dehiscence is the sufficient or necessary condition of pathogenic venous sound.

PURPOSE: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. METHODS: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. RESULTS: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. CONCLUSION: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.
Area Under Curve ; Biomarkers ; Biomarkers, Tumor ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Data Mining ; Early Detection of Cancer ; Female ; Genome ; Humans ; Methods ; MicroRNAs* ; Plasma ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity

Objective To analyze the clinical features and onset factors of esophageal cancer.Methods The SPSS 13.0 software was adopted to establish the computer records management system of esophageal cancer.The clinical data in 2 261 clinically cured discharged cases of esophageal cancer from January 2011 to December 2013 were statistically analyzed.Results Forty-nine cases (2.17％) were in the 30-＜40 years old group,324 cases (14.33％) were in the 40-＜50 years old group,963 cases (42.59％) were in the 50-＜60 age group,790 cases (34.94％) were in the 60-＜70 age group and 135 cases (5.97％) were in the 70 years old or more group.Among 2 240 cases,2 031 cases (90.36 ％) showed the different differentiation degrees of squamous epithelial carcinoma by histological analysis,the invaded range displayed fibrous membrane(T3) in 759 cases(33.57％) and peripheral tissue(T4) in 682 cases(30.16％);having smoking and drinking history was in 1 281 cases(56.67％) and 1 025 cases (45.33 ％) respectively;596 cases (26.36 ％) had genetic family history,75.08 ％ was father positive or mother positive.Conclusion Esophageal cancer is mainly squamous cell carcinoma,the onset age is mainly concentrated at the age 50-＜70 years old,which is correlated with smoking and drinking years,moreover has obvious genetic susceptibility.

AIM: To observe the effects of Helicobacter pylori (Hp) on the apoptosis of human gingival tissue.METHODS: Gingival tissue samples were taken from 30 patients without chronic periodontitis, and Hp was detected by conventional PCR.The apoptosis of the gingivival cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to analyze the correlation between Hp infection and apoptosis of the gingival tissues.RESULTS: The Hp positive detections were 12 in the 30 patients without periodontitis, so the positive rate of Hp in the gingival tissue samples was 40%.The gingival tissue showed a large number of apoptotic cells in Hp positive group, and less apoptotic cells in Hp negative group.The apoptotic index in Hp positive group (0.498±0.092) was significantly higher than that in normal group (0.207±0.053) (P<0.05).CONCLUSION: Hp might play a role in the apoptosis of gingival tissues.

Objective: To investigate the significance of Twist2 in glioma and whether it is involved in the malignant transformation of glioma by epithelial-mesenchymal transition (EMT). Methods: Using immunohistochemical method detected the expression level of Twist2 in 60 cases of gliomas (including WHO grades Ⅱ, Ⅲ and Ⅳ, each for 20 cases) and 20 cases of non-tumor brain tissues. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression level of Twist2 mRNA and protein in 61 cases of fresh glioma tissue (WHO grade Ⅱ 16 cases, Ⅲ 21 cases, Ⅳ 24 cases) and 12 cases of adjacent tissues, and the expression levels of E-cadherin, N-cadherin and vimentin were also investigated in fresh glioma tissue. Results: Immunohistochemistry results showed that the percentages of Twist2 expression in glioma was 90%(54/60) compared with 30%(6/20) in non-tumor brain tissues(P<0.01). The percentages of Twist2 expression were 75% (15/20), 95% (19/20), and 100% (20/20) in the WHO gradesⅡ, Ⅲ and Ⅳ gliomas, respectively. WHO grades Ⅳ and Ⅲ were significantly higher than that of WHO grade Ⅱ (P<0.01). There was no significant difference between WHO grade Ⅳand WHO Ⅲ glioma (P>0.05). Real-time fluorescence quantitative PCR and Western blot showed that the expression level of Twist 2 in gliomas was significantly higher than that in para-cancerous tissues (P<0.01), and those in WHO grades Ⅳ and Ⅲ gliomas were significantly higher than that in WHO grade Ⅱ glioma (P<0.01). There was no significant difference between WHO grade Ⅳand grade Ⅲ glioma (P>0.05). Detection of key protein expression in EMT by Western blot displayed that the expression of E-cadherin was negatively associated with Twist2 in glioma (r=-0.972, P<0.01). The expression of N-cadherin and vimentin was positively associated with Twist2 in glioma(r=0.971, P<0.01; r=0.968, P<0.01). Conclusions The expression of Twist2 in human glioma is positively correlated with the malignant grade of glioma, which may be involved in the malignant progression of glioma by EMT.

This study investigated the effect of prolonged walking with load carriage on body posture, muscle fatigue, heart rate and blood pressure of the tested subjects. Ten healthy volunteers performed 30 min walking trials on treadmill (speed = 1.1 m/s) with different backpack loads [0% body weight (BW), 10% BW, 15% BW and 20% BW]. The change of body posture, muscle fatigue, heart rate and blood pressure before and after walking and the recovery of muscle fatigue during the rest time (0, 5, 10 and 15 min) were collected using the Bortec AMT-8 and the NDI Optotrak Certus. Results showed that the forward trunk and head angle, muscle fatigue, heart rate and blood pressure increased with the increasing backpack loads and bearing time. With the 20% BW load, the forward angle, muscle fatigue and systolic pressure were significantly higher than with lighter weights. No significantly increased heart rate and diastolic pressure were found. Decreased muscle fatigue was found after removing the backpack in each load trial. But the recovery of the person with 20% BW load was slower than that of 0% BW, 10% BW and 15% BW. These findings indicated that the upper limit of backpack loads for college-aged students should be between 15% BW and 20% BW according to muscle fatigue and forward angle. It is suggested that backpack loads should be restricted to no more than 15% BW for walks of up to 30 min duration to avoid irreversible muscle fatigue.
Blood Pressure ; Body Weight ; Exercise Test ; Healthy Volunteers ; Heart Rate ; Humans ; Muscle Fatigue ; Posture ; Walking ; physiology ; Weight-Bearing