Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.

Objective    To assess outcomes of transcatheter aortic valve replacement (TAVR) for pure native aortic valve regurgitation. Methods    A total of 129 patients underwent transfemoral TAVR in Fuwai Hospital from May 2019 to October 2020 were retrospectively analyzed. There were 83 males and 46 females with an average age of 72.26±8.97 years. The patients were divided into a pure native aortic valve regurgitation group (17 patients) and an aortic valve stenosis group (112 patients). Results    The incidence of valve in valve was higher in the pure native aortic valve regurgitation group (47.0% vs. 16.1%, P<0.01). There was no statistical difference between the two groups in conversion to surgery, intraoperative use of extracorporeal circulation, intraoperative left ventricular rupture, postoperative use of extracorporeal membrane oxygenation (ECMO), peripheral vascular complications, disabled stroke, death, or pacemaker implantation. There was no statistical difference in the diameter of annulus (25.75±2.21 mm vs. 24.70±2.90 mm, P=0.068) or diameter of outflow tract (25.82±3.75 mm vs. 25.37±3.92 mm, P=0.514) between the pure native aortic valve regurgitation group and the aortic valve stenosis group. Conclusion    Transfemoral TAVR is a feasible method for patients with pure native aortic valve regurgitation. The diameter of annulus plane, the diameter of outflow tract and the shape of outflow tract should be evaluated.

PURPOSE: Caffeine is the most widely consumed psychostimulant. It is often adopted as a tool to modulate brain activations in fMRI studies. However, its pharmaceutical effect on task-induced deactivation has not been fully examined in fMRI. Therefore, the purpose of this study was to examine the effect of caffeine on both activation and deactivation under sustained attention. MATERIALS AND METHODS: Task fMRI was acquired from 26 caffeine naive healthy volunteers before and after taking caffeine pill (200 mg). RESULTS: Statistical analysis showed an increase in cognition-load dependent task activation but a decrease in load dependent de-activation after caffeine ingestion. Increase of attention and memory task activation and its load-dependence suggest a beneficial effect of caffeine on the brain even though it has no overt behavior improvement. The reduction of deactivation by caffeine and its load-dependence indicate reduced facilitation from task-negative networks. CONCLUSION: Caffeine affects brain activity in a load-dependent manner accompanied by a disassociation between task-positive network and task-negative network.
Brain ; Caffeine* ; Eating* ; Healthy Volunteers ; Magnetic Resonance Imaging ; Memory ; Memory, Short-Term*

OBJECTIVETo evaluate the efficacy of self-made gasbag double-cannula stool drainage device for prevention of anastomotic leakage following anterior resection.

METHODSClinical data of 169 rectal cancer patients in the 8th Affiliated Hospital of Sun Yat-sen University between October 2010 and October 2016 were retrospectively analyzed. Among them, a self-made gasbag double-cannula stool drainage device was placed in 71 patients(stool drainage group), and the remaining 98 patients were taken as control. After an anastomosis, the drainage device was transanally placed by the assistant and the distal tube of drainage device was stretched more than 15 cm from anastomosis. The gasbag was inflated to fully expand the intestine. The main tube was fixed on perianal skin with 7-0 suture, kept more than 3-5 cm outside the anus, and connected to the drainage bag. The incidence of anastomotic leakage was compared between the two groups.

RESULTSThe baseline data were similar between the two groups (all P>0.05). The differences in operative time, intraoperative blood loss, and time to bowel function recovery were not statistically significant (all P>0.05), however, time to oral intake and postoperative stay were shorter in stool drainage group as compared to the control group (both P<0.05). There was no perioperative death in both groups. In stool drainage group, there were 6 cases whose drainage device was pulled out within 48 hours due to intolerance. The ruptured gasbag was replaced 5 times and the tube was clogged by fecal material 21 times. After flushing, the tube did not recanalized and was pulled out in 3 cases. The incidence of anastomotic leakage in stool drainage group was significantly lower than that in the control group (2.8% vs. 11.2%, P=0.043). As for the low anastomosis (the distance to anal verge less than 5 cm), the incidence of anastomotic leakage in stool drainage group was also significantly lower than that in the control group (2.3% vs. 15.4%, P=0.028), while as for the high anastomosis, the difference was not statistically significant (3.6% vs. 3.0%, P=0.906). Logistic regression analysis revealed that the presence of a stool drainage device was an independent protective factor for anastomotic leakage (OR=0.316, 95%CI:0.114 ~ 0.769, P=0.003).

CONCLUSIONSThe self-made gasbag double-cannula stool drainage device effectively prevents anastomotic leakage after anterior resection of rectal cancer. However it is not suitable for those patients with high anastomosis.

Objective To explore the feasibility of endoscopic resection without arterial embolism for nasopharyngeal angiofibroma and the strategy of decreasing the bleeding during the operation.Methods The clinical data of twenty-five cases of nasopharyngeal angiofibroma were retrospective analyzed,including 3 cases of Radowski stage Ⅱ a,5 cases of stage Ⅱ b,4 cases of stage Ⅱ c and with 13 cases of stage Ⅲ a.All cases did not receive the arterial embolism,and controlled hypotension were adopted under endoscopic transnasal approach during the tumor resection.Two cases were added the labiogingival incision.During the operation,under the opening vision,cutting out the outside of the infratemporal fossa,and the pterygoid process to adequate exposure the pterygopalatina fossa and infratemporal fossa.Early recognition of anatomical landmarks and establish the safety plane,along the periphery of the tumor to proceed with micro-separation,early blocking tumor nutrient vessels,en bloc resection of the tumor and some other ways to reduce bleeding and tumor resection.Results Amount of bleeding during operation was 600-1500 ml,none of them had internal carotid artery injury and intracranial injury or some other complication.Follow-up 2-3 years was available in all patients,except 1 case with residual of tumor surrounding the optic nerve,the other 24 cases had no residual tumor and relapses.Conclusions The preoperative occlusion and artery ligation may not be needed.Surgical technique is the key to reduce blood loss,and it is feasible to have endoscopic resection of nasopharyngeal angiofibroma with proper operating technique.

OBJECTIVE: To explore the endoscopic management of petrous apex cholesterol granuloma through trans-sphenoid sinus-clivus approach. METHOD: One case of right-side petrous apex cholesterol granuloma were undertaken surgical treatment through trans-sphenoid sinus-clivus approach, then the possibility of any other approach and their advantages and disadvantages were analyzed. RESULT: The operation was success without any complications. Patient's hearing was recovered and tinnitus vanished. The patient was discharge from hospital at the third day after operation, and followed up for four month without recurrence. CONCLUSION Trans-sphenoid sinus clivus endoscopic management of petrous apex cholesterol granuloma is effective and safe. The operators can monitor internal carotid artery then to access to the diseased region with reducing risk.
Cranial Fossa, Posterior ; surgery ; Endoscopy ; methods ; Female ; Granuloma ; etiology ; surgery ; Humans ; Sphenoid Sinus ; surgery ; Young Adult

Objective To investigate the distributions of PAH gene mutation and provide guidance for gene diagnosis and prenatal diagnosis of patients with PKU in Xinjiang of China.Methods A total of 15 patients (aged from 2 to 10 years, all with blood Phe concentration over 700 μmol/L) who visited Urumqi general hospital of Lanzhou Command were clinically diagnosed as PKU and were included in this study. PCR followed by DNA sequencing was performed to analyze the promoters, all the 13 exons and their flanking introns of PAH gene in these 15 PKU patients.Results PAH gene of 15 PKU patients was amplified by PCR, and PCR products were subjected to DNA sequencing directly.Four PAH gene mutation types, including 5′- Flanking-626G > A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G>C, were identified in each of four PKU patients.Consequently reverse DNA sequencing showed G>A at -626 site, ACT deletion at -480 position in the promoter of PAH gene, an insertion at 584 site in the coding region and G>C at the border between exon 8 and intron 8 of PAH gene, respectively. After inquirying from PAH website and international PAH database (www.pahdb.mcgill.ca), these four PAH gene mutation types were verified as novel PAH gene mutations. Additionally, four patients carrying either of these four PAH gene mutation aged 3-5 years old were characterized by typical clinical phenotypes including blood Phe levels between 1 572-1 782 μmol/L, mental retardation, yellow hair and mousy odor of hair, skin and urine. Conclusions 5′-Flanking-626G>A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G > C are identified as four novel PAH gene mutations to cause PKU directly probably either by disrupting the normal 3-D structure and affecting enzymatic activity of PAH or depressing the transcription and translation of PAH gene.Together, our identification of four novel PAH gene mutations will provide important clues for future gene diagnosis and prenatal diagnosis of PKU.

OBJECTIVE: To investigate the expression of myosin heavy chain (MHC) in normal laryngeal muscle and the difference between the adductor and abductor. METHOD: Seven patients with total laryngectomy were enrolled in this study. The adductor muscles were acquired from the lateral cricoarytenoid (LCA) muscle and the abductor muscles were acquired from the posterior cricoarytenoid (PCA) muscle. The expression of myosin heavy chain were detected with fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining respectively. RESULT: (1) MHC-II b was expressed in laryngeal muscles at mRNA levels, and not expressed at the protein level; (2) At both mRNA level and protein level, the expression of MHC-I was higher in the PCA muscles than in the LCA muscles while MHC-II level was higher in the LCA muscles than in the PCA muscles. CONCLUSION (1) MHC-II b protein was not expressed in human laryngeal muscles; (2) Phenotypic differences were significant in laryngeal adductor and abductor muscles based on their different functions. PCA contained larger percentage of MHC-I fibers, while LCA contained more MHC-II fibers.
Aged ; Female ; Humans ; Laryngeal Muscles ; chemistry ; metabolism ; Male ; Middle Aged ; Myosin Heavy Chains ; genetics ; metabolism ; Phenotype ; Protein Isoforms

OBJECTIVE: To investigate the influence of denervation on myofiber morphology of the adductor and the abductor in patients with recurrent laryngeal nerve (RLN) paralysis and to provide experimental evidence for the clinical feasibility of RLN repair. METHOD: Adductor muscles were acquired from the lateral cricoarytenoid muscle (LCAM) and abductor muscles from the posterior cricoarytenoid muscle(PCAM). Normal human PCAM and LCAM are treated as control group (n = 7). Thirty-eight cases of PCAM with damaged RLN were divided into five groups according to the duration of their RLN damage: 0.5-1 year (7 cases), > 1-2 years (10 cases), > 2-3 years (8 cases), > 3-6 years (8 cases) and > 6 years (5 cases); twenty-nine cases of LCAM were also divided into five groups: 0.5-1 year (7 cases), > 1-2 years (6 cases); > 2-3 years (6 cases), > 3-6 years (6 cases) and > 6 years group(4 cases). They were all stained with HE and Masson three-color staining, the fiber cross-sectional area of muscle tissue and collagen connective tissue were quantitative analyzed. The changes of myofiber morphology of adductor and abductor muscles after the loss of the RLN were analyzed with image analysis system. RESULT: The transverse areas of myofibers gradually decreased and those of collagen fibers gradually increased with the prolongation of denervation. (1) Difference between the denervated groups of LCAM of 0.5-1 year, > 1-2 years and > 2-3 years groups were not significant (P > 0.05). Fiber cross-sectional area of > 3-6 years group decreased most obviously with significantly difference compared with > 2-3 years group (P < 0.05); (2) There were obvious difference between the control group, 0.5-1 year group, > 1-2 years group, > 2-3 years group and > 3-6 years of PCAM(P < 0.05); (3) There was no significant difference between the group of > 3-6 years and > 6 years of two kinds of laryngeal intrinsic muscle (P > 0.05); (4) Fiber cross-sectional area of each group of the LCAM after 1 year denervation were significantly greater than that of the PCAM under same conditions (P < 0.05). CONCLUSION The influence of denervation on myofiber morphology following denervation is different between the abductor and adductor owing to the different fiber type composition and functional properties. The rate of muscle atrophy of the adductor is slower than that of the abductor. To restore the structure and function of denervated laryngeal muscles better, the recurrent laryngeal nerve injury repair surgery for PCA muscle function recovery should be carried out within 1 year after denervation while the surgery for LCA muscle function recovery should be carried out within 3 years after denervation.
Case-Control Studies ; Denervation ; Humans ; Laryngeal Muscles ; innervation ; pathology ; Myofibrils ; pathology ; Neurosurgical Procedures ; Recurrent Laryngeal Nerve ; pathology ; Staining and Labeling ; Vocal Cord Paralysis ; pathology ; surgery