ATM: To explore the effect and mechanism on blood pressure and heart protection of renal hypertension in rats treated with ?_1 receptor antisense oligodeoxynucleotides (?_1-AS-ODN) by delivery with cationic liposomes DOTAP/DOPE. METHODS: 24 SD rats were divided randomly into 4 groups of 6 each group: two groups of 2K1C rats were treated via tail vein injection with ?_1-AS-ODN or inverted oligonucleotides against rat ?_1-AR mRNA (?_1-IN-ODN) of 0.5 mg?kg~(-1) once. 6 untreated 2K1C rats and shamed rats served as positive and normal controls. Blood pressure (BP), cardiac haemodynamics, and left ventricular index (LVW/BW) were measured. The histological changes of myocardium were observed by optical microscope and the expressions of Bcl-2 and Bax in myocardium were examined by immunohistochemical method. RESULTS: The single dose management of ?_1-AS-ODN decreased blood pressure to 120 mmHg for 27 days and improved the LV function obviously (P

Objective To explore the relationship between quality of life and acceptance of disability of colostomy patients.Methods Using convenience sampling method to investigate 111 colostomy patients.General information questionnaire,QLQ-C30 scale,QLQ-CR38 scale and Acceptance of Disability Scale were used to investigate patients' general condition,quality of life and acceptance of disability.Data was analyzed by SPSS 17.0.Results The general health condition of colostomy patients was better than reference value and the score of ADS was at an average level.There was a relationship between general health condition,functioning dimensions,symptom dimensions and acceptance of disability.Conclusions There was a close relationship between quality of life and acceptance of disability.The acceptance of disability should be improved to help patients to obtain better quality of life.

The antinociceptive effect of epidural administration of huwentoxin-I was elucidated in a tonic visceral pain rat model produced by acute colon inflammation. The nociceptive behaviors were induced by perendoscopically injecting dilute formalin (50 μl) into the depth of the colonic wall in rats. Both ω-conotoxinMVIIA and morphine hydrochloride were given epidurally as positive control while saline as negative control.Similar to ω-conotoxin-MVIIA and hydrochloride morphine, the epidural administration of HWTX-Ⅰ significantly reduced the nociceptive responses in a dose-dependent manner in tonic visceral pain rat model ( P ＜ 0.05). The suppression effects of both huwentoxin- Ⅰ and ω-conotoxin-MVIIA at 20 μg/kg were kept steady compared with the saline group and reached their maximum effects at the doses of 50 ～ 75 μg/kg within 1 hour when the nociception had been observed. It was also found that at the same doses, huwentoxin- Ⅰ was less effective in antinociception than ω-conotoxin-MVIIA. However, ω-conotoxin-MVIIA, but not huwentoxinⅠ , caused an obvious motor dysfunction at these doses. The action of morphine hydrochloride was initiated faster, but lasted for a shorter time than that of huwentoxin- Ⅰ and ω-conotoxin-MVIIA. Thus, huwentoxinⅠ , a potent blocker of neuronal N-type voltage-sensitive calcium channels, induced a remarkable dosedependent restrain effect similar to ω-conotoxin-MVIIA and morphine on the tonic visceral pain produced by colonic wall injection of formalin in conscious rats.

Extensive attention was paid on how to ensure the cultivation quality for postgraduates with professional degree under the background of the enrollment expansion.The problems in the cultivation of postgraduates with professional degree including declined quality among enrolled students,inefficient training program,unsound management system and little clinical operation chance were analyzed combined with the practice and explore in the clinical competence training for postgraduates with professional degree in Guangxi university of Traditional Chinese Medicine.Some countermeasures were put forward in improving clinical competence for postgraduates with professional degree,for instance the improvement of the management system,tutor team,quality supervision system,clinical skill training and the construction of training bases.

Objective To analyze the drug resistance and detect the drug resistance genes of pathogenic bacteria isolated from hospital sewage , and to investigate the sources of antibiotic resistant microorganisms in the environment .Methods The enteric pathogenic bacteria , such as thermotolerant Escherichia coli , Salmonella and Shigella , were isolated from the sewage of Shaoxing hospitals from January 2016 to December 2016 , and the detection of drug resistance of thermotolerant Escherichia coli , the drug resistance of Escherichia coli isolated from clinical specimens of three hospitals was compared and analyzed . Meanwhile , extended spectrum beta lactamases ( ESBLs ) resistance genes were detected in thermotolerant Escherichiacoliinsewage.Results 48strainsofpathogenswereisolatedinsewage,including32strainsof Escherichia coli , 2 strains of Shigella sonnei and 1 strain of Salmonella arizonae .Escherichia coli has a low rate of resistance to most antibiotics .Compared to Escherichia coli isolated from clinical specimens , there were significant differences among the drug resistance rates of Ampicillin , Aztreonam, Amoxicillin/Clavulanic acid and the first to four generation Cephalosporins (P<0.05).11 strains of ESBLs positive bacteria were detected in sewage .Among them , 7 carried CTX-M9 resistance genes , and 4 carried TEM resistance genes , while 1 strain of CTX-M1 and SHV was carried .There were 2 strains carrying CTX-M9 and TEM resistance genes simultaneously , 1 strain simultaneously carrying TEM and SHV resistance genes . Conclusions There are different kinds of intestinal pathogens in hospital sewage , which may lead to contamination of drug-resistant microorganisms in the environment .Therefore the hospitals should strengthen the quality of sewage treatment and improve the qualified rate of sewage disinfection .

Jingzhaotoxin-V(JZTX-V) isolated from the venom of the spider Chilobrachys jingzhao is a novel potent inhibitor that acts on tetrodotoxin-resistant and tetrodotoxin-sensitive sodium channels in adult rat dorsal root ganglion(DRG) neurons. It is a 29-residue polypeptide toxin including three disulfide bridges. To investigate the structure-function relationship of the toxin, a mutant of JZTX-V in which Arg20 was substituted by Ala, was synthesized by solid-phase chemistry method with Fmoc-protected amino acids on the PS3 automated peptide synthesizer. The synthetic linear peptide was then purified by reversed-phase high performance liquid chromatography and oxidatively refolded under the optimal conditions. The refolded product was analyzed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry(MALDI-TOF MS) and electrophysiological experiments for its relative molecular weight and prohibitive activity of sodium channels respectively. The present findings show that the prohibitive effect of R20A-JZTX-V on TTX-S sodium channels in DRG neurons is almost the same as that of native JZTX-V, suggesting that Arg20 does not play any important role in inhibiting TTX-S sodium currents in DRG neurons. In contrast, the prohibitive level of R20A-JZTX-V on TTX-R sodium channels is reduced by at last 18.3 times, indicating that Arg20 is a key amino acid residue relative to the bioactivity of JZTX-V. It is presumed that the decrease in activity of R20A-JZTX-V is due to the changes of the property in the binding site in TTX-R sodium channels.
Amino Acid Substitution ; Animals ; Arginine ; genetics ; Ganglia, Spinal ; drug effects ; Mutagenesis, Site-Directed ; Mutant Proteins ; pharmacology ; Neurons ; drug effects ; Patch-Clamp Techniques ; Peptides ; chemistry ; genetics ; pharmacology ; Rats ; Sodium Channel Blockers ; pharmacology ; Sodium Channels ; drug effects ; Spider Venoms ; chemistry ; genetics ; isolation & purification ; pharmacology ; Spiders ; Tetrodotoxin ; pharmacology

BACKGROUNDThe excision repair cross-complementing gene 1 (ERCC1), which is important in the repair of cisplatin-DNA adducts, is reported to be related to cisplatin resistance in tumor cells. The aim of this study is to investigate the influence of low-dose cisplatin on expression of ERCC1 gene and to confirm the correlation between ERCC1 and cisplatin resistance in human lung adenocarcinoma cell lines.

METHODSA549 and A549/DDP cell lines were treated with 10 μmol/L cisplatin for 12, 24, 48 and 72 h, or treated with 5, 10, 20, 40 μmol/L cisplatin for 24 h respectively. Then the expression of ERCC1 mRNA and protein was measured by RT-PCR and immunocytohistology SABC assay respectively. The resistance of A549/DDP cells was measured by MTT assay.

RESULTSAfter treating with 10 μmol/L cisplatin for 12 h, up-regulation of ERCC1 mRNA and protein was observed in A549 cells, then reached the peak levels in 72 h group. After treating with 5 μmol/L cisplatin for 24 h, up-regulation of ERCC1 mRNA and protein was observed in A549 cells, and when treated with 20 μmol/L cisplatin for 24 h, the ERCC1 mRNA and protein reached the peak levels. Comparing with the parental cells, ERCC1 expression increased obviously in A549/DDP cells, which were established by continuous low-dose cisplatin treatment.

CONCLUSIONSUp-regulation of ERCC1 expression can be induced by low-dose cisplatin in human lung adenocarcinoma cell line A549, and ECRR1 may play roles in cisplatin resistance.

Objective:To explore the teaching effectiveness of curriculum ideological and political teaching model for Fundamentals of Nursing based on outcome based education concept.Methods:Using the convenient sampling method, a total of 194 undergraduates of grade 2019 from School of Nursing at University of South China were selected as the control group from February to December 2021, and 146 undergraduates from 2020 were selected as the experimental group from February to December 2022. The control group was taught in accordance with the conventional teaching methods, and the experimental group was taught in the ideological and political teaching model of Fundamentals of Nursing based on outcome based education concept. After the intervention, the total course scores of nursing undergraduates in the two groups were compared, and the cognitive attitude, implementation effect and teaching satisfaction of the experimental group students on "ideological and political curriculum" were compared.Results:After the intervention, the total course score of nursing undergraduates in the experimental group was (85.65±7.31), and that in the control group was (77.71±7.28), and the difference between the two groups was statistically significant ( P<0.01). The cognitive attitude score of undergraduate nursing students in the experimental group towards "ideological and political curriculum" was (32.62±2.15), and the implementation effect score of "ideological and political curriculum" was (22.78±1.78). The satisfactory form of ideological and political cases for undergraduate nursing students in the experimental group was news reports and hot events, and the satisfactory ideological and political teaching method was experiential teaching method and case-based teaching method. Conclusions:The curriculum ideological and political teaching model of Fundamentals of Nursing based on outcome based education concept can improve the academic performance of nursing undergraduate students and provide reference for the construction of ideological and political teaching courses in nursing basic courses. In the future, this teaching model can be applied to the teaching reform of other nursing courses in order to accelerate the progress of ideological and political construction of professional courses.

Kv2.1 channel currents in pancreatic beta-cells are thought to contribute to action potential repolarization and thereby modulate insulin secretion. Because of its central role in this important physiological process, Kv2.1 channel is a promising target for the treatment of type 2 diabetes. Jingzhaotoxin-XI (JZTX-XI) is a novel peptide neurotoxin isolated from the venom of the spider Chilobrachys jingzhao. Two-microelectrode voltage clamp experiments had showed that the toxin inhibited Kv2.1 potassium currents expressed in Xenopus Laevis oocytes. In order to investigate the structure-function relationship of JZTX-XI, the natural toxin and a mutant of JZTX-XI in which Arg3 was replaced by Ala, were synthesized by solid-phase chemistry method with Fmoc-protected amino acids on the PS3 automated peptide synthesizer. Reverse-phase high performance liquid chromatography (RP-HPLC) and matrix assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to monitor the oxidative refolding process of synthetic linear peptides to find the optimal renaturation conditions of these toxins. The experiments also proved that the relative molecular masses of refolded peptides were in accordance with their theoretical molecular masses. RP-HPLC chromatogram of co-injected native and refolded JZTX-XI was a single peak. Under the whole-cell patch-clamp mode, JZTX-XI could completely inhibit hKv2.1 and hNav1.5 channels currents expressed in HEK293T cells with IC50 values of 95.8 nmol/L and 437.1 nmol/L respectively. The mutant R3A-JZTX-XI could also inhibit hKv2.1 and hNav1.5 channel currents expressed in HEK293T cells with IC50 values of 1.22 micromol/L and 1.96 micromol/L respectively. However, the prohibitive levels of R3A-JZTX-XI on hKv2.1 and hNav1.5 channels were reduced by about 12.7 times and 4.5 times respectively, indicating that Arg3 was a key amino acid residue relative to the hKv2.1 channel activity of JZTX-XI, but it is also an amino acid residue correlated with the binding activity of JZTX-XI to hNav1.5 channel. Our findings should be helpful to develop JZTX-XI into a molecular probe and drug candidate targeting to Kv2.1 potassium channel in the pancreas.
Animals ; HEK293 Cells ; Humans ; Insulin-Secreting Cells ; metabolism ; Mutant Proteins ; genetics ; pharmacology ; NAV1.5 Voltage-Gated Sodium Channel ; metabolism ; Neurotoxins ; chemical synthesis ; genetics ; pharmacology ; Protein Refolding ; Shab Potassium Channels ; antagonists & inhibitors ; metabolism ; Sodium Channel Blockers ; pharmacology ; Spider Venoms ; genetics ; pharmacology ; Transfection

Objective: To evaluate the effect of biofeedback training on bowl function among rectal cancer patients with chemoradiotherapy and temporary enterostomy. Methods: Using randomized controlled trial design, 109 rectal cancer patients were randomly divided into three groups, the first blank control group, the second group pelvic floor muscle exercise group, the third group biofeedback group. High resolution anorectal manometry was used for 6 longitudinal traces in 16 months. Data of bowel function were collected by Memorial Sloan Kettering Cancer Center (MSKCC) Bowel Function Instrument. Results: The main effect of the change of five indicators, anal resting pressure, rectal resting pressure, maximum squeeze pressure, maximum squeeze time and high pressure zone, was time. The other four indicators, rectal volume at first senory, rectal volume at sense of convenience, maximal tolerable rectal volume and rectal compliance, among patients of biofeedback group were (32.71±5.00) ml, (74.26±8.30) ml, (188.40±12.68) ml, (5.69±1.18) ml/kPa and (68.09±6.38). The rectal volume at first senory, rectal volume at sense of convenience, maximal tolerable rectal volume and rectal compliance, among patients of biofeedback group were significant higher than blank control group and pelvic floor muscle exercise group (F=3.589-26.826, P<0.05). Conclusion The biofeedback could significantly improve the sensory indicators of patients with middle and low rectal cancer. High-resolution anorectal manometry could effectively evaluate the effect of biofeedback training in patients with middle and low rectal cancer.