Objective To study the effects of efflux pump inhibitors(CCCP and PAβN)on carbapenems in Pseudomonas aernginosa(P.aeruginosa)clinical isolates and investigate the association between the resistance to imipenem or meropenem and expression levels of efflux pumps of P.aeruginosa.Methods MICs of imipenem or meropenem combined with efflux pump inhibitors including carbonyl cyanide m-chlorophenylhydrazone(CCCP,107 strains)and Phe-Arg-β-naphthylamide(PAβN,71 strains)against imipenem-resistant strains were determined by agar dilution method,and changes of MICs were observed.For 32 strains with different resistant phenotypes to imipenem and meropenem,the mRNA expression levels of three efflux pump genes(mexA,mexD and mexF)were quantified by real time fluorescent quantitative PCR.Results The resistance rate of imipenem and meropenem didn't prove any significant difference in the presence of efflux pump inhibitors.The X2 value of imipenem combined with CCCP and PAβN were 0.338 and 0.086,respectively(P＞0.05),while that of meropenem combined with CCCP and PAβN were 1.065 and 1.458(P＞0.05).No significant in MICs of carbapenems were seen in over half of P. aeruginesa isolates. MICs of carbapenems was significantly downregulated for 4-fold or above in eight isolates. Overexpression of efflux pumps genes were present in 24 of 27 carbapenem-resistant isolates(88. 9% ). Efflux pumps genes including MexAB-OprM, MexCD-OprJ and MexEF-OprN were all overexpressed in 13 isolates,constituting 54. 2% of all carbapenem-resistant isolates. There were 3 isolates in which beth MexAB-OprM and MexCD-OprJ showed overexpression,constituting 12. 5%. Also,MexAB-OprM and MexEF-OprN overexpressed in 3 isolates. There were 2 isolates (8.3%) showing MexEF-OprN overexpression and MexAB-OprM alone. MexCD-OprJ didn't showed overexpression alone. Furthermore,the expression levels of efflux pumps genes mexA,mexD and mexF in isolates susceptible to both in imipenem and meropenem were 0. 48±0. 48,0. 48±0. 53 and 0. 30±0. 41,respectively,which were much lower than that in carbapenem-resistant ones (P＜0. 05 ). MexA gene was expressed at a higher level in meropenemresistant isolates than meropenem-susceptible ones (P＜0. 05 ). Conclusions When the concentration of CCCP and PAβN were 5 μg/ml and 20 μg/ml respectively,the efforts on the carhapenems resistance of P.aeruginosa were small Overexpression of MexAB-OprM might play an important role in meropenemresistance in P. aerugines. Overexpression of MexCD-OprJ and MexEF-OprN was associated with imipenemresistance. However,the relationship between them and meropenem-resistance need to be explored in the future.

OBJECTIVETo assess the efficacy and safety of hyaluronate sodium (HS) for internal derangement of temporomandibular joint by means of systematic review on relevant randomized controlled trials.

METHODSAfter identifing the study question of the efficacy and safety of HS for internal derangement of temporomandibular joint, Medline, Cochrane Controlled Trials Register, EMBASE, OPEN SIGLE and CBM were searched electronically till October 3rd 2010. Hand-searching covering 19 dental journals in Chinese were also performed. Risk of bias assessment, with Cochrane Collaboration's tool, and data extraction of included studies were conducted by two reviewers in duplicate. Meta analysis was done with Revman 5.0.23 and the quality of evidence was evaluated by GRADE.

RESULTS10 randomized controlled trials met the eligibility criteria and were included. All these studies had unclear risk of bias. When compared with negative control, HS showed a significant advantage on maximal mouth opening in short and long-term (P < 0.05), and clinical overall assessment in short-term (P < 0.05), but its effect on pain control and long-term effect on clinical overall assessment had no extra benefit (P > 0.05). Additionally, when compared with glucocorticoids, the participants who received HS injection would get a better clinical overall assessment in short-term and less adverse drug reactions (P < 0.05), but presented a similar temporomandibular joint pain relief and maximal mouth opening (P > 0.05).

CONCLUSIONTo a certain extent, HS had good efficacy and better safety than controls when treating internal derangement of temporomandibular joint. However, as the quality of some included studies were limited, more randomized controlled trials are needed to reinforce the conclusion.

Glucocorticoids ; Humans ; Hyaluronic Acid ; Temporomandibular Joint

Estrogen receptor alpha (ERalpha) has been a primary target of treatment as well as a prognostic indicator for breast cancer. The level of human X-box binding protein 1 (XBP-1) mRNA was related with that of ERalpha in breast tumors and was over-expressed in some breast tumors. These previous studies suggested that XBP-1 may interact with ERalpha. XBP-1 has two isoforms, XBP-1S and XBP-1U, as the result of unique splicing. GST pull-down assay showed that both XBP-1S and XBP-1U bound to ERalpha in vitro. The binding of XBP-1S to ERalpha was stronger than that of XBP-1U to ERalpha. Co-immunoprecipitation revealed that the binding was in a ligand-independent manner. XBP-1S and XBP-1U interacted with the region of ERalpha that contains a DNA-binding domain. The ERalpha-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, the N-terminal basic region leucine zipper domain (bzip) and the C-terminal activation domain. These findings suggest that XBP-1S and XBP-1U may participate in ERalpha signaling pathway through the mediation of ERalpha.
Breast Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; metabolism ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Protein Interaction Domains and Motifs ; physiology ; RNA, Messenger ; biosynthesis ; genetics ; Regulatory Factor X Transcription Factors ; Signal Transduction ; Transcription Factors ; genetics ; metabolism ; X-Box Binding Protein 1

OBJECTIVETo summarize the new knowledge of the anaplastic thyroid carcinoma (ATC).

METHODSThe clinical data of 58 patients (35 men, 23 women, aged 28 to 79 years) with ATC that were treated with various therapeutic modalities from 1981 to 2005 were retrospectively analyzed. Among them, 25 patients received surgery alone (SA group) and 33 received surgery plus radiation (S + R group). The dosage of postoperative radiotherapy was 40-70 Gy. Four patients received biopsy, 24 received palliative surgery, and 30 received radical surgery. Only 2 patients received complete chemotherapy.

RESULTSATC invaded trachea in 40 patients (69.0%), esophagus in 32 patients (55.2%), and carotid in 17 patients (29.3%). The cervical lymph node metastases occurred in 19 patients (32.8%). The overall 1-year survival rate was 37.8%, 3-year survival rate 31.2%, and 5-year survival rate 25.9%. The 5-year survival rate was 37.8% in S + R group but was only 9.9% in SA group (P = 0.0000). The 5-year survival rate was 41.4% in radical surgery subgroup but was only 12.4% in palliative surgery subgroup (P = 0.0023). In < or = 45-year-old subgroup (n = 4), the 5-year survival rate was 50.0%; however, in > 45-year-old subgroup, it was only 21.3%. In postoperative radiation < 60 Gy subgroup , the 5-year survival rate was 19.3%; however, in > or = 60 Gy group, it was 53.7% (P = 0.0000). Among all the 58 patients, some patients received palliative surgery because of tumor invasion in trachea (n = 16, 27.6%), esophagus (n = 8, 13.8%), carotid (n = 8, 13.8%), and other sites (n = 13, 22.4%). Twenty-four patients (61.5%) died of localrelapse, 2 (5.1%) of cervical lymphnode failure, 9 (23.1%) of metastasis, and 4 (10.3%) of other reasons.

CONCLUSIONSThe prognosis of ATC is poor. Radical surgery and postoperative radiation > or = 60 Gy can improve the survival rate. Tumor invasion in trachea, esophagus, and carotid are the main reasons of palliative surgery. Local relapse is lethal.

Adult ; Aged ; Carcinoma ; pathology ; surgery ; Carcinoma, Squamous Cell ; pathology ; surgery ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Thyroid Neoplasms ; pathology ; surgery

Objective To investigate the effect of isoliquiritigenin on airway inflammation mice with neutrophil asthma and its possible mechanism.Methods Neutrophil asthma mouse model were established using ovalbumin.Balb/c mice were randomly divided into control group(equal amounts of 0.9％NaCl were given),model group(ovalbumin modeling),DXM group(intraperitoneal injection of 4 mg·kg-1 dexamethasone),experimental-L,-H groups(intraperitoneal injection of 100,200 mg·kg-1 isoliquiritigenin),with 11 mice in each group.Airway resistance of each group of mice was detected within 24 h after the last atomization excitation,and lung tissue and bronchoalveolar lavage fluid were taken;the total cell count was performed by cell counting plate;the cell classification count was performed by Richs-giemsa staining;the levels of inflammatory factors in bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay;Weatern blot assay was used to detect protein expression in lung tissue.Results The airway resistance values of control group,model group,DXM group,experimental-L group and experimental-H group were(0.84±0.08),(3.34±0.34),(1.23±0.15),(2.47±0.19)and(1.54±0.18)cmH2 O·s-1;the total number of white blood cells were(15.03±0.11),(331.20±26.64),(38.73±3.28),(180.35±16.89)and(82.74±10.51)x 104·mL-1;interleukin 17(IL-17)levels were(4.79±0.58),(19.21±2.39),(6.35±0.81),(15.96±1.10)and(9.04±0.65)pg·mL-1;V-set and immunoglobulin domain-containing 4(VSIG4)protein expression levels were 0.67±0.04,0.24±0.04,0.59±0.06,0.37±0.04 and 0.53±0.05;Nod-like receptor family heat protein domain associated protein 3(NLRP3)protein expression levels were 0.24±0.02,0.74±0.07,0.35±0.04,0.65±0.08 and 0.44±0.03,respectively.The above indexes were compared between the model group and the control group,and the above indexes of DXM,experimental-L and experimental-H groups were compared with model group,and the differences were statistically significant(all P＜0.05).Conclusion Isoliquiritigenin may regulate the VSIG4/NLRP3 complex inflammatory pathway,reduce airway resistance,inhibit the release of inflammatory mediators and improve airway inflammation in mice with neutrophil asthma.

OBJECTIVETo study the necessary amount of fluid consisting of electrolyte and colloid, the ratio of electrolyte and colloid used, and the change of blood sodium during early resuscitation in severely burned patients.

METHODSSixty-seven patients with total burn surface area (TBSA) equal to or over 70% and full-thickness area equal to or over 50%TBSA, hospitalized from March 2004 to March 2009, were resuscitated with fluid. The infusion amount of electrolyte, colloid, and water, and urinary output of patients at post injury hour (PIH) 24, 48, and 72 were analyzed retrospectively. The variation in blood sodium and fluid infusion at different time points was recorded. Data were processed with SPSS 13.0 software.

RESULTSAmong the 67 patients, hyponatremia occurred in 9 cases, hypernatremia occurred in 5 cases, and 53 patients had normal blood sodium level. The urinary output of patients within PIH 72 was above 70 mL/h. K value was calculated through the formula: actual total infusion amount of electrolyte and colloid (mL) = burn area (%TBSA) x body weight (kg) x K. In the first 24 PIH, K value was about 1.7, and the ratio of electrolyte and colloid was 1.4. In the second 24 PIH, K value was about 1.3 with electrolyte and colloid ratio 1.6. K value in the third 24 PIH was about 0.9 with electrolyte and colloid ratio 2.0.

CONCLUSIONSThe actual amount of resuscitation fluid is slightly larger than that calculated from traditional formula during the early stage in severely burned patients. The amount of electrolytes and the proportion of electrolyte and colloid will influence blood sodium level of patients.

Adult ; Burns ; blood ; therapy ; Female ; Fluid Therapy ; Humans ; Male ; Middle Aged ; Sodium ; blood ; Young Adult

BACKGROUNDPachymic acid (PA), a natural triterpenoid, is known to significantly reduce cell proliferation and induce apoptosis in vitro through initiation of mitochondria dysfunction. However, its effect on immune cells and anti-rejection following organ transplantation remains unknown.

METHODSIn this study, we investigated PA as a treatment to control acute rejection occurred in rats which had accepted cardiac transplantation. We measured apoptosis of peripheral blood lymphocyte (PBLs), and CD4(+) lymphocyte, as well as the number of CD4(+) and CD8(+) lymphocytes and the effect of PA on acute rejection in rats 7 days after cardiac transplantation.

RESULTSPA treatment might decrease allograft rejection, protect PBLs from apoptosis, and reduce the percentage of CD8(+) lymphocyte. PA neither regulated the number nor the apoptosis rate of CD4(+) lymphocyte.

CONCLUSIONSOur findings indicated that PA has an anti-apoptotic effect acting on PBLs through a novel mechanism involving stabilization of the PBLs mitochondrial transmembrane potential, an anti-rejection effect in rats after cardiac transplantation and an inhibiting effect to CD8(+) lymphocyte.

Animals ; Apoptosis ; drug effects ; Graft Rejection ; drug therapy ; Heart Transplantation ; Lymphocytes ; drug effects ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Transplantation, Homologous ; Triterpenes ; therapeutic use

BACKGROUNDCelecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4(+) and CD8(+) lymphocytes.

METHODSAfter cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4(+) and CD8(+) lymphocytes.

RESULTSCelecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4(+) lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8(+) lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days.

CONCLUSIONSThe results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Apoptosis ; drug effects ; Celecoxib ; Cells, Cultured ; Graft Rejection ; immunology ; prevention & control ; Heart Transplantation ; immunology ; Lymphocytes ; cytology ; drug effects ; immunology ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Pyrazoles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sulfonamides ; pharmacology ; Transplantation, Homologous ; immunology

OBJECTIVETo explore the efficacy of neuromodulation (including sacral neuromodulation and dorsal penile/clitoral nerve neuromodulation) for the treatment to neurogenic bowel dysfunction due to spinal cord injury.

METHODSFrom January 2006 to April 2008, 9 patients with neurogenic constipation after spinal cord injury underwent the therapy of neuromodulation, 1 patient underwent the therapy of sacral neuromodulation, 8 patients underwent the therapy of dorsal penile/clitoral nerve neuromodulation. The therapeutic efficacy was evaluated and followed up by means of Wexner constipation score.

RESULTSOne patient received permanent electrode and neurostimulator implantation and constipation were improved continuously. A significant improvement in the Wexner constipation score was observed compared with the preoperative baseline level (preoperative baseline: median 22; after implantation: median 9). Four patients were effective after the therapy of dorsal penile/clitoral nerve neuromodulation. Wexner constipation score decrease from 19 to 11 after 12 weeks dorsal penile/clitoral nerve neuromodulation. Patients also showed a significant improvement in their symptoms and quality of life during follow up.

CONCLUSIONSSacral neuromodulation and dorsal penile/clitoral nerve neuromodulation may be effective for some neurogenic constipation. However there are no methods successfully identify the candidate who will be beneficial before the procedure. Good quality research data are needed to evaluate the effects of sacral neuromodulation and dorsal penile/clitoral nerve neuromodulation for these conditions.

Constipation ; etiology ; therapy ; Electric Stimulation Therapy ; methods ; Electrodes, Implanted ; Female ; Follow-Up Studies ; Humans ; Male ; Spinal Injuries ; complications ; Treatment Outcome

Objective To investigate the effectiveness and cost of 50% and 80% wettable powder of niclosamide ethanolamine salt (NESWP) and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in hilly schistosomiasis-endemic regions, so as to provide insights into the selection of chemical molluscicides in hilly regions. Methods In September 2020, a wasteland in Guanshanqiao Village, Yanrui Township, Yushan County of Jiangxi Province was selected as the experimental region, which was sectioned into five blocks and defined as four experimental groups (A₁, A₂, B, C) and a blank control group (D). 80% NESWP were given at doses of 1 g/m² and 1.5 g/m² in groups A₁ and A₂ using the spraying method, 50% NESWP was given at a dose of 2 g/m² in Group B using the spraying method, and 26% MNSC was at a dose of 4 g/m² in Group C using the spraying method, while no chemical treatment was given in Group D. Snail survey was performed using a systematic sampling method before chemical treatment and 1, 3, 7 d and 15 d post-treatment to examine the molluscicidal effect, and all molluscicidal costs were estimated to calculate the cost of chemical treatment per 1 m² and the cost of the reduction in the mean density of living snails per 1%. Results The highest mortality of snails was 78.95% and the lowest density of living snails was 0.2388 snails/0.1 m² in the experimental groups within 7 d of chemical treatment, and the highest mortality of snails was 94.74% and the lowest density of living snails was 0.058 0 snails/0.1 m² 7 d post-treatment. There were no significant differences in the snail mortality among the A₁, A₂, B and C groups 1 (χ² = 2.250, P > 0.05), 3 (χ² = 1.779, P > 0.05) or 15 d post-treatment (χ² = 2.286, P > 0.05), while a significant difference was detected in the snail mortality among the four groups 7 d post-treatment (χ² = 7.990, P = 0.046). In addition, there were no significant differences in the snail mortality between A₁ and A₂ groups 1 (χ² = 0.724, P > 0.05), 3 (χ² = 0.584, P > 0.05), 7 (χ² = 0.400, P > 0.05) or 15 d post-treatment (χ² = 0.251, P > 0.05). The costs of chemical treatment per 1 m² were 0.58, 0.60, 0.64 Yuan and 0.73 Yuan in groups A₁, A₂, B and C, and the costs of the mean density of living snail per 1% reduction were 19.29, 20.44, 21.68 Yuan and 23.53 Yuan in groups A₁, A₂, B and C, respectively. Conclusion 80% NESWP shows a high molluscicidal efficacy and low cost in hilly schistosomiasis-endemic regions.