Efficacy and nephrotoxicity of polymyxin B in elderly patients with carbapenem resistant bacterial infection.

BACKGROUND: To study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection. METHODS: The clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared. RESULTS: The effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2-37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931. CONCLUSIONS: Rational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI.

Efficacy and safety of polymyxin B in carbapenem-resistant gram-negative organisms infections.

OBJECTIVE: To investigate how to use polymyxin B rationally in order to produce the best efficacy and safety in patients with carbapenem-resistant gram-negative organisms (CRO) infection. METHODS: The clinical characteristics and microbiological results of 181 patients caused by CRO infection treated with polymyxin B in the First Affiliated Hospital from July 2018 to May 2020 were retrospectively analyzed. The bacterial clearance rate, clinical efficacy, adverse drug reactions and 28 days mortality were evaluated. RESULTS: The overall effective rate of 181 patients was 49.72%, the total bacterial clearance rate was 42.0%, and the 28 day all-cause mortality rate was 59.1%. The effective rate and bacterial clearance rate in the group of less than 24 h from the isolation of CRO to the use of polymyxin B were significantly higher than those in the group of more than 24 h. Logistics multivariate regression analysis showed that the predictive factors for effective treatment of CRO with polymyxin B were APACHEII score, duration of polymyxin B treatment, combination of polymyxin B and other antibiotics, and bacterial clearance. 17 cases (9.36%) of acute kidney injury were considered as polymyxin B nephrotoxicity and 4 cases (23.5%) recovered after polymyxin B withdrawal. After 14 days of polymyxin B use, 3 cases of polymyxin B resistance appeared, and there were 2 cases of polymyxin B resistance in the daily dose 1.5 mg/kg/day group. CONCLUSION: For CRO infection, the treatment of polymyxin B should be early, combined, optimal dose and duration of treatment, which can achieve better clinical efficacy and microbial reactions, and reduce the adverse reactions and drug resistance.

[Effects of calcineurin gene silencing on the remodeling of transient outward potassium current ionic channel in hypertrophic ventricular myocytes from neonatal rats].

Objective: To investigate the effects of calcineurin gene silencing on the remodeling of transient outward potassium current (Ito) ionic channel and action potential duration (APD) in phenylephrine (PE)-induced hypertrophic ventricular myocytes from neonatal rats. Methods: The ventricular myocytes of 1-day-old Sprague-Dawley rats were isolated and cultured for 48 h. RNA interference mediated by adenovirus carrying short hairpin RNA was used to knock down the gene which encodes the beta subtype of calcineurin A subunit (CnAß) and the cells were divided into 4 groups as Ad-null group, Ad-null+ PE group, Ad-CnAßshRNA1(A1) group and A1+ PE group, and then cultured for 48 h. The gene expression of Kv4.2 was assayed by real-time reverse transcriptase-polymerase chain reaction. The protein expressions of CnAß and Kv4.2 were assayed by Western blot test. Whole cell patch clamp technique was used to record Ito and action potential. Results: Treatment of the neonatal rat ventricular myocytes with PE induced the cell hypertrophy, up-regulated the protein expression of CnAß, attenuated the gene and protein expressions of Kv4.2 and the Ito current density, and prolonged APD. Silencing of CnAß in the neonatal rat ventricular myocytes using Ad-CnAßshRNA1 inhibited the aforementioned ability of PE significantly. Conclusion: CnAß gene silencing inhibits the remodeling of transient outward potassium current ionic channel and change of APD in PE-induced hypertrophic ventricular myocytes from neonatal rats.

Transmission of hepatitis C virus in an orthopedic hospital ward.

Healthcare-associated infections with hepatitis C virus (HCV) hitherto have been observed mainly in hemodialysis settings as well as in hematology and oncology wards. In this communication, molecular and epidemiologic investigations to elucidate an HCV outbreak in an orthopedic ward are reported. One hundred and thirty-five patients hospitalized in the ward and 104 staff members were tested. In addition to extensive epidemiologic reviews and hygienic inspections, direct sequencing of HCV PCR fragments and phylogenetic analysis of more than 300 partial HCV sequences obtained by end-point limiting-dilution real-time PCR assay were carried out. Six patients were infected with very closely related HCV variants. Patient-to-patient spread of the virus was inferred to have started from one patient with previous HCV infection to the other five patients during their hospital stay. Inspections did not reveal substantial breaches in basic infection control practices and did not identify a specific activity that might have led to nosocomial transmission. As a result of the investigations, the hospital corrected the documentation of all medical and nursing activities undertaken in the ward, abandoned the use of all multidose saline and other medication vials, and included explicitly recommendations for the safe preparation and administration of injectable drugs into internal infection control guidelines. Thereafter, no further nosocomial transmissions of HCV have been recorded in the orthopedic ward. The events observed suggest that nosocomial transmission of HCV is not limited to hemodialysis, hematology or oncology settings, and they also reinforce the mandatory adherence to basic infection control practices.

Electroejaculation and semen characteristics of Asiatic black bears (Ursus thibetanus).

This study details the seminal traits in the rare Asiatic black bear, revealing that this species generally produces high quality, concentrated ejaculates containing sperm of high motility and morphological integrity and similar to other members of the Ursine lineage. Semen was collected by electroejaculation and 23 trials were performed on 18 bears. The mean values were obtained for volume (0.61 ml), pH (7.1), sperm concentration (1049 x 10(6) ml(-1)), total sperm counts (502.8 x 10(6)), motility percentage (63.8%), forward progressive status (3.5), abnormal sperm percentage (37.9%) and intact acrosome percentage (76.6%).

Short time priming of pig cumulus-oocyte complexes with FSH and forskolin in the presence of hypoxanthine stimulates cumulus cells to secrete a meiosis-activating substance.

This study evaluated the effect of forskolin and FSH on pig oocyte maturation when cultured in a maturation inhibiting system. Ovaries from prepubertal gilts were collected at a local slaughterhouse. Oocytes were cultured in a hypoxanthine (HX 4 mM) containing M 199 for 24 or 40 h with or without forskolin and FSH treatment. After the culture, we examined germinal vesicle breakdown (GVBD) and polar body (PB) formation. Two experiments were designed. (1) Cumulus enclosed oocytes (CEO) were cultured for 24 or 40 h with or without different doses of forskolin and FSH. (2) CEO were primed by forskolin and FSH for different times and then transferred into an HX-medium for a further culture. The total culture period was 24 h. The results revealed that 4 mM HX markedly prevented pig CEO from undergoing GVBD. After 24 and 40 h culture, FSH (50-200 U/L) stimulated oocytes to resume meiosis by overcoming the inhibition of HX. Both GVBD and PB formation were increased (P < 0.002 and 0.01 respectively) after 40 h exposed to FSH. Forskolin showed a biphasic effect on CEO maturation. Within 24 h forskolin, in combination with HX, inhibited oocytes maturation. The GVBD percentage was significantly decreased compared to HX alone group (2% to 20%, P < 0.01), whereas no inhibition was observed after 40 h of culture. The second experiment showed that forskolin (3 microM) and FSH (100 U/L) priming CEO could time-dependently induce oocyte maturation by overriding the inhibition of HX. After 30 and 60 min priming by FSH or forskolin, the GVBD and PB percentage was significantly increased (P < 0.002 and 0.01 respectively). No difference of GVBD percentage was observed between FSH short time priming group and FSH long time presentation group. In conclusion, we found that forskolin and FSH in vitro can stimulate pig cumulus cells to secrete a meiosis-activating substance which induces the oocyte to overcome the inhibition of hypoxanthine and undergo GVBD.

Induction of xenotransplant tolerance.

Clinical xenotransplantation will depend on the induction of xeno-tolerance. Conversely, xenotransplantation may offer opportunities to induce transplantation tolerance. We have previously shown that, xenotransplant tolerance for vascularized hamster organs could be achieved in athymic rats as far as the T-cell independent xeno-reactivity is concerned. This tolerance was shown to be based on specific T-independent B lymphocyte and NK cell unresponsiveness. In the present study we have shown that this T-independent xeno-tolerance can be achieved also in a semi-discordant situation using rat recipients with high titers of pre-existing anti-hamster IgM xenoantibodies. In addition, we showed that T-independent xeno-tolerance can also be induced together with T-dependent xeno-tolerance using xeno-thymus transplantation. These experiments may be of relevance for clinical xenotransplantation. The major next question to be addressed is to see how self tolerance in xeno-thymus grafted recipients can be improved as until now the latter recipients usually develop a multi-organ autoimmune syndrome, several weeks after transplanting a xeno-thymus.

[The regulating mechanism of anti-fungicides on mouse oocyte development].

AIM: To study the mechanism of the effect of gonadotropin-induced oocyte maturation. METHODS: Mouse oocytes were cultured in HX-medium, and the effects of amphotericin B and ketoconazole on resumption of meiosis of mouse oocyte were examined. RESULTS: 1. FSH(10-200 IU/L) induced a dose-dependent manner of oocytes maturation in CEO. A maximum increase in GVBD was observed with 25-50 IU/L FSH. 2. Amphotericin tericim B (0.025-2.5 micrograms/L) caused significant increases in GVBD in CEO, which mimicked the function of FSH. 3. Ketoconazole (10(-7)-10(-3) mol/L) inhibited the effect of FSH on resumption of meiosis, but no effect on oocyte spontaneous maturation. CONCLUSION: Amphotericin B and ketoconazole are able to affect mouse oocyte maturation, and indicates that they have a regulation on FSH-induced synthesis of meiosis-activating sterol.

Protein kinase C and intracellular calcium are involved in follicle-stimulating hormone-mediated meiotic resumption of cumulus cell-enclosed porcine oocytes in hypoxanthine-supplemented medium.

The present experiments were conducted to examine the hypothesis that follicle-stimulating hormone (FSH) can stimulate the hydrolysis of phosphoinositide, generating the intracellular second messengers to activate protein kinase C and mobilizing intracellular calcium, thus inducing oocyte meiotic resumption. Pig cumulus cell-enclosed oocytes (CEO) were cultured for 24 hr in 4 mM hypoxanthine (HX)-supplemented medium and treated with different agents in the following designs: (1) CEO were treated with neomycin (an inhibitor of phosphoinositide hydrolysis) in the presence of FSH or only treated with 7,12-dimethylbenzin(a) anthracene (DMBA, a tumor promoter which can cause phosphorylation of phospholipase C (PLC), formation of inositol triphophate, and mobilization of intracellular calcium) to mimic the direct activation of PLC; (2) CEO were challenged by FSH, together with sphingosine or staurosporine (two kinds of PKC inhibitors); or treated with phorbol myristate acetate (PMA, an activator of PKC) separately; (3) CEO were primed with BAPTA/AM (an intracellular calcium chelator) or BAPTA/AM +FSH for 60 min, and then transferred into a new culture medium supplemented with FSH but without BAPTA/AM; total culture time was 24 hr. At the end of the culture, the incidence of germinal vesicle breakdown (GVBD) was calculated. The results showed that: (1) FSH (100 U/liter) could stimulate pig CEO to override the arrest of HX and resume meiosis; DMBA (10(-8)-10(-5) M) itself also had such a kind of effect; whereas neomycin, at the level of 10-20 mM, could dramatically inhibit the stimulatory effect of FSH. (2) Staurosporine (10(-9)-10(-6) M) or sphingosine (10(-8)-10(-5) M) could also inhibit the effect of FSH in a dose-dependent manner on stimulating CEO to resume meiosis. However, PMA (10(-8)-10(-5) M) alone had a dual effect on the meiotic resumption of pig CEO. PMA, at the level of 10(-8)-10(-6) M, could stimulate CEO to resume meiosis, and at high concentration of 10(-5) M , it could even enhance the inhibitory effect of HX. (3) Priming CEO with BAPTA/AM only or BAPTA/AM +FSH for 60 min could significantly inhibit the effect of FSH in a dose-dependent manner. These results indicate that in the process of ligand-mediated meiotic resumption of pig CEO, FSH can stimulate the hydrolysis of phosphoinositide leading to the activation of PKC and mobilization of intracellular calcium; and suggest that multiple signaling pathways and signal interaction are involved in this process.

Use of the appendix to replace the choledochus.

Ten cases of choledochal cyst (CC) were treated by biliary-appendicoduodenostomy. The follow-up comprised a patient interview, ultrasonography (US), and single-proton ejected computerized tomography (SPECT) scanning. In all cases an anti-reflux submucosal tunnel was added to the distal appendico-duodenostomy; all showed an uneventful postoperative course. All the dilated intrahepatic bile ducts had normalized on B-US postoperatively. Four children under went SPECT examination; all of them had patent neo-bile ducts. In the authors' opinion: (1) Anastomosing the cecal end of the appendix to the common hepatic duct seemed more favorable than the other way around, because the cecal end could be easily trimmed to the size of the common hepatic duct, which was more or less dilated in the presence of a CC; (2) It is necessary to add a submucosal tunnel to the distal appendicoduodenostomy to achieve a more reliable anti-reflux effect; and (3) Transposing the vascularized appendix through the retro-transverse colon simplified the procedure and might reduce the risk of retroperitoneal complications if bile leakage should occur.

[Introduction and cultivation of Cinnamomum cassia Presl].

Based on the study of biological characteristics, growth determination, quality examination, harvest and processing features, it has been proved that the introduction and cultivation of Cinnamomum cassial are feasible in such southern subtropics as the valleys along the Yangtze River in the southern part of Sichuan province. Specific cultivating techniques to adapt to the local climate are reviewed in the paper.