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.

[Preliminary study of the fourth-generation CAR-T cells targeting CS1 in the treatment of refractory and recurrent multiple myeloma].

Objective: To design the fourth-generation chimeric antigen receptor-T (CAR-T) cells that secrete interleukin-7 (IL7) and chemokine C legend 19 (CCL19) on the basis of the second-generation CAR, and to analyze and compare the differences in proliferation, chemotaxis, tumor cell clearance and persistence in the microenvironment of multiple myeloma (MM) between them. Methods: The fourth-generation CAR vector plasmid was constructed by using 2A self-cleaving peptide technology. The third-generation lentiviral packaging system was used to prepare high-titer lentivirus. Flow cytometry was used to monitor the transduction efficiency of lentivirus and the subtype changes of CAR-T cells. The enzyme-linked immunosorbent assay (ELISA) was used to quantify the IL7 and CCL19 secreted by CAR-T cells.The calculation of absolute number of CAR-T cells during culture was used to analysis cell proliferation activity. Transwell migration assay was used to verify the chemotactic ability of CAR-T cells. The specific killing activity of CAR-T cells was detected by using the luciferase bioluminescence method. The NOD-Prkdcem26Cd52Il2rgem26Cd22/Nju (NOD) mouse xenograft model was used to verify the anti-myeloma activity and safety of CAR-T cells in vivo. Results: Flow cytometry results showed that the stable CAR expression rates of the second-generation anti-CS1 CAR-T and fourth-generation anti-CS1-IL7-CCL19 CAR-T cells were (91.50±0.29)% and (46.7±0.12)%, respectively. CAR-T cells were successfully constructed. Subtype analysis demonstrated that the ratio of stem memory T cell (TSCM) in anti-CS1-IL7-CCL19 CAR-T cells was (67.58±0.59)%, which was significantly higher than (50.74 ± 1.01)% of anti-CS1 CAR-T (P=0.000 1), with more strong immune memory function and better durability. Anti-CS1-IL7-CCL19 CAR-T cells can continuously secrete IL7 and CCL19 compared to MOCK-T and anti-CS1 CAR-T (P<0.000 1). The number of anti-CS1-IL7-CCL19 CAR-T cells reached (22.77±0.79)×10(6) on the 9th day after lentivirus transduction, which was significantly higher than (9.40±0.79)×10(6) of anti-CS1 CAR-T cells (P=0.000 1), with stronger proliferation ability. The number of chemotaxis cells of anti-CS1-IL7-CCL19 CAR-T cells to reactive T cells was (109.0±4.04), which was significantly higher than (9.33±1.20) of MOCK-T (P<0.000 1) and (7.33±0.88) of anti-CS1 CAR-T (P<0.000 1), with stronger chemotactic ability. The specific killing activity showed that both anti-CS1-IL7-CCL19 CAR-T and anti-CS1 CAR-T cells had specific killing efficacies when compared with the MOCK-T cells (P<0.000 1). Animal experiment indicated that anti-CS1-IL7-CCL19 CAR-T cells significantly reduced the tumor burden (P<0.000 1) and extended the overall survival time (P=0.006 1) of tumor-bearing mice. Conclusions: The anti-CS1-IL7-CCL19 CAR-T cells designed in this study show stronger proliferative activity, chemotactic ability, and durability without affecting the anti-myeloma activity in vivo and in vivo, which provides strategies for overcoming the defects of low survival rate, poor durability and inhibition by tumor microenvironment of traditional CAR-T cells, and offers preliminary experimental basis for the clinical application of the fourth-generation CAR-T cells.

[The correlation between the degree of anxiety/depression and the improvement of subjective and objective symptoms after functional endoscopic sinus surgery in chronic sinusitis].

Objective: To explore whether the improvement of subjective symptoms and objective grades after endoscopic sinus surgery in patients with chronic sinusitis (CRS) are related to the degree of preoperative anxiety or depression and to provide reference for improving the effects of clinical treatment. Methods: The clinical data of one hundred and sixty patients with CRS treated by endoscopic sinus surgery in the First Affiliated Hospital of Chongqing Medical University from April 2018 to August 2019 were collected prospectively. The visual analogue scale (VAS) scores, self-rating anxiety scale (SAS) scores, self-rating depression scale (SDS) scores, Lund-Kennedy scores of nasal endoscopy and the Lund-Mackay scores of CT before and 6 months after surgery were used to analyse the correlation between the scores of anxiety or depression and the subjective and objective scores of patients before and after operation by grouping and layering. One hundred and one males (63.1%) and 59 females (36.9%) with an average age of 47.3 years (18-75 years) were included. Single-sample, independent or paired t-test, one-way ANOVA and rank-sum test were used for comparison and Pearson correlation analysis was used for the correlation between groups. Results: There was no statistical difference of anxiety or depression between different groups in terms of age, gender and course in the 160 effective patients (t values were -0.151, -0.487, -0.846, all P values>0.05; t values were -0.473, -1.302, -1.069, all P values>0.05). And the degree of preoperative anxiety or depression was positively correlated with the subjective scores, including overall discomfort, nasal obstruction, runny nose and olfactory decline (r values were 0.515, 0.606, 0.424, 0.306, all P values<0.01; r values were: 0.518, 0.584, 0.448, 0.308, all P values<0.01), but not significantly correlated with objective scores of Lund-Mackay and Lund-Kennedy (all P value>0.05). Moreover, as far as the symptoms of overall discomfort, nasal obstruction, headache and runny nose, the results of one-way ANOVA showed that the improvement of symptoms in patients with serious anxiety or depression was worse than that of the normal, mild and moderate patients (all P values<0.05). However, there was no significant difference in the scores of Lund-Kennedy 6 months after surgery between them (both P values>0.05). Conclusion: The state of anxiety or depression affects the improvement of symptoms after endoscopic sinus surgery for CRS patients. Compared with the patients with normal and mild to moderate anxiety or depression, the improvement of symptoms in patients with severe anxiety and depression is worse. It is necessary to evaluate the anxiety or depression of the patients with CRS who are going to undergo endoscopic sinus surgery.

[C5-6 nerve root block technique for postoperative analgesia of shoulder arthroscope: a randomized controlled trial].

OBJECTIVE: To compare the effects of ultrasound-guided interscalene brachial plexus block and C5-6 nerve root block for analgesia after shoulder arthroscopy. METHODS: In the study, 40 patients of ASA I-II were selected for elective general anesthesia to repair the shoulder ligament rupture in Peking University Third Hospital, who were randomly divided into two groups, respectively for the intermuscular brachial plexus block group (group I) and C5-6 nerve root block group (group C), n=20. The forty patients underwent ultrasound-guided brachial plexus block or C5-6 nerve root block before general anesthesia. Group I: 0.2% ropivacaine 10 mL was injected into brachial plexus intermuscular approach; Group C: 0.2% ropivacaine 10 mL was injected around the nerve roots of C5 and C6, and the ultrasound images showed that the liquid wrapped nerve roots. The time of sensory and motor block after puncture, operation time, the time of postoperative analgesia, numerical rating scale (NRS) scores at 1, 6, 12, and 24 h postoperatively and the finger movements were recorded. The adverse drug reactions and the patient satisfaction were recorded. The primary end point was the study of shoulder rest and movement pain in the patients with postoperative nerve blockage; the secondary end point was the patient's limb movements and thepatient satisfaction. RESULTS: The duration of analgesia was (571.50±70.11) min in group I and (615.60±112.15) min in group C, and there was no difference between the two groups (P>0.05). The static and dynamic NRS scores at 1, 6, and 12 h in group C were lower than those in group I (P<0.05). There was no difference in static and dynamic NRS scores between the two groups during 24 hours (P>0.05). There was a significant difference in grade of muscle strength between group C [5(4,5)] and group I [4(2,4)] in the patients with nerve block hind limb (P<0.01), and there were significant differences between the two groups' sensation in the radial nerve group C [1(0,2)] and group I [2(1,2)], the median nerve group C [0(0,2)] and group I [2(1,2)], and the ulnar nerves group C [0(0,1)] and group I [1(1,2)] (P<0.01). There was no statistical difference between the two groups in the sencation of the shoulder, group C 2(1,2) and group I 2(1,2) , P>0.05. Compared with group I 8(6,9), group C 9(8,10) was a significant difference in satisfaction (P<0.01). CONCLUSION: Interscalene brachial plexus block and C5-6 nerve root block could satisfy the needs of analgesia after shoulder arthroscopy, but C5-6 nerve root blockage does not limit the limb activity, the numbness is less, and the patient's satisfaction is higher.

[Relationship and clinical significance between mutated BRAF with prophylactic central-neck nodal dissection in papillary thyroid carcinoma].

OBJECTIVE: To evaluate the molecular diagnosis marker of papillary thyroid carcinoma (PTC), the relationship between lymphatic metastasis of central neck compartment PTC, and the operation indication of prophylactic central neck dissection. METHODS: We conducted a retrospective study, including 275 PTC patients and detected their BRAF mutation rates during 2012 and 2014 and explored the risk factors of the central node lymphatic metastasis by Logistic regression model. RESULTS: Of the 275 PTC patients, 224 (81.5%) were female and 51 (18.5%) were male. BRAF mutational rates were 53.8% (148/275) and lymphatic metastasis 57.8% (159/275). Multivariate analysis showed calcification (OR(adjusted)=1.47, 95%CI: 1.10-1.98, P=0.01), tumor diameter (OR(adjusted)=1.48, 95%CI: 1.04-2.30, P=0.048) and age (OR(adjusted)=1.48, 95%CI: 1.04-2.30, P=0.048) were associated with lymphatic metastasis. In stratified analysis, BRAF mutation (OR(adjusted)=3.19, 95%CI: 1.18-9.43, P=0.023) in clear boarder group and BRAF mutation (OR(adjusted)=4.84, 95%CI: 1.68-13.84, P=0.003) in calcification group were more likely to have lymphatic metastases. CONCLUSION: Central neck metastasis takes up a high ratio in papillary thyroid cancer patients, BRAF mutation in papillary thyroid carcinoma is a characteristic molecular event. Furthermore, patients with calcification under ultrasound detection, lower age group and longer tumor diameter are more susceptible to suffer central neck metastasis. Especially for stratified analysis, non-calcified BRAF mutation or BRAF mutation with clear border under ultrasound detection are more susceptible to suffer central neck metastasis, and radical prophylactic central neck dissection should be carried on for these patients.

Joint probabilistic model of shape and intensity for multiple abdominal organ segmentation from volumetric CT images.

We propose a novel joint probabilistic model that correlates a new probabilistic shape model with the corresponding global intensity distribution to segment multiple abdominal organs simultaneously. Our probabilistic shape model estimates the probability of an individual voxel belonging to the estimated shape of the object. The probability density of the estimated shape is derived from a combination of the shape variations of target class and the observed shape information. To better capture the shape variations, we used probabilistic principle component analysis optimized by expectation maximization to capture the shape variations and reduce computational complexity. The maximum a posteriori estimation was optimized by the iterated conditional mode-expectation maximization. We used 72 training datasets including low- and high-contrast CT images to construct the shape models for the liver, spleen and both kidneys. We evaluated our algorithm on 40 test datasets that were grouped into normal (34 normal cases) and pathologic (6 datasets) classes. The testing datasets were from different databases and manual segmentation was performed by different clinicians. We measured the volumetric overlap percentage error, relative volume difference, average square symmetric surface distance, false positive rate and false negative rate and our method achieved accurate and robust segmentation for multiple abdominal organs simultaneously.

MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia.

Acute myeloblastic leukemia (AML) is characterized by the accumulation of abnormal myeloblasts (mainly granulocyte or monocyte precursors) in the bone marrow and blood. Though great progress has been made for improvement in clinical treatment during the past decades, only minority with AML achieve long-term survival. Therefore, further understanding mechanisms of leukemogenesis and exploring novel therapeutic strategies are still crucial for improving disease outcome. MicroRNA-100 (miR-100), a small non-coding RNA molecule, has been reported as a frequent event aberrantly expressed in patients with AML; however, the molecular basis for this phenotype and the statuses of its downstream targets have not yet been elucidated. In the present study, we found that the expression level of miR-100 in vivo was related to the stage of the maturation block underlying the subtypes of myeloid leukemia. In vitro experiments further demonstrated that miR-100 was required to promote the cell proliferation of promyelocytic blasts and arrest them differentiated to granulocyte/monocyte lineages. Significantly, we identified RBSP3, a phosphatase-like tumor suppressor, as a bona fide target of miR-100 and validated that RBSP3 was involved in cell differentiation and survival in AML. Moreover, we revealed a new pathway that miR-100 regulates G1/S transition and S-phase entry and blocks the terminal differentiation by targeting RBSP3, which partly in turn modulates the cell cycle effectors pRB/E2F1 in AML. These events promoted cell proliferation and blocked granulocyte/monocyte differentiation. Our data highlight an important role of miR-100 in the molecular etiology of AML, and implicate the potential application of miR-100 in cancer therapy.

Expression of N-methyl-D-aspartate receptor and its effect on nitric oxide production of rat alveolar macrophages.

We early show that glutamate (Glu) mediate hyperoxia-induced newborn rat lung injury through N-methyl-D-aspartate receptor (NMDAR). In this study, we search for evidence of NMDAR expression on newborn rat alveolar macrophages (AMs) and the difference between newborn and adult rat AMs, and the possible effect on nitric oxide (NO) production of AMs by exogenous NMDA. The protein of NMDAR was showed by immunocytochemistry, and the mRNA was examined by RT-PCR and real-time PCR. The results show that: (i) both newborn and adult rat AMs express NMDAR1 and the four NMDAR2 subtypes and newborn rat AMs are higher expression. (ii) NMDA administration increase NO production, inducible nitric oxide synthase (iNOS) activity and iNOS mRNA expression of AMs. (iii) NMDAR activation elevates NO secretion of AMs, which suggests that AM may be one of the key cellular origin of the elevated NO secretion in hyperoxia-induced lung injury.

Medical image registration via steerable pyramid.

Image registration is enabling in integrating complementary and heterogeneous information from multiple images, and is particularly important for high-quality healthcare. To improve registration efficiency and accuracy, in this paper, a two-resolution-scale registration approach is proposed. Firstly, to speed up calculation, the images will be decomposed into multi-scale and multi-band representation by steerable pyramid that outweighs wavelets by providing invariance for both translation and rotation. Then, to avoid transformation error accumulation and magnification during the parameter transmission in the traditional multi-scale registration, the registration will be performed only in the lowest-resolution scale and the highest-resolution scale. In the former scale, the global rotation and scaling parameters will be calculated rapidly and accurately, which then will be directly used to initialize optimization in the latter scale, where, the translation differences will be corrected. The experiments on medical images demonstrate that the proposed registration is of good performance.

An ontology for the integration of multiple genetic disorder data sources.

As a huge amount of gene disorder information is available on the Internet, there is an increasing requirement to integrate these data sources. The integration of gene disorder data sources provides an important tool in the research of life science, therapeutics, and genetic disease prevention and inhibition. The key challenge of such integration is how to deal with semantic heterogeneity of multiple information resources. The paper proposes an ontology-based approach to describe and extract the semantics of genetic disorder terminologies and provides a mechanism for sharing and reusing genetic disorder knowledge. According to this unified meta model, heterogeneous gene disorder data sources can be integrated, and a semantic middleware has the ability to do reasoning on the knowledge base of gene disorder for users and applications' various queries.

Discovery of an orally bioavailable alkyl oxadiazole beta3 adrenergic receptor agonist.

5-n-Pentyl oxadiazole substituted benzenesulfonamide 8 is a potent and selective beta3 adrenergic receptor agonist (beta3 EC50 = 23 nM, beta1 IC50 = 3000 nM, beta2 IC50 = 3000 nM). The compound has high oral bioavailability in dogs (62%) and rats (36%) and is among the most orally bioavailable beta3 adrenergic receptor agonists reported to date.

Synthesis and SAR of benzyl and phenoxymethylene oxadiazole benzenesulfonamides as selective beta3 adrenergic receptor agonist antiobesity agents.

Benzyl and phenoxymethylene substituted oxadiazoles are potent and orally bioavailable beta3 adrenergic receptor (AR) agonists. The 4-trifluormethoxy substituted 5-benzyl oxadiazole 5f has an EC50 of 8 nM in the beta3 AR agonist assay with 100-fold selectivity over beta1 and beta2 AR binding inhibition activity. Its oral bioavailability in dogs is 30 +/- 4%, with a half-life of 3.8 +/- 0.4 h. In the anesthetized rhesus, 5f evoked a dose-dependent glycerolemia (ED50Gly = 0.15 mg/kg). Under these conditions a heart rate increase of 15% was observed at a dose level of 10 mg/kg.

Content-based retrieval of dynamic PET functional images.

The recent information explosion has led to massively increased demand for multimedia data storage in integrated database systems. Content-based retrieval is an important alternative and complement to traditional keyword-based searching for multimedia data and can greatly enhance information management. However, current content-based image retrieval techniques have some deficiencies when applied in the biomedical functional imaging domain. In this paper, we presented a prototype design for a content-based functional image retrieval database system for dynamic positron emission tomography. The system supports efficient content-based retrieval based on physiological kinetic features and reduces image storage requirements. This design makes it possible to maintain a large number of patient data sets online and to rapidly retrieve dynamic functional image sequences for interpretation and generation of physiological parametric images, and offers potential advantages in medical image data management and telemedicine, as well as providing possible opportunities in the statistical and comparative analysis of functional image data.

Wrap-clipping with a Dacron mesh silastic sheet. Technical note.

A technique combining wrapping and clipping using a Silastic sheet coated with Dacron mesh is described for treatment of fusiform or broad-based cerebral aneurysms. This sheet is easily tailored to wrapping the aneurysm base while avoiding involvement of the cranial nerves or branching vessels. The sheet is semitransparent so that the caliber of the newly constructed parent artery is easily adjusted during wrap-clipping. After the aneurysm and the parent artery have been circumferentially wrapped with the sheet, aneurysm clips are applied on the sheet so that the base of the aneurysm is clipped between the two leaves of the sheet. This wrap-clipping technique avoids the risks involved in extracting the aneurysm from the parent artery. The Dacron mesh coating the outer surface and sufficient clip closing pressure are both helpful in preventing the clip blades from sliding. Similar previously reported techniques are reviewed and discussed in detail.

The effect of low-dose estrogen and progestogen on menopausal symptoms and urinary excretion of calcium.

The effects of low-dose estrogen and progestogen on menopausal symptoms were studied with Kuppermen score and urinary excretion of calcium as fasting morning urine Ca/Cr ratio in 69 perimenopausal women. The subjects were divided into 3 groups: amenorrhea less than 1 year (14 women); post menopause 1-3 years (19); and post menopause more than 3 years (36). Fasting urine Ca/Cr ratio in the post menopause 1-3 years group was 0.19 +/- 0.01, significantly higher than that (0.14-0.01) in the amenorrhea less than 1 year group and (0.11 +/- 0.006) the post menopause more than 3 years group. 18 women had 4 patterns of low-dose oral estrogen and progestogen: MPA 2 mg QOD, EE 5 micrograms QD, EE 5 micrograms QOD, and EE 5 micrograms and MPA 2 mg QOD. Each pattern was used in turn for 3 weeks, and discontinued for 2 weeks, then the next pattern started and so on. EE 5 micrograms and MPA 2 mg QOD alternately gave the best results both in improving symptoms and lowering urine Ca/Cr ratio. Seven women given intermittent large dose, namely, EE 50 micrograms every 10 days or premarin 2.5 mg every 7 days had symptoms relieved but inconsistent decrease of urine Ca/Cr ratio.