Improving image quality of triple-low-protocol renal artery CT angiography with deep-learning image reconstruction: a comparative study with standard-dose single-energy and dual-energy CT with adaptive statistical iterative reconstruction.

AIM: To investigate the improvement in image quality of triple-low-protocol (low radiation, low contrast medium dose, low injection speed) renal artery computed tomography (CT) angiography (RACTA) using deep-learning image reconstruction (DLIR), in comparison with standard-dose single- and dual-energy CT (DECT) using adaptive statistical iterative reconstruction-Veo (ASIR-V) algorithm. MATERIALS AND METHODS: Ninety patients for RACTA were divided into different groups: standard-dose single-energy CT (S group) using ASIR-V at 60% strength (60%ASIR-V), DECT (DE group) with 60%ASIR-V including virtual monochromatic images at 40 keV (DE40 group) and 70 keV (DE70 group), and the triple-low protocol single-energy CT (L group) with DLIR at high level (DLIR-H). The effective dose (ED), contrast medium dose, injection speed, standard deviation (SD), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of abdominal aorta (AA), and left/right renal artery (LRA, RRA), and subjective scores were compared among the different groups. RESULTS: The L group significantly reduced ED by 37.6% and 31.2%, contrast medium dose by 33.9% and 30.5%, and injection speed by 30% and 30%, respectively, compared to the S and DE groups. The L group had the lowest SD values for all arteries compared to the other groups (p<0.001). The SNR of RRA and LRA in the L group, and the CNR of all arteries in the DE40 group had highest value compared to others (p<0.05). The L group had the best comprehensive score with good consistency (p<0.05). CONCLUSIONS: The triple-low protocol RACTA with DLIR-H significantly reduces the ED, contrast medium doses, and injection speed, while providing good comprehensive image quality.

[Incidence and case fatality rates of cardiovascular diseases in urban and rural community-dwelling populations in eastern, central and western regions of China].

Objective: To evaluate the incidence and case fatality rate of cardiovascular disease (CVD) among populations in urban and rural communities in eastern, central and western regions of China. Methods: The present study was based on the data of the Prospective Urban and Rural Epidemiology (PURE)-China cohort, which enrolled participants who had at least one follow-up visit and complete information on age and sex. Information on baseline demographics, cardiovascular risk factors, and prevention and treatment for CVD were collected. CVD and mortality events were documented using the standardized case report form of the PURE Global Study to assess the incidence and case fatality rate of CVD among populations in urban and rural communities in eastern, central and western China. Results: This study included a total of 47 262 community-dwelling participants (age: (51.1±9.6) years; female, n=27 529, 58.2%) from 115 urban and rural communities in 12 provinces across the eastern, central, and western regions of China. Over a follow-up period of 11.9 (9.5, 12.6) years, 2 686 deaths and 5 873 cardiovascular events were documented. The incidence of CVD was 11.90 (95%CI: 11.60-12.21)/1 000 person-years. A significant difference in CVD incidence was observed across regions (Ptrend<0.001), which was highest in the western provinces (13.99 (95%CI: 13.33-14.65)/1 000 person-years), intermediate in the eastern provinces (11.92 (95%CI: 11.52-12.33)/1 000 person-years), and lowest in the central provinces (8.87 (95%CI: 8.25-9.50)/1 000 person-years). The 1-year case fatality rate of CVD demonstrated an increasing trend from eastern to western regions (eastern: 10.20% (95%CI: 6.95-14.73); central: 13.50% (95%CI: 9.90-18.14); western: 18.62% (95%CI: 14.95-22.94); Ptrend<0.001). Moreover, the incidence of major CVD was consistently higher in rural areas compared with urban areas across eastern (P<0.001), central (P=0.01) and western (P<0.001)_regions, respectively. The 1-year case fatality rate in rural areas was also significantly higher compared with that in urban areas in both eastern (P<0.001) and western regions (P=0.02). Conclusions: The incidence and case fatality rate of CVD were high among middle-aged population in China, especially those in western regions with low socioeconomic levels and in rural areas.

Effectiveness of China-PAR and Framingham risk score in assessment of 10-year cardiovascular disease risk in Chinese hypertensive patients.

OBJECTIVES: Estimating the total risk of cardiovascular disease (CVD) using risk prediction models represents a huge improvement in identifying and treating each of the risk factors. The objective of this study was to evaluate the effectiveness of the China-PAR (Prediction of atherosclerotic CVD risk in China) and Framingham risk score (FRS) in predicting the 10-year risk of CVD in Chinese hypertensive patients. The results of the study can be used to design health promotion strategies. STUDY DESIGN: A large cohort study was used to assess the validity of models by comparing model predictions with actual incidence rates. METHODS: In total, 10,498 hypertensive patients aged 30-70 years in Jiangsu Province, China, participated in the baseline survey that took place between January and December 2010 and were followed up to May 2020. China-PAR and FRS were used to calculate the predicted 10-year risk of CVD. The 10-year observed incidence of new cardiovascular events was adjusted by the Kaplan-Meier method. The ratio of the predicted risk to the actual incidence was calculated to evaluate the effectiveness of the model. The discrimination Harrell's C statistics and calibration Chi-square value were used to evaluate the predictive reliability of the models. RESULTS: Of the 10,498 participants, 4411 (42.02%) were male. During the mean follow-up of 8.30 ± 1.45 years, a total of 693 new cardiovascular events occurred. Both models overestimated the risk of morbidity to varying degrees, and the FRS overestimated to a greater extent. After adjustment for covariates, the results of Cox proportional hazards regression showed that the risk of CVD in the high-risk group was higher than in low-risk group. The degree of discrimination in both models was approximately 0.6, which showed that discrimination was not ideal in the models. In addition, Chi-square calibrations of the two models were <20 in males, which showed that calibration of the models was better for men than women. CONCLUSIONS: The China-PAR and FRS models overestimated the risk of CVD for participants in this study. In addition, the degree of discrimination was not ideal, and both models performed better in males than in females in terms of calibration. The results of this study suggest that a more suitable risk prediction model should be established according to the characteristics of the hypertensive population in Jiangsu Province.

[Extraocular silicone oil migration to orbit: a case report].

Silicone oil insertion is a common modality in vitreoretinal surgeries after ocular perforating injury. It needs surgical removal after several months. Extraocular silicone oil migration to orbit and eyelid is uncommon complication. We reports a case of silicone oil migration to orbit and eyelid. A 41-year-old male presented with left upper eyelid swelling following silicone oil injection 3 years before admission. Orbital computed tomography scan showed multiple high-density well-defined masses in vitreous, left upper eyelid and orbit. We diagnosed the patient with orbital and eyelid mass, meanwhile, speculated mechanical ptosis. Excision of orbital and eyelid masses were performed. Cystic spaces with delicate fibrous wall and small vessels, and clear fluid in cyst were discovered on histologic examination. The patient was followed up after 1 week. The left upper eyelid slightly depressed and the mechanical ptosis was significantly improved.

MicroRNA-29a-3p regulates chemosensitivity in hypopharyngeal carcinoma via targeting Cdc42.

INTRODUCTION: Hypopharyngeal carcinoma is one kind of high malignant tumour followed by poor prognosis in head and neck carcinomas. This study aimed to detect miR-29a-3p and Cdc42 in patients with hypopharyngeal carcinoma. MATERIALS AND METHODS: The expression of miR-29a-3p and Cdc42 mRNA were detected, and the correlation between miR-29a-3p/Cdc42 and clinical stages was investigated. RESULTS: The relative expression of miR-29a-3p in stage II, III and IV hypopharyngeal carcinoma tissues was significantly lower than that of stage I (P< 0.05). The relative expression of Cdc42 mRNA in stage I, III and IV tissues was significantly higher than that of stage I (P< 0.05). The expression of miR-29a-3p in hypopharyngeal carcinoma with lymph node metastasis was significantly lower than that without lymph node metastasis (P = 0.045). CONCLUSION: MiR-29a-3p and Cdc42 mRNA could be potential diagnostic biomarkers of hypopharyngeal carcinoma.

Effect of fasting blood glucose on risk of new-onset hypertension in rural Chinese population: a 15-year follow-up cohort.

BACKGROUND: The purpose of this study was to examine the correlation between fasting blood glucose and new-onset hypertension and examine any synergistically effect modification with multiple risk factors. METHODS: We conducted post-hoc analyses of repeated-measures data in the original Dongzhi osteoporosis cohort study. In total, 3985 participants without hypertension aged 25-64 years were included in the current analyses. Generalized estimating equation models were used to assess the relationship between fasting blood glucose and risk of new-onset hypertension after adjusting for pertinent covariates and autocorrelations among siblings. RESULTS: 393 men (19.4%) and 398 women (20.3%) without hypertension at the baseline developed hypertension by the end of the study period. Compared to lower baseline fasting blood glucose levels (Q1-Q3: < 5.74 mmol/L; clinical cut points: < 5.6 mmol/L), higher baseline fasting blood glucose levels (Q4: ≥ 5.74 mmol/L; clinical cut points: ≥ 5.6 mmol/L and < 7.0 mmol/L) increased the risk of new-onset hypertension significantly [(OR: 1.54, 95% CI 1.19-1.98, P < 0.001); (OR: 1.38, 95% CI 1.09-1.75, P = 0.008)] in women. Additionally, a stronger significant association was found in women with elevated fasting blood glucose on risk of new-onset of hypertension with higher total cholesterol (≥ 5.2 mmol/L) [(OR: 2.76; 95% CI: (1.54, 4.96), P < 0.001)]. However, no association was found between fasting blood glucose and risk of new-onset hypertension in men. CONCLUSIONS: High fasting blood glucose may be significantly associated with risk of new-onset hypertension in Chinese women, especially in women with higher total cholesterol. Further randomized studies are needed to confirm our findings.

The potential of cadmium ion-immobilized Rhizobium pusense KG2 to prevent soybean root from absorbing cadmium in cadmium-contaminated soil.

AIMS: Because the effect of Cd2+ -immobilized microbe on Cd uptake of plants in Cd-contaminated soil remains underexplored, this study focuses on the effect of Cd2+ -immobilized rhizobia on Cd uptake of soybean. METHODS AND RESULTS: Strain KG2 from soybean nodule was identified as Rhizobium pusense KG2 by phylogenetic analysis. Rhizobium pusense KG2 showed the 120 mg l-1 of minimal lethal concentration for Cd2+ . In 50 and 100 mg l-1 of Cd2+ liquid, approximately 2 × 1010 cells removed 56·71 and 22·11% of Cd2+ , respectively. In pot soil containing 50 and 100 mg kg-1 of Cd2+ , strain KG2 caused a 45·9 and 35·3% decrease in soybean root Cd content, respectively. Meanwhile, KG2 improved the root and shoot length, nitrogen content and biomass of soybean plants and superoxide dismutase activity. CONCLUSIONS: The Cd2+ -immobilized rhizobia could inhibit soybean plants to absorb Cd2+ from soil, promote plant growth and improve plant's tolerance against Cd. This study is the first time to report that R. pusense is an effective nodulating rhizobium of legume. SIGNIFICANCE AND IMPACT OF THE STUDY: Some Cd2+ -immobilized microbe lowering Cd uptake of plant and promoting plant growth should be considered as an effective strategy for producing safety crops in the Cd-contaminated agricultural soil.

[Different effects of pravastatin on sFlt-1, PlGF and VEGF in different preeclampsia-like mouse models].

Objective: To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)-like mouse models. Methods: C57BL/6J mice were randomly subcutaneously injected with N-nitro-L-arginine methyl ester (L-NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE-like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L-NAME+Pra, LPS+Pra, Con+Pra) and saline (L-NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt-1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real-time fluorescence quantitative PCR (RT-PCR). Results: (1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50±4.31) levels were significantly increased in L-NAME+Pra group compared with L-NAME+NS group (all P<0.05). Serum VEGF (202.30±4.90, 144.50±6.71) and PlGF (121.50±3.86, 95.41±4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt-1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt-1 level in L-NAME+Pra group was significantly lower than that in L-NAME+NS group (2.60±0.06, 583.70±9.83; all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66±0.14) in the liver of mice in the L-NAME+Pra group were significantly higher than those in the L-NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L-NAME+Pra group were not significantly different from those of L-NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT-PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L-NAME+Pra group were not significantly different from those in L-NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05). Conclusions: Pra has different regulatory effects on vascular endothelial function in different PE-like models. It reveals that different pathogenesis and pathways exist in different PE-like changes.

[Inhibitory effect of DAPT on Notch signaling pathway in curcumin mediated photodynamic therapy for cervical cancer xenografts in nude mice].

Objective: Curcumin was used as photosensitizers in photodynamic therapy on cervical cancer xenografts in nude mice.Analysis the expression changes of Notch and downstream gene as NF-κB and VEGF before and after DAPT inhibition of Notch signaling pathway in vivo experiments.Our aim was to investigate the possible mechanism of Notch signaling pathway in the treatment of cervical cancer with PDT. Methods: A cervical cancer model of nude mice was established by subcutaneous inoculation of human cervical cancer Me180 cells 200 µl.After the success of the model, the experimental animals were divided into 4 groups (model group, curcumin PDT group, simple DAPT group, curcumin-PDT+ DAPT group), each group was 12.Tumor volume changes were analyzed and HE staining was observed in each group.MRNA and protein expression of Notch1 and its downstream NF-κB, VEGF were detected by RT-PCR, immunohistochemistry and Western blot before and after inhibition of Notch signaling pathway by DAPT. Results: Except the control group, the tumor volume of the other three groups remained unchanged or slightly reduced after 1-7 days of treatment.The difference was significant (P<0.05). HE staining showed the most obvious necrosis of curcumin-PDT group with DAPT.Both DAPT and curcumin-PDT could reduce the expression level of Notch1 in mRNA.The inhibition rates were 42.17% and 40.54%, respectively.And the inhibitory effect of curcumin-PDT with DAPT on Notch-1 was the strongest (79.22%) (P<0.01), and two of them had synergistic effect after combination with curcumin-PDT.But the expression of Notch-2 has no obvious inhibitory effect (P>0.05). Both DAPT and curcumin-PDT can inhibit the protein expression of Notch1, NF-κB and VEGF, and two of them have synergistic effect after combined use. Conclusions: DAPT can effectively block the Notch signaling pathway and inhibit the proliferation of cervical cancer cell line Me180.The application of DAPT to inhibit Notch signaling pathway after photodynamic therapy can achieve synergistic effect, which is mainly related to the down-regulation of the expression of Notch1 and NF-κB.Notch signaling pathway may be one of the targets of curcumin-PDT photodynamic therapy.

[Regulation of pravastatin on long-chain fatty acid oxidative enzyme in pre-eclampsia-like mouse model].

Objective: To investigate the modulation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression by pravastatin in pre-eclampsia-like mouse model. Methods: C57BL/6J mice were randomly injected with N-nitro-L-arginine methyl ester (L-NAME) as pre-eclampsia-like model group (PE) or saline as normal pregnancy control group (Con) respectively, from gestational the 7th to 18th day. For each group, pravastatin (PE+Pra, Con+Pra group) or saline (PE+N, Con+N Group) was given from the 8th to 18th day of gestation, respectively. Liver and placenta of pregnant mice were collected on gestational day 18. The LCHAD protein expression and mRNA levels of liver and placenta were detected through western blot, immunohistochemistry and real-time quantitative PCR. Results: (1) The average arterial pressure of pregnant mice increased gradually from the 8th to 18th day in PE+N group, but decreased in PE+Pra group from gestational 10th day, 24 hour urinary protein levels in PE+N group [(1 494 ± 201) µg] were significantly higher than that in Con+N group [(935±128) µg, P<0.01], and also higher than that in PE+Pra group [(981±116) µg, P<0.01].(2) The results of western blot: the expression of LCHAD was significantly lower in PE+N group (liver: 0.64±0.11, placenta: 0.48±0.06) than that in Con+N group (liver: 1.06±0.10, placenta: 0.60±0.10), and lower than that in PE+Pra group (liver: 0.99±0.04, placenta: 0.60±0.08; all P<0.01).(3)The results of real-time quantitative PCR: the levels of LCHAD mRNA in liver and placenta in PE+N group (liver: 0.621±0.128, placenta: 0.646±0.129) were significantly decreased compared with Con+N group (liver: 1.007±0.130, placenta: 1.004±0.103; all P<0.01), but there was no significant difference between PE+Pra group (liver: 0.693±0.678, placenta: 0.662±0.183; P>0.05). (4) LCHAD protein was expressed widely and evenly in liver. The expression in placental cytotrophoblast and syncytial trophoblast cells located in outer layer of villous in labyrinth layer was the most. The expression of LCHAD was significantly lower in PE+N group (liver: 0.062±0.016, placenta: 0.147±0.018) than that in Con+N group (liver: 0.126±0.013, placenta: 0.183±0.024), and lower than that in PE+Pra group (liver: 0.111±0.017, placenta: 0.174±0.027; all P<0.05). Conclusion: Pravastatin could upregulate the LCHAD protein expression of liver and placenta in the pre-eclampsia-like mouse, which may be a mechanism to improve the clinical manifestations of pre-eclampsia.

An indoleacetic acid-producing Ochrobactrum sp. MGJ11 counteracts cadmium effect on soybean by promoting plant growth.

AIMS: To analyse whether some indoleacetic acid (IAA)-secreting plant growth-promoting bacteria can alleviate cadmium (Cd) stress, the role of an Ochrobactrum sp. MGJ11 from rhizosphere of soybean in promoting plant growth, and to evaluate the counteracting Cd effects on soybean. METHODS AND RESULTS: Ochrobactrum sp. MGJ11 produced 121·2 mg l-1 of IAA. MGJ11 increased soybean root length, shoot length and biomass by 30·1, 30·8 and 13·4% respectively. In liquid medium, no IAA production was detected in Cd concentration of 100 mg l-1 . In soil with 20-80 mg kg-1 Cd, MGJ11 promoted soybean root elongation (29·4-161·4%) and increased the shoot length (up to 52·7%) and biomass (up to 87·2%). After growing for 38 days, Cd concentrations in the roots of inoculated soybean were lower than in those of noninoculated plants. Only a little Cd (2·6-16·9 µg g-1 ) was translocated from the root to shoot. CONCLUSIONS: Ochrobactrum sp. MGJ11 secretes IAA and shows tolerance against Cd. MGJ11 inoculation improves the root length, shoot length and biomass of soybean in both vermiculite and Cd vermiculite, and decreases Cd concentration of soybean root. The characteristics of MGJ11 suggest that it could be used for promoting soybean growth and lowering bioavailability of soil Cd for soybean root. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we isolated a plant growth-promoting Ochrobactrum with the activity of mitigating Cd toxicity to plant roots. The Ochrobactrum can be considered as a potential bioaugmentation agent that promotes plant growth, especially in some agricultural systems, or that helps in the phytoremediation of Cd-contaminated soil.

The influence of CYP3A5*3 and BCRPC421A genetic polymorphisms on the pharmacokinetics of felodipine in healthy Chinese volunteers.

WHAT IS KNOWN AND OBJECTIVE: The role of CYP3A5 in drug metabolism has been receiving attention because CYP3A5 may be more involved in the metabolism of CYP3A substrates in vivo than previously thought. The polymorphism of transporters, such as P-gp (P-glycoprotein) and breast cancer-related protein (BCRP), influences the metabolism of these substrates, and felodipine is a substrate of P-gp. The aim of this study was to evaluate the pharmacogenetic variability in the disposition of felodipine in healthy Chinese subjects. METHODS: A single dose of 5 mg felodipine was orally administered to 45 healthy Chinese subjects. The serum concentration of felodipine was measured by using LC/MS/MS. We detected the SNPs of cytochromes P450 enzymes and transporters, which play vital roles in drug metabolism and have a high frequency of mutation in Chinese population. RESULTS AND DISCUSSION: The area under the plasma concentration-time curve (AUC) within the time points 0 to 72 h (AUC(0-72) ) after felodipine administration was significantly higher in subjects possessing the BCRP421AA alleles than in those with the BCRP421 CC or CA genotype (P = 0·034). The subjects with CYP3A5*3/*3 (n = 27) had higher felodipine exposure than CYP3A5*1/*3 (n = 15) (P = 0·035). WHAT IS NEW AND CONCLUSION: This study showed that the genetic polymorphisms of CYP3A5*3 and BCRPC421A might explain the variability in the pharmacokinetics of felodipine in the Chinese population.

[Effect of dexmedetomidine alone for postoperative analgesia after laparoscopic cholecystectomy].

Objective: To investigate the effect of dexmedetomidine alone for postoperative analgesia after laparoscopic cholecystectomy. Methods: Forty patients scheduled for elective laparoscopic cholecystectomy in First Hospital of Ninghai County, American Society of Anesthesiologists (ASA) gradeⅠor Ⅱ, were randomly divided into dexmedetomidine group (Group D, n=20) and fentanyl group (Group F, n=20). The patient controlled analgesia (PCA) pumps were used after the operation. In the group D, the intravenous PCA protocol was dexmedetomidine 0.2 µg·kg(-1)·h(-1) diluted to 100 ml in 0.9% saline. In the group F, the PCA protocol was fentanyl 20 µg /kg diluted to 100 ml in 0.9% saline. Mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before induction of anaesthesia, end of operation and 4, 6, 8, 24, 48 hours after the operation. The pain score on a visual analogue scale (VAS) and the Ramsay sedation score were recorded at 4, 6, 8, 24, 48 hours after the operation. The incidences of postoperative nausea and vomiting (PONV), respiratory depression, dizziness, time to recovery of gastrointestinal function (time to first passage of flatus) and satisfaction with pain control were also recorded. Results: There were no significant difference in the general data of patients, duration of surgery, total dose of intraoperative propofol, fentanyl and sevoflurane, and total fluids during the operation (P>0.05). No patients received rescue analgesic. The MAP and HR values at different time points showed no significant difference between the groups (P>0.05). Similarly, the VAS scores and Ramsay sedation scale at 4, 6, 8, 24, 48 hours after the operation were not significantly different between the groups (P>0.05). The incidence of PONV was significantly reduced in group D, rating as 5%, comparing with 40% in Group F (P<0.05). Patients of Group D experienced a faster gastrointestinal function recovery, and the time to the first passage of flatus were (41.3±10.1) h in Group D and (55.6±11.4) h in Group F (t=-4.195, P<0.05), respectively. The pain treatment satisfactory score (PTSS) in Group D was (8.1±1.3) points, higher than that in Group F (6.1±1.5) points (t=4.426, P<0.05). Meanwhile, there was no statistic difference in the incidence of respiratory depression and dizziness in both groups (P>0.05). Conclusion: Intravenous infusion of dexmedetomidine alone at 0.2 µg·kg(-1)·h(-1) after laparoscopic cholecystectomy not only reduces postoperative pain, but also enhances satisfaction with pain control and improves the recovery of gastrointestinal function.

Peripheral nerve injury induces persistent vascular dysfunction and endoneurial hypoxia, contributing to the genesis of neuropathic pain.

Nerve injury is associated with microvascular disturbance; however, the role of the vascular system has not been well characterized in the context of neuropathic pain. Furthermore, ischemia is thought to play a role in a number of neuropathic pain conditions, and yet the role of hypoxia has also not been characterized in neuropathic pain conditions. In this study, we observed the presence of persistent endoneurial hypoxia in a mouse model of traumatic peripheral nerve injury, causing painful mononeuropathy. We attribute the ongoing hypoxia to microvascular dysfunction, endoneurial fibrosis, and increased metabolic requirements within the injured nerve. Increased lactate levels were observed in injured nerves, as well as increased oxygen consumption and extracellular acidification rates, suggesting that anaerobic glycolysis is required to maintain cellular ATP levels. Hypoxia causes a reduction in levels of the Na(+)/K(+) ATPase ion transporter in both cultured primary dorsal root ganglion neurons and injured peripheral nerve. A reduction of Na(+)/K(+) ATPase ion transporter levels likely contributes to the hyperexcitability of injured nerves. Physiological antagonism of hypoxia with hyperbaric oxygen alleviated mechanical allodynia in nerve-injured animals. These results suggest that hypoxia and the Na(+)/K(+) ATPase ion transporter may be a novel mechanistic target for the treatment of neuropathic pain. In addition, the findings support the possibility of using hypoxia activated pro-drugs to localize treatments for neuropathic pain and nerve injury to injured nerves.

Comparing the effectiveness of pharmacist-managed warfarin anticoagulation with other models: a systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulation management services are well known to improve the quality of patient care and to reduce the rates of hospitalization and emergency department visits following adverse events related to anticoagulation therapy. The complexity of managing warfarin has led to the development of a variety of specialized models managed by pharmacists, physicians, nurses, and self-managed care. The aim of the study is to compare the effectiveness of pharmacist-managed anticoagulation control of warfarin with other models. METHODS: We performed a systematic literature search of the PubMed, Medline@Web of Knowledge, EMBASE, Cochrane Library and Cumulative Index to Nursing and Allied Health Literature to identify randomized controlled trials (RCTs) from database inception up to July 2015. The search terms used for the study were 'warfarin', 'pharmacists', 'Vitamin K antagonist', 'anticoagulation' and 'management model.' We used the Cochrane Collaboration's tool from the Cochrane Handbook to assess the risk of bias of RCTs. We performed statistical analyses using RevMan 5.3 and used the Grading of Recommendations, Assessment, Development, and Evaluations profiler to rate the quality of evidence of the outcomes. The anticoagulation control outcomes were the percentage of time within the standard and expanded therapeutic range and thrombosis events; the safety outcomes were bleeding events and mortality, and patients' satisfaction of anticoagulation service. RESULTS AND DISCUSSION: Eight RCTs from 981 potentially relevant publications with a total of 1493 patients were included. Meta-analysis of the RCTs showed that a significant difference existed between pharmacist-managed care and other models for satisfaction (mean difference (MD) = 0·41, 95% CI, 0·01-0·81, P = 0·04, low-quality evidence) with heterogeneity, and the percentage of time within the standard therapeutic range (MD = 3·66, 95% CI 2·20-5·11, P < 0·00001, high-quality evidence) without heterogeneity. However, the pharmacist-managed group demonstrated no significant improvement on the percentage of time within the expanded therapeutic range (MD = 2·85, 95% CI -0·56 to 6·26, P = 0·10, moderate-quality evidence) with heterogeneity, mortality [odds ratio (OR) = 0·97, 95% CI, 0·44-2·11, P = 0·09, high-quality evidence] without heterogeneity, the prevention of bleeding events (OR = 0·89, 95% CI, 0·56-1·44, P = 0·64, high-quality evidence) without heterogeneity, and thrombosis events (OR = 0·81, 95% CI, 0·34-1·92, P = 0·64, high-quality evidence) without heterogeneity. WHAT IS NEW AND CONCLUSION: The advantage of pharmacist-managed warfarin anticoagulation therapy in terms of anticoagulation control, safety and mortality are unclear, but resulted in significantly better patient satisfaction. Compared with other models, the superiority of pharmacist-managed warfarin anticoagulation needs to be further evaluated and validated in future research.

[Clinical characteristics of bone disease in multiple myeloma and clinical significance of monitoring bone metabolic markers].

OBJECTIVE: To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers. METHODS: The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease. The levels of bone metabolic markers total procollagen type Ⅰ N-terminal peptide (tPINP) and ß C-terminal telopeptide of type Ⅰ collagen (ß-CTX) were monitored regularly in the two years following treatment in 66 cases. RESULTS: (1) Among the 178 newly diagnosed MM cases, 167 cases complained of pain in bones on first visit, 35 cases combined with hypercalcemia, 83 cases combined with osteoporosis, 154 cases combined with osteolytic bone destruction, and 73 cases combined with pathologic fracture. The most common osteolytic location was the spine. The most common fracture sites was the spine. (2) According to bone disease grading, the 178 cases were divided into group A (bone grade 0-2, n=51) and group B(bone grade 3-4, n=127). There were no significant differences between group A and group B in gender, median age, therapeutic effect/ineffec, median overall survival, median progress-free survival, mean serum lactic dehydrogenase, mean albumin, urine light chains and serum creatinine(all P>0.05). Compared with group A, group B had lower hemoglobin level[(99.78±29.93)vs (108.84±29.30) g/L], and higher blood calcium level[(2.47±0.40)vs (2.30±0.29) mmol/L], serum ß2-microglobuin level[(6.04±4.84)vs (4.12±3.97)mg/L], and bone marrow plasma cells percentage(33.30%±24.87% vs 23.51%±22.67%)(all P<0.05). (3) Before treatment, the levels of ß-CTX and tPINP in patients of group B(n=47) were higher than those in group A(n=19)(median 0.78 vs 0.42 µg/L, 60.95 vs 43.47 µg/L, both P<0.05). The ratio of ß-CTX /tPINP in group B was higher than that in group A (median 0.017 vs 0.012, P<0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both group A and group B (both P>0.05), the level of ß-CTX decreased significantly compared with that before treatment in both groups(median 0.16 vs 0.42 µg/L, 0.26 vs 0.78 µg/L, both P<0.05); the ratio of ß-CTX /tPINP decreased significantly compared with that before treatment in both group A and in group B(median 0.008 vs 0.012, 0.011 vs 0.017, both P<0.05). There were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that after 3 months in both group A and group B (all P>0.05). (4)All patients were divided into two groups according to the therapeutic effect: effective group included patients who reach the effect of partial remission or better remission(n=48), while ineffective group included patients who did not reach the effect of partial remission(n=18). Before treatment there were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio between the effective groupand the ineffective group (all P>0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both effective group and ineffective group (all P>0.05), but the level of ß-CTX decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.24 vs 0.60 µg/L, 0.44 vs 0.95 µg/L, both P<0.05). The ratio of ß-CTX /tPINP decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.005 vs 0.012, 0.005 vs 0.011, both P<0.05). There were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that for 3 months both in effective group and ineffective group (all P>0.05). CONCLUSIONS: Pain in bones, osteolysis and pathological fracture are the most common clinical manifestations in myeloma-related bone disease. The severity of bone disease can reflect the tumor load, but may not affect the therapeutic effect and the overall survival. The bone metabolic markers tPINP and ß-CTX can be used to evaluate the severity of myeloma-related bone disease at diagnosis and to monitor the effect of treatment for bone disease.

Detection of soluble expression and in vivo interactions of the inner membrane protein OppC using green fluorescent protein.

In this study, the in vivo interaction system of oligopeptide permease (Opp) proteins was analyzed, and a high expression system of inner membrane protein OppC was constructed by flexible usage of the green fluorescent protein (GFP). The Escherichia coli OppC gene, which encodes a transmembrane component of oligopeptide transporter, was cloned into different vectors. Recombinant plasmids were transformed into different E. coli strains, and the expression conditions were optimized. The effect of plasmids and expression strains on OppC production was evaluated by in-gel and western blot analyses. OppC produced by the pWaldo-GFPe vector, harboring the GFP reporter gene, transformed into E. coli C43(DE3) provided sufficient functional protein for biochemical and biophysical studies. In vivo protein-protein interactions were detected among oligopeptide permease proteins using a GFP fragment reassembly protocol. The substrate binding protein OppA showed no interaction with the other components, while the ATP-binding component OppD did not interact with OppF. OppD and OppF interacted with the transmembrane components OppB and OppC. OppB also showed direct interaction with OppC. In vivo OppC functionality was determined by constructing an OppC gene deletion strain. OppC was shown to be essential for peptide uptake, and non-essential for cell viability. These results could help in elucidating the oligopeptide transport mechanism in bacteria.

Melkersson-Rosenthal syndrome with isolated unilateral eyelid edema: an immunopathologic study.

Lymphedema is caused by defective drainage of the lymphatic system. In Melkersson-Rosenthal syndrome, involvement is predominantly of the lumens with blockage of lymphatic channels by histiocytic-epithelioid cell clusters accompanied by dermal granulomas and lymphocytes. It is a localized, painless, nonitching, and nonpitting form of lymphedema. Besides the eyelids, the disease can cause lip edema, facial palsy, and/or fissured tongue. It is rare and has received little attention in the ophthalmic literature, either in its complete triadic form, or more frequently, in its monosymptomatic forms. Pathogenesis is not well understood, and there is no effective therapy. The authors describe a case of Melkesson-Rosenthal syndrome in a 45-year-old Hispanic man with isolated unilateral upper eyelid edema. Histopathological and immunohistochemical evaluations of an eyelid biopsy specimen revealed intravascular and extravascular clusters of histiocytic-epithelioid cells that were CD68/163-positive. Variable numbers of mostly T-lymphocytes were found in the epidermis, dermis, and orbicularis muscle and by virtue of the associated granulomas established the diagnosis of Melkersson-Rosenthal syndrome. CD4 helper and CD8 suppressor T-lymphocytes were equally represented. CD20 B-lymphocytes were exceedingly sparse. Conspicuous CD1a-positive Langerhans' cells were present in the epidermis, sometimes formed subepithelial loose aggregates and were also incorporated in the granulomas. The differential diagnosis includes the far more common condition of acne rosacea. Management of Melkersson-Rosenthal syndrome, and of angioedema in general, is reviewed.

Characterization of the nuclear localization signals of duck circovirus replication proteins.

Duck circovirus (DuCV) possess a circular, single-stranded DNA genome that requires the replication protein (Rep) for its replication. Based on the viral genotype, there are two categories of Rep proteins: Rep1 and Rep2. To characterize the nuclear localization signals (NLSs) conferring the nuclear localization of the Rep proteins, defined coding regions of the rep gene of two genotypes of DuCV were cloned and co-expressed with the red fluorescent protein DsRed2. The results showed that deleting the putative N-terminal NLS located at amino acid residues 10-37 of Rep1 and Rep2 abrogated nuclear translocation, while deleting the putative C-terminal NLS located at residues 244-274 of Rep1 did not significantly alter its subcellular localization, confirming that only the NLS located at residues 10-37 in the N-termini of the Rep proteins had nuclear targeting activity.