[Palliative Care for End-Stage Renal Disease:A Case Report and Literature Review].

Since end-stage renal disease leads to a variety of problems such as disability,reduced quality of life,and mental and psychological disorders,it has become a serious public health problem around the globe.Renal palliative care integrates palliative care philosophy in the care for patients with end-stage renal disease.As a planned,comprehensive,patient-centered care,renal palliative care focuses on the patient's symptoms and needs,aiming to reduce the suffering throughout the course of the disease,including but not limited to end-of-life care.This study reports the palliative care practice for a patient on maintenance dialysis in the Blood Purification Center of Peking Union Medical College Hospital and reviews the present situation of palliative care in end-stage renal disease.

Invention of a non-invasive intracranial pressure (ICP) monitoring system - an enlightenment from a hydrocephalus study.

BACKGROUND: Mechanical obstruction is the most common cause of shunt failure for hydrocephalic patients. However, the diagnosis is extremely challenging and often requires invasive testing methods. Thus, a simple and non-invasive technique is in urgent need to predict the intracranial pressure (ICP) of hydrocephalic patients during their post-surgical follow-up, which could help neurosurgeons to determine the conditions of the shunt system. MATERIALS AND METHODS: Two groups of patients were enrolled in the current study. In group I, patients were enrolled as they were diagnosed with high ICP hydrocephalus and received shunt surgery. The shunt valve pressures were taken for their post-surgical ICP. Meanwhile, the participants of group II exhibited abnormally increased lumbar puncture opening pressure (LPOP; from 180 to 400 mmH2O). Both the ICP and LPOP were used to match with their corresponding tympanic membrane temperature (TMT). RESULTS: When patients' ICP were in the normal range (group I, from 50 to 180 mmH2O), the TMT correlated with ICP in a linear regression model (R2 = 0.59, p < 0.001). Interestingly, when patients exhibited above-normal ICP (LPOP was from 180 to 400 mmH2O), their TMT fit well with the ICP in a third-order polynomial regression (R2 = 0.88). When the ICP was 287.98 mmH2O, the TMT approached the vertex, which was 38.54 °C. Based on this TMT-ICP algorithm, we invented a non-invasive ICP monitor system. Interestingly, a tight linear correlation was detected between the ICP data drawn from the non-invasive device and Codman ICP monitoring system (R2 = 0.93, p < 0.01). CONCLUSIONS: We believe the TMT-ICP algorithm (the Y-Jiang model) could be used for preliminary prediction of shunt malfunction as well as monitoring ICP changes.

Selective dopamine D3 receptor antagonist YQA14 inhibits morphine-induced behavioral sensitization in wild type, but not in dopamine D3 receptor knockout mice.

Increasing preclinical evidence demonstrates that dopamine D3 receptor (D3R) antagonists are a potential option for the treatment of drug addiction. The reinstatement of the addiction can be triggered by environmental stimuli that acquire motivational salience through repeated associations with the drug's effects. YQA14 is a novel D3R antagonist that has exhibited pharmacotherapeutic efficacy in reducing cocaine and amphetamine reward and relapse to drug seeking in mice. In this study we investigated the effects of YQA14 on morphine-induced context-specific locomotor sensitization in mice. We showed that repeated injection of YQA14 (6.25-25 mg/kg every day ip) prior to morphine (10 mg/kg every day sc) not only inhibited the acquisition, but also significantly attenuated the expression of morphine-induced locomotor sensitization. Furthermore, in the expression phase, one single injection of YQA14 (6.25-25 mg/kg, ip) dose-dependently inhibited the expression of morphine-induced behavioral sensitization. Moreover, YQA14 inhibited the expression of morphine-induced behavioral sensitization in wild mice (WT), but not in D3R knockout (D3R-/-) mice in the expression phase. In addition, D3R-/- mice also displayed the reduction in the expression phase compared with WT mice. In summary, this study demonstrates that blockade or knockout of the D3R inhibits morphine-induced behavior sensitization, suggesting that D3R plays an important role in the pathogenesis and etiology of morphine addiction, and it might be a potential target for clinical management of opioid addiction.

[Expression of calcineurin in podocytes in response to endoplasmic reticulum stress in diabetic nephropathy].

OBJECTIVE: To investigate the regulation of calcineurin (CaN) by endoplasmic reticulum stress (ERS) in podocytes in vitro and in vivo at the stage microalbuminuria in diabetic nehropathy (DN). METHODS: The urinary albumin excretions of C57BLKS/J (Lepr) db/db and db/m mice at the ages of 6, 9, and 12 weeks were measured. The expressions of CaN and synaptopodin of these mice were observed. In immortalized mouse podocytes, the expression of podocyte CaN incubated with different concentrations of paltimate was quantitatively determined by real-time PCR. The changes of CaN incubated with paltimate with or without ursodeoxy-cholic acid (UDCA) were analyzed by confocal microscopy and Western blotting. RESULTS: As urine protein increased, the expression of CaN was enhanced and the expression of synaptopodin was reduced in early stage DN db/db mice potocytes. In immortalized mouse podocytes, as the concentrations of palmitate increased, CaN mRNA increased. By confocal microscopy, the fluorescence intensity of CaN increased in palmitate treatment group. After co-incubation with palmitate and UDCA, the fluorescence intensity decreased. The similar results were shown by Western blotting. CONCLUSION: At the stage of microalbuminuria in DN, ERS in podocytes up-regulates the expression of CaN.

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System.

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

[Echocardiographic diagnosis of partial anomalous pulmonary venous connection].

OBJECTIVE: To investigate partial anomalous pulmonary venous connection (PAPVC) with echocardiography. METHODS: The right ventricular volume overload was detected by routine echocardiography in 37 child patients, who underwent further echocardiography to find the abnormal locations of pulmonary vein opening at superior, inferior vena cava and right atrium. The ultrasound results were compared with surgical findings. RESULTS: In 30 patients the ultrasound diagnosis was consistent with surgery results, 7 were misdiagnosed by ultrasound with a detective rate of 81.1 %. All 37 PAPVC patients presented varying degrees of right heart enlargement; PAPVC combined with atrial septal defect (ASD) was found in 34 cases. CONCLUSION: The possibility of PAPVC should be considered when unexplained right heart volume overload was detected by echocardiography. Superior, inferior vena cava and right atrium should be inspected when the pulmonary veins were not seen in echocardiography.

Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.

BACKGROUND: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons leading to brain dysfunction. Recurrent seizures can lead to cognitive and behavioral deficits, and irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve), an mTOR inhibitor, may modulate neuronal excitability and therefore exert protection against epilepsy. Therefore, this study aimed to investigate the neuroprotective effect of Everolimus on seizure-induced brain injury and its regulation of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Kainic acid (KA) 15 mg/kg was used to induce seizures and Everolimus (1, 2, 5 mg/kg) was administered as a pretreatment. Hippocampal tissue was extracted 24 h post-seizure. RESULTS: The protein and mRNA expression levels of PI3K、p-AKt、p-mTOR、NF-kB and IL-6 as well as neuronal apoptosis and microglia activation, significantly increased after KA-induced seizures, however, these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency. CONCLUSIONS: Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.

Effects and complications of placement of motility coupling post in porous polyethylene orbital implants.

OBJECTIVE: To investigate the effects and complications of primary and secondary placements of motility coupling post (MCP) in the unwrapped porous polyethylene orbital implant (PPOI) following enucleation. METHODS: We investigated 198 patients who received PPOI implantation following the standard enucleation procedure in the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, from 2002 to 2004. These patients were subgrouped into PPOI-only patients (112 cases, received PPOI following enucleation), primary MCP patients (46 cases, received primary placement of MCP during PPOI operation), and secondary MCP patients (40 cases, received secondary placement of MCP 6 months after the initial surgery). Effects and complications among these three groups were compared. RESULTS: The PPOI-only patients took shorter treatment course when compared with other two MCP groups (P<0.001), without significant difference noted between the two MCP groups. However, the two MCP groups had better prosthetic motility than PPOI-only group (P<0.001), without significant difference between the two MCP groups. In the early stage, 2 eyes in the PPOI-only group and 1 eye in the primary MCP group had PPOI infection. In PPOI-only group, 3 (2.68%) eyes had PPOI exposure, which occurred after fitting the prostheses; 4 eyes (8.70%) in primary MCP group and 1 eye (2.50%) in secondary MCP had PPOI exposure, which occurred before fitting the prostheses. After prosthesis was fit successfully, the excessive discharge and granuloma were 33.9% and 1.79% in PPOI group-only, 53.3% and 8.9% in primary MCP group, and 52.5% and 7.5% in secondary MCP group, respectively. CONCLUSION: Both primary and secondary placements of MCP into the PPOI following enucleation can help patients to obtain desirable prosthetic motility, but may be associated with more complications. The primary placement of MCP with skilled operation in selected patients is more recommendable than secondary placement.

A novel biosensor for Escherichia coli O157:H7 based on fluorescein-releasable biolabels.

New techniques are required for the rapid and sensitive detection of Escherichia coli O157:H7 (E. coli O157:H7), a pathogenic bacterium responsible for serious and sometimes life-threatening diseases in humans. In this study, we developed a highly sensitive and efficient biosensor for the quantitative detection of E. coli O157:H7 by integrating fluorescein-releasable biolabels with a magnetism-separable probe. Hollow silica nanospheres with a diameter of approximately 350 nm were synthesized, enriched with fluorescein, and surface-protected with macromolecule layers of poly (acrylic acid) and poly (dimethyldiallylammonium chloride). These fluorescein-enriched hollow silica nanospheres were characterized using scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. They were further functionalized as immune labels of E. coli O157:H7 for a sandwich-type immune reaction between this bacterium and magnetic nanoparticles (Fe3O4@SiO2). Next, the E. coli O157:H7 cells were captured, magnetically separated, and quantified based on the fluorescence intensity of the fluorescein released from the biolabels of the fluorescein-enriched hollow silica nanospheres. This analytic process can be completed within 75 min, and the biosensor showed a linear relationship ranging from 4 to 4.0 × 10(8)cfu/mL with a detection limit of 3 cfu/mL. These results show that the developed fluorescent sensor has excellent specificity, and good reproducibility and stability. This study used real spiked samples for detection, indicating that this technique has a wide range of potential applications and may be readily adapted for detecting other pathogens.

Antitumor efficacy, toxicity and pharmacokinetics of 9-nitrocamptothecin: role of lactone ratio.

PURPOSE: Since the carboxylate form could be regarded as a possible "source" of lactone form, the optimum ratio of lactone should be determined for the administration of camptothecin (CPT) analogues such as 9-nitrocamptothecin (9-NC). METHODS: 9-NC solutions with different lactone ratios (100, 75, 50, 25 and 0 %) were obtained by the change of pH. The resultant 9-NC solution and corresponding blank solvent were intravenously injected to mice to evaluate toxicity. The S180 tumor-bearing mice were intravenously administered 9-NC solutions with different lactone ratios, and the antitumor efficacy and toxicity were compared. The tissue distribution of lactone and total (the total of lactone and carboxylate forms) 9-NC was also investigated as a function of lactone ratio. RESULTS: Toxicity of 9-NC was found to be increased with the increase in lactone ratio. The tumor inhibitory rates of 9-NC solution were determined to be 64.17, 60.43, 42.78, 41.71 and 8.60 % for 100, 75, 50, 25 and 0 % lactone ratio, respectively. The lactone stability of 9-NC in most tissues was found to be higher than in plasma. In tumor and plasma, whether for lactone or total 9-NC AUC values, there was no difference between 100 and 75 % groups. CONCLUSIONS: Although carboxylate form of CPTs is inactive, the administration of carboxylate form in an appropriate ratio is active as a result of its conversion to lactone form in vivo.

Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine.

OBJECTIVE: Brucine was encapsulated into stealth liposomes using the ammonium sulfate gradient method to improve therapeutic index. MATERIALS AND METHODS: Four brucine stealth liposomal formulations were prepared, which were made from different phosphatidylcholines (PCs) with different phase transition temperatures (T(m)). The PCs used were soy phosphatidylcholine (SPC), dipalmitoyl phosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC), and distearoyl phosphatidylcholine (DSPC). The stabilities, pharmacokinetics, and toxicities of these liposomal formulations were evaluated and compared. RESULTS: Size, zeta potential, and entrapment efficiency of brucine-loaded stealth liposomes (BSL) were not influenced by PC composition. In vitro release studies revealed that drug release rate increased with decreased T(m) of PCs, especially with the presence of rat plasma. After intravenous administration, the area under the curve (AUC) values of BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC in plasma were 7.71, 9.24, 53.83, and 56.83-fold as large as that of free brucine, respectively. The LD(50) values of brucine solution, BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC following intravenous injection were 13.17, 37.30, 37.69, 51.18, and 52.86 mg/kg, respectively. It was found in calcein retention experiments that the order of calcein retention in rat plasma was SPC < DPPC << HSPC < DSPC stealth liposomes. CONCLUSION: PC composition could exert significant influence on the stabilities, pharmacokinetics, and toxicities of brucine-loaded stealth liposomes. DSPC or HSPC with T(m) above 50°C should be used to prepare the stealth liposomal formulation for the intravenous delivery of brucine. However, it was found in the present paper that the pharmacokinetics and toxicity of BSL were not influenced by the PC composition when the T(m) of the PC was in the range of -20°C to 41°C.

Aged black garlic extract induces inhibition of gastric cancer cell growth in vitro and in vivo.

There is mounting evidence that garlic extracts possess significant anticancer actions. However, no studies have been reported on the effects of aged black garlic extracts (ABGE) on gastric cancer in vitro or in vivo. To examine the potential action of ABGE against gastric cancer, the present study evaluated its effect on the inhibition of cell proliferation and induction of apoptosis in SGC-7901 human gastric cancer cells. Additionally, we performed an in vivo study by inoculating the murine foregastric carcinoma cell line in Kunming mice and treating them with various doses of ABGE (0, 200, 400 and 800 mg/kg, intraperitoneally) for 2 weeks. Dose-dependent apoptosis was detected in ABGE-treated cells in in vitro studies. In tumor-bearing mice, significant antitumor effects of ABGE were observed, such as growth inhibition of inoculated tumors. Further investigation of serum superoxide dismutases, glutathione peroxidase, interleukin-2 and the increased indices of spleen and thymus indicated that the anticancer action of ABGE may be partly due to its antioxidant and immunomodulative effects.

Persistent subretinal fluid after successful scleral buckle surgery for macula-off retinal detachment.

BACKGROUND: After successful scleral buckle and cryotherapy for macular-off retinal detachment (RD), some patients have poor visual acuity without any clinically detected macular change, and the unsatisfactory postoperative visual acuity is difficult to explain. The purpose of this study was to determine the characteristics of subretinal fluid (SRF) after successful scleral buckle surgery for macula-off RD. METHODS: Twenty-eight eyes from 28 patients were included in this study. The patients underwent scleral buckle surgery combined with cryopexy for macular-off RD. After surgery, all eyes underwent thorough ophthalmologic examinations including slit-lamp biomicroscopy, best-corrected visual acuity (BCVA) test, and binocular indirect ophthalmoscopy. The BCVA prior to the operation, duration of RD, the duration of postoperative retinal reattachment, BCVA when SRF was observed, period required for the SRF to become undetectable, and the BCVA at the final follow-up were included in the clinical data for this study. Optical coherence tomography (OCT) and B-ultrasonography were used to confirm SRF, and fluorescein angiography (FFA) was carried out in several patients. BCVA when SRF was observed and BCVA at the final follow-up were evaluated using a paired t test. Correlations between BCVA before the operation and duration of RD and BCVA at the final follow-up were analyzed using the Pearson correlation test. The type of SRF under OCT and BCVA at the final follow-up were compared using one-way analysis of variance (ANOVA). RESULTS: Postoperative retinal reattachment was achieved in 1.0 - 7.0 days (average, (2.7 ± 2.1) days). After retinal reattachment, SRF was detected in all eyes by OCT 2 weeks postoperative, while B ultrasonography found no changes. The mean logMAR BCVA was 0.35 ± 0.27 at the time of the detection of SRF. The period for SRF to become undetectable ranged from 2.0 to 11.0 months (average, (6.3 ± 2.3) months). The time of follow-up ranged from 24.0 to 36.0 months (average, (28.9 ± 3.4) months). The mean logMAR BCVA improved to 0.30 ± 0.23 at the final follow-up, which was significantly different from the mean logMAR BCVA at the time of SRF detection (paired t-test, t = 3.82, P < 0.05). Postoperative OCT images were classified into three categories. FFA was carried out in 10 eyes and revealed no leakage or strain in the lesions. BCVA before the operation was significantly correlated with BCVA at the final follow-up (r = 0.56, P < 0.05). No significant correlation was observed between BCVA at the final follow-up and duration of RD (r = 0.23, P = 0.22). One-way analysis of variance (ANOVA) showed no significant difference between the type of SRF under OCT and BCVA at the final follow-up (F = 0.21, P = 0.81). CONCLUSIONS: The presence of persistent SRF after successful scleral buckle surgery for macular-off rhegmatogenous RD may influence the BCVA or anatomic attachment. SRF was detected in all eyes by OCT at 2 weeks after the operation. Residual detachment persisted for almost a year after surgery in certain patients. Fluorescein angiography revealed no leakage or strain in the lesions.

Combined trabeculectomy and vitrectomy for intractable glaucoma with severe ocular contusion involving the posterior segment.

BACKGROUND: Intractable secondary glaucoma with severe ocular contusion involving the posterior segment is difficult to treat. In this study, we evaluated the safety and efficacy of combined trabeculectomy and vitrectomy for intractable glaucoma with severe ocular contusion involving the posterior segment. METHODS: This retrospective interventional study enrolled 18 eyes from 18 consecutive cases with uncontrolled intraocular pressure, angle recession exceeding 180°, dense vitreous hemorrhage, and/or limited retinal detachment after severe ocular contusion. Combined trabeculectomy and vitrectomy was performed after giving the patient sufficient anti-inflammatory and intraocular pressure (IOP)-lowering medication. Follow-up averaged 26.2 (range, 6.0- 48.0) months. RESULTS: The mean IOP decreased from (36.4 ± 10.0) mmHg on maximum IOP-lowering medications to (14.6 ± 4.4) mmHg on (0.7 ± 1.2) topical medications at the final follow-up (P < 0.0001). During the first postoperative month, four eyes (22%) had a short hypertensive phase and six eyes (33%) had early hypotony, including one case (5.6%) of bleb leakage. Seven eyes (39%) developed recurrent hypertension 3- 6 months postoperatively, five of which were controlled by topical medications. Ten (55.6%) eyes were classified as a complete success, five (27.8%) as a qualified success, and three eyes (16.7%) as failures. Kaplan-Meier survival analysis for complete and cumulative success showed 53.5% and 80.0% survival at 48 months, respectively. Visual acuity was improved in 15 eyes (83.3%). Three eyes (16.7%) had unchanged visual acuity, one (5.6%) of which developed atrophia bulbi despite a normal intraocular pressure. No recurrent retinal detachment or vitreous hemorrhage developed. CONCLUSION: Combined trabeculectomy and vitrectomy is a viable surgical procedure for the management of intractable glaucoma with severe ocular contusion involving the posterior segment in selected cases.

Pharmacokinetics of brucine after intravenous and oral administration to rats.

The toxicity depending on both dose and administration route is the major obstacle to the development of brucine, a bioactive alkaloid from Semen Strychni. In this study, the apparent partition coefficient and plasma protein binding extent of brucine were determined. In addition, the dose-dependency of the pharmacokinetics of brucine was investigated. Three intravenous (2.5, 5 and 10 mg/kg) and three oral (10, 20 and 40 mg/kg) doses were administered to rats. After intravenous administration, the systemic clearance was reduced and AUC was nonlinearly increased as a function of dose. Upon oral administration, brucine was rapidly absorbed (T(max)<0.5h), which was consistent with previously reported high Caco-2 P(app) values. The increase in AUC was proportional to the increase in dose. The oral bioavailability (F) did not vary with the dose (F=40.31%, 47.15% and 43.02% for 10, 20, 40 mg/kg doses, respectively). However, the dose-proportionality was not observed with C(max). The values of C(max)/Dose were calculated to be 92.92±45.83, 55.73±24.01 and 36.29±22.44 µg/L for 10, 20 and 40 mg/kg, respectively. The results of dose-dependent pharmacokinetic behavior under different administration routes may account for the significantly different toxicities of brucine between intravenous and oral administration.