Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System / 神经科学通报·英文版

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.

The influencing factors of renal response in newly diagnosed multiple myeloma patients with renal impairment / 中华血液学杂志

Objective: To investigate the causative factors of renal function in newly diagnosed multiple myeloma (MM) patients with renal inadequacy. Methods: 181 MM patients with renal impairment from August 2007 to October 2021 at Peking Union Medical College Hospital were recruited, whose baseline chronic kidney disease (CKD) stage was 3-5. Statistical analysis was performed based on laboratory tests, treatment regimens, hematological responses, and survival among various renal function efficacy groups. A logistic regression model was employed in multivariate analysis. Results: A total of 181 patients were recruited, and 277 patients with CKD stages 1-2 were chosen as controls. The majority choose the BCD and VRD regimens. The progression-free survival (PFS) (14.0 months vs 24.8 months, P<0.001) and overall survival (OS) (49.2 months vs 79.7 months, P<0.001) of patients with renal impairment was considerably shorter. Hypercalcemia (P=0.013, OR=5.654) , 1q21 amplification (P=0.018, OR=2.876) , and hematological response over a partial response (P=0.001, OR=4.999) were independent predictive factors for renal function response. After treatment, those with improvement in renal function had a longer PFS than those without (15.6 months vs 10.2 months, P=0.074) , but there was no disparity in OS (56.5 months vs 47.3 months, P=0.665) . Conclusion: Hypercalcemia, 1q21 amplification, and hematologic response were independent predictors of the response of renal function in NDMM patients with renal impairment. MM patients with CKD 3-5 at baseline still have worse survival. Improvement in renal function after treatment is attributed to the improvement in PFS.

Palliative Care for End-Stage Renal Disease:A Case Report and Literature Review / 中国医学科学院学报

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.

Expression of calcineurin in podocytes in response to endoplasmic reticulum stress in diabetic nephropathy / 中国医学科学院学报

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>At the stage of microalbuminuria in DN, ERS in podocytes up-regulates the expression of CaN.</p>

Echocardiographic diagnosis of partial anomalous pulmonary venous connection / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate partial anomalous pulmonary venous connection (PAPVC) with echocardiography.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Combined trabeculectomy and vitrectomy for intractable glaucoma with severe ocular contusion involving the posterior segment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Persistent subretinal fluid after successful scleral buckle surgery for macula-off retinal detachment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Effects and complications of placement of motility coupling post in porous polyethylene orbital implants / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>