The Relationship Between Systemic Lupus Erythematosus and Osteoporosis Based on Different Ethnic Groups: a Two-Sample Mendelian Randomization Analysis.

The previous observational studies could not overcome the effects of confounding variables and reverse causality. We aimed to determine whether there is a causal relationship between systemic lupus erythematosus and osteoporosis in East Asian and European populations, respectively, by two-sample Mendelian Randomization analysis. We obtained and downloaded data from publicly available genome-wide association study databases and analyses for East Asian and European populations, including systemic lupus erythematosus (SLE), osteoporosis (OP), multisite bone mineral density (BMD), and OP with fracture. After screening for instrumental single-nucleotide polymorphisms (SNPs) significantly correlated to SLE, the inverse-variance weighted (IVW) method was used for calculating the ratio and 95% confidence interval, besides utilizing MR-Egger, weighted median, and weighted mode to assess the robustness of the primary outcome. Moreover, multiple analyses, including MR-PRESSO, MR-Egger intercept, Cochran's Q test, as well as "leave-one-out" sensitivity, were used for evaluating horizontal pleiotropy, heterogeneity, and stability. Finally, we exchanged exposure and outcome and performed a reverse MR analysis. IVW (OR = 1.05, 95% CI = 1.01-1.09, P = 0.009) indicated a significant positive correlation between genetically predicted SLE and OP in East Asians. Furthermore, neither heterogeneity nor horizontal pleiotropy was observed. In Europe, there was no significant genetically predicted causal relation between SLE and OP. Bi-directional MR analysis showed no reverse causality between SLE and OP. In the East Asian population, genetically predicted SLE may have had a positive causal relationship with OP. In Europe, there is insufficient evidence for a potential causal relation between SLE and OP or BMD and fracture, and the correlations currently observed may be attributed to a variety of confounder variables.

Prognostic value of serial coronary computed tomography angiography-derived perivascular fat-attenuation index and plaque volume in patients with suspected coronary artery disease.

AIMS: To investigate the prognostic value of serial coronary computed tomography angiography (CCTA) derived plaque information, fractional flow reserve (CT-FFR), and perivascular fat-attenuation index (FAI) on major adverse cardiac events (MACE) in patients with suspected coronary artery disease. MATERIALS AND METHODS: A total of 252 patients who underwent serial CCTA between January 2018 and December 2021 and were followed until June 2022. MACE were recorded. The analysis indexes included percent diameter stenosis (%DS), lesion length, plaque volume, CT-FFR, and FAI, with an emphasis on their changes between the baseline and follow-up CCTAs. Multivariate regression analysis were employed to identify independent risk factors for MACE. RESULTS: After a median follow-up of 48-month, MACE occurred in 32 patients (12.7%). Patients with MACE displayed more severe stenosis, longer lesions, and larger plaque volumes in both baseline and follow-up CCTAs compared with no-MACE patients (all P<0.05). Patients with MACE displayed more severe stenosis, longer lesion, and larger plaque volume in both baseline and follow-up CCTAs compared with no-MACE patients. In addition, MACE patients also showed lower CT-FFR and higher △CT-FFR. Although FAI was significantly higher in MACE patients at baseline CCTA, FAI was notably increased in MACE patients, and decreased in the no-MACE patients (all P<0.05). Logistic regression analysis showed that ΔFAI, %DS, and plaque volume were independent predictors of MACE, with ΔFAI being the most significant (OR: 16.725, P<0.000). A multivariable model showed a significantly improved C-index of 0.903 (95% confidence interval: 0.836-0.970) for MACE prediction, when compared with single index alone. CONCLUSIONS: Serial CCTA-derived ΔFAI, %DS, and plaque volume are crucial independent predictors of MACE in patients with suspected coronary artery disease, highlighting the importance of CCTA in patient risk stratification and prognostic assessment.

The liquid Kangfuxin (KFX) has efficient antifungal activity and can be used in the treatment of vulvovaginal candidiasis in mice.

Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50 ) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug-resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae-related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin-17A (IL-17A); however, the levels of interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL-17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC.

[Application and challenges of neuroimaging technology in mechanisms and treatment of drug addiction].

Neuroimaging technologies can non-invasively characterize the structure and function of addiction brain, reveal the neural mechanism of addictive behavior, and provide a priori for the potential targets of brain stimulation. Neuroimaging technologies has played an important role in the study of drug addiction diseases, relapse prediction, and therapeutic evaluation of non-invasive brain stimulations, but it also faces many challenges. In this manuscript, we discuss the classification and analysis methods of neuroimaging technologies, its application in addiction and challenges, thus to promote the application of neuroimaging technology in the treatment of drug addiction.

[Advances in the relationship between lung cancer and microbiota].

Interaction exists in lung cancer and microbiota. Lung microecological homeostasis can improve the immune tolerance, enhance immune suppression, and inhibit inflammatory responses, to reduce the lung cancer; while lung cancer can lead to pulmonary microecological imbalance, change the lung environment, and promote tumor cell proliferation. Therefore, modulating microbial flora and microecological immunotherapy may be a potential and preventive treatment for lung cancer, to restore tumor immunosuppression and improve patient survival. However, the individual differences in the lung microecology, because of different genetics, ethnic characteristics, and dietary habits, increasing the difficulty of precise diagnosis and treatment, which is also the current bottleneck in the application of microecological immunotherapy. Otherwise, the effectiveness of regulatory measures such as probiotics, prebiotics or antimicrobials is questionable. The research on microbial flora is still in its infancy, and further exploration is needed to form a standardized, effective, and precise treatment plan. So, standardized, effective, and precise microbial flora treatment strategies need to be further explored.

Correction: Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.

Following publication of this article, the authors noted that the bands of Na-K ATPase in Figure S1B were mislabelled when selecting representative blots, and were erroneously duplicated from GluA2. However, the data analysis was still made with the correct immunoblots. The Supplementary Information file has now been updated to include the corrected Figure S1 with the correct western blot bands of Na-K ATPase.The authors would like to apologise for this error and the inconvenience this may have caused. This has been corrected in both the PDF and HTML versions of the article.

Nomogram predicting early neurological improvement in ischaemic stroke patients treated with endovascular thrombectomy.

BACKGROUND AND PURPOSE: Early neurological improvement (ENI) after endovascular thrombectomy (EVT) has been associated with favorable outcomes. This study aimed to identify the optimal definition of ENI and develop a nomogram for predicting ENI after EVT in acute ischaemic stroke. METHODS: Patients with EVT were enrolled from a multicenter registry as the training cohort. The receiver operating characteristic curve was used to estimate the optimal threshold for ENI at 24 h of EVT. Logistic regression analysis was utilized to generate the best-fit nomogram for predicting ENI. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC). An additional 447 patients from two stroke centers were prospectively recruited as the test cohort for validating the nomogram. RESULTS: A total of 612 patients with EVT were included in the training cohort. The optimal threshold for predicting 3-month favorable outcome (modified Rankin Scale 0-2) was an improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥6 points (AUC 0.875; sensitivity 79.5%; specificity 90.7%). Age, blood glucose, recanalization, symptomatic intracranial hemorrhage (sICH) and baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were independently associated with ENI, and were incorporated in the nomogram. The AUC of the nomogram was 0.795 in the training cohort and 0.752 in the test cohort. CONCLUSIONS: A reduction of NIHSS score ≥6 appeared to be the optimal definition of ENI. The nomogram composed of age, blood glucose, recanalization, sICH and baseline ASPECTS may predict the probability of ENI in ischaemic stroke patients treated with EVT.

Controlling selectivity in N-heterocycle directed borylation of indoles.

Electrophilic borylation of indoles with BX3 (X = Cl or Br) using directing groups installed at N1 can proceed at the C2 or the C7 position. The six membered heterocycle directing groups utilised herein, pyridines and pyrimidine, result in indole C2 borylation being the dominant outcome (in the absence of a C2-substituent). In contrast, C7 borylation was achieved using five membered heterocycle directing groups, such as thiazole and benzoxazole. Calculations on the borylation of indole substituted with a five (thiazole) and a six (pyrimidine) membered heterocycle directing group indicated that borylation proceeds via borenium cations with arenium cation formation having the highest barrier in both cases. The C7 borylated isomer was calculated to be the thermodynamically favoured product with both five and six membered heterocycle directing groups, but for pyrimidine directed indole borylation the C2 product was calculated to be the kinetic product. This is in contrast to thiazole directed indole borylation with BCl3 where the C7 borylated isomer is the kinetic product too. Thus, heterocycle ring size is a useful way to control C2 vs. C7 selectivity in N-heterocycle directed indole C-H borylation.

The safety and efficacy of transarterial chemoembolisation with bleomycin for hepatocellular carcinoma unresponsive to doxorubicin: a prospective single-centre study.

AIM: To investigate the safety and efficacy of transarterial chemoembolisation (TACE) with bleomycin for hepatocellular carcinoma (HCC) unresponsive to doxorubicin. MATERIALS AND METHODS: A randomised controlled trial was undertaken of HCC patients resistant to TACE with doxorubicin to assess the survival benefits of the experimental group (TACE with bleomycin) compared with the control group (TACE with doxorubicin). One hundred and seventy patients were allocated randomly between December 2015 and December 2017, and 80 patients of each group were analysed. The modified response evaluation criteria in solid tumours (mRECIST) was used to evaluated the tumour response every 4-6 weeks. The primary endpoint was median progression-free survival (mPFS) and median overall survival (mOS). Safety was assessed by post-procedure complications. RESULTS: The study was completed in October 2018. Objective response rate (ORR) of the experimental group was 27.5% (22/80), mPFS and mOS was 5.8 and 8.1 months. ORR of the control group was 7.5% (6/80), mPFS and mOS was 2.9 and 4 months. The ORR were significantly different between two groups (χ2 = 0.348, p<0.05). The differences of mPFS and mOS between the two groups were statistically significant (χ2 = 2.865, p<0.05 and χ2 = 0.926, p<0.05, respectively). There were no significant difference in post-procedure complications (p>0.05) and no major complications occurred. CONCLUSION: It is suggested that TACE with bleomycin is a safe and effective method for HCC and bleomycin can be a second-line chemotherapeutic agent for the HCC patients unresponsive to TACE with doxorubicin.

Intramolecular (directed) electrophilic C-H borylation.

The intramolecular C-H borylation of (hetero)arenes and alkenes using electrophilic boranes is a powerful transition metal free methodology for forming C-B bonds. These C-H borylation reactions are preceded by intermolecular bond (both dative and covalent) formation, with examples proceeding via initial C-B and N-B bond formation dominating this field thus both are discussed in depth herein. Less prevalent intramolecular electrophilic C-H borylation reactions that proceed by intermolecular O-B, S-B and P-B bond formation are also summarised. Mechanistic studies are presented that reveal two mechanisms for C-H borylation, (i) electrophilic aromatic substitution (prevalent with B-X electrophiles); (ii) σ-bond metathesis mediated (prevalent with B-H and B-R electrophiles). To date, intramolecular electrophilic C-H borylation is utilised mainly for accessing boron containing conjugated organic materials, however recent developments, summarized herein alongside early studies, have highlighted the applicability of this methodology for forming synthetically versatile organo-boronate esters and boron containing bioactives. The multitude of synthetic procedures reported for intramolecular electrophilic C-H borylation contain many common features and this enables key requirements for successful C-H borylation and the factors effecting regioselectivity and substrate scope to be identified, discussed and summarized.

[Analysis of factors related to one-year mortality in elderly patients following hip fracture surgery].

Objective: To analyze the related factors that affect the one-year mortality in elderly patients following hip fracture surgery. Methods: The clinical data of the elderly patients who needed a surgery for hip fracture in the Second Affiliated Hospital of Wenzhou Medical University from January 2017 to April 2018 were retrospectively analyzed. According to the inclusion criteria of the study, 489 cases were included. Then the information of patients including age, sex, Charlson comorbidity index, type of fracture, Braden score at admission, American Society of Anesthesiologists (ASA) score, length of hospital stay, type of anesthesia, whole blood cells analysis were collected. Univariate and multivariate Cox regression analyses were conducted to investigate the factors related to one-year mortality of patients. Results: After excluding 39 patients, 450 patients were finally included. Patients in this cohort study had a mortality rate of 3.33% (15/450) at 1 month, 7.78% (35/450) at half a year, and 10.89% (49/450) at 1 year after surgery. Univariate analysis showed that age, sex, ASA score, type of fracture, Charlson comorbidity index, Braden score at admission, type of analgesia, preoperative hemoglobin concentration, preoperative albumin concentration, postoperative delirium of high activity correlated with one-year mortality after surgery. Further, multivariate Cox regression analysis revealed that age>80 years old (HR=2.32, 95%CI: 1.11-4.85, P=0.025), Charlson comorbidity index ≥ 3 (HR=3.24, 95%CI:1.75-6.03, P<0.001), Braden score at admission ≤16 (HR=1.93, 95%CI:1.03-3.57, P=0.040) and postoperative delirium of high activity (HR=2.49, 95%CI:1.16-5.35, P=0.019) were risk factors for one-year mortality. Conclusions: The current study indicates that one-year mortality rate of elderly patients following hip fracture surgery is 10.89%. Meanwhile, age>80 years, Charlson comorbidity index ≥ 3, Braden score at admission ≤ 16, postoperative delirium of high activity are risk factors for one-year mortality.

Uric acid level and risk of symptomatic intracranial haemorrhage in ischaemic stroke treated with endovascular treatment.

BACKGROUND AND PURPOSE: There are limited data on the association between uric acid (UA) and symptomatic intracranial haemorrhage (SICH) in patients who have undergone mechanical thrombectomy [endovascular treatment (EVT)]. In the present study, we aimed to investigate the role of serum UA level in SICH after EVT in a real-world practice. METHODS: Patients were selected from the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke (ACTUAL) registry. SICH was identified using the Heidelberg Bleeding Classification. Multivariable logistic regression analysis was performed to explore the relationship between serum UA and SICH. RESULTS: Among 611 enrolled patients, 90 (14.7%) were diagnosed with SICH within 72 h after EVT. Patients with SICH had a significantly higher level of serum UA (median, 341.0 vs. 302.0 µmol/L; P = 0.003) than those without SICH. Univariate logistic regression analysis indicated that patients with UA levels in the fourth quartile, compared with the first quartile, were more likely to have SICH (odds ratio, 2.846; 95% confidence intervals, 1.429-6.003; P = 0.003). The association remained significant after multivariable adjustment for potential confounders. Furthermore, the multiple-adjusted spline regression model showed an inverted U-shaped association between UA and SICH (P = 0.047 for non-linearity). CONCLUSION: Our study indicated that increased serum UA level was independently associated with SICH after EVT in acute ischaemic stroke.

Comparison of angio-CT versus multidetector CT in the detection and location for insulinomas.

AIM: To compare the diagnostic performance of angio-computed tomography (CT) with multidetector CT (MDCT) in the detection and location for insulinomas. MATERIALS AND METHODS: From April 2015 to April 2018, 60 consecutive patients who underwent MDCT and angio-CT for clinically suspected insulinomas were identified retrospectively. The CT attenuation values of tumours, normal pancreatic parenchyma, and tumour-to-pancreas contrast were measured quantitatively in the arterial phase (AP) and portal venous phase (PVP) of both methods by two radiologists with interobserver agreement. The detection sensitivity and localisation accuracy were calculated based on surgical and pathological findings, which are the reference standard, and compared between both methods using the chi-square test. Receiver operating characteristic (ROC) analysis was performed to compare diagnostic performance. RESULTS: Fifty-four patients with insulinoma with a mean age of 53.8 years old (range 21-69 years) were reviewed. The detection sensitivity and location accuracy were 68.5%, 58.3% for MDCT and 94.4%, 90.7% for angio-CT, respectively; the detection sensitivity and location accuracy of angio-CT were significantly higher than those obtained with MDCT (p < 0.05). The mean tumour-to-pancreas attenuations were 105.1±25 HU in the AP of MDCT and 285±48.7 HU in the AP of angio-CT. There were significant differences in the tumour-to-pancreas contrast in the AP between MDCT and angio-CT (p < 0.05). The Az values were 0.93 and 0.84 for the AP of angio-CT and MDCT, 0.62 and 0.54 for the PVP. The AP of angio-CT was significantly more accurate for insulinoma detection (p < 0.05). CONCLUSION: Angio-CT produces higher tumour conspicuity and is superior in the detection and location of insulinomas compared to MDCT.

[Influence of fasting duration on blood volume status of pediatric patients evaluated by ultrasonic technique].

Objective: To evaluate the influence of preoperative fasting duration on blood volume status of pediatric patients during induction based on ultrasonic technique. Methods: One hundred and ten pediatric patients, scheduled for elective operation in the Second Affiliated Hospital & Yuying Children's Hospital, were recruited during January and October in 2018. After sedation by inhalation of sevoflurane, the maximum (expiratory) and minimum (inspiratory) diameter of inferior vena cava (IVC(max), IVC(min)) and aorta velocity-time integral (VTI) in apical five-chamber cardiac view were measured with an ultrasound machine. Respiratory variabilities of these parameters were further calculated. Furthermore, passive leg raising (PLR) test was performed and above measurements/calculations were repeated. The correlation between the duration of fasting and IVC respiratory variations index (IVC(RVI)) or aortic VTI variability (ΔVTI) was then analyzed. Results: Before PLR, IVC(max), IVC(min) and IVC(RVI) were (0.78±0.19), (0.43±0.15) cm and 0.45±0.12, respectively. After PLR, IVC(max) and IVC(min) increased to (0.94±0.20), (0.55±0.18) cm, while IVC(RVI) decreased to 0.42±0.13, the differences were statistically significant (t=15.66, 10.85, 3.14, all P<0.05). However, IVC(max), IVC(min) and IVC(RVI) were not significantly correlated with the duration of fasting analyzed by linear regression (before PLR: r=0.052, 0.163, 0.171; after PLR, r=0.062, 0.169, 0.165, all P>0.05). Before PLR, expiratory aortic VTI (VTI(max)), inspiratory aortic VTI (VTI(min)) and ΔVTI were 21±5, 17±4 and 17±8, respectively. After PLR, the VTI(max) and VTI(min) significantly increased to 23±5 and 19±4 (t=13.60, 10.43, all P<0.05), but ΔVTI was not changed significantly, which was 17±8(t=0.34, P>0.05). Linear regression analysis showed that VTI(max), VTI(min) and ΔVTI were not significantly correlated with the duration of fasting (before PLR: r=0.111, 0.100, 0.047; after PLR: r=0.003, 0.033, 0.073, all P>0.05). Further multiple linear regression analysis indicated that, age and body weight were independent factors influencing IVC(RVI) and ΔVTI before and after PLR (IVC(RVI): ß=-0.441, 0.515, -0.451, 0.507; ΔVTI: ß=-0.442, 0.545, -2.422, 2.850; all P<0.05). However, the duration of fasting was not correlated with IVC(RVI) and ΔVTI after adjusting the age and weight (IVC(RVI): ß=0.177, 0.160; ΔVTI: ß=0.037, 0.054; all P>0.05). Conclusion: Age and weight, but not preoperative fasting duration, are correlated with respiratory variabilities of inferior vena cava diameter and aortic VTI in pediatric patients.

[Value of lenvatinib for the treatment of advanced hepatocellular carcinoma].

Objective: To observe the safety and efficacy of lenvatinib for the treatment of medium-advanced hepatocellular carcinoma. Methods: A total of 36 patients with medium-advanced hepatocellular carcinoma from the First Medical Center of the Chinese PLA General Hospital were retrospectively analyzed from January 2018 to May 2019. All patients had shown tumor progression after at least 2 sessions of TACE. The patients were consisted of 30 males and 6 females with age range of 35 to 76 (54±10) years. Patients received orally administered lenvatinib at a dose of 12 mg once daily for patients ≥ 60 kg and 8 mg once daily for patients<60 kg. According to modified RECIST criteria the tumor response, disease control rate, overall survival and progression free survival were evaluated once every 6-8 weeks. The adverse events were recorded. Results: No patient was in complete response, 2 cases (5.7%) in partial response, and 5 cases (14.3%) in stable disease, respectively. Disease control rate was 20.0% (7/35), the overall survival was 11.5 months, and the progression free survival was 5.3 months. The overall incidence of adverse events was 66.7% (24/36). The most frequent adverse events were hypertension, proteinuria, hand-foot skin reaction and abdominal distension. Conclusion: Lenvatinib can extend the overall survival in a percentage of medium-advanced hepatocellular carcinoma patients who were unresectable and refractory to TACE. Although the incidence of adverse events is high, most of them are mild and reversible.

Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects.

Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC). CUS also enhanced GluN2B-mediated NMDA currents and extrasynaptic responses that were induced by bursts of high-frequency stimulation, which may be associated with the loss of astrocytes and low expression of glutamate transporter-1 (GLT-1). The blockade of GLT-1 in the mPFC was sufficient to induce depressive-like behavior and cause similar molecular changes. Selective GluN2B antagonist, DAPK1 knockdown by adeno-associated virus-mediated short-hairpin RNA or a pharmacological inhibitor, and the uncoupling of DAPK1 from the NMDAR GluN2B subunit produced rapid antidepressant-like effects and reversed CUS-induced alterations in the mPFC. The inhibition of DAPK1 and its interaction with GluN2B subunit in the mPFC also rescued CUS-induced depressive-like behavior 7 days after treatment. A selective GluN2B antagonist did not have rewarding effects in the conditioned place preference paradigm. Altogether, our findings suggest that the DAPK1 interaction with the NMDAR GluN2B subunit acts as a critical component in the pathophysiology of depression and is a potential target for new antidepressant treatments.

Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.

Neuronal atrophy and alterations of synaptic structure and function in the medial prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression, but the underlying molecular mechanisms are largely unknown. The protein kinase Mζ (PKMζ), a brain-specific atypical protein kinase C isoform, is important for maintaining long-term potentiation and storing memory. In the present study, we explored the role of PKMζ in mPFC in two rat models of depression, chronic unpredictable stress (CUS) and learned helplessness. The involvement of PKMζ in the antidepressant effects of conventional antidepressants and ketamine were also investigated. We found that chronic stress decreased the expression of PKMζ in the mPFC and hippocampus but not in the orbitofrontal cortex. Overexpression of PKMζ in mPFC prevented the depressive-like and anxiety-like behaviors induced by CUS, and reversed helplessness behaviors. Inhibition of PKMζ in mPFC by expressing a PKMζ dominant-negative mutant induced depressive-like behaviors after subthreshold unpredictable stress and increased learned helplessness behavior. Furthermore, stress-induced deficits in synaptic proteins and decreases in dendritic density and the frequency of miniature excitatory postsynaptic currents in the mPFC were prevented by PKMζ overexpression and potentiated by PKMζ inhibition in subthreshold stress rats. The antidepressants fluoxetine, desipramine and ketamine increased PKMζ expression in mPFC and PKMζ mediated the antidepressant effects of ketamine. These findings identify PKMζ in mPFC as a critical mediator of depressive-like behavior and antidepressant response, providing a potential therapeutic target in developing novel antidepressants.

Transarterial embolisation with bleomycin and N-butyl-2-cyanoacrylate -Lipiodol mixture for symptomatic polycystic liver disease: preliminary experience.

AIMS: To evaluate the therapeutic effect and safety of transarterial embolisation using a bleomycin-Lipiodol mixture and N-butyl-2-cyanoacrylate (NBCA)-Lipiodol mixture (BNL) for the treatment of polycystic liver disease (PLD). MATERIALS AND METHODS: From June 2012 to July 2018, a total of consecutive 14 symptomatic patients (13 women and 1 man; mean age, 49.3±9.9 years) with PLD were referred and underwent transcatheter arterial embolisation (TAE) with BNL. RESULTS: Technical success was achieved in all cases. PLD-related severe symptoms were improved remarkably in 13 of the treated patients. The mean maximum abdominal circumference decreased significantly from 100.6±9.4 to 94.9±9.1 cm (p<0.01). The total liver volume decreased significantly compared with pre-TAE in 13 patients at 6-12 months after TAE. It decreased from 9,776±2,219 to 8,303±2,009 cm3 (p<0.01). There were no major complications associated with the procedure. CONCLUSION: TAE with the bleomycin-Lipiodol mixture and NBCA-Lipiodol mixture may be an effective method for treating symptomatic PLD patients, with improvement of symptoms and shrinkage of cyst volume.

[Ultrasound screening and follow-up study of congenital anomalies of the kidney and urinary tract in neonates].

OBJECTIVE: To investigate the incidence of congenital anomalies of the kidney and urinary tract (CAKUT) in neonates, and to evaluate the value of urinary ultrasound screening in the early postnatal period. METHODS: The neonates born or treated in Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University between January 2016 and December 2018 accepted the urinary ultrasound screening, and the neonates with problem were followed up. In the meanwhile, the maternal pregnancy data were analyzed to screen out the risk factors associated with the onset of CAKUT. RESULTS: (1)A total of 2 655 neonates were screened by ultrasonography, of whom 82 neonates had been diagnosed with CAKUT (male: 60 cases, female: 22 cases), the positive rate was 3.1% (82/2 655). There were 66 cases of hydronephrosis, 6 cases of duplicate kidney, 2 cases of multiple renal cysts, 2 cases of renal cystic dysplasia, 1 case of medullary sponge kidney, 3 cases of small kidney, 1 case of isolated kidney, and 1 case of horseshoe kidney. (2)Of the 66 children with hydronephrosis, 4 cases were lost to the follow-up; 8 cases were followed for less than six months with no significant changes found, and still in the follow-up observation; 54 cases were followed up for 1 year, among which 32 cases were returned to normal within 1 year, 3 cases were alleviated, 7 cases were aggravated, and 12 cases were unchanged. One case underwent surgery for repeated urinary tract infections and decreased renal function. (3) Abnormal fetal urinary ultrasound in the late pregnancy was found to be the most common in the high risk factors of CAKUT. There were 44 high-risk newborns with abnormal fetal urinary ultrasound, and 35 cases of CAKUT were diagnosed after birth. The incidence rate was 79.5%(35/44). (4)Among the 2 655 newborns screened, 2 611 newborns had normal antenatal urinary ultrasonography. Among these neonates with normal urinary ultrasound during pregnancy,47 cases of CAKUT were diagnosed after birth, with an incidence of 1.8% (47/2 611). CONCLUSION: The most common CAKUT in neonates is hydronephrosis and most cases with hydronephrosis had a good prognosis, but they should be followed up regularly. Urinary ultrasound screening for neonates, especially those high-risk neonates with abnormal fetal urinary ultrasound, has important clinical implications for the early detection of CAKUT.

Apical stress distribution under vertical compaction of gutta-percha and occlusal loads in canals with varying apical sizes: a three-dimensional finite element analysis.

AIM: To investigate and compare the effects of two apical canal instrumentation protocols on apical stress distribution at the root apex under vertical compaction of gutta-percha and occlusal loads using finite element analysis. METHODOLOGY: Three finite element analysis models of a mandibular first premolar were reconstructed: an original canal model, a size 35, .04 taper apical canal enlargement model and a Lightspeed size 60 apical canal enlargement model. A 15 N compaction force was applied vertically to the gutta-percha 5 mm from the apex. A 175 N occlusal load in two directions (vertical and 45° to the longitudinal axis of the tooth) was simulated. Stresses in the apical 2 mm of the root were calculated and compared among the three models. RESULTS: Under vertical compaction, stresses in the apical canal instrumented by Lightspeed size 60 (maximal 3.3 MPa) were higher than that of the size 35, .04 taper model (maximal 1.3 MPa). In the case of the two occlusal forces, the Lightspeed size 60 apical enlargement was associated with the greatest stress distribution in the apical region. The greatest stress and the most obvious stress difference between the models appeared at the tip of the root when occlusal and vertical compaction loads were applied. CONCLUSIONS: Apical enlargement caused stress distribution changes in the apical region of roots. The larger apical size led to higher stress concentration at the root apex.