Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients.

BACKGROUND: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. METHODS: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. RESULTS: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. CONCLUSION: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

CaMKII and CaV3.2 T-type calcium channel mediate Connexin-43-dependent inflammation by activating astrocytes in vincristine-induced neuropathic pain.

Vincristine (VCR), an alkaloid isolated from vinca, is a commonly used chemotherapeutic drug. However, VCR therapy can lead to dose-dependent peripheral neurotoxicity, mainly manifesting as neuropathic pain, which is one of the dominant reasons for limiting its utility. Experimentally, we discovered that VCR-induced neuropathic pain (VINP) was accompanied by astrocyte activation; the upregulation of phospho-CaMKII (p-CaMKII), CaV3.2, and Connexin-43 (Cx43) expression; and the production and release of inflammatory cytokines and chemokines in the spinal cord. Similar situations were also observed in astrocyte cultures. Interestingly, these alterations were all reversed by intrathecal injection of KN-93 (a CaMKII inhibitor) or L-Ascorbic acid (a CaV3.2 inhibitor). In addition, KN-93 and L-Ascorbic acid inhibited the increase in [Ca2+]i associated with astrocyte activation. We also verified that knocking down or inhibiting Cx43 level via intrathecal injection of Cx43 siRNA or Gap27 (a Cx43 mimetic peptide) relieved pain hypersensitivity and reduced the release of inflammatory factors; however, they did not affect astrocyte activation or p-CaMKII and CaV3.2 expression. Besides, the overexpression of Cx43 through the transfection of the Cx43 plasmid did not affect p-CaMKII and CaV3.2 expressions in vitro. Therefore, CaMKII and CaV3.2 may activate astrocytes by increasing [Ca2+]i, thereby mediating Cx43-dependent inflammation in VINP. Moreover, we demonstrated that the CaMKII signalling pathway was involved in VCR-induced inflammation, apoptosis, and mitochondrial damage. Collectively, our findings show a novel mechanism by which CaMKII and CaV3.2 mediate Cx43-dependent inflammation by activating astrocytes in neuropathic pain induced by VCR.

Oncogenic role of microRNA-19b-3p-mediated SOCS3 in glioma through activation of JAK-STAT pathway.

The altered expression of microRNA (miRNA) has been implicated in glioma. Here, the current study aimed to clarify the oncogenic effects of miR-19b-3p on cellular processes of glioma and to elucidate the underlying mechanism associated with SOCS3 and the JAK-STAT signaling pathway. Differentially expressed genes related to glioma were initially identified via microarray analysis. Twenty-five glioma patients were selected for clinical data collection, while additional 12 patients with traumatic brain injuries were selected as controls. Cell senescence was assessed by ß-galactosidase staining, proliferation by MTT assay and apoptosis by flow cytometry following gain- and/or loss-of-function of miR-19b-3p or SOCS3. Glioma xenograft mouse model was developed through subcutaneous injection to nude mice to provide evidence in vivo. The glioma patients exhibited overexpressed miR-19b-3p and poorly-expressed SOCS3. SOCS3 was identified as a target gene of miR-19b-3p through dual-luciferase reporter gene assay. miR-19b-3p repressed SOCS3 expression and activated the JAK-STAT signaling pathway. Furthermore, miR-19b-3p inhibition promoted apoptosis and senescence, and suppressed cell proliferation through inactivation of the JAK-STAT signaling pathway and up-regulation of SOCS3. The reported regulatory axis was validated in nude mice as evidenced by suppressed tumor growth. Taken together, this study demonstrates that miR-19b-3p facilitates glioma progression via activation of the JAK-STAT signaling pathway by targeting SOCS3, highlighting a novel therapeutic target for glioma treatment.

3D shape measurement in the presence of strong interreflections by using single-pixel imaging in a camera-projector system.

Optical 3D shape measurements, such as fringe projection profilometry (FPP), are popular methods for recovering the surfaces of an object. However, traditional FPP cannot be applied to measure regions that contain strong interreflections, resulting in failure in 3D shape measurement. In this study, a method based on single-pixel imaging (SI) is proposed to measure 3D shapes in the presence of interreflections. SI is utilized to separate direct illumination from indirect illumination. Then, the corresponding points between the pixels of a camera and a projector can be obtained through the direct illumination. The 3D shapes of regions with strong interreflections can be reconstructed with the obtained corresponding points based on triangulation. Experimental results demonstrate that the proposed method can be used to separate direct and indirect illumination and measure 3D objects with interreflections.

[Correlation between serum level of miRNA-106a expression with clinicopathological characteristics and prognosis of patients with renal cell carcinoma].

OBJECTIVE: To analyze the expression of microRNA-106a(miR-106a) in renal cell carcinoma (RCC) and its correlation with clinicopathological characteristics and prognosis of patients. METHODS: Serum samples of 64 patients with newly diagnosed RCC were collected as the study group, and serum samples of 40 healthy individuals were used as the control group. Real-time fluorescence quantitative PCR was used to determine the expression level of miR-106a in each group. The correlation between miR-106a expression and clinicopathological characteristics of the patients was studied with single factor analysis and multiple Logistic regression model. Kaplan-Meier survival curve was used to analyze its correlation with the prognosis of patients. RESULTS: Before surgery, compared with the control group (1.17± 0.58), RCC patients with high- (9.15± 0.96) and low-expression(3.45± 0.37) had increased expression of miR-106a. Postoperatively, the expression level of miR-106a in both groups of patients decreased to 1.53± 0.18 and 1.75± 0.21, respectively. The area under the curve (AUC) of the diagnostic value of serum miR-106a for RCC was 0.782 (95% CI: 0.661-0.902). With an optimal cutoff value of 0.531, the sensitivity was 78.10% and the specificity was 75.00%. Serum miR-106a level of RCC patients with TNM stage T3 or T4, clinical stage II or III, lymph node metastasis, and recurrence were significantly increased. The high expression of serum miR-106a in RCC patients has an independent relationship with the tumor TNM stage and lymph node metastasis. Of the 64 follow-up patients, 4 were lost and 30 had died. Among them, the median survival time of patients in the miR-106a high expression group was 30 months, which was significantly shorter than that of the low expression group (52 months). CONCLUSION: The serum level of miR-106a is elevated in RCC patients, and may be used as a molecular marker for the diagnosis of RCC. High serum expression of miR-106a is an independent predictor for tumor TNM stage and lymph node metastasis, as well as an independent predictor for poor prognosis of RCC patients.

Creating the Chinese version of the transgender attitudes and beliefs scale.

BACKGROUND: Trans persons' physical and mental health is easily affected by the attitude of those around them. However, China currently lacks a valid psychometric instrument to investigate people's attitudes toward trans persons. Therefore, this study modifies the English version of the Transgender Attitudes and Beliefs Scale (TABS) to suit the Chinese context. It subsequently examines the reliability and validity of the Chinese version of the TABS. METHODS: This study recruited 1164 university students, aged 18-25 years, from 7 regions of China. SPSS26.0 and AMOS24.0 were used for data statistical analysis. Critical ratio method and correlation coefficient method were used for item analysis. Exploratory factor analysis and confirmatory factor analysis were used to test the structural validity of the Chinese version of Transgender Beliefs and Attitudes Scale, and the internal consistency reliability of the scale was tested. RESULTS: The TABS-C contains 26 items with 3 factors. The Cronbach's alpha was 0.957 for the total scale and 0.945, 0.888, and 0.885 for the 3 factors. The half-point reliability of the scale was 0.936, and the retest reliability was 0.877. The Pearson correlation coefficients for the 3 factors and the total scale score ranged from 0.768 to 0.946. CONCLUSION: The TABS-C has reliable psychometric properties and is suitable for usage among college students in the Chinese context.

Assessment of psychological personality traits in transgender groups using the Minnesota multiphasic personality inventory.

Objective: To explore the psychological personality characteristics of transgender groups and to determine whether these characteristics differ according to sociodemographic factors. Methods: This cross-sectional study was conducted between January 2021 and April 2023 at a psychosexual outpatient clinic in a psychiatric hospital in Beijing, China. In total, 481 individuals were included in this study, and demographic information was collected using a self-administered general questionnaire. Psychological personality traits were assessed using the Minnesota Multiphasic Personality Inventory (MMPI). Results: The mean scores of the assigned male at birth (AMAB) group were significantly higher than those of the male controls for all 10 clinical factors of the MMPI (p < 0.01 or p < 0.001). The scores for both the Masculinity-femininity (Mf) and Depression (D) factors in the AMABs group exceeded the clinical threshold (T > 60) and were the highest and second-highest scores on the entire scale, respectively. Individuals assigned female at birth (AFAB) had significantly higher scores than female controls for Hysteria (Hy), Psychopathic Deviate (Pd), and Hypomania (Ma) (p < 0.05, p < 0.01, and p < 0.001, respectively). There were significant differences in the rates of abnormal values for the various factors of the MMPI (T > 60) according to gender, age, and education (p < 0.05, p < 0.01, and p < 0.001, respectively). Compared to AFABs, AMABs had higher rates of abnormal scores (T > 60) on the Hypochondriasis (Hs), D, Hy, Mf, Paranoia (Pa), Psychasthenia (Pt), Schizophrenia (Sc), and Social Introversion (Si) scales (p < 0.05, p < 0.01, and p < 0.001, respectively). Second, the transgender group aged ≤25 years had higher rates of abnormal scores (T > 60) on the Hs, D, Hy, Pd, Pa, Pt, Sc, and Ma scales (p < 0.05, p < 0.01, and p < 0.001, respectively). Finally, outliers (T > 60) for the Hs, D, Hy, Pd, Pa, Pt, Ma, and Si factors were more prevalent among those with a primary to high school level of education (p < 0.05, p < 0.01, and p < 0.001, respectively). Conclusion: Assigned male at births may have a variety of psychological vulnerabilities, and there is a need to focus especially on those with a primary to high school level of education, those aged ≤25 years, and transgender females.

Upper thoracic spine puncture and caudal advance of an epidural catheter for adequate analgesia in a patient with breast cancer with chest and upper back pain: A case report.

Patients with advanced cancer and metastasis frequently require analgesic treatments to relieve pain and maintain an acceptable quality of life. Continuous analgesic treatment with epidural drug infusion is one interventional approach to provide adequate pain relief. Most epidural analgesia procedures are performed with the catheter inserted in the lower thoracic or lumbar spine areas, which is then advanced in a cephalad direction to reach the level that requires analgesia. The present study reported on a patient with chest and upper back pain who failed oral oxycodone treatment. Epidural analgesia to target the T5 level was planned. However, a lower spinal puncture with cephalad advance of the catheter was not possible due to metastasis and compression in the T5-8 levels. Thoracic spine puncture was performed between the T1 and T2 vertebrae and the infusion catheter was advanced in a caudal direction to reach the T5 level. Successful pain relief and amelioration of clinical symptoms demonstrated that the method may be considered a feasible and safe approach to achieve adequate analgesia and improve the quality of life of patients with similar conditions.

Repetitive transcranial magnetic stimulation combined with cognitive training for cognitive function and activities of daily living in patients with post-stroke cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Despite the potential effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for post-stroke cognitive impairment (PSCI), there is uncertainty regarding rTMS combined with cognitive training for PSCI. OBJECTIVE: To determine the effectiveness of rTMS combined with cognitive training for improving global cognitive function, specific domains of cognitive function and activities of daily living (ADL) in patients with PSCI. METHODS: Databases including Cochrane Central, EMBASE (Ovid SP), CHINAL, APA PsycINFO, EBSCO, Medline, Web of science and other sources were systematically searched on March 23, 2022, and updated on December 5, 2022. All randomized controlled trials (RCTs) applied rTMS + cognitive training for patients with PSCI were screened for inclusion. RESULTS: A total of 8 trials was finally included and 336 participants provided data for meta-analyses. Large effects were found for rTMS + cognitive training on global cognition (g = 0.780, 95 % CI = 0.477-1.083), executive function (g = 0.769, 95 % CI = 0.291-1.247), working memory (g = 0.609, 95 % CI = 0.158-1.061) and medium improvement on ADL (g = 0.418, 95 % CI = 0.058-0.778) were seen. While, no effects were found on memory or attention. Subgroup analyses showed that combinations of phase of stroke onset, rTMS frequency, stimulation site and stimulation sessions were potent factors that modulate the effects of rTMS + cognitive training for cognitive function. CONCLUSIONS: The pooled data showed more positive effects of rTMS + cognitive training for global cognition, executive function, working memory and ADL in patients with PSCI. While, robust evidence of rTMS + cognitive training for global cognition, executive function, working memory and ADL from the Grade recommendations is lacking. Further, rTMS + cognitive training did not show no better effects on memory. Future definitive trials are needed to determine the benefits of rTMS + cognitive training for cognitive function and ADL in the field of PSCI.

The mitochondria in schizophrenia with 22q11.2 deletion syndrome: From pathogenesis to therapeutic promise of targeted natural drugs.

Schizophrenia is a complex multi-factor neurological disorder that caused an array of severe indelible consequences to the individuals and society. Additionally, anti-schizophrenic drugs are unsuitable for treating negative symptoms and have more significant side effects and drug resistance. For better treatment and prevention, we consider exploring the pathogenesis of schizophrenia from other perspectives. A growing body of evidence of 22q11.2 deletion syndrome (22q11DS) suggested that the occurrence and progression of schizophrenia are related to mitochondrial dysfunction. So combing through the literature of 22q11DS published from 2000 to 2023, this paper reviews the mechanism of schizophrenia based on mitochondrial dysfunction, and it focuses on the natural drugs targeting mitochondria to enhance mitochondrial function, which are potential to improve the current treatment of schizophrenia.

Machine learning algorithms assisted identification of post-stroke depression associated biological features.

Objectives: Post-stroke depression (PSD) is a common and serious psychiatric complication which hinders functional recovery and social participation of stroke patients. Stroke is characterized by dynamic changes in metabolism and hemodynamics, however, there is still a lack of metabolism-associated effective and reliable diagnostic markers and therapeutic targets for PSD. Our study was dedicated to the discovery of metabolism related diagnostic and therapeutic biomarkers for PSD. Methods: Expression profiles of GSE140275, GSE122709, and GSE180470 were obtained from GEO database. Differentially expressed genes (DEGs) were detected in GSE140275 and GSE122709. Functional enrichment analysis was performed for DEGs in GSE140275. Weighted gene co-expression network analysis (WGCNA) was constructed in GSE122709 to identify key module genes. Moreover, correlation analysis was performed to obtain metabolism related genes. Interaction analysis of key module genes, metabolism related genes, and DEGs in GSE122709 was performed to obtain candidate hub genes. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and random forest, were used to identify signature genes. Expression of signature genes was validated in GSE140275, GSE122709, and GSE180470. Gene set enrichment analysis (GSEA) was applied on signature genes. Based on signature genes, a nomogram model was constructed in our PSD cohort (27 PSD patients vs. 54 controls). ROC curves were performed for the estimation of its diagnostic value. Finally, correlation analysis between expression of signature genes and several clinical traits was performed. Results: Functional enrichment analysis indicated that DEGs in GSE140275 enriched in metabolism pathway. A total of 8,188 metabolism associated genes were identified by correlation analysis. WGCNA analysis was constructed to obtain 3,471 key module genes. A total of 557 candidate hub genes were identified by interaction analysis. Furthermore, two signature genes (SDHD and FERMT3) were selected using LASSO and random forest analysis. GSEA analysis found that two signature genes had major roles in depression. Subsequently, PSD cohort was collected for constructing a PSD diagnosis. Nomogram model showed good reliability and validity. AUC values of receiver operating characteristic (ROC) curve of SDHD and FERMT3 were 0.896 and 0.964. ROC curves showed that two signature genes played a significant role in diagnosis of PSD. Correlation analysis found that SDHD (r = 0.653, P < 0.001) and FERM3 (r = 0.728, P < 0.001) were positively related to the Hamilton Depression Rating Scale 17-item (HAMD) score. Conclusion: A total of 557 metabolism associated candidate hub genes were obtained by interaction with DEGs in GSE122709, key modules genes, and metabolism related genes. Based on machine learning algorithms, two signature genes (SDHD and FERMT3) were identified, they were proved to be valuable therapeutic and diagnostic biomarkers for PSD. Early diagnosis and prevention of PSD were made possible by our findings.

Cortical thickness of the inferior parietal lobule as a potential predictor of relapse in men with alcohol dependence.

Alcohol dependence is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with alcohol dependence. This study enrolled 58 male patients with alcohol dependence who had undergone acute detoxification. General demographic information and clinical features were collected. Magnetic resonance imaging data were used to measure cortical thickness across 34 regions of the brain. Patients were followed up at six months, and 51 patients completed the follow-up visit. These patients were divided into a relapser and an abstainer group. A binary logistic regression analysis was performed to investigate the potential risk factors of relapse. Compared to abstainers, relapsers showed higher inattention and non-planning impulsivity on the 11th version of the Barratt Impulsive Scale. The cortical thicknesses of the inferior-parietal lobules were significantly higher in abstainers compared with those in relapsers. Furthermore, binary logistic regression analysis showed that the thickness of the inferior parietal lobule predicted relapse, and lower non-planning impulse was a protective factor against relapse. Relapsers show poorer impulse control than abstainers, and structural magnetic resonance imaging revealed a decreased thickness of the inferior parietal lobule in relapsers. Our results indicate the thickness of the inferior parietal lobule as a potential relapse predictor in male patients with alcohol dependence.

Cortical thickness of the inferior parietal lobule as a potential predictor of relapse in men with alcohol dependence.

Background: Alcohol dependence (AD) is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with AD. Methods: This study enrolled 58 male patients with AD who had undergone acute detoxification. General demographic information and clinical features were collected. Magnetic resonance imaging (MRI) data were used to measure cortical thickness across 34 regions of the brain. Patients were followed up at 6 months, and 51 patients completed the follow-up visit. These patients were divided into a relapser and an abstainer group. A binary logistic regression analysis was performed to investigate the potential risk factors of relapse. Results: Compared to abstainers, relapsers showed higher inattention and non-planning impulsivity on the 11th version of the Barratt Impulsive Scale. The cortical thicknesses of the inferior-parietal lobule were significantly greater in abstainers compared with those in relapsers. Furthermore, binary logistic regression analysis showed that the thickness of the inferior parietal lobule predicted relapse. Conclusions: Relapsers show poorer impulse control than abstainers, and MRI imaging shows a decreased thickness of the inferior parietal lobule in relapsers. Our results indicate the thickness of the inferior parietal lobule as a potential relapse predictor in male patients with AD.

Severe Vincristine-Induced Neuropathic Pain: A Case Report with Pharmacogenetic Analysis and Literature Review.

Vincristine-induced peripheral neuropathy (VIPN) is a common adverse effect of vincristine (VCR) for which there is no preventative or curative treatment. Here, we report a case of a patient suffering from severe VCR-related neurotoxicity. To explore the possible causes of severe VIPN in this patient, a set of genes involved in VCR metabolism, transport or are related to the cytoskeleton, microtubules, and inherited neurological diseases gene polymorphisms were examined via pharmacogenetic analyses. The genotyping results revealed the presence of a complex pattern of polymorphisms in CYP3A5, ABCC2, SYNE2, BAHD1, NPSR1, MTNR1B, CEP72, miR-4481 and miR-3117. A comprehensive understanding of all the pharmacogenetic risk factors for VIPN may explain the occurrence of severe neurotoxicity in our patient. This case brings to light the potential importance of pharmacogenetic testing in clinical practice. It also exemplifies the importance of developing early-detection strategies to optimize treatment regimens through prior risk stratification while reducing adverse drug reactions and personalizing therapy.

Associations of the serum kynurenine pathway metabolites with P50 auditory gating in non-smoking patients with first-episode schizophrenia.

Objective: Our study aimed to investigate the associations between the serum level of kynurenine pathway (KP) metabolites and P50 auditory gating in non-smoking patients with first-episode schizophrenia (FES). Materials and methods: In this study, 82 non-smoking patients with FES and 73 healthy controls (HC). P50 auditory gating was measured using a fully functional digital 64-channel EEG system, and the components included S1 amplitude, S2 amplitude, gating ratio (S2/S1), and amplitude difference (S1-S2). Serum levels of kynurenine and kynurenine acid were assessed using a combination of liquid chromatography with tandem mass spectrometry. Psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Results: The serum kynurenine (251.46 ± 65.93 ng/ml vs. 320.65 ± 65.89 ng/ml, t = -6.38, p < 0.001), and kynurenine acid levels (5.19 ± 2.22 ng/ml vs. 13.26 ± 4.23 ng/ml, t = -14.73, p < 0.001), S1 amplitude [2.88 (1.79, 3.78) µV vs. 3.08 (2.46, 4.56) µV, Z = -2.17, p = 0.030] and S1-S2 [1.60 (0.63, 2.49) µV vs. 1.92 (1.12, 2.93) µV, Z = -2.23, p = 0.026] in patients with FES were significantly lower than those in HC. The serum kynurenine and kynurenine acid levels were negatively associated with S1-S2 (r = -0.32, p = 0.004 and r = -0.42, p < 0.001; respectively) and positively correlated with S2/S1 ratio (r = 0.34, p = 0.002 and r = 0.35, p = 0.002; respectively) in patients. Conclusion: Our findings suggested that neuroactive metabolites of the KP might play an important role in sensory gating deficit in first episode patients with schizophrenia. Furthermore, metabolites of the KP may be a new target for the treatment of cognitive impairments in schizophrenia.

Vincristine-Induced Peripheral Neuropathy in Childhood Acute Lymphoblastic Leukemia: Genetic Variation as a Potential Risk Factor.

Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is the main factor restricting VCR's clinical application. VCR-induced peripheral neuropathy (VIPN) sometimes results in dose reduction or omission, leading to clinical complications or affecting the patient's quality of life. With regard to the genetic basis of drug responses, preemptive pharmacogenomic testing and simultaneous blood level monitoring could be helpful for the transformation of various findings into individualized therapies. In this review, we discussed the potential associations between genetic variants in genes contributing to the pharmacokinetics/pharmacodynamics of VCR and VIPN incidence and severity in patients with acute lymphoblastic leukemia. Of note, genetic variants in the CEP72 gene have great potential to be translated into clinical practice. Such a genetic biomarker may help clinicians diagnose VIPN earlier. Besides, genetic variants in other genes, such as CYP3A5, ABCB1, ABCC1, ABCC2, TTPA, ACTG1, CAPG, SYNE2, SLC5A7, COCH, and MRPL47, have been reported to be associated with the VIPN, but more evidence is needed to validate the findings in the future. In fact, a variety of complex factors jointly determine the VIPN. In implementing precision medicine, the combination of genetic, environmental, and personal variables, along with therapeutic drug monitoring, will allow for a better understanding of the mechanisms of VIPN, improving the effectiveness of VCR treatment, reducing adverse reactions, and improving patients' quality of life.

Retrospective Observation of Low-Dose Rituximab Treatment in Chinese Patients With Neuromyelitis Optica Spectrum Disorders in a Real-World Setting.

Objective: This study aimed to investigate the efficacy and safety of low-dose rituximab (RTX) in the treatment of neuromyelitis optica spectrum disorders (NMOSD) patients. Methods: NMOSD patients were treated with RTX at ~25% of the standard dose. The annualized relapse rate (ARR), expanded disability status scale (EDSS) score, visual function system scale (VFSS) and length of spinal cord lesions before and after treatment were statistically compared. The dynamic changes in the proportion of CD19+ B lymphocytes after treatment were monitored, and adverse reactions were recorded. Results: In total, 36 NMOSD patients who received a low-dose RTX treatment (375-mg/m2 induction dose and 500 mg every 6 months) were recruited. The mean follow-up time after the RTX treatment was 19.83 ± 7.74 months. After the treatment, the ARR decreased from 1.97 ± 1.93 to 0.12 ± 0.32, the EDSS score decreased from 3.43 ± 1.49 to 3.10 ± 1.88, and the spinal cord lesion length decreased from 5.54 ± 3.96 to 4.31 ± 3.73. These differences were all statistically significant. The subgroup analysis of the patients who had previously received non-steroidal immunosuppressants (NSISs) (n = 20) showed that after the RTX treatment, the ARR decreased from 0.66 ± 0.51 to 0.08 ± 0.26, the EDSS score decreased from 3.65 ± 1.22 to 3.40 ± 1.99, and the spinal cord lesion length decreased from 5.68 ± 3.73 to 4.21 ± 3.58. These differences were all statistically significant. The VFSS scores did not show a significant change. The Kaplan-Meier analysis showed that low-dose RTX significantly delayed recurrence, which was also observed in the subgroup analysis of patients who previously received NSISs. Five relapses in 5 cases were noted after the low-dose RTX administration, and the percentage of CD19+ B cells remained < 1% in 3 cases during relapse. During the RTX treatment and subsequent follow-up, 8 (22.2%) patients reported adverse reactions, all of which were minor. Conclusion: Low-dose RTX is an effective and safe treatment method for NMOSDs. This method is worth popularizing in developing countries or regions, especially in areas where RTX is not covered by medical insurance.

Cortical Thickness in Alcohol Dependent Patients With Apathy.

OBJECTIVES: Many studies reported structural brain changes in patients with alcohol dependence (PADs). However, no studies identified structural correlates of apathy that might aggravate alcohol misuse. Here, we explored regional differences in cortical thickness in PADs relative to healthy controls (HCs), and examined the potential correlation of regional thickness with the severity of apathy. METHODS: Magnetic resonance imaging data were collected from 33 male PADs and 35 male age- and education-matched HCs. We used the FreeSurfer software to investigate group differences in cortical thickness across 148 regions. Apathy was evaluated using the Lille Apathy Rating Scale-Informant (LARS-I). Regression analyses examined the relationship between cortical thickness of regions of interest and apathy score in PADs. RESULTS: Compared to HCs, PADs showed significant decreases in the cortical thickness of occipito-temporal cortex (OTC), including the left middle occipital gyrus and occipital pole, right superior occipital gyri, and bilateral lingual gyrus; bilateral superior parietal cortex (SPC), including the right intraparietal sulcus; and bilateral inferior parietal cortex (IPC). Furthermore, the cortical thickness of all of the three regions was negatively correlated with the apathy total scores. The cortical thickness of the IPC was also negatively correlated with the action initiation subscore of the LARS-I. CONCLUSIONS: The current results suggest the thickness of bilateral parietal and occipital temporal cortices as neural markers of apathy in PADs. These findings add to the literature by identifying the neural bases of a critical clinical feature of individuals with alcoholism.

Supplier Selection and Order Allocation under a Carbon Emission Trading Scheme: A Case Study from China.

In implementing carbon emission trading schemes (ETSs), the cost of carbon embedded in raw materials further complicates supplier selection and order allocation. Firms have to make decisions by comprehensively considering the cost and the important intangible performance of suppliers. This paper uses an analytic network process-integer programming (ANP-IP) model based on a multiple-criteria decision-making (MCDM) approach to solve the above issues by first evaluating and then optimizing them. The carbon embedded in components, which can be used to reflect the carbon competitiveness of a supplier, is integrated into the ANP-IP model. In addition, an international large-scale electronic equipment manufacturer in China is used to validate the model. Different scenarios involving different carbon prices are designed to analyze whether China's current ETS drives firms to choose more low-carbon suppliers. The results show that current carbon constraints are not stringent enough to drive firms to select low-carbon suppliers. A more stringent ETS with a higher carbon price could facilitate the creation of a low-carbon supply chain. The analysis of the firm's total cost and of the total cost composition indicates that the impact of a more stringent ETS on the firm results mainly from indirect costs instead of direct costs. The indirect cost is caused by the suppliers' transfer of part of the low-carbon investment in the product, and arises from buying carbon permits with high carbon prices. Implications revealed by the model analysis are discussed to provide guidance to suppliers regarding the balance between soft competitiveness and low-carbon production capability and to provide guidance to the firm on how to cooperate with suppliers to achieve a mutually beneficial situation.