Effects of media exposure on PTSD symptoms in college students during the COVID-19 outbreak.

Objective: We aimed to investigate the influence of media on college students' mental health during the COVID-19 pandemic. Methods: After the COVID-19 outbreak, we used cross-sectional surveys through online questionnaires to investigate the mental health of college students in lockdown at home. We identified the influencing factors of PTSD symptoms using the Chi-Square test and ordinal logistic regression analysis. Results: In 10,989 valid questionnaires, 9,906 college students with no PTSD symptoms, 947 college students with subclinical PTSD symptoms (1-3 items), and 136 college students with four or more PTSD symptoms were screened out. The results showed that media content impacted the mental health of college students in lockdown at home. Positive media content was negatively correlated with PTSD symptoms among college students. PTSD symptoms were not associated with sources of information. Moreover, College students with PTSD symptoms would reduce their willingness to learn and could not complete online learning efficiently. Conclusion: PTSD symptoms are related to media exposure and excessive information involvement of COVID-19 in college students, which influences the willingness to attend online classes.

[N2O Emission from the Processes of Wastewater Treatment: Mechanisms and Control Strategies].

As a direct carbon emission source, the amount of nitrous oxide (N2, which is actually caused by AOB denitrification. To control the N2O emission during biological N-removal, complete HND and NO2- accumulation for AOB denitrification should be avoided to a large extent. For this purpose, DO in aerobic tanks should be controlled at a normal level (approximately 2 mg·L-1), and solid retention time (SRT) should be extended, up to 20 d, which would avoid accumulating N2O for AOB denitrification. Additionally, external carbon should be supplemented in time to promote HDN approaching the end, N2. This review summarizes the mechanisms of all the mentioned N2O emission pathways and discusses the control strategies of N2O emission according to the associated mechanisms.

Cellular and Molecular Mechanisms Underly the Combined Treatment of Fasudil and Bone Marrow Derived-Neuronal Stem Cells in a Parkinson's Disease Mouse Model.

Bone marrow-derived neural stem cells (BM-NSCs) have shed light on novel therapeutic approaches for PD with the potential to halt or even reverse disease progression. Various strategies have been developed to promote therapeutic efficacy via optimizing implanted cells and the microenvironment of transplantation in the central nervous system (CNS). This current study further proved that the combination of fasudil, a Rho-kinase inhibitor, and BM-NSCs exhibited a synergetic effect on restoring neuron loss in the MPTP-PD mice model. It simultaneously unveiled cellular mechanisms underlying synergistic neuron-protection effects of fasudil and BM-NSCs, which included promoting the proliferation, and migration of endogenous NSCs, and contributing to microglia shift into the M2 phenotype. Corresponding molecular mechanisms were observed, including the inhibition of inflammatory responses, the elevation of neurotrophic factors, and the induction of WNT/ß-catenin and PI3K/Akt/mTOR signaling pathways. Our study provides evidence for the co-intervention of BM-NSCs and fasudil as a promising therapeutic method with enhanced efficacy in treating neurodegenerative diseases.

Uncovering the pharmacology of Ginkgo biloba folium in the cell-type-specific targets of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease with a fast-growing prevalence. Developing disease-modifying therapies for PD remains an enormous challenge. Current drug treatment will lose efficacy and bring about severe side effects as the disease progresses. Extracts from Ginkgo biloba folium (GBE) have been shown neuroprotective in PD models. However, the complex GBE extracts intertwingled with complicated PD targets hinder further drug development. In this study, we have pioneered using single-nuclei RNA sequencing data in network pharmacology analysis. Furthermore, high-throughput screening for potent drug-target interaction (DTI) was conducted with a deep learning algorithm, DeepPurpose. The strongest DTIs between ginkgolides and MAPK14 were further validated by molecular docking. This work should help advance the network pharmacology analysis procedure to tackle the limitation of conventional research. Meanwhile, these results should contribute to a better understanding of the complicated mechanisms of GBE in treating PD and lay the theoretical ground for future drug development in PD.

Corrigendum: Uncovering the pharmacology of Ginkgo biloba folium in the cell-type-specific targets of Parkinson's disease with a deep learning algorithm.

[This corrects the article DOI: 10.3389/fphar.2022.1007556.].

Disease progression in Parkinson's disease patients with subjective cognitive complaint.

OBJECTIVE: Little is known about the disease progression of Parkinson's disease patients with subjective cognitive complaint (PD-SCC). This longitudinal cohort study aims to compare the progression of clinical features and quality of life (QoL) in PD patients with normal cognition (NC), SCC, and mild cognitive impairment (MCI). METHODS: A total of 383 PD patients were enrolled, including 189 PD-NC patients, 59 PD-SCC patients, and 135 PD-MCI patients, with 1-7 years of follow-up. Linear mixed models were applied to evaluate longitudinal changes in motor symptoms, nonmotor features (cognitive impairment, depression, and excessive daytime sleepiness), and QoL in PD. RESULTS: At baseline, PD-SCC patients had lower Beck Depression Inventory (BDI) scores and Parkinson's Disease Questionnaire-39 (PDQ-39) scores than PD-NC patients (all p < 0.05). Longitudinal analyses revealed that the PD-SCC group exhibited faster progression in terms of BDI scores (p = 0.042) and PDQ-39 scores (p = 0.035) than the PD-NC group. The PD-MCI group exhibited faster progression rates in the Epworth Sleepiness Scale scores (p = 0.001) and PDQ-39 scores (p = 0.005) than the PD-NC group. In addition, the PD-SCC group exhibited a greater reduction in attention (Trail Making Test Part A, p = 0.047) and executive function (Stroop Color-Word Test, p = 0.037) than the PD-NC group. INTERPRETATION: PD-SCC patients exhibited faster deterioration of depression and QoL than PD-NC patients, and SCC may be an indicator of initial attention and executive function decline in PD. Our findings provided a more accurate prognosis in PD-SCC patients.

Discovery of styrylaniline derivatives as novel alpha-synuclein aggregates ligands.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Early diagnosis is the key to treatment but is still a great challenge in the clinic now. The discovery of alpha-synuclein (α-syn) aggregates ligands has become an attractive strategy to meet the early diagnosis of PD. Herein, we designed and synthesized a series of styrylaniline derivatives as novel α-syn aggregates ligands. Several compounds displayed good potency to α-syn aggregates with Kd values less than 0.1 µM. The docking study revealed that the hydrogen bonds and cation-pi interaction between ligands and α-syn aggregates would be crucial for the activity. The representative compound 7-16 not only detected α-syn aggregates in both SH-SY5Y cells and brain tissues prepared from two kinds of α-syn preformed-fibrils-injected mice models but also showed good blood-brain barrier penetration characteristics in vivo with a brain/plasma ratio over 1.0, which demonstrates its potential as a lead compound for further development of in vivo imaging agents.

Neuroprotection of Exendin-4 by Enhanced Autophagy in a Parkinsonian Rat Model of α-Synucleinopathy.

Glucagon-like peptide-1 (GLP-1) receptor stimulation ameliorates parkinsonian motor and non-motor deficits in both experimental animals and patients; however, the disease-modifying mechanisms of GLP-1 receptor activation have remained unknown. The present study investigated whether exendin-4 (a GLP-1 analogue) can rescue motor deficits and exert disease-modifying effects in a parkinsonian rat model of α-synucleinopathy. This model was established by unilaterally injecting AAV-9-A53T-α-synuclein into the right substantia nigra pars compacta, followed by 4 or 8 weeks of twice-daily intraperitoneal injections of exendin-4 (5 µg/kg/day) starting at 2 weeks after AAV-9-A53T-α-synuclein injections. Positron emission tomography/computed tomography (PET/CT) scanning and immunostaining established that treatment with exendin-4 attenuated tyrosine-hydroxylase-positive neuronal loss and terminal denervation and mitigated the decrease in expression of vesicular monoamine transporter 2 within the nigrostriatal dopaminergic systems of rats injected with AAV-9-A53T-α-synuclein. It also mitigated the parkinsonian motor deficits assessed in behavioral tests. Furthermore, through both in vivo and in vitro models of Parkinson's disease, we showed that exendin-4 promoted autophagy and mediated degradation of pathological α-synuclein, the effects of which were counteracted by 3-methyladenine or chloroquine, the autophagic inhibitors. Additionally, exendin-4 attenuated dysregulation of the PI3K/Akt/mTOR pathway in rats injected with AAV-9-A53T-α-synuclein. Taken together, our results demonstrate that exendin-4 treatment relieved behavioral deficits, dopaminergic degeneration, and pathological α-synuclein aggregation in a parkinsonian rat model of α-synucleinopathy and that these effects were mediated by enhanced autophagy via inhibiting the PI3K/Akt/mTOR pathway. In light of the safety and tolerance of exendin-4 administration, our results suggest that exendin-4 may represent a promising disease-modifying treatment for Parkinson's disease.

Effects of viral infection and microbial diversity on patients with sepsis: A retrospective study based on metagenomic next-generation sequencing.

BACKGROUND: The study aims to investigate the performance of a metagenomic next-generation sequencing (NGS)-based diagnostic technique for the identification of potential bacterial and viral infections and effects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients. METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February 1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for blood cultures and metagenomic NGS when the patients' body temperature was higher than 38 °C. Patients' demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded. The correlations between pathogen types and sepsis severity and survival rate were evaluated. RESULTS: NGS produced higher positive results (105 of 118; 88.98%) than blood cultures (18 of 118; 15.25%) over the whole study period. Concomitant viral infection correlated closely with sepsis severity and had the negative effect on the survival of patients with sepsis. However, correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis. CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and the survival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviral drugs combined with antibiotics may be beneficial to ICU sepsis patients.

Eomesodermin in CD4+T cells is essential for Ginkgolide K ameliorating disease progression in experimental autoimmune encephalomyelitis.

Eomesodermin (Eomes), a transcription factor, could suppress the Th17 cell differentiation and proliferation through directly binding to the promoter zone of the Rorc and Il17a gene, meanwhile the expression of Eomes is suppressed when c-Jun directly binds to its promoter zone. Ginkgolide K (1,10-dihydroxy-3,14-didehydroginkgolide, GK) is a diterpene lactone isolated from the leaves of Ginkgo biloba. A previous study indicated that GK could decrease the level of phospho JNK (c-Jun N-terminal kinase). Here, we reported the therapeutic potential of Ginkgolide K (GK) treatment to ameliorate experimental autoimmune encephalomyelitis (EAE) disease progression. Methods: EAE was induced in both wildtype and CD4-Eomes conditional knockout mice. GK was injected intraperitoneally. Disease severity, inflammation, and tissue damage were assessed by clinical evaluation, flow cytometry of mononuclear cells (MNCs), and histopathological evaluation. Dual-luciferase reporter assays were performed to measure Eomes transcription activity in vitro. The potency of GK (IC50) was determined using JNK1 Kinase Enzyme System. Results: We revealed that GK could ameliorate EAE disease progression by the inhibition of the Th17 cells. Further mechanism studies demonstrated that the level of phospho JNK was decreased and the level of Eomes in CD4+T cells was dramatically increased. This therapeutic effect of GK was almost completely interrupted in CD4-Eomes conditional knockout mice. Conclusions: These results provided the therapeutic potential of GK treatment in EAE, and further suggested that Eomes expression in CD4+T cells might be essential in this process.

Disease Progression in Patients with Parkin-Related Parkinson's Disease in a Longitudinal Cohort.

BACKGROUND: There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients. METHODS: Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition. RESULTS: At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027). CONCLUSION: Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society.

Propagated α-synucleinopathy recapitulates REM sleep behaviour disorder followed by parkinsonian phenotypes in mice.

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson's disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson's disease in this animal model.

Fasudil Promotes α-Synuclein Clearance in an AAV-Mediated α-Synuclein Rat Model of Parkinson's Disease by Autophagy Activation.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, but the disease-modifying therapies focusing on the core pathological changes are still unavailable. Rho-associated protein kinase (ROCK) has been suggested as a promising target for developing neuroprotective therapies in PD. OBJECTIVE: We aimed to explore the promotion of α-synuclein (α-syn) clearance in a rat model. METHODS: In a rat model induced by unilateral injection of adeno-associated virus of serotype 9 (AAV9) expressing A53T α-syn (AAV9-A53T-α-syn) into the right substantia nigra, we aimed to investigate whether Fasudil could promote α-syn clearance and thereby attenuate motor impairments and dopaminergic deficits. RESULTS: In our study, treatment with Fasudil (5 mg/kg rat weight/day) for 8 weeks significantly improved the motor deficits in the Cylinder and Rotarod tests. In the in vivo positron emission tomography imaging with the ligand 18F-dihydrotetrabenazine, Fasudil significantly enhanced the dopaminergic imaging in the injected striatum of the rat model (p < 0.05 vs. vehicle group, p < 0.01 vs. left striatum in Fasudil group). The following mechanistic study confirmed that Fasudil could promote the autophagic clearance of α-syn by Becline 1 and Akt/mTOR pathways. CONCLUSION: Our study suggested that Fasudil, the ROCK2 inhibitor, could attenuate the anatomical and behavioral lesions in the Parkinsonian rat model by autophagy activation. Our results identify Fasudil as a drug with high translational potential as disease-modifying treatment for PD and other synucleinopathies.

Design, synthesis and identification of N, N-dibenzylcinnamamide (DBC) derivatives as novel ligands for α-synuclein fibrils by SPR evaluation system.

PET imaging of α-synuclein (α-syn) deposition in the brain will be an effective tool for earlier diagnosis of Parkinson's disease (PD) due to α-syn aggregation is the widely accepted biomarker for PD. However, the necessary PET radiotracer for imaging is clinically unavailable until now. The lead compound discovery is the first key step for the study. Herein, we initially established an efficient biologically evaluation system well in highthroughput based on SPR technology, and identified a novel class of N, N-dibenzylcinnamamide (DBC) compounds as α-syn ligands through the assay. These compounds were proved to have high affinities against α-syn aggregates (KD < 10 nM), which well met the requirement of binding activity for the PET probe. These DBC compounds were firstly reported as α-syn ligands herein and the preliminary obtained structure has been further modified into F-labeled ones. Among them, a high-affinity tracer (5-41) with 1.03 nM (KD) has been acquired, indicating its potential as a new lead compound for developing PET radiotracer.

Structures of ß-glycosidase LXYL-P1-2 reveals the product binding state of GH3 family and a specific pocket for Taxol recognition.

LXYL-P1-2 is one of the few xylosidases that efficiently catalyze the reaction from 7-ß-xylosyl-10-deacetyltaxol (XDT) to 10-deacetyltaxol (DT), and is a potential enzyme used in Taxol industrial production. Here we report the crystal structure of LXYL-P1-2 and its XDT binding complex. These structures reveal an enzyme/product complex with the sugar conformation different from the enzyme/substrate complex reported previously in GH3 enzymes, even in the whole glycohydrolases family. In addition, the DT binding pocket is identified as the structural basis for the substrate specificity. Further structure analysis reveals common features in LXYL-P1-2 and Taxol binding protein tubulin, which might provide useful information for designing new Taxol carrier proteins for drug delivery.

Quality of Life in Newly Diagnosed Patients With Parkin-Related Parkinson's Disease.

Introduction: Mutations in the Parkin gene are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, little is known about the quality of life (QoL) in Parkin-related PD. Here, we investigated the patterns of QoL in newly diagnosed Parkin-related PD patients. Methods: Newly diagnosed PD patients (diagnosis made within 12 months) who had an age of onset (AOO) below 40 and underwent a PD-related genetic testing, were recruited (n = 148). Among them, 24 patients carried bi-allelic variants in Parkin (PD-Parkin) and 24 patients did not have any known causative PD mutations, or risk variants (GU-EOPD). The clinical materials, relevant factors and determinants of QoL were analyzed. Results: PD-Parkin patients had a younger AOO (p = 0.003) and longer disease duration (p = 0.005). After adjustment for AOO and disease duration, more dystonia (p = 0.034), and worse scores of non-motor symptoms including Beck depression inventory (BDI, p = 0.035), Epworth sleepiness scale (ESS, p = 0.044), and subdomains of depression/anxiety (p = 0.015) and sleep disorders (p = 0.005) in Non-motor symptoms questionnaire, were found in PD-Parkin comparing with GU-EOPD. PD-Parkin patients had poorer QoL (adjusted p = 0.045), especially in the mobility (adjusted p = 0.025), emotional well-being (adjusted p = 0.015) and bodily discomfort dimensions (adjusted p = 0.016). BDI scores (p = 0.005) and ESS scores (p = 0.047) were significant determinants of QoL in PD-Parkin. Conclusion: Newly diagnosed PD-Parkin patients showed worse QoL. More depression and excessive daytime sleepiness predicted worse QoL. For clinicians, management of depression and excessive daytime sleepiness is suggested to better improve QoL in patients with Parkin mutations.

Ginkgolide K supports remyelination via induction of astrocytic IGF/PI3K/Nrf2 axis.

Although several therapies are approved, none promote re-myelination in multiple sclerosis (MS) patients, limiting their ability for sustained recovery. Thus, treatment development in MS has the opportunity to tackle the challenges, including experimental therapies targeting neuroprotection and re-myelination. Here, we provide a novel therapeutic target for Ginkgolide K (GK) that is now becoming a very critical natural compound to treat demyelination and neurodegeneration. GK improves behavioral dysfunction and demyelination in cuprizone (CPZ) model, followed by the migration and enrichment of astrocytes in the corpus callosum. Both in vitro and in vivo experiments demonstrates that GK triggers the upregulation of Nrf2/HO-1 in astrocytes and inhibition of p-NF-kB/p65, which is associated with the outcome of anti-inflammation and anti-oxidation by suppressing the production of IL-6 and TNFα as well as nitric oxide and iNOS in astrocytes. Further findings suggest that IGF/PI3K, but not BDNF, was induced in the corpus callosum after GK treatment, revealing that Nrf2 activation inhibited caspase-3 and apoptosis in O4+ oligodendrocytes possibly through IGF/PI3K signaling molecules. Since the current immunomodulatory therapies for MS have failed to prevent patients from entering the progressive phase of the disease, thus targeting Nrf2 in astrocytes with GK would be an ideal strategy for myelin protection and regeneration.

Inhibition of ROCK activity regulates the balance of Th1, Th17 and Treg cells in myasthenia gravis.

Aberrant ROCK activation has been found in patients with several autoimmune diseases, but the role of ROCK in myasthenia gravis (MG) has not yet been clearly investigated. Here, we demonstrated that ROCK activity was significantly higher in peripheral blood mononuclear cells (PBMCs) from MG patients. ROCK inhibitor Fasudil down-regulated the proportions of Th1 and Th17 cells in PBMCs of MG patients in vitro. Intraperitoneal injection of Fasudil ameliorated the severity of experimental autoimmune myasthenia gravis (EAMG) rats and restored the balance of Th1/Th2/Th17/Treg subsets. Furthermore, Fasudil inhibited the proliferation of antigen-specific Th1 and Th17 cells, and inhibited CD4 + T cells differentiated into Th1 and Th17 through decreasing phosphorylated Stat1 and Stat3, but promoted Treg cell differentiation through increasing phosphorylated Stat5. We conclude that dysregulated ROCK activity may be involved in the pathogenic immune response of MG and inhibition of ROCK activity might serve as a novel treatment strategy for MG.

The therapeutic potential of ginkgolide K in experimental autoimmune encephalomyelitis via peripheral immunomodulation.

Multiple sclerosis is a T cell-mediated inflammatory, demyelinating disease of the central nervous system, accompanied by neuronal degeneration. Based on the anti-inflammatory effects of Ginkgolide K (GK), a platelet activating factor antagonist, we explored the possible application of GK in the treatment of MS. The results showed that GK effectively ameliorated the severity of experimental autoimmune encephalomyelitis. The intervention of GK inhibited the infiltration of inflammatory cells and demyelination in the spinal cord. At the same time, the expression of the inflammation-related molecules TLR4, NF-κB, and COX2 in the spinal cord was significantly lower in the GK-treated mice, indicating that GK intervention can inhibit the inflammatory microenvironment of the spinal cord in EAE mice. In mouse spleen lymphocytes, GK increased the proportion of regulatory T cells (Treg) and reduced the proportion of T helper 17 cells (Th17), modifying the imbalance between Th17/Treg cells. Additionally, GK shifted macrophage/microglia polarization from M1 to M2 cell type. Importantly, GK inhibited the expression of chemotactic molecules CCL-2, CCL-3 and CCL-5, thereby limiting the migration of inflammatory cells to the spinal cord. Our results provide the possibility that GK may be a promising naturally small molecule compound for the future treatment of MS.

Alcohol Drinking in Chinese Methadone-maintained Clients: A Self-medication for Depression and Anxiety?

OBJECTIVES: Unhealthy alcohol use is associated with negative health outcomes in clients attending methadone maintenance therapy (MMT) programs. However, debates exist regarding the methadone dose of drinkers, and little is known about the health outcomes of drinkers with other types of alcohol use. This study examined the drinking pattern and its association with methadone dose, and depressive and anxiety symptoms in Chinese clients undergoing MMT. METHODS: A secondary data analysis was conducted with data from a large-scale cross-sectional survey of 549 clients of 3 MMT clinics in Wuhan, China. Depression, anxiety, and alcohol dependence were measured with Zung Self-rating Depression Scale, Zung Self-rating Anxiety Scale, and Alcohol Dependence Scale, respectively. Drinking pattern was assessed using 3 indicators: weekly amount of alcohol consumed, weekly frequency of alcohol consumed, and severity of alcohol dependence. RESULTS: The prevalence of current drinking, hazardous drinking, regular drinking, and alcohol abuse/dependence was 29.0%, 10.4%, 14.2%, and 8.7%, respectively. In adjustment analyses, relative to nondrinkers, drinkers had significantly lower weight-based methadone dose (ß = -0.136, P = 0.008); hazardous drinkers, irregular drinkers, and drinkers without alcohol abuse/dependence had less severe depression (ß = -3.67, P = 0.004; ß = -2.37, P = 0.034; ß = -3.20, P = 0.001) and anxiety (ß = -4.90, P < 0.001; ß = -3.24, P = 0.006; ß = -4.52, P < 0.001), but drinkers with alcohol abuse/dependence had more severe depression (ß = 5.55, P < 0.001) and anxiety (ß = 4.31, P = 0.005). CONCLUSION: In Chinese MMT clinics, drinkers may use alcohol to compensate for inadequate MMT and self-medicate negative emotions. Compared with nondrinkers, the severities of depression and anxiety were lower among drinkers without alcohol abuse/dependence, but higher among those with alcohol abuse/dependence.