Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

BackgroundAlcohol use disorder （AUD） is a common chronic and relapsing psychiatric disorders. Identifying severe AUD early and intervening promptly is crucial to prevent irreversible harm. Currently， the assessment of AUD severity primarily relies on psychiatric examination by clinicians， and there is limited research on the factors influencing AUD severity and the development of prediction models. ObjectiveTo analyze the factors influencing AUD severity， and construct a risk prediction model to aid in the assessment of disease progression in AUD patients. MethodsA retrospective analysis was conducted on 1 358 first-time hospitalized patients admitted to Nanning Fifth People's Hospital from January 1， 2017 to December 31， 2022. These patients met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） criteria for AUD. Basic patient data was collected， and the patients were divided into two groups based on disease severity： mild-moderate group （n=330） and severe group （n=1 028）. The patients were randomly divided into training and test sets in a 7∶3 ratio. A Logistic regression model was constructed in the training set， and the predictive ability of the model for disease severity was evaluated using the receiver operating characteristic （ROC） curve in the test set. ResultsCompared with the mild-moderate group， the severe group had a higher proportion of patients living in urban areas （χ²=7.804）， were farmers （χ²=17.991）， had a higher frequency of alcohol consumption （more than 1 to 2 drinks/day） （χ²=35.267）， had a higher age at first drinking （t=-3.858）， had a greater number of comorbid somatic disorders （Z=-22.782）， and had higher proportions of γ-Glutamyl transpeptidase （χ²=259.940） and total bilirubin abnormalities （χ²=148.552） （P<0.01）. Logistic analysis conducted in the training set showed that being a farmer （OR=2.024， 95% CI： 1.352~3.029）， having an older age at first drinking （OR=1.075， 95% CI： 1.025~1.129）， drinking outside of mealtimes （OR=3.988， 95% CI： 2.408~6.606）， having total bilirubin abnormalities （OR=1.034， 95% CI： 1.000~1.069）， and having more comorbid somatic diseases （OR=4.386， 95% CI： 2.636~7.298） were identified as risk factors for disease severity in AUD patients. The area under curve （AUC） for this model in the test set was 0.906. ConclusionIn psychiatric hospitals， being a farmer， having an older age at first drinking， drinking outside of mealtimes， having abnormal total bilirubin levels， and having comorbidities with somatic illnesses may be risk factors for severe AUD.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

Objective To investigate neutrophil lymphocyte ratio (NLR) in early-stage diabetic nephropathy and its clinic significance. Methods The 145 subjects were divided into two groups:the healthy control group (n=54) and early stage diabetic nephropathy group (n=91). The numbers of neutrophils (N) and lymphocytes (L) as well as the NLR values of peripheral blood and other biochemistry index were examined. Factors of early stage diabetic nephropathy were calculated us?ing variance and logistic regression analysis. Results Creatinine(Cr), total cholesterol(TC), triglyceride(TG), LDL-C, neu?trophils number and CRP in DN group were significantly higher than those of the control group and lymphocytes numbers of DN group were significantly lower than that of the control group (P<0.05 respectively);NLR values were significantly higher in diabetic nephropathy group compared with those of healthy control group(2.52±0.57 vs 1.82±0.60,t=6.997, P<0.01). Lo?gistic regression analysis showed that the risk factors of DN include NLR, TG and total cholesterol. NLR ( P <0.001, OR=8.951, OR 95%CI:3.595-22.287) was significantly associated with DN. Conclusion High NLR values may be a predic?tive and reliable marker ofearly-stage DN.

Objective To investigate the effects of supported employment(SE) on the vocational rehabilitation for schizophrenic rehabilitants.Methods 108 schizophrenic rehabilitants with stable conditions were recruited and randomly allocated into the control group and experimental group.Fifty-four cases in the control group received the general outpatient service and follow-up service with drug maintenance therapy and 54 cases in the experimental group received SE with drug maintenance therapy.At the baseline and the end of the sixth month,all of the 108 cases were assessed by the Positive and Negative Syndrome Scale (PANSS) and Work-related Social Skills Scale (WSSS) respectively.The competitive employment rate and average working days of the two groups were evaluated at the end of the sixth month.Results There was no significant difference in the total score of WSSS,and the total score of PANSS and its sub-scores on the Positive Scale,Negative Scale and General Psychopathological Scale betweeu the two groups at the baseline(P＞ 0.05).At the cnd of the sixth months,significant differences (P＜0.01 ～ 0.05) were found in the total score of WSSS,the sub-score of the Negative Scale,the competitive employment rate and the average working days((35.11 ± 12.71) d vs(20.15 ± 8.04) d) between the experimental and control groups.Conclusion SE can increase the employment rate of schizophrenic rehabilitants,improve their abilities to acquire and maintain competitive employment,and meanwhile relieve their negative symptoms.

In this paper,the authors elaborated the difficulties of schistosomiasis control and analyzed shortages and problems of the skills currently used.In order to consolidate the progress in schistosomiasis control and reach the transmission-blocking target,research priorities on the disease control technologies are proposed.