TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

Associations of Body Mass Index-Metabolic Phenotypes with Cognitive Decline in Parkinson's Disease.

BACKGROUND: Growing evidence suggests important effects of body mass index (BMI) and metabolic status on neurodegenerative diseases. However, the roles of BMI and metabolic status on cognitive outcomes in Parkinson's disease (PD) may vary and are yet to be determined. METHODS: In total, 139 PD patients from the whole PD cohort in Parkinson's Progression Markers Initiative database underwent complete laboratory measurements, demographic and anthropometric parameters at baseline, and were enrolled in this study. Further, they were categorized into 4 different BMI-metabolic status phenotypes using Adult Treatment Panel-III criteria. Motor and cognition scales at baseline and longitudinal changes after a 48-month follow-up were compared among the 4 groups. Repeated-measure linear mixed models were performed to compare PD-related biomarkers among BMI-metabolic status phenotypes across time. RESULTS: We found that PD patients in the metabolically unhealthy normal weight group showed more cognitive decline in global cognition and visuospatial perception after a 48-month follow-up than those in the other 3 groups (p < 0.05). No difference was found in motor scales among different BMI-metabolic status phenotypes. Finally, compared to the metabolically healthy normal weight group, the metabolically healthy obesity group had lower CSF Aß42 and serum neurofilament levels in repeated-measure linear mixed models adjusting for age, gender, APOE e4 carrier status, and years of education (p = 0.031 and 0.046, respectively). CONCLUSION: The MUNW phenotype was associated with a rapid cognitive decline in PD.

Hesperetin inhibits KSHV reactivation and is reversed by HIF1α overexpression.

Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus, has two life cycle modes: the latent and lytic phases. KSHV lytic reactivation is important for both viral propagation and KSHV-induced tumorigenesis. The KSHV replication and transcription activator (RTA) protein is essential for lytic reactivation. Hesperetin, a citrus polyphenolic flavonoid, has antioxidant, anti-inflammatory, hypolipidemic, cardiovascular and anti-tumour effects. However, the effects of hesperetin on KSHV replication and KSHV-induced tumorigenesis have not yet been reported. Here, we report that hesperetin induces apoptotic cell death in BCBL-1 cells in a dose-dependent manner. Hesperetin inhibits KSHV reactivation and reduces the production of progeny virus from KSHV-harbouring cells. We also confirmed that HIF1α promotes the RTA transcriptional activities and lytic cycle-refractory state of KSHV-infected cells. Hesperetin suppresses HIF1α expression to inhibit KSHV lytic reactivation. These results suggest that hesperetin may represent a novel strategy for the treatment of KSHV infection and KSHV-associated lymphomas.

Coding mutations in NUS1 contribute to Parkinson's disease.

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

Efficacy and safety of wait and see strategy versus radical surgery and local excision for rectal cancer with cCR response after neoadjuvant chemoradiotherapy: a meta-analysis.

BACKGROUND: Neoadjuvant therapy can shrink tumors, increase anus preservation rate, and protect anal function. Radical surgery need cut off the diseased bowel, clean up the lymph nodes, and then restore bowel function. It could bring traumatic effect and poor postoperative quality of life to the patient. Local resection requires removal of the diseased bowel with circular negative margin. The surgical trauma is small, and the postoperative quality of life is good. In this meta-analysis, we aimed to evaluate the efficacy and safety between wait and see strategy (WS), radical surgery (RS), and local excision (LE) of rectal cancer patients with clinical complete response (cCR) response after neoadjuvant chemoradiotherapy. METHODS: We searched PubMed, Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang databases to compare wait and see strategy with radical surgery and local excision for rectal cancer with cCR response after neoadjuvant chemoradiotherapy up to March 2020. We collected the data of local recurrence, distant metastasis, cancer-related death, overall survival, and disease-free survival and used RevMan 5.0 to carry out the meta-analysis. Continuous data were evaluated by the standardized mean differences (SMD) with 95% confidence intervals (95% CIs), and dichotomous data were evaluated by relative risks (ORs or RRs) with 95% CIs. We aimed to compare the advantages and disadvantages of the three groups. RESULTS: Eleven English studies with 1131 patients were included. There were 412 patients in WS group, 678 patients in RS group, and 41 patients in LE group. WS group had a higher local recurrence rate than RS group (OR 7.32, 95% CI 3.58 to 14.95, P < 0.001). There was no significant difference in the other data between the three groups. CONCLUSION: Compared with the RS group, the WS group had an increased risk of local recurrence. However, the WS group had a similar DFS and OS compared with the RS group and the local excision group. Hence, we speculated that the WS group would have similar results as the surgery group for patients with cCR status.

Dating Whole Genome Duplication in Ceratopteris thalictroides and Potential Adaptive Values of Retained Gene Duplicates.

Whole-genome duplications (WGDs) are widespread in plants and frequently coincide with global climatic change events, such as the Cretaceous-Tertiary (KT) extinction event approximately 65 million years ago (mya). Ferns have larger genomes and higher chromosome numbers than seed plants, which likely resulted from multiple rounds of polyploidy. Here, we use diploid and triploid material from a model fern species, Ceratopteris thalictroides, for the detection of WGDs. High-quality RNA-seq data was used to infer the number of synonymous substitutions per synonymous site (Ks) between paralogs; Ks age distribution and absolute dating approach were used to determine the age of WGD events. Evidence of an ancient WGD event with a Ks peak value of approximately 1.2 was obtained for both samples; however, the Ks frequency distributions varied significantly. Importantly, we dated the WGD event at 51-53 mya, which coincides with the Paleocene-Eocene Thermal Maximum (PETM), when the Earth became warmer and wetter than any other period during the Cenozoic. Duplicate genes were preferentially retained for specific functions, such as environment response, further support that the duplicates may have promoted quick adaption to environmental changes and potentially resulted in evolutionary success, especially for pantropical species, such as C. thalictroides, which exhibits higher temperature tolerance.

A Panel of Serum Noncoding RNAs for the Diagnosis and Monitoring of Response to Therapy in Patients with Breast Cancer.

BACKGROUND The aim of this study was to identify a panel of serum noncoding RNAs (ncRNAs) as potential diagnostic and prognostic biomarkers for breast cancer. MATERIAL AND METHODS Patients with breast cancer (n=30), and normal controls (n=30) were included in the 'training set.' A 'validation set' included cases of breast cancer (n=128) and controls (n=77). All cases provided blood samples for serum analysis. All cases of breast cancer were confirmed histologically and were staged. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of 11 candidate ncRNAs, including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), in the serum. The expression of the panel of ncRNAs was further analyzed following surgery or chemotherapy. RESULTS The four ncRNAs identified in the serum of patients with breast cancer included let-7a, miR-155, miR-574-5p, and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Analysis based on the risk score showed that the panel of these four ncRNAs could effectively distinguish between patients with breast cancer and the control group. For the training set and the validation set, analysis of the receiver-operating characteristic (ROC) curve showed that the areas under the curve (AUCs) were 0.960 and 0.968, respectively. Also, the serum expression levels of the four ncRNAs differed in the pre-treatment and the post-treatment patients with breast cancer, with levels of miR-155 showing a significant decrease following chemotherapy. CONCLUSIONS A panel of serum ncRNAs, including let-7a, miR-155, miR-574-5p, and MALAT1, was shown to be present in patients with breast cancer.

A novel tyrosine hydroxylase variant in a group of Chinese patients with dopa-responsive dystonia.

Dopa-responsive dystonia (DRD) comprises a heterogeneous group of movement disorders. A limited number of studies of Chinese patients with DRD have been reported. In the present study, we investigated the clinical and genetic features of 12 Chinese DRD families. Point mutation analysis of the GTP-cyclohydrolase I (GCH1), tyrosine hydroxylase (TH) and sepiapterin reductase (SPR) genes was conducted by direct sequencing. In addition, multiplex ligation-dependent probe amplification targeting GCH1 and TH was performed in "mutation-free" patients. Three reported mutations (IVS2-2A>G, c.293C>T, c.550C>T) were detected in GCH1, whereas two compound heterozygous variants were identified in TH, one of which was novel (c.1083C>A). Furthermore, this novel variant was not detected in any of the 250 ethnicity-matched, healthy controls. No exon deletions or duplicate mutations in the two genes were found in patients with DRD. No mutation in SPR was found. In addition, one patient with the IVS2-2A>G mutation in GCH1 showed signs of Parkinsonism. In conclusion, we here identified a novel heterozygous variant in TH (c.1083C>A). It is important to perform routine screening of GCH1 and TH for patients with DRD. While for patients with Parkinsonism, GCH1 mutation analysis should be performed after screening of genes like PARKIN, PARK7 (DJ-1) and PINK1.

[Anti-tumor metastatic constituents from Rhodiola wallichiana].

To study the anti-tumor metastatic constituents in Rhodiola wallichiana (HK) S H Fu var Cholaensis (Praeg) S H Fu, chemical constituents were isolated and purified by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). Their structures were elucidated on the basis of spectral data analysis. The anti-tumor metastasis assay was applied to evaluate the activities of the isolated compounds. Ten compounds (1-10) were isolated and their structures were identified by comparison of their spectral data with literature as follows: syringic acid (1), salidroside (2), tyrosol (3), scaphopetalone (4), berchemol (5), 2,6-dimethoxyacetophenone (6), rhobupcyanoside A (7), miyaginin (8), chavicol-4-O-ß-D-apiofuranosyl-(1 --> 6)-O-ß-D-glucopyranoside (9), eugenyol-O-ß-D-apiofuranosyl-(1 --> 6)-O-ß-D-glucopyranoside (10). Compounds 4-6 and 8-10, were isolated from this genus for the first time, while compound 7 was isolated from this plant for the first time. Compounds 2, 6-8 showed positive anti-tumor metastatic activities, and compounds 2 and 8 showed significant anti-tumor metastatic activities.

[Construction of wild-type and mutant SPAST vectors for the study of molecular mechanism of hereditary spastic paraplegia].

OBJECTIVE: To construct wild-type and mutant pEGFP SPAST vectors and to explore the molecular mechanism of hereditary spastic paraplegia. METHODS: Mutant SPAST vector was constructed using overlap PCR method following construction of wild-type SPAST vector. Wild-type and mutant constructs were transfected to COS7 cells and subcellular localization of spastin was observed. Co-localizations of spastin and microtubule, spastin and mitochondria were viewed by immunofluorescence staining. RESULTS: Wild-type spastin is localized in plasma, and mutant spastin did not change its cellular localization. Wild-type and mutant spastins did not co-localize with microtubules and mitochondria by immunofluorescence analysis. CONCLUSION: Wild-type and mutant SPAST constructs were successfully generated. Mutant spastin did not change its localization in cells. Spastin does not co-localize with microtubules and mitochondria. This study may facilitate further studies on molecular mechanism of hereditary spastic paraplegia.

[Establishment of surgical blood ordering schedule and relative influential factors for tumor patients].

OBJECTIVE: To design a blood ordering schedule and explore the influencing factors of blood utilizing and ordering for tumor surgical patients. METHODS: For a total of 58 306 tumor surgical patients, 22 643 applications of blood ordering and 7430 person-times of blood utilization from October 2002 to May 2012 were retrospectively analyzed at Cancer Hospital of Chinese Academy of Medical Sciences. Their clinical profiles and test results were analyzed. RESULTS: The operative transfusion rate was 32.81%. According to the operation position and the blood transfusion and preparation data, the surgical blood ordering schedule of tumor patients was established. Patient gender, hemoglobin, hematocrit, platelet, total protein and albumin level test results had significant effect on the transfusion of red blood cells (OR = 0.797, 9.614, 1.949, 0.437,0.444, 2.038, all P < 0.05). Patient gender, hemoglobin, hematocrit, activated partial thromboplastin time, prothrombin time, albumin and total protein level test results had significant effect on the transfusion of plasma (OR = 0.851, 1.367, 1.801, 1.652, 2.922, 2.224, 1.362, all P < 0.05) . CONCLUSION: For surgical tumor patients, blood ordering should be based upon the test results of routine blood, blood coagulation and protein level test results to ensure that blood transfusion is both rational and safe.

[Treatment of non-motor symptoms of Parkinson's disease patients of Gan-Shen deficiency syndrome by guling pa'an granule: a multi-center double-blinded randomized controlled trial].

OBJECTIVE: To observe the therapeutic efficacy of guiling pa'an granule (GPG) in treating non-motor symptoms of Parkinson's disease (PD) patients of Gan-Shen deficiency syndrome (GSDS). METHODS: A multi-center,third party-central online, network randomized, double-blinded, double-dummy, and placebo controlled clinical trial was conducted. Totally 121 patients with confirmed diagnosis of PD by Western medicine and of GSDS by syndrome typing were assigned to the control group and the treatment group. Under the premise of the same treatment baseline, the placebo and GPG at the same dose was respectively administered to patients in the control group and the treatment group. The therapeutic course was 6 months for all. The changes of 8 non-motor symptoms (including witless expression, seborrhea, sialorrhea, cognitive impairment, constipation, hyperhidrosis, insomnia and dreaminess, and psychosis) were observed in the two groups, when compared with the baseline. RESULTS: Satisfactory effectiveness in the 8 non-motor symptoms of PD patients were obtained in the treatment group (P<0.01). Besides, less adverse reactions occurred. CONCLUSION: GPG could improve the non-motor symptoms of PD patients.

Evidence of Bariatric Surgery Benefits Cardiac Function in Non-HFpEF Patients with Obesity: a Meta-Analysis.

BACKGROUND/OBJECTIVE: Nowadays, increasing clinical evidence on metabolic and weight-loss effects of bariatric surgery on improving cardiac structure in obese patients, but its application in improving the cardiac function of HF (heart failure) patients remains controversial. The objective of this meta-analysis was to assess the effects of BS on cardiac function by quantifying the changes of LVEF (left ventricular ejection fraction) and NYHA (New York Heart Association classification) after operations in non-HFpEF (heart failure and preserved ejection fraction) patients. METHODS: Articles were searched using PubMed and Embase from inception to December 9, 2022, and the Minors scale was used for quality assessments. The included patients should be non-HFpEF and clinically severely obese, and their pre-operative and post-operative values of LVEF or NYHA should be reported. RESULT: Nine studies involving 146 patients were eventually included with a final result showing that the cardiac functional parameters were improved in non-HFpEF patients. After a weighted mean follow-up time of 15.8 months, the mean NYHA decreased by 0.59 (I2 = 0; 95% CI 0.27 ~ 0.92; p = 0.003), and the mean LVEF increased by 7.49% (I2 = 0; 95% CI - 9.99 ~ - 4.99; p < 0.00001). CONCLUSION: Bariatric surgery offers beneficial cardiac effects on non-HFpEF patients with obesity but failed to show a significant improvement in the pooled analysis for the changes of cardiac parameters. The improving degree may be related to the baseline BMI, the extent of BMI loss, and the baseline age. Future studies should focus on finding out the influencing factors of effectivenesses and defining the suitable crowd.

[Logistic regression analysis of platelet transfusion effects in cases of cancer patients].

OBJECTIVE: To explore the influencing factors of platelet transfusion effects in cancer patients. METHODS: A total of 363 cases of cancer patients undergoing platelet transfusion at our hospital from January 1, 2010 to June 30, 2011 were enrolled. Only one transfusion was randomly selected for each patient for single-factor analysis. Then a binary Logistic regression analysis was performed with transfusion effects as a dependent variable and the variables with P ≤ 0.2 as covariates in single-factor analysis. RESULTS: Among them, there were 280 effective and 83 ineffective transfusions with an overall effective rate of 77.1%. The single-factor analysis revealed that the P values were < 0.05 for age, platelet transfusion history, fever and antibiotic. Logistic analysis of multiple variables showed that platelet transfusion history (1-4 times compared to none, OR = 1.969,95%CI: 1.135 - 3.417; ≥ 5 times compared to none, OR = 5.260,95% CI:2.344 - 11.806), antibiotic (OR = 2.020,95%CI: 1.139 - 3.583), fever(OR = 1.789,95%CI: 1.015 - 3.153) and storage days of platelets (OR = 1.559,95%CI: 1.112 - 2.186) were independent risk factors. CONCLUSIONS: Influenced by multiple factors, the effects of platelet transfusion may be improved through reducing unreasonable transfusions, using fewer storage days of platelets and avoiding transfusions during fever and antibiotic uses.

[Analysis of the epidemic characteristics of fever and thrombocytopenia syndrome in Henan province, 2007 - 2011].

OBJECTIVE: To analyze the epidemiological characteristics of fever thrombocytopenia and leukopenia syndrome (FTLS) in Henan province, China in 2007 - 2011. METHODS: Data from specific surveillance system for FTLS in Henan and Information Management System of Chinese Center for Disease Control and Prevention were used to collect the information of the cases.Descriptive epidemiological methods were used to analyze the surveillance data during 2007 - 2011. Patients' sera were collected to detect new bunyavirus using fluorescent RT-PCR and virus isolation. RESULTS: During 2007 - 2011, 1021 FTLS cases were reported in Henan province. The fatality rate was 2.25%with 23 deaths. The cases reported in Xinyang city were 1007, accounting for 98.75%.Cases were mainly occurred between April and October, accounting for 96.47% (985/1021). Epidemic peak was May to July, accounting for 59.16% (604/1021). The second peak occurred in September, accounting for 12.05% (123/1021). The age of the cases ranged from 1 to 88 years old with the median age of 59. Sex ratio (male:female) was 1:1.50 (408:613). In all cases, 93.73% (957/1021) were farmers. In 465 patients' sera, the positive rate of new bunyavirus was 69.25% (322/465) using fluorescent RT-PCR. In 164 patients' sera, 67 strains of new bunyavirus were isolated with isolation rate of 40.85% (67/164). CONCLUSION: FTLS in Henan province is caused mainly by the new bunyavirus and has certain regional and seasonal characteristics. Most cases are female older farmers.

[Analysis on the diagnosis and treatment of a cluster of cases infected by new bunyavirus].

OBJECTIVE: To analyze and summarize the clinical characteristics, experience of diagnosis and treatment of cases infected by new bunyavirus, which occurred in Henan province in 2010. METHODS: The clinical characteristics and effect of diagnosis and treatment of 5 cases were analyzed using descriptive epidemiological method. Blood specimens were detected by RT-PCR and pathogen separation. RESULTS: PCR testing was positive for all 5 cases. New bunyavirus were isolated from 2 cases. In 5 cases, fever (5/5), the whole body aches (5/5), fatigue (5/5), anorexia (5/5), nausea (5/5), the chills (4/5), cough (4/5), expectoration (4/5), vomiting (3/5), conjunctival hyperemia (3/5); Leukocyte reduction (5/5), thrombocytopenia (5/5), elevated alanine aminotransferase (4/5), elevated aspartate aminotransferase (4/5), elevated lactate dehydrogenase (5/5), creatine kinase elevations (4/5), urinary protein (3/5). By symptomatic and supportive treatment and prophylactic antibiotics, the first case died and the other 4 cases were cured. The average course of disease was 15.4 days. CONCLUSION: Cases infected by new bunyavirus have complicated clinical feature and multiple organ damage. If symptomatic treatment is in time, prognosis will be good.

Concomitant Othello syndrome and impulse control disorders in a patient with Parkinson's disease: A case report.

BACKGROUND: Othello syndrome (OS) is characterized by delusional beliefs concerning the infidelity of a spouse or sexual partner, which may lead to extreme behaviors. Impulse control disorders refer to behaviors involving repetitive, excessive, and compulsive activities driven by an intense desire. Both OS and impulse control disorders in Parkinson's disease (PD) may be side effects of dopamine agonists. At present, there are only a few case reports and studies related to PD with concomitant OS and impulse control disorders. CASE SUMMARY: We describe a 70-year-old male patient with PD, OS, and impulse control disorders, who presented with a six-month history of the delusional belief that his wife was having an affair with someone. He began to show an obvious increase in libido presenting as frequent masturbation. He had been diagnosed with PD ten years earlier and had no past psychiatric history. In his fourth year of PD, he engaged in binge eating, which lasted approximately one year. Both OS and hypersexuality were alleviated substantially after a reduction of his pramipexole dosage and a prescription of quetiapine. CONCLUSION: Given its potential for severe consequences, OS should be identified early, especially in patients undergoing treatment with dopamine agonists.

Mills' syndrome is a unique entity of upper motor neuron disease with N-shaped progression: Three case reports.

BACKGROUND: Mills' syndrome is an extremely rare degenerative motor neuron disorder first described by Mills in 1900, but its nosological status is still not clear. We aimed to analyze the clinical features of Mills' syndrome. CASE SUMMARY: Herein, we present 3 cases with similar features as those described in Mills' original paper and review the related literature. Our patients showed middle- and older-age onset, with only upper motor neuron symptoms evident throughout the course of the disease. Spastic hemiplegia began in the lower extremity with a unique progressive pattern. CONCLUSION: We consider that Mills' syndrome is a unique entity of motor neuron disorder with an N-shaped progression. Clinicians should maintain a high index of suspicion for the diagnosis of Mills' syndrome when the onset involves lower extremity paralysis without evidence of lower motor neuron or sensory involvement.

MiR-200c-3p Regulates DUSP1/MAPK Pathway in the Nonalcoholic Fatty Liver After Laparoscopic Sleeve Gastrectomy.

Aim: Non-alcoholic fatty liver disease (NAFLD) is a health burden worldwide, which is closely related to obesity. The effect of sleeve gastrectomy (SG) on NAFLD is efficient, and the underlying mechanism remains unknown. Our study sought to investigate the mechanism of dual-specificity protein phosphatase 1 (DUSP1) expression regulation following the SG procedure in NAFLD patients and C57BL/6J mice via miR-200c-3p. Methods: The serum was extracted from NAFLD patients who underwent laparoscopic sleeve gastrectomy (LSG) and volunteers. Next, the correlation between miR-200c-3p and DUSP1 was identified in vitro. NAFLD mice were modelled by high-fat diets (HFD). The hepatic tissue expression levels of miR-200c-3p, DUSP1, phospho-extracellular regulated protein kinases1/2 (p-ERK1/2), phospho -p38 mitogen-activated protein kinases (p-p38), and phospho-c-Jun N-terminal kinases (p-JNK) induced by SG procedure were evaluated. Results: The SG procedure contributed to significant weight loss, reduced lipids in NAFLD patients and mice. The increased expression level of miR-200c-3p and reduced expression of DUSP1 were observed in NAFLD patients and mice (p<0.05). The reduced expression levels of miR-200c-3p and increased expression of DUSP1 were observed in patients and mice with NAFLD who underwent SG procedure. DUSP1 is a potential target of miR-200c-3p. Conclusions: A novel mechanism was identified in which miR-200c-3p regulates the MAPK-dependent signals that are linked to the promotion of hepatosteatosis via DUSP1 after sleeve gastrectomy. The findings suggested that miR-200c-3p should be further explored as a potential target for the treatments of NAFLD.