Objective To investigate the association between depression and autonomic nervous function in Parkinson disease （PD）， and to provide a basis for clinical treatment. Methods Clinical and neurocirculation data were collected from 168 PD patients who attended Department of Neurology， The Second Affiliated Hospital of Hainan Medical College， from July 2022 to July 2023， and according to the score of Beck Depression Inventory， the patients were divided into depression in PD （dPD） group with 57 patients and non-dPD （nPD） group with 111 patients. General clinical data were collected from all patients. The supine-to-standing TCD test was performed for all patients to record systolic blood pressure （SBP）， diastolic blood pressure （DBP）， heart rate （HR）， and the mean velocity （Vm）， pulsatility index （PI）， and resistance index （RI） of the middle cerebral artery （MCA） at 1， 3， and 5 minutes in both the supine and standing positions. A network was constructed for depression symptoms in PD. Results In the network of non-motor symptoms in PD， depression showed the highest centrality and the strongest predictability and was strongly correlated with sleep/fatigue and mood/cognition， with a strength centrality stability coefficient （CS strength） of 0.440. Compared with the nPD group， the dPD group had significantly lower supine HR， ∆HR， Vm in the standing position， and ∆Vm%， a significantly greater ∆DBP， and a significantly higher proportion of patients with dizziness with orthostatic hypotension or orthostatic cerebral hypoperfusion （P<0.05）. Depression was positively correlated with ∆SBP， ∆DBP， Vm in the supine position， and RI in the standing position， and it was negatively correlated with ∆HR， DBP in the supine position， HR in the supine position， and ∆PI （CS strength=0.375 and 0.222）. Conclusion Impairment of cardiovascular and cerebral autonomic nervous function might be involved in the pathogenesis of depression in PD， and intervention of depression can help improve the overall non-motor symptoms of PD， with sleep， fatigue， and cognition as the effective targets for improving depression in PD.
Parkinson Disease ; Depression

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) injection in enhancing chin aesthetics.Methods:A retrospective analysis was conducted on patients with suboptimal chin aesthetics who underwent dual-plane BTX-A injection at Plastic Surgery Hospital, Chinese Academy of Medical Sciences between August 2023 and March 2024. Prior to injection, patients were instructed to repeatedly pucker their lips forward and upward to identify the most prominent points of the mentalis muscle for injection. A 13 mm 30 G needle was inserted perpendicularly into the muscle layer, and BTX-A was administered at a concentration of 20 U/ml, with 3 U per injection point. For the patients exhibiting significant orange peel signs at rest, intradermal deep-layer BTX-A injection was concurrently performed at a concentration of 5 U/ml, with 0.5 U per linear track. Postoperative follow-up was conducted, and third-party physicians assessed pre- and post-treatment photographs using the global aesthetic improvement scale (GAIS) (scores ranging from 5 to 1, representing worse, no improvement, mild improvement, moderate improvement, and significant improvement, respectively). Patient satisfaction was also surveyed [categorized as very satisfied, satisfied, dissatisfied, or very dissatisfied; satisfaction rate = (very satisfied + satisfied) cases/total cases × 100%], along with their willingness to undergo repeated injections and recommend the procedure to others. Descriptive statistical analysis was performed using SPSS 24.0 software. Normally distributed continuous data were expressed as Mean±SD, and categorical data were expressed as counts (%).Results:A total of 120 patients were included, comprising 11 males and 109 females, aged 22-39 years (mean age of 33.3 years). Follow-up ranged from 1 to 5 months (mean of 1.3 months). Postoperatively, 102 patients reported subjective improvement in chin appearance, characterized by enhanced fullness and roundness of the chin. Thirty-one patients noted a slight elevation of the submental fat pad and improved definition of the cervicomental angle. The mean GAIS score was 1.61±0.78, with 76 cases scoring 1, 24 cases scoring 2, 10 cases scoring 3, and 10 cases scoring 4. Improvement (scores 1-3) was achieved in 91.7% (110/120) of patients. The subjective satisfaction rate was 85.0% (102/120), and 94 patients (78.3%) expressed willingness to undergo repeated injections and recommend the procedure to family or friends. Early postoperative complications included localized bruising in 17 cases, which was resolved within 10 d, and transient fine motor dysfunction of the lower jaw in 23 cases, with normal chewing, swallowing, and facial expressions, all of which were resolved completely within 6 weeks. No cases of mouth deviation, facial paralysis, allergic reactions, or other complications were observed.Conclusion:The application of BTX-A via intramuscular mentalis injection combined with intradermal deep-layer injection significantly improves both dynamic and static chin aesthetics. However, some common complications also ask for the further attention of practitioners.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) injection in enhancing chin aesthetics.Methods:A retrospective analysis was conducted on patients with suboptimal chin aesthetics who underwent dual-plane BTX-A injection at Plastic Surgery Hospital, Chinese Academy of Medical Sciences between August 2023 and March 2024. Prior to injection, patients were instructed to repeatedly pucker their lips forward and upward to identify the most prominent points of the mentalis muscle for injection. A 13 mm 30 G needle was inserted perpendicularly into the muscle layer, and BTX-A was administered at a concentration of 20 U/ml, with 3 U per injection point. For the patients exhibiting significant orange peel signs at rest, intradermal deep-layer BTX-A injection was concurrently performed at a concentration of 5 U/ml, with 0.5 U per linear track. Postoperative follow-up was conducted, and third-party physicians assessed pre- and post-treatment photographs using the global aesthetic improvement scale (GAIS) (scores ranging from 5 to 1, representing worse, no improvement, mild improvement, moderate improvement, and significant improvement, respectively). Patient satisfaction was also surveyed [categorized as very satisfied, satisfied, dissatisfied, or very dissatisfied; satisfaction rate = (very satisfied + satisfied) cases/total cases × 100%], along with their willingness to undergo repeated injections and recommend the procedure to others. Descriptive statistical analysis was performed using SPSS 24.0 software. Normally distributed continuous data were expressed as Mean±SD, and categorical data were expressed as counts (%).Results:A total of 120 patients were included, comprising 11 males and 109 females, aged 22-39 years (mean age of 33.3 years). Follow-up ranged from 1 to 5 months (mean of 1.3 months). Postoperatively, 102 patients reported subjective improvement in chin appearance, characterized by enhanced fullness and roundness of the chin. Thirty-one patients noted a slight elevation of the submental fat pad and improved definition of the cervicomental angle. The mean GAIS score was 1.61±0.78, with 76 cases scoring 1, 24 cases scoring 2, 10 cases scoring 3, and 10 cases scoring 4. Improvement (scores 1-3) was achieved in 91.7% (110/120) of patients. The subjective satisfaction rate was 85.0% (102/120), and 94 patients (78.3%) expressed willingness to undergo repeated injections and recommend the procedure to family or friends. Early postoperative complications included localized bruising in 17 cases, which was resolved within 10 d, and transient fine motor dysfunction of the lower jaw in 23 cases, with normal chewing, swallowing, and facial expressions, all of which were resolved completely within 6 weeks. No cases of mouth deviation, facial paralysis, allergic reactions, or other complications were observed.Conclusion:The application of BTX-A via intramuscular mentalis injection combined with intradermal deep-layer injection significantly improves both dynamic and static chin aesthetics. However, some common complications also ask for the further attention of practitioners.

Schizophrenia is a serious mental disorder that is often associated with profound impairment in patients′ daily functioning, and its etiology and pathophysiology are still to be fully elucidated. There is a pathological correlation between inflammation, brain injuries, and the pathogenesis of schizophrenia, with microglia actively participating in these processes. This review provides a comprehensive overview of the impact of microglial cells on neurodevelopment and neuroplasticity, and microglia abnormalities mediating the onset of schizophrenia by contributing to damage in different brain regions.

Objective:To explore the efficacy and safety of whole-brain low-dose radiotherapy(LDRT)combined with PD-1 inhibitor sin-tilimab and intrathecal pemetrexed(IP)for the treatment of refractory non-small cell lung cancer(NSCLC)with leptomeningeal metastases(LM).Methods:Retrospective analysies were was performed on eight NSCLC patients with LM at the West China Hospital of Sichuan Uni-versity from December 2022 to May 2024.Among the eight patients,there were four were males and four were females,with a median age of 49 years(rangeing,between 34 to 58 years).All patients were treated with whole-brain LDRT combined with immune checkpoint inhibit-or(ICI)and intrathecal chemotherapy regimens,and the therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology(RANO)criteria and the Karnofsky physical status(KPS)score.Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events(CTCAE version 5.0).Survival analysis was performed using the Kaplan-Meier method.The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed using by single-cell sequencing,and the differential ana-lysis of gene expression in parallel cells was performed.Results:The best clinical treatment effects in eight patients were were evaluated us-ing the RANO criteria:five patients(62.5%)were evaluated as improved and three(37.5%)as stable.The median KPS score of the eight pa-tients was 30(20-50)before treatment,which was significantly improved to 60(40-90)after treatment(P=0.000 9).The remission rate of neurological symptoms was 100%(8/8)in eight patients.The median neurological progression-free survival(NPFS)was 12 months.The res-ults of single-cell sequencing in CSF of patientss(P1)showed that the proportion of T cells in the patient samples after whole-brain LDRT treatment was significantly higher than that before treatment(6.08%vs.68.87%),and the proportion of tumor cells was significantly lower(12.92%vs.0.6%).The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment.Conclusions:The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can signific-antly alleviate neurological symptoms,improve quality of life and prolong the NPFS of patients,which is a safe and effective treatment.