BACKGROUND:Anxiety disorders (ADs) and thyroid tumors (TTs) are prevalent and frequently co-occur. Previous studies suggest that the N-methyl-d-aspartate receptor (NMDAR) may play a role in their co-occurrence, but the understanding of their relationship is not comprehensive. The aim of this study was to investigate the role of NMDAR in the progression of animal models of AD with TT. METHODS:We developed an animal model of AD with TT in Balb/c mice using chronic unpredictable mild stress (CUMS) combined with subcutaneous IHH4 cell xenotransplantation. Mice were treated with d-serine and MK-801 to assess behavioral changes and tumor growth. The expression of NMDAR subunits in the thyroid and transplanted TT tissues was also analyzed. RESULTS:The combination of CUMS and IHH4 cell xenotransplantation helped successfully create an AD with TT model, which exhibited stable anxiety-like behavior, a high tumor formation rate, and ease of implementation. d-Serine alleviated anxiety behaviors but increased NR2A subunit activity in both thyroid and TT tissues, disrupted the normal structure of the thyroid, and accelerated TT growth. In contrast, MK-801 had the opposite effect. CONCLUSIONS:NMDAR, particularly the NR2A subunit, plays a crucial role in TT progression associated with AD. In the clinical drug selection for the patients with ADs with concomitant TT, special attention should be paid to the two-sidedness of drugs. The CUMS and IHH4 xenotransplantation model is an effective tool for studying AD with TT.

Background:Trimethylamine-N-oxide (TMAO), as a gut microbiota dependent metabolite, is involved in the occurrence and progression of many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, which are related to the disruption of the cerebral lymphatic system. However, the relationship between TMAO and cerebral lymphatic system remains to be elucidated. This study aimed to investigate the effects of TMAO on the astrocytes of the brain glymphatic system, and endothelial cells of the meningeal lymphatic vessels. Methods:Astrocytes and lymphatic endothelial cells were treated with different concentrations of TMAO. Alterations in cell proliferation or apoptosis, inflammatory cytokines, the nuclear factor-kappaB (NF-κB) signaling pathway, reactive oxygen species (ROS), and functional proteins such as aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), S100β, claudin-5, and Ocln were analyzed. C57BL/6 male mice were treated with TMAO after which alpha-synuclein (SNCA) was injected intracranially. Neuronal damage and expressions of above functional proteins in the ventral midbrain, and levels of SNCA and inflammatory factors in the cerebrospinal fluid (CSF) of mice were assessed. Results:TMAO activated the NF-κB signaling pathway, increased nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), tumor necrosis factor-alpha, interleukin (IL)-6, IL-1β, and ROS levels in astrocytes and lymphatic endothelial cells and promoted their apoptosis; increased the expression of GFAP and S100β, decreased the expression of AQP4 in astrocytes; decreased the expression of claudin-5 and Ocln in lymphatic endothelial cells. However, NF-κ B signaling pathway inhibitor BAY11-7082 improved the above indicators. Animal studies revealed that TMAO induced intracranial inflammation, affected the expression of functional proteins in the cerebral lymphatic system, and intensified SNCA aggregation in the mouse brain. Conclusion:TMAO can activate the NF-κB signaling pathway and damage the cellular function of brain glymphatic system and meningeal lymphatic vessels, and promote intracranial inflammation and SNCA deposition in mice, which may be a potential mechanism for TMAO involvement in neurodegenerative diseases.

INTRODUCTION:Thromboangiitis obliterans (TAO) is potentially associated with smoking, although its precise pathogenesis remains unclear. Trimethylamine N-oxide (TMAO) has been implicated in the induction of various cardiovascular and cerebrovascular diseases. However, the role of TMAO in TAO has not been reported. This study aimed to investigate the relationship between smoking, TMAO, and TAO. MATERIALS AND METHODS:Thirty-three patients diagnosed with TAO and hospitalized for treatment between January 2018 and July 2024 were included in the study. Healthy smokers (n = 38) and nonsmokers (n = 35) were randomly recruited and matched for age, sex, and education level as controls. Subsequently, we analyzed their clinical characteristics, levels of TMAO, and immune and inflammatory markers. RESULTS:Patients with TAO exhibited significantly higher levels of TMAO, Toll-like receptor 4 (TLR4), receptor for advanced glycation end products, interleukin (IL)-1β, IL-18, tumor necrosis factor-alpha, high mobility group box 1, nuclear factor-κB (NF-κB), and phosphorylated NF-κB (pNF-κB) than those in the smoking and nonsmoking control groups (all P < 0.05). The smoking control group also exhibited significantly higher levels of TMAO, TLR4, IL-1β, NF-κB, and pNF-κB (all P < 0.05) than the nonsmoking control group. TMAO, IL-1β, and tumor necrosis factor-alpha levels were significantly higher in the underage smoking group (all P < 0.05) than in the adult smoking group. The level of TMAO was significantly correlated with the Rutherford classification in patients with TAO, patients' smoking status (including total years of smoking and average daily cigarette consumption), and immune and inflammatory markers (all P < 0.05). CONCLUSIONS:These findings indicate that gut microbiota plays a significant role in the pathogenesis of TAO. TMAO is likely involved in the pathogenesis and progression of TAO, with smoking acting as a contributing factor. The underlying mechanism may involve the activation of immune-inflammatory pathways, specifically the high mobility group box 1-receptor for advanced glycation end products/TLR4-NF-κB pathway.

Objective Constipation frequently occurs in patients with Parkinson’s disease (PD) and may be related to cognitive and emotional disorders. The aim of this study is to investigate the clinical and brain functional characteristics of patients with PD presenting with constipation. Methods The motor and non-motor symptoms of patients with PD were evaluated, and a resting-state functional magnetic resonance imaging (RS-fMRI) study was conducted based on propensity score matching. Alterations in brain function were analyzed using regional homogeneity (ReHo) and functional connectivity (FC). Results Compared with patients without constipation (PD-NC group), patients with constipation (PD-C group) had more serious motor and non-motor symptoms (including cognitive and emotional disorders along with visual hallucinations). Further, emotional and cognitive disorders were correlated with the occurrence of constipation in patients with PD. Compared with the PD-NC group, the PD-C group showed a reduced ReHo of the right insula and bilateral orbitofrontal cortex (OFC), increased ReHo of the left postcentral gyrus, and enhanced FC between the right OFC and the left middle temporal gyrus (MTG) and middle occipital gyrus (MOG). Additionally, the activity of the OFC and insula was significantly correlated with the constipation, mood, and cognitive levels of patients with PD. Conclusions Constipation in patients with PD is closely related to emotional and cognitive impairments, abnormal activity and FC of brain regions such as the right insula and bilateral OFC may play an important role in this.

As a supplement to music therapy, natural sounds have become an effective means of relieving anxiety. This research investigates the natural acoustic characteristics that affect the perceived tranquility, emotional valence, and arousal in patients with anxiety disorders. This research conducted a subjective assessment experiment of natural sound involving 46 participants with anxiety disorders. It designed 56 natural sound stimuli by controlling four acoustic characteristic factors of natural sound: foreground sound types, the number of sound sources, the foreground-to-background signal-to-noise ratio (FBSNR), and the foreground sound duration ratio. Results show that patients with higher levels of anxiety may have a lower tolerance for mixed natural sounds. Natural sounds composed of two sources brought the highest emotional valence. When the number of sound sources increased from 2 to 6, perceived tranquility and emotional valence increased, while emotional arousal decreased. Anxious patients had the highest perceived tranquility and emotional valence of mixed natural sounds with a 75% foreground sound duration ratio. As the proportion of natural sounds in the foreground increased, there was a gradual decrease in emotional arousal. The number of sound sources, FBSNR, and the degree of anxiety may be the important acoustic characteristics that lead to the difference in anxious patients' perception. The acoustic characteristics of natural sounds need to be considered when creating a healing environment for anxious people.

Objective: Patients with anxiety disorder (AD) often have structural and functional abnormalities of the thyroid gland, but their specific causes remain unclear. N-methyl- D-aspartate receptors (NMDARs) play an important role in many psychosomatic diseases and tumorigenesis, but there are few reports on the role of NMDARs in AD with thyroid lesions, especially thyroid nodules (TNs). Methods: A cross-sectional study was conducted on patients admitted to the hospital with AD (n = 71) as the main diagnosis from April to October 2021. Meanwhile, patients with TNs with no AD (NAD-TN group, n = 20) and healthy subjects (HS group, n = 37) with matched age, sex, and education were randomly collected as controls. Patients with AD were sub-grouped into the AD with TNs (AD-TN group, n = 41) and the AD with no TNs (AD-NTN group, n = 30). The thyroid ultrasound reports, Hamilton Anxiety Scale (HAMA) scores, and the expression of NMDARs and their subunits (NR1, NR2A, and NR2B) and hypothalamic-pituitary-thyroid (HPT) axis-related hormones were analyzed in all subjects. Some patients with TNs underwent surgery and postoperative pathological examination. Results: Patients with AD showed a lower level of free triiodothyronine (FT3) and higher levels of thyrotropin-releasing hormone (TRH) and NMDARs and their subunits compared to the healthy controls. The expression of the NR2A subunit was higher in the AD-TN group than that in other three groups (AD-NTN, NAD-TN, and HS groups, F = 13.650, p < 0.001). Regression analysis showed that the level of NMDARs was positively correlated with the HAMA scores (B = 1.622, p = 0.029) and the maximum diameter of TNs (B = 3.836, p = 0.005). Immunohistochemical results showed that the NR2A subunit was widely expressed in multinodular goiter (MNG) and papillary thyroid carcinoma (PTC) tissues, while the expression of the NR2B subunit was lower in PTC adjacent and MNG tissues and almost absent in PTC tissues. Conclusion: In a sample of mostly women hospitalized with generalized anxiety disorder (GAD) or panic disorder, abnormal expression of NMDARs is closely related to AD with thyroid lesions, NMDAR subunits may have various activities and exert diverse effects in TNs, and the NR2A subunit may be an important regulator in AD with TNs.

Background: Coronavirus disease 2019 (COVID-19) is threatening human physical and mental health. The features of mild and severe cases of COVID-19 may be different, and the impact of psychological intervention is not clear. It is necessary to analyze clinical and psychological characteristics of COVID-19 patients simultaneously. Objective: To evaluate the clinical and psychological differences between mild and severe COVID-19 patients and determine the efficacy of psychological intervention on the patients. Methods: Clinical and psychological data of the patients with COVID-19 were collected. The patients were grouped into mild and severe groups according to their clinical symptoms, and subdivided into psychological intervention group and non-psychological intervention group according to whether they received psychological intervention. The efficiency of psychological interventions in patients with emotional disorder was further explored. Results: 162 participants were included in this study (severe group: 41 patients, mild group: 121 patients), 72 of them received psychological assessment. The demographic, clinical and laboratory characteristics of mild and severe cases were quite different. Most patients in both groups showed mild to moderate anxiety and depression at admission. After psychological intervention for about three weeks, psychological scale scores (HAMA and HAMD score) of patients in the psychological intervention group (n=54) were significantly lower than those in the non-psychological intervention group (n=18) (P<0.05). Conclusions: Early psychological intervention can significantly improve the emotional state of COVID-19 patients. Comprehensive treatments comprising combined clinical and psychological interventions may be effective in the treatment of COVID-19 patients. The physical and mental health of COVID-19 patients requires long-term follow-up.

Objective:To investigate the efficacy difference of totally laparoscopic total gastrectomy (TLTG) and laparoscopically assisted total gastrectomy (LATG) on radical gastrectomy for gastric cancer, and further to explore the safety and feasibility of totally laparoscopic esophagojejunostomy.Methods:PubMed, Web of Science, Wanfang and CNKI database were searched for all relevant articles regarding to TLTG versus LATG for gastric cancer published up to September 2019. The search keywords included: gastric/stomach cancer, total gastrectomy, totally/completely laparoscopic, laparoscopic-assisted/laparoscopy-assisted/laparoscopically assisted, esophagojejunostomy/esophagojejunal anastomosis. Meta-analysis was performed with RevMan 5.3 software.Results:A total of 258 articles were retrieved, and 11 studies were finally included after layer by layer screening, with a total sample size of 2421 cases, including 1115 cases in the TLTG group and 1306 cases in the LATG group. There were no statistical difference in age and gender between the two groups, while the mean BMI in the TLTG group was significantly higher than that in the LATG group ( P=0.01). Compared to the LATG group, shorter surgical incision ( P<0.001), less intraoperative blood loss ( P=0.003), larger number of retrieved lymph nodes ( P=0.04), less time to first oral intake ( P=0.03), and shorter postoperative hospital stay ( P=0.02) were found in the TLTG group. There were no significant differences in operation time, anastomotic time, tumor size, proximal resection margin length, postoperative pain score, time to first flatus, rate of postoperative anastomosis-related complication (including anastomotic fistula, stenosis and bleeding) and the overall incidence of postoperative complications ( P>0.05). Conclusions:Totally laparoscopic esophagojejunostomy is safe and feasible, and also suitable for obese patients. TLTG has advantages of minimally invasive, less intraoperative blood loss and easier access to lymph nodes compared to LATG. Totally laparoscopic gastrectomy will probably be the surgical trend for gastric cancer in the future.

BACKGROUND Laparoscopic radical gastrectomy is currently the most common surgical approach for gastric cancer. The main difference between totally laparoscopic total gastrectomy (TLTG) and laparoscopic-assisted total gastrectomy (LATG) is the route of digestive tract reconstruction. However, TLTG is currently not widespread as the safety and feasibility of intracorporeal esophagojejunostomy is uncertain. AIM To compare the short-term efficacy of TLTG and LATG for radical gastrectomy of gastric cancer, and to determine the safety and feasibility of intracorporeal esophagojejunostomy. METHODS PubMed, EMBASE, and Web of Science databases were searched for all relevant articles regarding TLTG vs LATG for gastric cancer published up to October 1, 2019. Inclusion and exclusion criteria were established. All the basic conditions of patients and important clinical data related to surgery were extracted, and a meta-analysis was performed with RevMan 5.3 software. RESULTS Eight studies involving a total of 1883 cases (869 cases in the TLTG group and 1014 cases in the LATG group) were included. Compared with the LATG group, reduced intraoperative blood loss (weighted mean difference = -35.37, 95%CI: -61.69 - -9.06, P = 0.008) and a larger number of retrieved lymph nodes (weighted mean difference = 3.11, 95%CI: -2.60 - 12.00, P = 0.01) were found in the TLTG group. There were no significant differences in operating time, anastomotic time, tumor size, proximal resection margin length, postoperative pain score, time to first flatus, time to first oral intake, postoperative hospital stay, postoperative anastomosis-related complication rate and overall complication rate between the two groups (P > 0.05). CONCLUSION Intracorporeal esophagojejunostomy is safe and feasible. TLTG has the advantages of being minimally invasive, reduced intraoperative blood loss and easier access to lymph nodes compared with LATG. Totally laparoscopic gastrectomy is likely to be the surgical trend for gastric cancer in the future.

Introduction: Long-term diabetes may cause oculomotor nerve palsy and anxiety disorder. Diabetic oculomotor nerve palsy is usually accompanied by diplopia, ptosis and eye movement disorders. The oculomotor nerve is often separated into superior and inferior divisions; diabetic third cranial nerve palsy may affect either division in isolation. However, anxiety disorder and alternating bilateral ptosis as the first symptoms of diabetes are extremely rare. Case Presentation: This case report describes a 63-year-old female patient who was admitted to the hospital for anxiety disorder with bilateral alternating ptosis. The patient had no diplopia or other new focal neurological symptoms. A neurological examination revealed left upper eyelid ptosis; other findings were negative. Except for hyperglycemia (13.96 mmol/L) and glycated hemoglobin (7.9%), laboratory tests showed no other abnormalities. The patient eventually recovered in a short time after a comprehensive treatment, including effective blood glucose control, microcirculation improvement and anxiety management. Conclusion: The upper eyelid droop caused by long-term diabetes may result in anxiety disorder. A comprehensive treatment may be considered for the patients admitted to the hospital for diabetes and its vascular neuropathy.

Objective To study the application of duloxetine in patients with functional dyspepsia (FD) complicated with anxiety and depression.Methods Ninety-six patients with FD complicated with anxiety and depression were equally divided into the control group and the treatment group according to the use of duloxetine.Patients in the control group were given routine treatment.On that basis,patients in the treatment group were treated with duloxetine and both groups were treated for 8 weeks.Relief of FD,depression,anxiety,improvement of quality of life and adverse reactions were compared between the two groups before treatment,at 2,4 and 8 weeks after the treatment.Results Two,4 and 8 weeks after treatment,the scores of adverse reactions in both groups decreased significantly,and there was significant difference between the two groups (P ＜0.05);2,4 and 8 weeks after treatment,the total effective rates of relieving FD in the treatment group (81％,88％,94％) were significantly higher than those in the control group (60％,67％,73％) (P ＜ 0.05);After treatment,the HAMD,HAMA and CGI-S1 scores of two groups were significantly decreased over time,and the decreasing ranges in treatment group were significantly higher than those in control group at 4 week and 8 weeks after treatment (P ＜0.05);8 weeks after treatment,the quality of life scores of the two groups increased significantly (P ＜ 0.05),and quality of life score in treatment group was significantly higher than that in control group (P ＜0.05);The total incidence of adverse reactions in the treatment group was 21％ while it was 19％ in the control group (P＞0.05).Conclusion Duloxetine is effective for treating FD with anxiety and depression.It can improve the quality of life of patients.And it is safe and effective,and worthy of clinical promotion.

Objective To explore the related factors of survival in the elderly patients with cerebral infarction treated by intravenous thrombolysis.Methods 100 patients with cerebral infarction who received intravenous thrombolysis in our hospital were enrolled in this study.All patients were divided into two groups according to the survival condition and the Rankin score, the survival group with 47 cases, and the non-survival group with 53 cases.The clinical indicators of the two groups in treatment process were analyzed and compared.Results The time from onset to thrombolysis, history of hypertension, hyperlipidemia, smoking, alcohol abuse, oxfordshire community stroke project (OCSP) type and TOASP type in survival group showed significant differences from those in non-survival group (P<0.05).Logistic regression analysis showed that the time from onset to thrombolysis, history of hypertension, hyperlipidemia, smoking, alcohol abuse, OCSP type and TOASP type were independent risk factors of death in the elderly patients with cerebral infarction treated by intravenous thrombolysis.Conclusions There are many factors affecting the survival of patients with cerebral infarction treated by intravenous thrombolytic therapy, including the time from onset to thrombolysis, hypertension, hyperlipidemia, smoking, alcohol abuse, OCSP type and TOASP type.

HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans. Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state. Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset.

BACKGROUND:Previous studies reported that the mild hypothermia therapy (MHT) could significantly improve the clinical outcomes for patients with hypertensive intracerebral hemorrhage (HICH). Therefore, this meta-analysis was conducted to systematically assess whether the addition of local MHT (LMHT) could significantly improve the efficacy of minimally invasive surgery (MIS) in treating HICH.METHODS:Randomized clinical trials on the combined application of MIS and LMHT (MIS+LMHT) vs MIS alone for treating HICH were searched up to September 2016 in databases. Response rate and mortality rate were the primary outcomes, and the neurologic function and Barthel index were the secondary outcomes. Side effects were also analyzed.RESULTS:Totally, 28 studies composed of 2,325 patients were included to compare the efficacy of MIS+LMHT to MIS alone. The therapeutic effects of MIS+LMHT were significantly better than MIS alone. The pooled odds ratio of response rate and mortality rate was 2.68 (95% confidence interval [CI]=2.22-3.24) and 0.43 (95% CI=0.32-0.57), respectively. In addition, the MIS+LMHT led to a significantly better improvement in the neurologic function and activities of daily living. The incidence of pneumonia was similar between the two treatment methods.CONCLUSION:These results indicated that compared to MIS alone, the MIS+LMHT could be more effective for the acute treatment of patients with HICH. This treatment modality should be further explored and optimized.

OBJECTIVE:To observe the growth characteristics of human umbilical cord mesenchymal stem cells (hUCMSCs) cultured on the alginate gel scaffolds and to explore the feasibility of hUCMSCs-alginate dressing for wound healing. METHODS:hUCMSCs were separated from human umbilical cords and cultured in vitro. After the 4th passage cells were co-cultured with alginate gel (experimental group), the cell growth characteristics were observed under the inverted phase contrast microscope. Vascular endothelial growth factor (VEGF) content was measured and the number of cells was counted at 0, 3, 6, and 9 days after culture; and the cell migration capacity was observed. The hUCMSCs were cultured without alginated gel as control. The model of full-thickness skin defects was established in 32 8-week-old Balb/c male mice and they were randomly divided into 4 groups (n=8): wounds were covered with hUCMSCs-alginate gel compound (MSC-gel group), cell supernatants-alginate gel compound (CS-gel group), 10% FBS-alginate gel compound (FBS-gel group), and 0.01 mol/L PBS-alginate compound (PBS-gel group), respectively. Wound healing rates at 5, 10, and 15 days were observed and calculated; and the wound tissues were harvested for histological and immunohistochemical staining to assess new skin conditions at 15 days after operation. RESULTS:hUCMSCs grew well with grape-like proliferation on the alginate gel, but no cell migration was observed at 7 days after cultivation. VEGF expression and cell number in experimental group were significantly less than those in control group at 3 days (P<0.05); then they gradually increased, and VEGF expression and cell number were significantly more than those in control group at 9 days (P<0.05). The wound healing rates of MSC-gel and CS-gel groups were significantly higher than those of FBS-gel and PBS-gel groups at 5, 10, and 15 days (P<0.05). The squamous epithelium, fibroblasts, sebaceous glands, capillaries and VEGF expression of the new skin in MSC-gel and CS-gel groups were significantly more than FBS-gel and PBS-gel groups (P<0.05). But there was no significance between MSC-gel and CS-gel groups (P>0.05). CONCLUSION:hUCMSCs can continuously express VEGF in alginate gel, which is necessary for wound healing. The hUCMSCs-alginate compound is probably a good wound dressing.

Background Hyposmia is a cardinal early symptom of Parkinson's disease (PD), but the pathophysiological mechanisms underlying it remain unclear. Resting-state functional MRI (RS-fMRI) demonstrates spontaneous neuronal activity. We hypothesized that there would be alterations in the olfaction-related regions of the limbic/paralimbic cortices in PD patients with obvious hyposmia by RS-fMRI. Methods We used the "Five Odors for Olfactory Detection Arrays" to test the threshold of olfactory detection (TOD) for 54 PD patients and 22 age-matched controls. Using the mean TOD of the control group, patients were subdivided into two groups: PD with obvious hyposmia (OH-PD, n = 38) and PD with none/less obvious hyposmia (NOH-PD, n = 16). The regional brain activity of all subjects was investigated using RS-fMRI, in combination with regional homogeneity (ReHo) and functional connectivity (FC) analysis. Results There were different ReHo values in the limbic/paralimbic cortices between the OH-PD and NOH-PD groups. ReHo was significantly decreased in OH-PD patients in parts of the traditional olfactory regions (e.g. the amygdala, olfactory gyrus, orbital frontal cortex, parahippocampal gyrus and insula) and some non-traditional olfactory centers (e.g. the rectal gyrus and superior temporal pole), while increased in the left anterior/posterior cingulate cortex. FC analysis revealed decreased functional connectivity within the limbic/paralimbic cortices, especially in regions with reduced ReHo in the OH-PD group. Conclusions PD with hyposmia is related to altered functional activity not only in the traditional olfactory center, but also in some non-traditional olfactory regions of the limbic/paralimbic cortices.

As patients with Parkinson's disease (PD) are at high risk for comorbid depression, it is hypothesized that these two diseases are sharing common pathogenic pathways. Using regional homogeneity (ReHo) and functional connectivity approaches, we characterized human regional brain activity at resting state to examine specific brain networks in patients with PD and those with PD and depression (PDD). This study comprised 41 PD human patients and 25 normal human subjects. The patients completed the Hamilton Depression Rating Scale and were further divided into two groups: patients with depressive symptoms and non-depressed PD patients (nD-PD). Compared with the non-depressed patients, those with depressive symptoms exhibited significantly increased regional activity in the left middle frontal gyrus and right inferior frontal gyrus, and decreased ReHo in the left amygdala and bilateral lingual gyrus. Brain network connectivity analysis revealed decreased functional connectivity within the prefrontal-limbic system and increased functional connectivity in the prefrontal cortex and lingual gyrus in PDD compared with the nD-PD group. In summary, the findings showed regional brain activity alterations and disruption of the mood regulation network in PDD patients. The pathogenesis of PDD may be attributed to abnormal neural activity in multiple brain regions.