Disassociation between fluctuation shift over frequency and glucose metabolism in motor cortex of Parkinson's disease: a hybrid PET/fMRI study.

Increased glucose metabolism and decreased low-frequency fluctuation have been consistently reported in the motor area of Parkinson's disease (PD). The reason for such seeming paradox is unclear. Here, we enrolled 34 PD patients and 25 healthy controls (HCs) for hybrid PET/fMRI scan (PET/fMRI(discovery) dataset). In addition, 2 replication datasets, namely fMRI(validation-1) and fMRI(validation-2) dataset, were also included. We computed ratio of standard uptake value (SUVr) to measure FDG-uptake. The amplitude of low-frequency fluctuations (ALFF) for the following 4 frequency bands was calculated: slow-5, slow-4, slow-3, and slow-2. We obtained a significant group-by-frequency interaction effect of ALFF in the paracentral lobule/supplementary motor area (PFWE = 0.003) and the right sensorimotor area (PFWE < 0.001) in the PET/fMRI(discovery) dataset, which could be replicated using fMRI(validation-1) and fMRI(validation-2) datasets (PFWE < 0.05). In detail, HCs exhibited power law-like fluctuation pattern, but PD patients did not. Correlation analyses further revealed significant associations between ALFF and FDG-uptake in HCs (P-values < 0.031), but not in PD (P-values > 0.28). Taken together, this study identified a fluctuation shift over frequency effect in PD patients, which further disassociated with glucose metabolism in the motor cortex.

Risk Factors for Hypoglycemia Among Neonates: A Prospective Cohort Study Among Pregnant People With Gestational Diabetes Mellitus.

OBJECTIVE: Neonatal hypoglycemia (NH) is the most frequent complication in neonates born to pregnant people with gestational diabetes mellitus (GDM) and an important cause of brain damage and death of neonates. We explored the risk factors for NH in neonates of pregnant people with GDM. METHODS: A prospective cohort study was conducted involving 322 pregnant people with GDM at the Guangzhou Women and Children's Medical Centre. Maternal sociodemographic, clinical, and biochemical data, as well as general characteristics of neonates, were collected to analyze their associations with NH in neonates of pregnant people with GDM. RESULTS: The incidence of NH among neonates of pregnant people with GDM was 19.57% (63/322). After adjustment for confounders, the factors significantly associated with an increased risk of NH were cesarean delivery (relative risk [RR] = 3.44; 95% confidence interval [CI], 1.83-6.45), red blood cell (RBC) count (RR = 2.19; 95% CI, 1.22-3.96), and 1-hour postprandial glucose (RR = 2.35; 95% CI, 1.23-4.46) during pregnancy, whereas later gestational age (RR = 0.58; 95% CI, 0.42-0.80) and multiparity (RR = 0.32; 95% CI, 0.16-0.66) were associated with a reduced risk of NH. CONCLUSION: Cesarean delivery, maternal 1-hour glucose of the oral glucose tolerance test, and increased RBC count of pregnant people with GDM are independent risk factors for NH, while later gestational age and multiparity are protective factors.

Association between gene expression and functional-metabolic architecture in Parkinson's disease.

Gene expression plays a critical role in the pathogenesis of Parkinson's disease (PD). How gene expression profiles are correlated with functional-metabolic architecture remains obscure. We enrolled 34 PD patients and 25 age-and-sex-matched healthy controls for simultaneous 18 F-FDG-PET/functional MRI scanning during resting state. We investigated the functional gradients and the ratio of standard uptake value. Principal component analysis was used to further combine the functional gradients and glucose metabolism into functional-metabolic architecture. Using partial least squares (PLS) regression, we introduced the transcriptomic data from the Allen Institute of Brain Sciences to identify gene expression patterns underlying the affected functional-metabolic architecture in PD. Between-group comparisons revealed significantly higher gradient variation in the visual, somatomotor, dorsal attention, frontoparietal, default mode, and subcortical network (pFDR < .048) in PD. Increased FDG-uptake was found in the somatomotor and ventral attention network while decreased FDG-uptake was found in the visual network (pFDR < .008). Spatial correlation analysis showed consistently affected patterns of functional gradients and metabolism (p = 2.47 × 10-8 ). PLS analysis and gene ontological analyses further revealed that genes were mainly enriched for metabolic, catabolic, cellular response to ions, and regulation of DNA transcription and RNA biosynthesis. In conclusion, our study provided genetic pathological mechanism to explain imaging-defined brain functional-metabolic architecture of PD.

Mediastinal shift angle (MSA) measurement with MRI: a simple and effective tool for prenatal risk stratification in fetuses with congenital diaphragmatic hernia.

OBJECTIVES: To investigate the predictive value of mediastinal shift angle (MSA) in congenital diaphragmatic hernia (CDH). METHODS: A retrospective analysis was performed on 87 fetuses with prenatally diagnosed left-sided CDH (LCDH) and 88 controls. MSA was measured on magnetic resonance imaging (MRI). Lung area to head circumference ratio (LHR), ratio of the observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected total fetal lung volume (O/E TFLV) were also measured. Correlation of MSA with pulmonary hypertension (PH), extracorporeal membrane oxygenation (ECMO) use, duration of hospitalization and survival in neonates with CDH was analyzed. Performance of MSA in prediction of postnatal outcomes was compared with LHR, O/E LHR, TFLV, and O/E TFLV. RESULTS: There were significant differences in MSA values not only between the CDH group and the control group but also in CDH patients with different survival outcomes. MSA was inversely correlated with O/E LHR, O/E TFLV, and TFLV. MSA, LHR, O/E LHR, TFLV, and O/E TFLV could all be used to predict survival of CDH patients. In addition, the receiver operating characteristic (ROC) curve showed that the test performance of MSA was similar to that of TFLV, O/E TFLV, and O/E LHR, but superior to that of LHR. MSA was also correlated with PH, need for ECMO support, and duration of hospitalization. CONCLUSION: MRI measurement of MSA can provide various prognostic information for prenatally diagnosed LCDH, in addition to postnatal survival. The test performance of MSA is similar to TFLV, O/E TFLV, and O/E LHR. KEY POINTS: • Mediastinal shift angle (MSA) can be measured quickly and reproducibly on MRI images. • MSA could provide more prognostic information other than postnatal survival for LCDH with good test performance. • MSA should be incorporated into prenatal risk stratification for LCDH to improve planning of postnatal management.

Simultaneous PET/fMRI revealed increased motor area input to subthalamic nucleus in Parkinson's disease.

Invasive electrophysiological recordings in patients with Parkinson's disease (PD) are extremely difficult for cross-sectional comparisons with healthy controls. Noninvasive approaches for identifying information flow between the motor area and the subthalamic nucleus (STN) are critical for evaluation of treatment strategy. We aimed to investigate the direction of the cortical-STN hyperdirect pathway using simultaneous 18F-FDG-PET/functional magnetic resonance imaging (fMRI). Data were acquired during resting state on 34 PD patients and 25 controls. The ratio of standard uptake value for PET images and the STN functional connectivity (FC) maps for fMRI data were generated. The metabolic connectivity mapping (MCM) approach that combines PET and fMRI data was used to evaluate the direction of the connectivity. Results showed that PD patients exhibited both increased FDG uptake and STN-FC in the sensorimotor area (PFDR < 0.05). MCM analysis showed higher cortical-STN MCM value in the PD group (F = 6.63, P = 0.013) in the left precentral gyrus. There was a high spatial overlap between the increased glucose metabolism and increased STN-FC in the sensorimotor area in PD. The MCM approach further revealed an exaggerated cortical input to the STN in PD, supporting the precentral gyrus as a target for treatment such as the repetitive transcranial magnetic stimulation.

New horizons in Parkinson's disease in older populations.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ageing is considered to be the greatest risk factor for PD, with a complex interplay between genetics and the environment. With population ageing, the prevalence of PD is expected to escalate worldwide; thus, it is of utmost importance to reduce the burden of PD. To date, there are no therapies to cure the disease, and current treatment strategies focus on the management of symptoms. Older adults often have multiple chronic diseases and geriatric syndromes, which further complicates the management of PD. Healthcare systems and care models necessary to address the broad needs of older PD patients are largely unavailable. In this New Horizon article, we discuss various aspects of PD from an ageing perspective, including disease management. We highlight recent advancements in PD therapies and discuss new care models with the potential to improve patient's quality of life.

Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease.

Neurodegeneration of the substantia nigra affects putamen activity in Parkinson's disease (PD), yet in vivo evidence of how the substantia nigra modulates putamen glucose metabolism in humans is missing. We aimed to investigate how substantia nigra modulates the putamen glucose metabolism using a cross-sectional design. Resting-state fMRI, susceptibility-weighted imaging, and [18 F]-fluorodeoxyglucose-PET (FDG-PET) data were acquired. Forty-two PD patients and 25 healthy controls (HCs) were recruited for simultaneous PET/MRI scanning. The main measurements of the current study were R2* images representing iron deposition (28 PD and 25 HCs), standardized uptake value ratio (SUVr) images representing FDG-uptake (33 PD and 25 HCs), and resting state functional connectivity maps from resting state fMRI (34 PD and 25 HCs). An interaction term based on the general linear model was used to investigate the joint modulation effect of nigral iron deposition and nigral-putamen functional connectivity on putamen FDG-uptake. Compared with HCs, we found increased iron deposition in the substantia nigra (p = .007), increased FDG-uptake in the putamen (left: PFWE < 0.001; right: PFWE < 0.001), and decreased functional connectivity between the substantia nigra and the anterior putamen (left PFWE < 0.001, right: PFWE  = 0.007). We then identified significant interaction effect of nigral iron deposition and nigral-putamen connectivity on FDG-uptake in the putamen (p = .004). The current study demonstrated joint modulation effect of the substantia nigra iron deposition and nigral-putamen functional connectivity on putamen glucose metabolic distribution, thereby revealing in vivo pathological mechanism of nigrostriatal neurodegeneration of PD.

Different expressions of aquaporin water channels and macrophages infiltration in human cervix remodeling during pregnancy.

Despite aquaporin water channels (AQPs) play a critical role in maintaining water homeostasis in female reproductive tract and prompt a gradual increase in water content in cervical edema as pregnancy progressed, their relationship with macrophage infiltration and collagen content in human cervical remodeling need to be further investigated. This is the first study to examine the expression and localization of AQP3, AQP4, AQP5, AQP8, and macrophages simultaneously in human cervical ripening. The immunoreactivity of these AQPs was 2.6 to 6-fold higher on gestational weeks 26 (GD26W) than that on GD6W and GD15W, but AQP4 expression on GD39W dropped a similar extent on GD15W, other AQPs continued to rise on GD39W. The AQP3, AQP4, and AQP5 intensity seemed more abundant in cervical stroma than in the perivascular area on GD26W; the distribution of AQP3, AQP5, and AQP8 in cervical stroma was equivalent to that in the perivascular area on GD39W. Macrophage numbers were 1.7-fold higher in subepithelium region and 3.0-fold higher in center area on GD26W than that on GD15W; such numbers remained elevated on GD39W. The electron micrographs showed that cervical extensibility increased significantly on GD26W and GD39W accompanied with increased macrophage infiltration, cervical water content, and much more space among collagen fibers. These findings suggest that the upregulation of AQPs expression in human cervix is closely related to enhanced macrophage infiltration during pregnancy; there may be a positive feedback mechanism between them to lead the increase of water content and the degradation of collagen.

Mediating effects of gut microbiota in the associations of air pollutants exposure with adverse pregnancy outcomes.

BACKGROUND: The aim of this study was to investigate alterations in gut microbiota after exposure to air pollutants during pregnancy and its mediation effect in inducing adverse pregnancy outcomes (APOs). METHODS: Participants (n = 916) were enrolled between 2017 and 2018 from a prospective cohort study of pregnant women in Guangzhou, China. The relative abundance of fecal microbiota was profiled using 16SrRNA V4 region sequencing. Exposure to air pollutants in each trimester of pregnancy was assessed using measurements from the nearest monitoring station. APOs including pre-term birth (PTB), post-term birth (POTB), low birth weight (LBW), macrosomia fetus (MF), birth defects (BDs), pathological cesarean section (PCS) and postpartum hemorrhage (PPH)) were determined by referring to reliable clinical records and diagnostic criteria. Univariate analysis, multivariate analysis and mediation analysis were performed to estimate the association among air pollutants, gut microbiota and APOs. RESULTS: Air pollutants exposure during pregnancy was significantly correlated with the alterations in the gut microbiota, and increased risks of various APOs by 1.07-1.36-fold (P < 0.05). The mediation analyses indicated that alterations in Eggerthella, Phascolarctobacterium and Clostridium partially mediated the effects of air pollutants exposure (PM2.5, PM10, O3, NO2 and SO2) on APOs. The relative abundance of f_Micrococcaceae explained 11.39%, 64.90% and 54.80% of the correlation between SO2, PM2.5, PM10 and POTB, respectively; whereas g_Rothia explained 11.97%, 67.80% and 54.50%, respectively. g_Parabacteroides explained 53.0% of the correlation between PM2.5 and PTB. CONCLUSIONS: Increased air pollutants exposure during pregnancy may induce adverse pregnancy outcomes via alteration of the gut microbiota.

Prenatal diagnosis and postnatal management of congenital mesoblastic nephroma: Experience at a single center in China.

OBJECTIVE: To review the prenatal and postnatal clinical characteristics and pathological subtypes, as well as the surgical outcome for congenital mesoblastic nephroma (CMN) cases. METHOD: A retrospective review was performed in 11 cases with CMN prenatally diagnosed at a single center between 2015 and 2019. The clinical characteristics, surgical outcome, histopathology, and follow-up were retrospectively obtained and reviewed. RESULTS: The median gestational age at which the sonographic diagnosis was made was 35 weeks. Polyhydramnios was found in four (36.4%) cases, and all resulted in a preterm birth. Nine infants had hypertension. Ten cases underwent radical nephrectomy, and one underwent radical nephrectomy and partial adrenalectomy. The pathological results showed that six tumors were classical variants, four mixed variants, and one was a cellular variant. Three cases presented as a stage I, eight as stage II, and no stage III or IV cases were diagnosed. All patients are alive so far. At a median follow-up of 14 months, no local recurrence, or remote metastases were found. CONCLUSION: The prognosis of prenatal CMN cases is excellent after early surgery.

Gentamycin irrigation significantly reduces 28-day surgical site infection after emergency neurosurgery.

OBJECTIVE: This study aims to evaluate the effectiveness of gentamycin irrigation in preventing postoperative surgical site infection (SSI) in emergency neurosurgical procedures. METHODS: A total of 518 consecutive emergency neurosurgeries, including craniotomies, endoscopic and burr hole procedures were reviewed retrospectively. Patients received either only normal saline (NS) irrigation or NS irrigation with gentamycin added (80 mg/L) during the whole process of surgery. SSIs including wound infection and intracranial infection were the primary outcome. SSI was considered while purulence was observed during wound dressing and confirmed with bacterial culture of wound exudation. In addition, positive result of bacterial growth culture of cerebrospinal fluid was also considered as infection. Infection rates were calculated 28 days after surgery. Statistical analysis was performed using t test or Chi-squared test where appropriate. RESULTS: This study included 444 patients. Gentamycin was used in 179 (40.3%) patients. Only 2 (1.1%) of 179 patients receiving gentamycin irrigation had an infection. However, among the other 265 patients receiving only NS irrigation, the infection rate was 8.3%. With the addition of gentamycin, the infection rate was decreased by 86.7% (P = 0.001). The two infected patients in gentamycin group were compromised postoperatively: one patient had removed his own extraventricular drainage tube accidentally due to restlessness, and the other had severely contaminated his wound with vomitus during the intracranial drainage tube removal process. If these two patients were excluded from analysis, the effective infection rate using gentamycin irrigation is 0%. CONCLUSION: The gentamycin plus NS irrigation during emergency neurosurgical procedures can lead to a significantly lower rate of postoperative infection than when NS is used alone.

Predicting poor outcomes and the need for surgical treatment in neonates with meconium peritonitis.

OBJECTIVE: The objective of this study is to determine factors associated with poor outcomes and the need for surgical treatment in neonates with meconium peritonitis (MP). METHODS: We evaluated the association between prenatal ultrasound features, maternal characteristics, and the likelihood of surgery, mortality, and serious morbidity in 49 neonates with a prenatal diagnosis of MP, who were born in Guangzhou Women and Children's Medical Center between January 2011 and December 2016. RESULTS: Thirty of 49 neonates (61.2%) required surgical treatment, and 17 (34.7%) had a poor outcome. Independent predictors of need for surgical treatment were polyhydramnios, maternal intrahepatic cholestasis of pregnancy (associated with lower risk), and persistence of peritoneal fluid. The model correctly predicted 70.0% of the neonates who required surgery (at a 10% false-positive rate; area under the curve [AUC]: 0.86 [95% CI, 0.75-0.97]). For poor outcomes, independent predictors were low gestational age at birth, persistence of peritoneal fluid, and polyhydramnios. For the latter, the model only achieved a detection rate of 52.9% (10% false-positive rate, AUC: 0.82 [95% CI, 0.70-0.94]). CONCLUSIONS: A combination of prenatal ultrasound features and maternal characteristics correctly predicted 70.0% the need for neonatal surgery. Prediction of poor outcome-based prenatal ultrasound features and gestational age did not perform well.

LncRNA TTN-AS1 drives invasion and migration of lung adenocarcinoma cells via modulation of miR-4677-3p/ZEB1 axis.

Lung adenocarcinoma is the most prevalent type of lung cancer with a high incidence and mortality worldwide. Metastasis is the major cause of high death rate in lung cancer and the potential mechanism of lung adenocarcinoma metastasis remains indistinct. Emerging investigations have demonstrated that long noncoding RNA is a kind of non-protein coding RNA and plays a critical role in cancer progression and metastasis. TTN antisense RNA 1 (TTN-AS1) has been reported to promote cell growth and metastasis in cancer. However, the function of TTN-AS1 in lung adenocarcinoma is still to be illustrated. In this study, we observed that TTN-AS1 was upregulated in tissues and cells of lung adenocarcinoma and associated with poor overall survival. TTN-AS1 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition in lung cancer. TTN-AS1 directly bound with miR-4677-3p and negatively regulated miR-4677-3p. MiR-4677-3p rescued the inhibitive impacts of TTN-AS1 knockdown on lung adenocarcinoma. Furthermore, zinc finger E-box binding homeobox 1 (ZEB1) was the target of miR-4677-3p, and TTN-AS1 modulated ZEB1 by competing for miR-4677-3p. TTN-AS1 drove the invasion and migration of lung adenocarcinoma cells by targeting the miR-4677-3p/ZEB1 axis. To sum up, our study offers insights into the mechanism of TTN-AS1 in lung adenocarcinoma metastasis and targeting the TTN-AS1/miR-4677-3p/ZEB1 axis may be the potential innovate therapeutic strategy for the patients with lung adenocarcinoma.

Circulating exosomal microRNA-96 promotes cell proliferation, migration and drug resistance by targeting LMO7.

Detection and treatment of lung cancer still remain a clinical challenge. This study aims to validate exosomal microRNA-96 (miR-96) as a serum biomarker for lung cancer and understand the underlying mechanism in lung cancer progression. MiR-96 expressions in normal and lung cancer patients were characterized by qPCR analysis. Changes in cell viability, migration and cisplatin resistance were monitored after incubation with isolated miR-96-containing exosomes, anti-miR-96 and anti-miR negative control (anti-miR-NC) transfections. Dual-luciferase reporter assay was used to study interaction between miR-96 and LIM-domain only protein 7 (LMO7). Changes induced by miR-96 transfection and LMO7 overexpression were also evaluated. MiR-96 expression was positively correlated with high-grade and metastatic lung cancers. While anti-miR-96 transfection exhibited a tumour-suppressing function, exosomes isolated from H1299 enhanced cell viability, migration and cisplatin resistance. Potential miR-96 binding sites were found within the 3'-UTR of wild-type LMO7 gene, but not of mutant LMO7 gene. LMO7 expression was inversely correlated with lung cancer grades, and LMO7 overexpression reversed promoting effect of miR-96. We have identified exosomal miR-96 as a serum biomarker of malignant lung cancer. MiR-96 promotes lung cancer progression by targeting LMO7. The miR-96-LMO7 axis may be a therapeutic target for lung cancer patients, and new diagnostic or therapeutic strategies could be developed by targeting the miR-96-LMO7 axis.

Impaired vestibular function associated with orthostatic hypotension in patients with multiple system atrophy.

BACKGROUND: Orthostatic hypotension (OH) is one of the most common symptoms in patients with multiple system atrophy (MSA). Vestibular system plays an important role in blood pressure regulation during orthostatic challenges through vestibular-sympathetic reflex. The current study aimed to investigate the relationship between vestibular function and OH in patients with MSA. METHODS: Participants with MSA, including 20 with OH (mean age, 57.55 ± 8.44 years; 7 females) and 15 without OH (mean age, 59.00 ± 8.12 years; 2 females) and 18 healthy controls (mean age, 59.03 ± 6.44 years; 8 females) were enrolled. Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) tests were conducted to evaluate vestibular function. RESULTS: Patients with MSA presented with significantly higher rate of absent cVEMPs (57.1% vs 11.1%, p = 0.001) and oVEMPs (25.7% vs 0, p = 0.021) than controls. MSA patients with OH showed more absent cVEMPs (75.0% vs 11.1%, Bonferroni corrected p < 0.001) and oVEMPs (40.0% vs 0, Bonferroni corrected p = 0.003) than controls. Patients with OH also showed higher rate of absent cVEMPs than those without OH (33.3%, Bonferroni corrected p = 0.014). CONCLUSIONS: Our results demonstrated that impairment of vestibular function was associated with MSA, particularly in those with OH. Absent VEMPs may be a potential marker for MSA severity. Our findings suggest that impaired vestibular function is involved in OH development and may serve as an intervention target.

Effect of acute levodopa challenge test on cerebral blood flow in Parkinson's disease with the supine-to-standing transcranial Doppler test.

BACKGROUND: Levodopa, a common drug that improves symptoms of Parkinson's disease (PD), can induce a reduction in blood pressure (BP); however, the effect of levodopa on cerebral blood flow (CBF) remains unclear. OBJECTIVES: To observe the changes in BP and CBF during active standing before and after the acute levodopa challenge test (ALCT) and analyse the influencing factors of CBF in patients with PD. METHODS: BP and CBF velocity were simultaneously recorded by continuous beat-to-beat non-invasive BP monitoring and transcranial Doppler at supine and orthostatic positions twice, before and after ALCT. The patients were divided into two groups according to those with increased and decreased CBF at baseline after ALCT to analyse the influencing factors. RESULTS: We examined 64 patients with PD (59.2 ± 11.6 years, 33 males). BP decreased at all timepoints after ALCT, while there was no significant change in the magnitude of the drop in BP induced by standing. CBF was reduced after ALCT, especially within 15 s to 1 min of standing (15 s: 48.95 ± 13.50 vs. 44.93 ± 13.26, p < 0.001; 30 s: 52.46 ± 12.06 vs. 50.11 ± 12.56, p = 0.033; 1 min: 52.19 ± 11.83 vs. 50.17 ± 13.21, p = 0.044). Lower body mass index (ß = -0.280, p = 0.027) was an independent factor associated with CBF reduction after ALCT. CONCLUSIONS: Additional attention should be paid to changes in CBF and BP within 1 min after standing in patients with PD taking levodopa, especially in those with low bodyweight.

A Network Pharmacology Study on the Similarities and Differences in the Mechanisms of Zuo Gui Wan/You Gui Wan for the Treatment of Premature Ovarian Failure.

BACKGROUND: Premature ovarian failure is a heterogeneous disease that severely affects the quality of life of women in their reproductive years. The ancient classical Chinese medicine compounds Zuo Gui Wan and You Gui Wan have great potential to treat premature ovarian failure, but the similarities and differences in their pharmacological mechanisms for treating POF are not yet clear. METHODS: In this study, the public database was used to screen the active ingredients and potential targets of Zuo Gui Wan and You Gui Wan. The similarities and differences in the potential targets of both pills for the treatment of POF were analysed using the POF-related genes obtained from OMIM and GeneCards. The protein-protein interaction network was established and collated to form a drug-active ingredient-target gene network using STRING. Finally, the drug-target-pathway network was constructed by enrichment analysis to find the differences in target enrichment on the same pathway. RESULTS: Pharmacological analysis of the network showed that Zuo Gui Wan contains 72 active ingredients, while You Gui Wan has 112. A total of 62 common compositions, such as quercetin and kaempferol, were identified. Amongst them were 10 unique compounds, such as hydroxyproline and cholesterol, in Zuo Gui Wan and 50 exclusive compounds, such as Karanjin and betacarotene, in You Gui Wan. In addition, 14 overlapping targets, including MAPK1, CXCL8, TNF, IL6, and EGFR, were determined amongst the first 20 targets in the treatment of POF by both pills, demonstrating that the core mechanism of POF treatment is similar between the two. Pathway enrichment analysis showed 87 identical and significant pathways between Zuo Gui Wan and You Gui Wan, including IL-17, TNF, PI3K-Akt, oestrogen, VEGF, and other pathways. Zuo Gui Wan has 12 special pathways, such as natural killer cell-mediated cytotoxicity and intestinal immune network for IgA production. You Gui Wan has nine unique pathways, such as insulin secretion and glucagon signalling pathway. CONCLUSION: Zuo Gui Wan and You Gui Wan could treat POF by inhibiting oxidative stress and inflammation, regulating hormone levels, improving ovarian function, and promoting follicular development. Zuo Gui Wan is inclined to immune regulation, while You Gui Wan prefers insulin regulation. Therefore, similarities and differences clearly exist in the specific mechanisms of Zuo Gui Wan and You Gui Wan in the treatment of POF.

Severity-dependent functional connectome and the association with glucose metabolism in the sensorimotor cortex of Parkinson's disease.

Functional MRI studies have achieved promising outcomes in revealing abnormal functional connectivity in Parkinson's disease (PD). The primary sensorimotor area (PSMA) received a large amount of attention because it closely correlates with motor deficits. While functional connectivity represents signaling between PSMA and other brain regions, the metabolic mechanism behind PSMA connectivity has rarely been well established. By introducing hybrid PET/MRI scanning, the current study enrolled 33 advanced PD patients during medication-off condition and 25 age-and-sex-matched healthy controls (HCs), aiming to not only identify the abnormal functional connectome pattern of the PSMA, but also to simultaneously investigate how PSMA functional connectome correlates with glucose metabolism. We calculated degree centrality (DC) and the ratio of standard uptake value (SUVr) using resting state fMRI and 18F-FDG-PET data. A two-sample t-test revealed significantly decreased PSMA DC (PFWE < 0.014) in PD patients. The PSMA DC also correlated negatively with H-Y stage (P = 0.031). We found a widespread reduction of H-Y stage associated (P-values < 0.041) functional connectivity between PSMA and the visual network, attention network, somatomotor network, limbic network, frontoparietal network as well as the default mode network. The PSMA DC correlated positively with FDG-uptake in the HCs (P = 0.039) but not in the PD patients (P > 0.44). In summary, we identified disease severity-dependent PSMA functional connectome which in addition uncoupled with glucose metabolism in PD patients. The current study highlighted the critical role of simultaneous PET/fMRI in revealing the functional-metabolic mechanism in the PSMA of PD patients.

The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy.

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) have similar clinical presentations in their early stages. Orthostatic hypotension (OH) is a common autonomic dysfunction associated with MSA and PD. Heart rate (HR) and systolic blood pressure (SBP) changes are measured in response to the active standing test, which is widely used to screen for cardiovascular autonomic function. Objectives and methods: Overall, 255 patients (67 MSA, 188 PD) underwent continuous beat-to-beat non-invasive BP monitoring and active standing test. The total standing time was 10 min, and the BP differences between both groups were compared to determine whether the ΔHR/ΔSBP can differentiate both conditions. Results: Classical orthostatic hypotension (COH) (52%) and initial OH (19%) were most common in MSA and PD, respectively. MSA had a higher HR (75.0 ± 9.7 vs. 71.0 ± 10.7, P = 0.008) than PD in the supine position. SBP (135.70 ± 15.68 mmHg vs. 127.31 ± 15.14 mmHg, P = 0.106), diastolic BP (78.45 ± 12.36 mmHg vs. 67.15 ± 13.39 mmHg, P = 0.009) and HR (73.94 ± 8.39 bpm vs. 71.08 ± 13.52 bpm, P = 0.389) at baseline were higher in MSA-COH than in PD-COH. After adjusting for age and disease duration, the ΔHR/ΔSBP-10 min significantly discriminated MSA-COH from PD-COH (P = 0.031). An ΔHR/ΔSBP-10 min of 0.517 showed a sensitivity of 67% and specificity of 84% (AUC = 0.77, 95% CI: 0.63-0.91). Conclusion: The SBP, diastolic BP, and HR were higher in the supine position; however, ΔHR and ΔSBP were lower after standing in MSA patients than in PD patients. The ΔHR/ΔSBP-10 min discriminated between MSA-COH and PD-COH with quiet acceptable accuracy.

Mediterranean Diet Combined With a Low-Carbohydrate Dietary Pattern in the Treatment of Overweight Polycystic Ovary Syndrome Patients.

Objectives: To determine the therapeutic effect of a Mediterranean diet (MED) combined with a low-carbohydrate (LC) dietary model in overweight polycystic ovary syndrome (PCOS) patients. Methods: In this 12-week randomized controlled clinical trial, 72 overweight patients with PCOS were randomly assigned to one of two energy-restricted dietary models: the MED/LC diet or the Low fat (LF) diet. After the intervention, the number of the two groups returned to normal menstruation was counted. Body weight, body mass index (BMI), waist circumference, waist-hip ratio (WHR), body fat percentage (BF%), serum fasting insulin(FINS), fasting plasma glucose(FPG), insulin resistance index (HOMA-IR), quantitative insulin sensitivity index (QUIKI), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were compared between 2 groups before and after intervention. Results: MED/LC group had more significant reduction trend in weight (-6.10 ± 1.52 kg vs -4.79 ± 0.97 kg, P < 0.05), BMI (-2.12 ± 0.57 kg/m2 vs -1.78 ± 0.36 kg/m2, P < 0.05), WC (-6.12 ± 5.95 cm vs -3.90 ± 1.58 cm, P < 0.05), WHR (-0.06 ± 0.02 vs -0.03 ± 0.02, P < 0.05), BF% (-2.97% ± 1.78% vs -1.19% ± 0.91%, P < 0.05), TT (-0.20 ± 0.24 ng/mL vs 0.08 ± 0.11 ng/Ml, P < 0.001), LH (-5.28 ± 3.31 mIU/mL vs -3.39 ± 3.64 mIU/mL, P < 0.05), and LH/FSH (-1.18 ± 0.75 vs -0.66 ± 1.05, P < 0.05) compared with the LF group. In addition, FPG (0.05 ± 0.38 mmol/mL vs -0.50 ± 1.01 mmol/mL, P < 0.001), FINS (-4.88 ± 6.11 µU/mL vs -8.53 ± 5.61 µU/mL, P < 0.01), HOMA-IR index (-1.11 ± 1.51 vs -2.23 ± 0.25, P < 0.05), and QUIKI index (0.014 ± 0.016 vs 0.028 ± 0.019, P < 0.05) decreased significantly in the MED/LC group compared with the LF group. Comparing the changes in lipid parameters between the two groups (LF vs MED/LC), significant differences in TG (-0.33 ± 0.32 mmol vs -0.76 ± 0.97 mmol, P < 0.05), TC (-0.40 ± 1.00 mmol vs -1.45 ± 2.00 mmol, P < 0.05), and LDL-C (-0.41 ± 1.05 mmol vs -0.73 ± 0.76 mmol, P < 0.05) were observed. Conclusion: The results of this study suggest that the MED/LC diet model is a good treatment for overweight PCOS patients, significantly restoring their menstrual cycle, improving their anthropometric parameters and correcting their disturbed endocrine levels, and its overall effectiveness is significantly better than the LF diet model. Therefore, this study recommends that the MED/LC diet model can be used in the clinical treatment of patients with overweight PCOS.