Disrupted topologic efficiency of brain functional connectome in de novo Parkinson's disease with depression.

Growing evidence supports that depression in Parkinson's disease (PD) depends on disruptions in specific neural networks rather than regional dysfunction. According to the resting-state functional magnetic resonance imaging data, the study attempted to decipher the alterations in the topological properties of brain networks in de novo depression in PD (DPD). The study also explored the neural network basis for depressive symptoms in PD. We recruited 20 DPD, 37 non-depressed PD and 41 healthy controls (HC). The Graph theory and network-based statistical methods helped analyse the topological properties of brain functional networks and anomalous subnetworks across these groups. The relationship between altered properties and depression severity was also investigated. DPD revealed significantly reduced nodal efficiency in the left superior temporal gyrus. Additionally, DPD decreased five hubs, primarily located in the temporal-occipital cortex, and increased seven hubs, mainly distributed in the limbic cortico-basal ganglia circuit. The betweenness centrality of the left Medio Ventral Occipital Cortex was positively associated with depressive scores in DPD. In contrast to HC, DPD had a multi-connected subnetwork with significantly lower connectivity, primarily distributed in the visual, somatomotor, dorsal attention and default networks. Regional topological disruptions in the temporal-occipital region are critical in the DPD neurological mechanism. It might suggest a potential network biomarker among newly diagnosed DPD patients.

GWAS of grain color and tannin content in Chinese sorghum based on whole-genome sequencing.

KEY MESSAGE: Seventy-three QTL related to grain color and tannin content were identified in Chinese sorghum accessions, and a new recessive allelic variant of TAN2 gene was discovered. Sorghum is mainly used for brewing distilled liquors in China. Since grain tannins play an important role in liquor brewing, accurately understanding the relationship between grain color and tannin content can provide basis for selection standards of tannin sorghum. We resequenced a panel of 242 Chinese sorghum accessions and performed population structure and genome-wide association study (GWAS) to identify quantitative trait locus (QTL) affecting pericarp color, testa pigment, and tannin content. Phylogenetic analysis, principal component analysis (PCA), and admixture model were used to infer population structure. Two distinct genetic sub-populations were identified according to their corresponding northern and southern geographic origin. To investigate the genetic basis of natural variation in sorghum grain color, GWAS with 2,760,264 SNPs was conducted in four environments using multiple models (Blink, FarmCPU, GLM, and MLM). Seventy-three QTL were identified to be associated for the color of exocarp, mesocarp, testa, and tannin content on all chromosomes except chromosome 5, of which 47 might be novel QTL. Some important QTL were found to colocalize with orthologous genes in the flavonoid biosynthetic pathway from other plants, including orthologous of Arabidopsis (Arabidopsis thaliana) TT2, TT7, TT12, TT16 and AT5G41220 (GST), as well as orthologous of rice (Oryza sativa) MYB61 and OsbHLH025. Our investigation of the variation in grain color and tannin content in Chinese sorghum germplasm may help guide future sorghum breeding for liquor brewing.

A CT-based nomogram established for differentiating gastrointestinal heterotopic pancreas from gastrointestinal stromal tumor: compared with a machine-learning model.

OBJECTIVE: To identify CT features and establish a nomogram, compared with a machine learning-based model for distinguishing gastrointestinal heterotopic pancreas (HP) from gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: This retrospective study included 148 patients with pathologically confirmed HP (n = 48) and GIST (n = 100) in the stomach or small intestine that were less than 3 cm in size. Clinical information and CT characteristics were collected. A nomogram on account of lasso regression and multivariate logistic regression, and a RandomForest (RF) model based on significant variables in univariate analyses were established. Receiver operating characteristic (ROC) curve, mean area under the curve (AUC), calibration curve and decision curve analysis (DCA) were carried out to evaluate and compare the diagnostic ability of models. RESULTS: The nomogram identified five CT features as independent predictors of HP diagnosis: age, location, LD/SD ratio, duct-like structure, and HU lesion/pancreas A. Five features were included in RF model and ranked according to their relevance to the differential diagnosis: LD/SD ratio, HU lesion/pancreas A, location, peritumoral hypodensity line and age. The nomogram and RF model yielded AUC of 0.951 (95% CI: 0.842-0.993) and 0.894 (95% CI: 0.766-0.966), respectively. The DeLong test found no statistically significant difference in diagnostic performance (p > 0.05), but DCA revealed that the nomogram surpassed the RF model in clinical usefulness. CONCLUSION: Two diagnostic prediction models based on a nomogram as well as RF method were reliable and easy-to-use for distinguishing between HP and GIST, which might also assist treatment planning.

Diagnostic Value of MRI Features in Dual-phenotype Hepatocellular Carcinoma: A Preliminary Study.

This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC.

Recent Advances in Well-Designed Therapeutic Nanosystems for the Pancreatic Ductal Adenocarcinoma Treatment Dilemma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with an extremely poor prognosis and low survival rate. Due to its inconspicuous symptoms, PDAC is difficult to diagnose early. Most patients are diagnosed in the middle and late stages, losing the opportunity for surgery. Chemotherapy is the main treatment in clinical practice and improves the survival of patients to some extent. However, the improved prognosis is associated with higher side effects, and the overall prognosis is far from satisfactory. In addition to resistance to chemotherapy, PDAC is significantly resistant to targeted therapy and immunotherapy. The failure of multiple treatment modalities indicates great dilemmas in treating PDAC, including high molecular heterogeneity, high drug resistance, an immunosuppressive microenvironment, and a dense matrix. Nanomedicine shows great potential to overcome the therapeutic barriers of PDAC. Through the careful design and rational modification of nanomaterials, multifunctional intelligent nanosystems can be obtained. These nanosystems can adapt to the environment's needs and compensate for conventional treatments' shortcomings. This review is focused on recent advances in the use of well-designed nanosystems in different therapeutic modalities to overcome the PDAC treatment dilemma, including a variety of novel therapeutic modalities. Finally, these nanosystems' bottlenecks in treating PDAC and the prospect of future clinical translation are briefly discussed.

Plasma α-synuclein and phosphorylated tau 181 as a diagnostic biomarker panel for de novo Parkinson's disease.

The use of a diagnostic panel comprising multiple biomarkers has the potential to accurately diagnose Parkinson's disease (PD). However, a panel consisting solely of plasma biomarkers to diagnose PD is not available. This study aimed to examine the diagnostic ability of plasma biomarker panels for de novo PD using novel digital ultrasensitive immunoassay technology. We recruited 45 patients with de novo PD and 20 healthy controls (HCs). The concentrations of plasma α-synuclein (α-syn), amyloid ß-42 (Aß42), Aß40, phosphorylated tau 181 (p-tau181), neurofilament light (NFL), and glial fibrillary acidic protein (GFAP) were quantified using the ultrasensitive single molecule array (Simoa) platform. Patients with de novo PD had higher plasma levels of α-syn and p-tau181 than HCs, adjusting for age and sex. Plasma levels of α-syn and p-tau181 were positively correlated in de novo PD patients. Higher plasma α-syn levels were significantly associated with worse Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor scores, modified Hoehn and Yahr (H-Y) stages, and increased risk of PD with mild cognitive impairment (PD-MCI). Higher plasma p-tau181 concentrations were linked to worse H-Y stages. The diagnostic panel using plasma α-syn and p-tau181, combined with age and sex, showed good performance in discriminating de novo PD patients from HCs (area under the curve = 0.806). These findings suggest that plasma α-syn and p-tau181 together may be a promising diagnostic biomarker panel for de novo PD patients.

Prevalence and genotype-phenotype correlations of GBA-related Parkinson disease in a large Chinese cohort.

BACKGROUND AND PURPOSE: Variants in the glucocerebrosidase (GBA) gene are recognized as a common and important genetic risk factor for Parkinson disease (PD). However, the impact of variant severity on the clinical phenotype of PD in the Chinese population remains unclear. Thus, the present study aimed to determine the frequency of GBA-related PD (GBA-PD) and the relationship of GBA variant severity with clinical characteristics in a large Chinese cohort. METHODS: Long-range polymerase chain reaction and next generation sequencing were performed for the entire GBA gene. GBA variant severity was classified into five classes: mild, severe, risk, complex, and unknown. RESULTS: Among the total 737 PD patients, 47 GBA variants were detected in 79 (10.72%) patients, and the most common GBA variants were R163Q, L444P, and R120W. Complete demographic and clinical data were obtained for 673 patients, which revealed that 18.50% of early onset PD patients had GBA variants. Compared with patients without GBA variants, GBA-PD patients experienced PD onset an average of 4 years earlier and had more severe motor and nonmotor symptoms. Patients carrying severe and complex variants had a higher burden of nonmotor symptoms, especially depression, and more mood/cognitive and gastrointestinal symptoms than patients carrying mild variants. CONCLUSIONS: GBA-PD is highly prevalent in the Chinese population. The severity of GBA variants underlies distinct phenotypic spectrums, with PD patients carrying severe and complex variants seeming to have similar phenotypes. PD patient stratification by GBA variant severity should become a prerequisite for selecting specific treatments.

[Lung Examination in Systemic Toxicitytest of Medical Devices].

The lung is an important organ in systemic toxicity test of medical devices and is significant in safety evaluation. Based on the authors' understanding of medical devices, this study provides a brief analysis of the lung examination and common problems in systemic toxicity, so as to provide references for the pre-clinical safety evaluation of medical devices. It should be noted that a reasonable risk assessment should be made after comprehensive assessment for specific medical device products.

A prediction model for lymph node metastases using pathologic features in patients intraoperatively diagnosed as stage I non-small cell lung cancer.

BACKGROUND: There is little information on which pattern should be chosen to perform lymph node dissection for stage I non-small-cell lung cancer. This study aimed to develop a model for predicting lymph node metastasis using pathologic features of patients intraoperatively diagnosed as stage I non-small-cell lung cancer. METHODS: We collected pathology data from 284 patients intraoperatively diagnosed as stage I non-small-cell lung cancer who underwent lobectomy with complete lymph node dissection from 2013 through 2014, assessing various factors for an association with metastasis to lymph nodes (age, gender, pathology, tumour location, tumour differentiation, tumour size, pleural invasion, bronchus invasion, multicentric invasion and angiolymphatic invasion). After analysing these variables, we developed a multivariable logistic model to estimate risk of metastasis to lymph nodes. RESULTS: Univariate logistic regression identified tumour size >2.65 cm (p < 0.001), tumour differentiation (p < 0.001), pleural invasion (p = 0.034) and bronchus invasion (p < 0.001) to be risk factors significantly associated with the presence of metastatic lymph nodes. On multivariable analysis, only tumour size >2.65 cm (p < 0.001), tumour differentiation (p = 0.006) and bronchus invasion (p = 0.017) were independent predictors for lymph node metastasis. We developed a model based on these three pathologic factors that determined that the risk of metastasis ranged from 3% to 44% for patients intraoperatively diagnosed as stage I non-small-cell lung cancer. By applying the model, we found that the values y > 0.80, 0.43 < y ≤ 0.80, y ≤ 0.43 plus tumour size >2 cm and y ≤0.43 plus tumour size ≤2 cm yielded positive lymph node metastasis predictive values of 44%, 18%, 14% and 0%, respectively. CONCLUSIONS: A non-invasive prediction model including tumour size, tumour differentiation and bronchus invasion may be useful to give thoracic surgeons recommendations on lymph node dissection for patients intraoperatively diagnosed as Stage I non-small cell lung cancer.

To identify important MRI features to differentiate hepatic mucinous cystic neoplasms from septated hepatic cysts based on random forest.

OBJECTIVE: To identify important MRI features to differentiate hepatic mucinous cystic neoplasms (MCN) from septated hepatic cysts (HC) using random forest and compared with logistic regression algorithm. METHODS: Pathologically diagnosed hepatic cysts and hepatic MCNs with pre-operative contrast-enhanced MRI in our hospital from 2010 to 2023 were collected and only septated lesions on enhanced MRI were enrolled. A total of 21 septated HC and 18 MCNs were included in this study. Eighteen MRI features were analyzed and top important features were identified based on random forest (RF) algorithm. The results were evaluated by the prediction performance of a RF model combining the important features and compared with the performance of the logistic regression (LR) algorithm. Finally, for each identified feature, diagnostic probability, sensitivity, and specificity were calculated and compared. RESULTS: Four variables, i.e., the septation arising from wall without indentation, multiseptate, intracapsular cyst sign, and solitary lesion were extracted as top important features with significance for MCNs by the random forest algorithm. The RF model using these variables had an AUC of 0.982 (0.95CI, 0.950-1.000), compared with the LR model based on two identified features with AUC of 0.931 (0.95CI, 0.846-1.000), p = 0.202. Among the four important features, multiseptate had the highest specificity (95.2%) and good sensitivity (72.2%, lower than the septation from wall without indentation, 94.4%) to diagnose MCNs. CONCLUSION: Four out of 18 MRI features were extracted as reliably important factors to differ hepatic MCNs from septated HC. The combination of these four features in a RF model could achieve satisfactory diagnostic efficacy.

Case report: Clinical, imaging, and genetic characteristics of type B niemann pick disease combined with segawa syndrome diagnosed via dual gene sequencing.

Niemann Pick disease B (NPB) often presents with hepatosplenomegaly and lung pathological changes, but it usually does not present with central nervous system symptoms. This report presents the unique case of a 21-year-old woman with a 10-year history of hard skin and hepatosplenomegaly. Genetic sequencing revealed NPB and also suggested Segawa syndrome. Although symptomatic supportive treatments were administered in an attempt to improve muscle tone and treat the skin sclerosis, their efficacy was not satisfactory, and the patient refused further treatment. This case provides several noteworthy findings. First, although NPB and Segawa syndrome are rare, both are autosomal recessive inherited diseases that share common clinical symptoms and imaging manifestations. Second, when NPB and Segawa syndrome are highly suspected, screening for tyrosine hydroxylase (TH) and sphingomyelin phosphodiesterase-1 (SMPD1) gene mutations is critical to determine an accurate diagnosis. Finally, early diagnosis and comprehensive therapies are crucial for improving the prognosis of patients with NPB and Segawa syndrome.

Remodeling mechanism of gel network structure of soy protein isolate amyloid fibrils mediated by cellulose nanocrystals.

The differences in the gelling properties of soy protein isolate (SPI) and soy protein isolate amyloid fibrils (SAFs) as well as the role of cellulose nanocrystals (CNC) in regulating their gel behaviors were investigated in this study. The binding of CNC to ß-conglycinin (7S), glycinin (11S), and SAFs was predominantly driven by non-covalent interactions. CNC addition reduced the particle size, turbidity, subunit segments, and crystallinity of SPI and SAFs, promoted the conversion of α-helix to ß-sheet, improved the thermal stability, exposed more tyrosine and tryptophan residues, and enhanced the intermolecular interactions. A more regular and ordered lamellar network structure was formed in the SAFs-CNC composite gel, which could be conducive to the improvement of gel quality. This study would provide theoretical reference for the understanding of the regulatory mechanism of protein amyloid fibrils gelation as well as the high-value utilization of SAFs-CNC complex as a functional protein-based material or food ingredient in food field.

Insight into the solubilization mechanism of wheat gluten by protease modification from conformational change and molecular interaction perspective.

The low solubility limits the utilization of other functional characteristics of wheat gluten (WG). This study effectively improved the solubility of WG through protease modification and explored the potential mechanism of protease modification to enhance the solubility of WG, further stimulating the potential application of WG in the food industry. Solubility of WG modified with alkaline protease, complex protease, and neutral protease was enhanced by 98.99%, 54.59%, and 51.68%, respectively. Notably, the content of ß-sheet was reduced while the combined effect of hydrogen bond and ionic bond were increased after protease modification. Meanwhile, the reduced molecular size and viscoelasticity as well as the elevated surface hydrophobicity, thermostability, water absorption capacity, and crystallinity were observed in modified WG. Moreover, molecular docking indicated that protease was specifically bound to the amino acid residues of WG through hydrogen bonding, hydrophobic interaction, and salt bridge.

A CT-based radiomics nomogram involving the cystic fluid area for differentiating appendiceal mucinous neoplasms from appendicitis with intraluminal fluid.

OBJECTIVE: To develop and validate a radiomics nomogram based on computed tomography (CT) to distinguish appendiceal mucinous neoplasms (AMNs) from appendicitis with intraluminal fluid (AWIF). METHOD: A total of 211 patients from two medical institutions were retrospectively analysed, of which 109 were pathologically confirmed as having appendicitis with concomitant CT signs of intraluminal fluid and 102 as having AMN. All patients were randomly assigned to a training (147 patients) or validation cohort (64 patients) at a 7:3 ratio. Radiomics features of the cystic fluid area of the appendiceal lesions were extracted from nonenhanced CT images using 3D Slicer software. Minimum redundancy maximum relevance and least absolute shrinkage and selection operator regression methods were employed to screen the radiomics features and develop a radiomics model. Combined radiomics nomogram and clinical-CT models were further developed based on the corresponding features selected after multivariate analysis. Lastly, receiver operating characteristic curves, and decision curve analysis (DCA) were used to assess the models' performances in the training and validation cohorts. RESULTS: A total of 851 radiomics features were acquired from the nonenhanced CT images. Subsequently, a radiomics model consisting of eight selected features was developed. The combined radiomics nomogram model comprised rad-score, age, and mural calcification, while the clinical-CT model contained age and mural calcification. The combined model achieved area under the curves (AUCs) of 0.945 (95% confidence interval [CI]: 0.895, 0.976) and 0.933 (95% CI: 0.841, 0.980) in the training and validation cohorts, respectively, which were larger than those obtained by the radiomics (training cohort: AUC, 0.915 [95% CI: 0.865, 0.964]; validation cohort: AUC, 0.912 [95% CI: 0.843, 0.981]) and clinical-CT models (training cohort: AUC, 0.884 [95% CI: 0.820, 0.931]; validation cohort: AUC, 0.767 [95% CI: 0.644, 0.863]). Finally, DCA showed that the clinical utility of the combined model was superior to that of the clinical CT and radiomics models. CONCLUSION: Our combined radiomics nomogram model constituting radiomics, clinical, and CT features exhibited good performance for differentiating AMN from AWIF, indicating its potential application in clinical decision-making.

MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto's thyroiditis.

Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.

[In vitro evaluation of the function of sheet biomaterials in platelet activation].

In China, the evaluation of hemocompatibility of biomaterials is limited to hemolysis, coagulation time,and the number and morphology of platelets adhered on biomaterials. The present research, however, is aimed to establish a method for evaluating the function of sheet biomaterials in platelet activation. Platelet activation caused by glass, polyvinyl chloride or polymethylvinylsiloxane sheets was evaluated by measuring alpha-granule membrane protein (GMP-140) in platelet poor plasma, using a reasonable blood-material contact model vibrating at different speed. The result showed that the difference in platelet activation was not significantly different among the three above-mentioned materials at 140r/m or 200r/m. However, when it comes to 230r/m, significant difference was observed among these three groups, with glass > polyvinyl chloride > polymethylvinylsiloxane. But the order was reversed at 270r/m, which may be due to the different interfacial tension of different materials. Therefore, the method is suitable to evaluate platelet activation caused by sheet biomaterials, but an appropriate vibrating speed should be chosen. The interfacial tension plays an important role in the model and should be considered for results assessment.

Optimize the pore size-pore distribution-pore geometry-porosity of 3D-printed porous tantalum to obtain optimal critical bone defect repair capability.

The treatment and reconstruction of large or critical size bone defects is a challenging clinical problem. Additive manufacturing breaks the technical difficulties of preparing complex conformation and anatomically matched personalized porous tantalum implants, but the ideal pore structure for 3D-printed porous tantalum in critical bone defect repair applications remains unclear. Guiding appropriate bone tissue regeneration by regulating proper pore size-pore distribution-pore geometry-porosity is a challenge for its fabrication and application. We fabricated porous tantalum (PTa) scaffolds with six different combinations of pore structures using powder bed laser melting (L-PBF) technology. In vitro biological experiments were conducted to systematically investigate the effects of pore structure characteristics on osteoblast behaviors, showing that the bionic trabecular structure with both large and small poress facilitated cell permeation, proliferation and differentiation compared to the cubic structure with uniform pore sizes. The osteogenesis of PTa with different porosity of trabecular structures was further investigated by a rabbit condyle critical bone defect model. Synthetically, T70% up-regulated the expression of osteogenesis-related genes (ALP, COLI, OCN, RUNX-2) and showed the highest bone ingrowth area and bone contact rate in vivo after 16 weeks, with the best potential for critical bone defect repair. Our results suggested that the bionic trabecular structure with a pore size distribution of 200-1200 µm, an average pore size of 700 µm, and a porosity of 70 % is the best choice for repairing critical bone defects, which is expected to guide the clinical application of clinical 3D-printed PTa scaffolds.

Aberrant inter-network functional connectivity in drug-naive Parkinson's disease patients with tremor dominant and postural instability and gait difficulty.

Background: Insight into neural mechanisms of tremor dominant (TD) and postural instability and gait disorder (PIGD) subtypes in Parkinson's disease (PD) is vital for understanding pathophysiological hypotheses underlying this phenotype. However, network disturbances and their correlation with motor subtypes of PD remain unclear. We aimed to investigate the alterations of intra- and inter-network functional connectivity (FC) in drug-naive PD patients with different motor subtypes. Methods: Resting-state functional magnetic resonance imaging was performed on 25 drug-naive PD patients with TD (PD-TD) and 40 drug-naive PD patients with PIGD (PD-PIGD), and 37 healthy controls (HCs) underwent. The following networks were extracted using independent component analysis: sensorimotor network (SMN), left executive control network (LECN), right executive control network, anterior salience network (aSN), posterior salience network (pSN), ventral attention network (VAN), dorsal attention network (DAN), default mode network (DMN), visual network, and auditory network (AN). We measured FC values within and between these networks. Results: There were no detectable variations in intra-network FC. PD-PIGD group demonstrated lower FC between aSN and pSN, as well as between VAN and DMN, in contrast to PD-TD group. Particularly, the FC strength between VAN and DMN was positively correlated with TD and tremor scores, and the best fitting classification models of TD and PIGD subtypes were based on the FC between aSN and pSN. Compared with HCs, both PD-TD and PD-PIGD patients displayed decreased FC between two SMN subnetworks, while PD-TD patients exhibited increased FC between the SMN subnetwork and pSN, and between LECN and VAN. Furthermore, PD-PIGD patients demonstrated decreased FC between the SMN subnetwork and AN. Conclusions: The altered FC between aSN and pSN can be an imaging marker to distinguish PD-TD from PD-PIGD. We for the first time disclosed that the PD-TD patients compensated by increasing attention resources and the PD-PIGD patients displayed reduced FC between SMN and AN. Our findings provide a basis for identification and precision treatment of PD motor subtypes.

Altered functional connectivity of the primary motor cortex in tremor dominant and postural instability gait difficulty subtypes of early drug-naive Parkinson's disease patients.

Background: The primary motor cortex (M1) is an important hub in the motor circuitry of Parkinson's disease (PD), but the subregions' function and their correlation to tremor dominant (TD) and postural instability and gait disturbance (PIGD) with PD remain unclear. This study aimed to determine whether the functional connectivity (FC) of the M1 subregions varied between the PD and PIGD subtypes. Methods: We recruited 28 TD patients, 49 PIGD patients, and 42 healthy controls (HCs). M1 was divided into 12 regions of interest using the Human Brainnetome Atlas template to compare FC among these groups. Results: Compared with HCs, TD and PIGD patients exhibited increased FC between the left upper limb region (A4UL_L) and the right caudate nucleus (CAU)/left putamen (PUT), between the right A4UL (A4UL_R) and the left anterior cingulate and paracingulate gyri (ACG)/bilateral cerebellum4_5 (CRBL4_5)/left PUT/right CAU/left supramarginal gyrus/left middle frontal gyrus (MFG), as well as decreased connectivity between the A4UL_L and the left postcentral gyrus and the bilateral cuneus, and between the A4UL_R and the right inferior occipital gyrus. TD patients showed increased FC between the right caudal dorsolateral area 6 (A6CDL_R) and the left ACG/right MFG, between the A4UL_L and the right CRBL6/right middle frontal gyrus, orbital part/bilateral inferior frontal gyrus, and orbital part (ORBinf), and between the A4UL_R and the left ORBinf/right MFG/right insula (INS). PIGD patients displayed increased connectivity between the A4UL_L and the left CRBL4_5. Compared with PIGD patients, TD patients exhibited increased connectivity between the A6CDL_R and the left ACG/right MFG and between the A4UL_R and the left ACG/left ORBinf/right INS/right MFG. Furthermore, in TD and PIGD groups, the FC strength between the A6CDL_R and right MFG was negatively correlated with PIGD scores, while the FC strength between the A4UL_R and left ORBinf/right INS was positively correlated with TD scores and tremor scores. Conclusion: Our results demonstrated that early TD and PIGD patients share some common injury and compensatory mechanisms. TD patients occupied more resources in the MFG, ORBinf, INS, and ACG, which can be used as biomarkers to distinguish them from PIGD patients.

Persistent Nocardia beijingensis infection in a patient with postoperative abscess and misuse of antibiotics in China.

Here we describe the first case of abscess infection caused by Nocardia beijingensis in China. The patient was immunocompetent but suffered from postoperative abscess for 6 years. This study highlights the necessity of long-term infected foci to be thoroughly examined to identify the pathogen, as well as the importance of accurate Nocardia identification and antimicrobial susceptibility tests for understanding the pathogen's epidemiology, clinical significance, and treatment strategy.