Cognitive-Affective Functions of the Cerebellum.

The cerebellum, traditionally associated with motor coordination and balance, also plays a crucial role in various aspects of higher-order function and dysfunction. Emerging research has shed light on the cerebellum's broader contributions to cognitive, emotional, and reward processes. The cerebellum's influence on autonomic function further highlights its significance in regulating motivational and emotional states. Perturbations in cerebellar development and function have been implicated in various neurodevelopmental disorders, including autism spectrum disorder and attention deficit hyperactivity disorder. An increasing appreciation for neuropsychiatric symptoms that arise from cerebellar dysfunction underscores the importance of elucidating the circuit mechanisms that underlie complex interactions between the cerebellum and other brain regions for a comprehensive understanding of complex behavior. By briefly discussing new advances in mapping cerebellar function in affective, cognitive, autonomic, and social processing and reviewing the role of the cerebellum in neuropathology beyond the motor domain, this Mini-Symposium review aims to provide a broad perspective of cerebellar intersections with the limbic brain in health and disease.

Regulatory mechanisms of PD-1/PD-L1 in cancers.

Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Antitumor mechanisms and future clinical applications of the natural product triptolide.

Triptolide (TPL) is a compound sourced from Tripterygium wilfordii Hook. F., a traditional Chinese medicinal herb recognized for its impressive anti-inflammatory, anti-angiogenic, immunosuppressive, and antitumor qualities. Notwithstanding its favorable attributes, the precise mechanism through which TPL influences tumor cells remains enigmatic. Its toxicity and limited water solubility significantly impede the clinical application of TPL. We offer a comprehensive overview of recent research endeavors aimed at unraveling the antitumor mechanism of TPL in this review. Additionally, we briefly discuss current strategies to effectively manage the challenges associated with TPL in future clinical applications. By compiling this information, we aim to enhance the understanding of the underlying mechanisms involved in TPL and identify potential avenues for further advancement in antitumor therapy.

SN-38, an active metabolite of irinotecan, enhances anti-PD-1 treatment efficacy in head and neck squamous cell carcinoma.

Anti-programmed cell death 1 (anti-PD-1) therapy shows definite but modest activity in patients with advanced/metastatic head and neck squamous cell carcinoma (HNSCC). Preliminary evidence suggests that SN-38, an activated form of irinotecan that increases expression of the transcription factor FoxO3a, can suppress programmed cell death ligand-1 (PD-L1) expression in breast and ovarian tumor models. We analyzed the SN-38-mediated activation of natural killer cells in vitro and explored the efficacy of SN-38 in combination with anti-PD-1 for treatment in vivo. In vitro, SN-38 enhanced the expression of FoxO3a and reduced the expression of c-Myc and PD-L1 dose-dependently in tumor cells. Low-dose SN-38 increased interferon-γ secretion by NK cells and promoted NK cell-mediated cytotoxicity in tumor cells. In vivo studies revealed that at non-cytotoxic drug concentrations, SN-38 significantly enhanced anti-PD-1 activity in suppressing murine tumor growth. We found increased NK cell and CD8+ T-cell infiltration in post-treatment tumors. RNA-seq analysis indicated that SN-38 increased the enrichment of immune cells and biological function genes related to the immune responses. SN-38 is a potentially beneficial adjunct to checkpoint inhibitor therapy in HNSCC. Further studies exploring its mechanism of action and possible applications are necessary. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Budesonide Induces Favourable Histologic and Symptomatic Recovery in Patients with Non-responsive and Refractory Coeliac Disease When Given in an Open Capsule Format.

INTRODUCTION: Non-responsive coeliac disease (NRCD), where symptoms and enteropathy persist despite a prolonged gluten-free diet (GFD), is common. Refractory coeliac disease (RCD), characterised by malabsorption and extensive enteropathy, is rare but serious. In both, treatment options are limited. Topical budesonide may help and an open capsule format promoting proximal small intestinal delivery may be advantageous. AIM: To describe the effect of budesonide and its presentation on mucosal healing, symptoms, and tolerability in NRCD and RCD. METHODS: A retrospective cohort study of NRCD and RCD patients who received budesonide for enteropathy despite a strict GFD for over 12 months. Primary outcome was improvement in histology. Symptoms and adverse treatment effects were recorded. RESULTS: 50 patients with NRCD (n = 14; 86% F), RCD type 1 (n = 30; 60% F), and RCD type 2 (n = 6 based on aberrant duodenal T cells; 33% F) were identified. Common RCD symptoms were diarrhoea (68%), fatigue (40%), and weight loss (34%). 16 received closed capsule budesonide (CCB) 9 mg OD and 35 open capsule budesonide (OCB) 3 mg 3 times a day. Complete and partial mucosal healing was significantly higher after OCB compared to CCB (p < 0.001, Mann-Whitney U test). Symptom improvement was also significantly higher after OCB compared to CCB (p = 0.002, Mann-Whitney U test). Side effects were mild and self-limiting and were reported in 25% of both cohorts. CONCLUSION: OCB was well tolerated and associated with improvements in enteropathy (83%) and symptoms (90%) in NRCD and RCD. Our findings support OCB as the preferred 1st-line therapy for NRCD and RCD type 1.

Extending the diabetic retinopathy screening intervals in Singapore: methodology and preliminary findings of a cohort study.

BACKGROUND: The Diabetic Retinopathy Extended Screening Study (DRESS) aims to develop and validate a new DR/diabetic macular edema (DME) risk stratification model in patients with Type 2 diabetes (DM) to identify low-risk groups who can be safely assigned to biennial or triennial screening intervals. We describe the study methodology, participants' baseline characteristics, and preliminary DR progression rates at the first annual follow-up. METHODS: DRESS is a 3-year ongoing longitudinal study of patients with T2DM and no or mild non-proliferative DR (NPDR, non-referable) who underwent teleophthalmic screening under the Singapore integrated Diabetic Retinopathy Programme (SiDRP) at four SingHealth Polyclinics. Patients with referable DR/DME (> mild NPDR) or ungradable fundus images were excluded. Sociodemographic, lifestyle, medical and clinical information was obtained from medical records and interviewer-administered questionnaires at baseline. These data are extracted from medical records at 12, 24 and 36 months post-enrollment. Baseline descriptive characteristics stratified by DR severity at baseline and rates of progression to referable DR at 12-month follow-up were calculated. RESULTS: Of 5,840 eligible patients, 78.3% (n = 4,570, median [interquartile range [IQR] age 61.0 [55-67] years; 54.7% male; 68.0% Chinese) completed the baseline assessment. At baseline, 97.4% and 2.6% had none and mild NPDR (worse eye), respectively. Most participants had hypertension (79.2%) and dyslipidemia (92.8%); and almost half were obese (43.4%, BMI ≥ 27.5 kg/m2). Participants without DR (vs mild DR) reported shorter DM duration, and had lower haemoglobin A1c, triglycerides and urine albumin/creatinine ratio (all p < 0.05). To date, we have extracted 41.8% (n = 1909) of the 12-month follow-up data. Of these, 99.7% (n = 1,904) did not progress to referable DR. Those who progressed to referable DR status (0.3%) had no DR at baseline. CONCLUSIONS: In our prospective study of patients with T2DM and non-referable DR attending polyclinics, we found extremely low annual DR progression rates. These preliminary results suggest that extending screening intervals beyond 12 months may be viable and safe for most participants, although our 3-year follow up data are needed to substantiate this claim and develop the risk stratification model to identify low-risk patients with T2DM who can be assigned biennial or triennial screening intervals.

Ultrasound analysis of cervical thoracic duct for patients with constrictive pericarditis and chylothorax.

PURPOSE: To analyze ultrasound features of cervical thoracic duct for patients with constrictive pericarditis and chylothorax. METHODS: Patients were retrospectively assessed. The patients were divided into a non-pleural effusion (PE) group (n = 54), a chylothorax group (n = 23), and non-chylothorax group (n = 28). Conventional ultrasound was used to obtain the maximum inner diameter and collapse of the inferior vena cava, the inner diameter of left cervical thoracic duct, and the frequency of opening of the valve at the end of the left thoracic duct. Contrast ultrasonography was used to score the reverse flow of the thoracic tube. RESULTS: The percentage of PE was 48.5%, and the percentage of chylothorax was 21.9%. The three groups had significant differences in five parameters. The inner diameter of left cervical thoracic duct was correlated with the degree of central venous pressure. Contrast ultrasonography was effective in quantitative assessment of the degree of intravenous-thoracic cord reverse flow which correlated with all parameters of central venous pressure. CONCLUSION: Thoracic duct dilation and regurgitation secondary to central venous pressure can lead to chyloreflux disorder and may be the mechanism of chylothorax occurrence in constrictive pericarditis.

Effects of secukinumab combined with tretinoin on metabolism, liver enzymes, and inflammatory factors in patients with moderate to severe psoriasis vulgaris.

Introduction: Psoriasis is a T cell-mediated polygenic chronic inflammatory disease. Interleukin (IL)-17A plays a major role in psoriasis pathogenesis. Secukinumab is a high-affinity human monoclonal antibody against IL-17A. Aim: This article explored efficacy and safety of secukinumab plus tretinoin in moderate to severe psoriasis (MSP) vulgaris, and assessed metabolism, liver function, and inflammation. Material and methods: A total of 135 patients diagnosed with moderate or severe psoriasis vulgaris were enrolled and randomized into three groups at a 1 : 1 : 1 ratio, receiving treatment with rretinoin, secukinumab, or combination therapy for a duration of 16 weeks. Psoriasis area and severity index (PASI) scores, serum T lymphocyte subsets, glucose, lipid, and uric acid (UA) metabolism, liver enzymes, and inflammatory factors (IFs) were measured. Results: Following the therapy, subjects had decreased PASI scores, increased serum CD3+, CD4+, and CD4+/CD8+, decreased serum CD8+, and decreased serum UA and IL-2, IL-6, IL-23, interferon-γ (IFN-γ), and tumor necrosis factor (TNF)-α (p < 0.05). Total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, apolipoproteins A1, B, fasting blood glucose, alanine transaminase, aspartate transaminase, and alkaline phosphatase had no obvious differences among the subjects (p > 0.05). As against the Tretinoin and the Secukinumab groups, the PASI score was visiblysmaller, the changes in serum T lymphocyte subsets were more obvious, and serum UA and IFs were lower in the Combination group following the therapy (p < 0.05). Conclusions: Secukinumab combined with tretinoin is more effective in MSP vulgaris, which can visibly reduce inflammatory response without affecting glucose and lipid metabolism and liver function.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Aberrant Expressions of PSMD14 in Tumor Tissue are the Potential Prognostic Biomarkers for Hepatocellular Carcinoma after Curative Resection.

Introduction: Hepatocellular carcinoma (HCC) has a high mortality rate, with curative resection being the primary treatment. However, HCC patients have a large possibility of recurrence within 5 years after curative resection. Methods: Thus, identifying biomarkers to predict recurrence is crucial. In our study, we analyzed data from CCLE, GEO, and TCGA, identifying eight oncogenes associated with HCC. Subsequently, the expression of 8 genes was tested in 5 cases of tumor tissues and the adjacent non-tumor tissues. Then ATP6AP1, PSMD14 and HSP90AB1 were selected to verify the expression in 63 cases of tumor tissues and the adjacent non-tumor tissues. The results showed that ATP6AP1, PSMD14, HSP90AB1 were generally highly expressed in tumor tissues. A five-year follow-up of the 63 clinical cases, combined with Kaplan-Meier Plotter's relapse-free survival (RFS) analysis, found a significant correlation between PSMD14 expression and recurrence in HCC patients. Subsequently, we analyzed the PSMD14 mutations and found that the PSMD14 gene mutations can lead to a shorter disease-free survival time for HCC patients. Results: The results of enrichment analysis indicated that the differentially expressed genes related to PSMD14 are mainly enriched in the signal release pathway. Conclusion: In conclusion, our research showed that PSMD14 might be related to recurrence in HCC patients, and the expression of PSMD14 in tumor tissue might be a potential prognostic biomarker after tumor resection in HCC patients.

Xanthogranulomatous pyelonephritis with polycystic kidney disease as a mimic of cystic renal cell carcinoma: a case report.

BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is a rare chronic pyelonephritis that often mimics other renal diseases, when combined with autosomal dominant polycystic kidney disease(ADPKD), preoperative diagnosis is exceedingly difficult. It is important for clinicians to be aware of an XGP with ADPKD since a misdiagnosis can lead to unnecessary surgical intervention. CASE PRESENTATION: Here, we report a case of a 66-year-old female with a history of bilateral ADPKD and urinary tract infection admitted to our hospital due to right flank pain, feeble, and low-grade fever. Contrast-enhanced ultrasound revealed a malignant mass of the right kidney suspected to be a cystic renal cell carcinoma with polycystic kidney disease. In addition, contrast-enhanced computed tomography (CT) and fluorine 18 fluorodeoxyglucose PET/CT (18F FDG PET/CT) showed similar results. Subsequently, the patient underwent a right radical nephrectomy, but histopathological examination revealed XGP with ADPKD. On the follow-up, the patient's symptoms were relieved. CONCLUSIONS: XGP should be kept in mind during the differential diagnosis of renal masses with ADPKD even in the absence of characteristic clinical symptoms and imaging manifestations.

Exploring the expression of SNHG1 and its effect on the PI3K-AKT axis in nasopharyngeal cancer.

Radiotherapy and chemotherapy have improved the 5-year survival rate of nasopharyngeal carcinoma (NPC) patients, but the side effects generally lead to unsatisfactory clinical efficacy. It's imperative to explore the pathogenesis of NPC to find better diagnostic and therapeutic methods. Small nucleolar RNA host genes (SNHGs) are special lncRNAs, which can be further spliced to produce small nucleolar RNAs (snoRNAs). SNHG1 has been found to be associated with various cancers. However, only a few studies reported the relationship between SNHG1 and NPC. This study first analyzed the diagnostic performance and related signaling pathways of SNHG1 in NPC through bioinformatics. The expression of SNHG1 was verified by RT-qPCR, and the expression of the signaling pathway was detected using immunohistochemistry. Bioinformatics analysis results showed that SNHG1 was significantly overexpressed in head and neck squamous cell carcinoma (HNSC) and NPC tissues. RT-qPCR detection confirmed the significant overexpression of SNHG1 in NPC tissues. Enrichment analysis showed that SNHG1 may act on NPC through the PI3K-AKT signaling pathway. Immunohistochemistry experiment revealed PI3K-AKT signaling pathway proteins (PI3K AKT and EGFR) positively expressed and CASP3 weakly positively expressed in NPC tissues. Therefore, we concluded that SNHG1 is a prospective biomarker and may act on NPC through the PI3K-AKT signaling pathway.

Multidimensional evaluation of offline and online education in dermatology teaching during the COVID-19 pandemic in a chinese teaching hospital: a cross-sectional study.

BACKGROUND: The global spread of Coronavirus disease (COVID-19) has led to the use of online teaching methods in universities, but the effect of online education on dermatology teaching remains unclear. METHODS: We designed a multi-dimensional teaching evaluation form for data collection, student teaching feedback evaluation, and assessed the scores of final theoretical and clinical skill tests, to compare the effective difference between online and offline teaching of dermatology. RESULTS: A total of 311 valid questionnaires of medical undergraduates were collected, 116 of which were enrolled for offline learning, and 195 for online learning. The average score of final theoretical test in the online teaching group had no significant difference compared with that in the offline teaching group (75.33 ± 7.37 vs.75.63 ± 7.51, P = 0.734). However, both scores of skin lesion recognition test and medical history collection test in the online teaching group were significantly lower than that in the offline teaching group (6.53 ± 0.86 vs. 7.10 ± 1.11, P < 0.001; 6.70 ± 1.16 vs. 7.62 ± 0.85, P < 0.001). Additionally, the scores of understanding skin lesions in the online teaching group were significantly lower than that in the offline group (P < 0.001), and the scores of overall understanding of skin diseases and evaluating their learning mode in the online teaching group also decreased (P < 0.05). Among the 195 students enrolled in the online learning group, 156 students (80.0%) recognized that the time of offline teaching should be increased. CONCLUSIONS: Both online and offline education can be used in dermatology theory teaching, but online education is less efficient in skin lesion and practical skills learning. More online teaching software with skin diseases characteristic should be developed to improve the online teaching effect.

Metabolism-related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation.

Diabetes mellitus (DM) can lead to diabetic ulcers (DUs), which are the most severe complications. Due to the need for more accurate patient classifications and diagnostic models, treatment and management strategies for DU patients still need improvement. The difficulty of diabetic wound healing is caused closely related to biological metabolism and immune chemotaxis reaction dysfunction. Therefore, the purpose of our study is to identify metabolic biomarkers in patients with DU and construct a molecular subtype-specific prognostic model that is highly accurate and robust. RNA-sequencing data for DU samples were obtained from the Gene Expression Omnibus (GEO) database. DU patients and normal individuals were compared regarding the expression of metabolism-related genes (MRGs). Then, a novel diagnostic model based on MRGs was constructed with the random forest algorithm, and classification performance was evaluated utilizing receiver operating characteristic (ROC) analysis. The biological functions of MRGs-based subtypes were investigated using consensus clustering analysis. A principal component analysis (PCA) was conducted to determine whether MRGs could distinguish between subtypes. We also examined the correlation between MRGs and immune infiltration. Lastly, qRT-PCR was utilized to validate the expression of the hub MRGs with clinical validations and animal experimentations. Firstly, 8 metabolism-related hub genes were obtained by random forest algorithm, which could distinguish the DUs from normal samples validated by the ROC curves. Secondly, DU samples could be consensus clustered into three molecular classifications by MRGs, verified by PCA analysis. Thirdly, associations between MRGs and immune infiltration were confirmed, with LYN and Type 1 helper cell significantly positively correlated; RHOH and TGF-ß family remarkably negatively correlated. Finally, clinical validations and animal experiments of DU skin tissue samples showed that the expressions of metabolic hub genes in the DU groups were considerably upregulated, including GLDC, GALNT6, RHOH, XDH, MMP12, KLK6, LYN, and CFB. The current study proposed an auxiliary MRGs-based DUs model while proposing MRGs-based molecular clustering and confirmed the association with immune infiltration, facilitating the diagnosis and management of DU patients and designing individualized treatment plans.

Epidemiololgical and etiological analysis of two clusters of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which is primarily transmitted via tick bites. Clusters of SFTS caused by human-to-human transmission have been reported both at home and abroad, mainly focused on the transmission or exposure modes. However, the correlation between SFTS clusters and viral genotypes has not been investigated. This study mainly reported two clusters of SFTS in Xinyang City, Henan Province, from 2022 to 2023, discussed the possible route of person-to-person transmission of SFTSV infection and analyzed the association between SFTS clusters and virus genotypes. We found that two groups of SFTSV in two clusters were clustered separately into different genotypes through viral sequence analysis of 4 confirmed patients. We also performed phylogenetic analysis, after including SFTSV sequences obtained from SFTS clusters deposited in the GenBank. Three SFTSV genotypes have been reported among cases of human-to-human transmission, suggesting that the occurrence of SFTS clusters may not be related to SFTSV genotypes. This study provided genetic evidence for revealing the chain of human-to-human transmission of SFTS clusters, indicating that contact with patients' blood is an important transmission route of SFTSV. The findings laid the foundation for preventing and controlling human-to-human transmission of SFTS.

[Distinguishing between Artemisia stolonifera and A. argyi by specific PCR of leaves and non-glandular trichomes].

Artemisia stolonifera is a relative of A. argyi. The two species are difficult to be distinguished due to the similarity in leaf shape and have even less distinctive features after processing. This study aims to establish a method to quickly distinguish between them. At the same time, we examined the reasonability and applicability of the specific polymerase chain reaction(PCR) method. The C/T single nucleotide polymorphism was detected at the position 202 of the sequence, based on which specific primers were designed to identify these two species. The PCR with the specific primer JNC-F and the universal primer ITS3R produced a specific band at 218 bp for A. argyi and no band for A. stolonifera, which can be used to detect at least 3% of A. argyi samples mixed in A. stolonifera samples. The PCR with the specific primer KY-F and the universal primer ITS3R produced a specific band at 218 bp for A. stolonifera and no band for A. argyi, which can be used to detect at least 5% of A. stolonifera samples mixed with A. argyi. The limit of detection of the established method was 5 ng DNA. The established PCR method can accurately distinguish between A. stolonifera and A. argyi, which provides an experimental basis for the quality control of A. stolonifera and determines whether the herbs are adulterated.

Cerebellar Oscillations in Familial and Sporadic Essential Tremor.

Enhanced cerebellar oscillations have recently been identified in essential tremor (ET) patients as a key pathophysiological change. Since ET is considered a heterogeneous group of diseases, we investigated whether cerebellar oscillations differ in ET subtypes (familial vs. sporadic). This study aims to determine cerebellar physiology in familial and sporadic ET. Using surface electroencephalogram, we studied cerebellar physiology in 40 ET cases (n = 22 familial and n = 18 sporadic) and 20 age-matched controls. Both familial and sporadic ET cases had an increase in the intensity of cerebellar oscillations when compared to controls. Interestingly, cerebellar oscillations correlated with tremor severity in familial ET but not in sporadic ET. Our study demonstrated that ET cases have enhanced cerebellar oscillations, and the different relationships between cerebellar oscillations and tremor severity in familial and sporadic ET suggest diverse cerebellar pathophysiology.

[Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats].

Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.

[Bifidobacterium bifidum TMC3115 Promotes Early Life Intestinal Microbiota Building to Alleviate Symptoms of Inflammatory Bowel Disease].

Objective: To investigate the effects of using Bifidobacterium bifidum TMC3115 in early life on intestinal microbiota and immune functions and the long-term impact on inflammatory bowel disease. Methods: Fourteen pregnant BALB/c mice were purchased and 84 newborn BALB/c mice were subsequently obtained. Then, the newborn mice were randomly assigned to a normal saline (NS) group and a TMC3115 group, given via oral gavage normal saline and TMC3115, respectively, at a daily volume of 0.2 mL for each mouse. About 42 mice were assigned to each group. The gavage was stopped after 3 weeks. At this point, half of the mice in each group were sacrificed, and then the remaining mice in each group were randomly divided into NS-water group, NS-DSS group, TMC3115-water group, and TMC3115-DSS group, with about 10 mice in each group. The mice were given regular feed until the end of week 6 when they were given 3% dextran sulphate sodium (DSS) ad libitum for 4 days to establish the enteritis model, while the non-modeling groups were given pure water ad libitum. The experiment ended after 6 weeks and 4 days. The weekly body mass changes of the mice were documented. The intestinal tissue at the end of the experiment and the fecal samples, spleen and serum of the mice at 3 weeks and at the end of the experiment were collected to determine the pathology scores of colonic inflammation, the composition of fecal gut microbiota, spleen organ index and the mass concentration of serum cytokines. Results: 1) At the end of the experiment, the inflammatory pathology score was significantly lower in the TMC3115-DSS group compared with that of the Saline-DSS group ( P<0.05), with less disruption of colonic crypt structures and other structures, less inflammatory infiltration, and more intact epithelial structures. 2) At 3 weeks, in comparison with those of the NS group, the relative abundance of Bifidobacteriumwas significantly higher in the feces of the TMC3115 ( P<0.05), the relative abundance of both Enterococcusand Staphylococcuswas lower ( P<0.05), the splenic organ index was significantly higher ( P<0.05), and interleukin (IL)-10 was significantly decreased ( P<0.05), while there was no significant change in IL-6 or TNF-α ( P>0.05). At the end of the experiment, in comparison with those of the NS-DSS group that undergone DSS induction, the TMC3115-DSS group had reduced relative abundance of Staphylococcus, Staphylococcus tumefaciens and Escherichia/ Shigellain the feces ( P<0.05), while the splenic organ index was significantly higher ( P<0.05), and there were no significant changes in IL-6 or TNF-α ( P>0.05). Conclusion: The use of TMC3115 in early life promotes the construction of gut microbiota in neonatal mice, thereby producing a long-term effect that alleviates colitis in mice, but the mechanisms involved are still not fully understood.