BACKGROUND:Depression is a common and early non-motor symptom of Parkinson's disease (PD) with significant sexual dimorphism, yet its underlying molecular mechanisms remain poorly understood. This study aimed to elucidate the sex-specific plasma proteomic profiles of depression in patients with PD (DPD) and to investigate the role of complement-mediated synaptic pruning in its pathophysiology. METHODS:Plasma proteomic analysis was performed on data from the Parkinson's Progression Markers Initiative (PPMI) and an independent validation cohort, stratified by sex. Functional enrichment analyses identified dysregulated pathways. A chronic MPTP/probenecid-induced mouse model of PD was used to validate findings. Behavioural tests assessed motor and depressive-like phenotypes. Proteomic, biochemical, and imaging techniques were used to evaluate protein expression, synapse density, and microglial phagocytosis. The therapeutic mechanism of Botulinum Neurotoxin A (BoNT/A) on DPD was investigated in wild-type, C3-/- and C3aR-/- mice and in microglial cultures. FINDINGS:Proteomic profiling revealed both conserved complement-driven immune dysfunction and profound sex-divergent molecular perturbations underlying PD and DPD. Complement and coagulation cascades were consistently upregulated in both sexes. In MPTP-treated male and female mice, hippocampal complement components (C1Q, C3, C3aR) and downstream signalling (p-STAT3, p-P65) were elevated, accompanied by microglial synapse phagocytosis and depressive-like behaviours. Genetic deletion of C3 rescued both MPTP-induced motor and depressive-like behavioural deficits and prevented hippocampal synaptic loss associated with microglial synaptic engulfment. BoNT/A treatment alleviated depressive-like behaviours and reduced microglial synaptic engulfment in an MPTP model; these therapeutic effects were abolished in C3-/- and C3aR-/- mice. Single-cell RNA sequencing and in vitro phagocytosis assay confirmed that BoNT/A modulated phagocytosis-related microglial subclusters. INTERPRETATION:DPD exhibits distinct sex-specific immune signatures, with convergent complement pathway activation driving microglial synaptic pruning and depressive symptoms. The antidepressant effect of BoNT/A is mediated through inhibition of the C3-C3aR signalling axis. These findings highlight the potential for sex-stratified diagnostics and complement-targeted therapies for depression in patients with PD. A key limitation is that our clinical analyses were constrained by limited validation cohort sizes, and mechanistic studies were limited to male mice, which may restrict the generalisability of our findings to female populations. FUNDING:National Natural Science Foundation of China, Key Project of the Natural Science Foundation of Jiangsu Provincial Higher Education Institutions, Project of Biomedical Basic Research Center (BBRC) of Jiangsu, Clinical Research Center of Neurological Disease in The Second Affiliated Hospital of Soochow University, Project of MOE Key Laboratory of Geriatric Diseases and Immunology, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases; The Lingang Laboratory fund; Shanghai Science and Technology Innovation Sailing Special Project, and Shanghai Municipal Science and Technology Major Project; Zhejiang Provincial Natural Science Foundation of China.

Introduction The combination of venetoclax and azacitidine shows significant efficacy in newly diagnosed acute myeloid leukemia (ndAML) patients. In specific contexts, low-dose venetoclax may be preferred to optimize patient tolerance.Method The study included 64 adult ndAML patients treated at the Affiliated Hospital of Nantong University between April 1, 2021, and April 30, 2024, investigated the efficacy and outcomes of standard-dose versus reduced-dose venetoclax in combination with azacitidine for induction chemotherapy in adult ndAML patients.Results The analysis found no significant difference in composite complete remission (CRc) rates after the first cycle between groups; however, the median event-free survival (EFS) (P = 0.006) and overall survival (OS) (P = 0.014) were markedly shorter in the reduced-dose cohort. Additionally, validation analysis of the 2024 LeukemiaNet (ELN) risk classification revealed a noteworthy distinction in OS among patients with distinct risk classifications receiving reduced-dose venetoclax plus azacitidine (P = 0.048).Conclusion These findings suggest that while both dosing strategies may yield comparable initial responses, long-term outcomes could be adversely influenced by dose reduction, and the 2024 ELN risk classification is more suitable for adult patients with ndAML receiving a reduced-dose regimen of venetoclax and azacitidine.

BoNT type A (BoNT-A) is a neurotoxic protein produced by the anaerobic bacterium Clostridium botulinum. In recent years, BoNT-A has demonstrated substantial efficacy in the management of various diseases, particularly neurological disorders, and has served as a versatile therapeutic agent in modern medicine. This review is aimed at comprehensively examining the application of BoNT-A in various non-dystonia disorders—including hyperhidrosis, salivation, chronic migraine, trigeminal neuralgia, postherpetic neuralgia, primary tremor, depression, and Parkinson’s disease—in the field of neurology.

Circular RNAs (circRNAs) are a group of important molecules involved in the progression of various cancers, including colorectal cancer (CRC). Here, we aim to investigate the role and molecular mechanism of circ_0007422 in regulating CRC malignant progression. The expression levels of circ_0007422, miR-1256, and PDL1 were detected by qRT-PCR. Cell viability, proliferation, apoptosis, invasion, and self-replication ability were analyzed by CCK-8, EdU, flow cytometry, transwell, and spheroid formation experiments, respectively. Protein levels were determined by western blotting assay. CRC cells were co-cultured with CD8 + T cells, phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs), or cytokine-induced killer (CIK) cells in vitro, and CD8 + T-cell apoptosis, IFN-γ and TNF-α levels, and survival rate of CRC cells were analyzed to reveal the role of circ_0007422 in antitumor immunity. The relationship between miR-1256 and circ_0007422 or PDL1 was identified by a dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft tumor model was established to verify the function of circ_0007422 in tumor growth in vivo. Immunohistochemistry (IHC) assay was used to detect positive expression rates of Ki67, E-cadherin, N-cadherin, and PDL1 expression in primary tumors from CRC cells. Circ_0007422 was upregulated in CRC tissues and cells and its knockdown inhibited proliferation, invasion, self-replication ability, and immune escape and promoted apoptosis of CRC cells. Additionally, circ_0007422 bound to miR-1256, which was identified to target PDL1. MiR-1256 inhibition reversed the effects of circ_0007422 knockdown on the tumor properties and immune escape of CRC cells. Moreover, miR-1256 introduction interacted with PDL1 to suppress proliferation, invasion, self-replication ability, and immune escape and promote apoptosis of CRC cells. Further, circ_0007422 knockdown hampered tumorigenesis of CRC cells in vivo. Circ_0007422 knockdown inhibited tumor property and immune escape of colorectal cancer through the miR-1256/PDL1 pathway, providing a potential novel therapeutic target for CRC.

Objective:Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods:Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results:Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion:In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Central lymphoma includes two types, primary and secondary. Current treatment regiments are not effective in many patients. zanubrutinib is a BTK inhibitor and pomalidomide is an immunomodulator, which have been reported to be used in the treatment of central nervous system lymphoma. Aims: To investigate the efficacy and safety of zanubrutinib combined with pomalidomide in the treatment of primary or secondary central nervous system lymphoma. Methods: A total of 8 patients diagnosed with primary or secondary central nervous system lymphoma from October 2021 to January 2023 were included. They received zanubrutinib combined with pomalidomide based regimen for at least 2 courses, and the short-term efficacy and safety were analyzed. Results: Among the 8 patients, 7 were effective after 2 courses of treatment, 1 was lost to follow-up. 7 remained effective after 4 courses of treatment,2 patients had central recurrence after 5 courses of treatment, all of which were secondary central nervous system lymphoma involving cerebrospinal fluid, and 1 patient died of coronavirus disease (COVID-19） infection. The adverse reactions were mainly hemocytopenia and pulmonary infection. One case of hypokalemia was aggravated. The adverse events were controllable and improved after symptomatic treatment. Summary/Conclusion: The regimen based on zanubrutinib and pomalidomide has certain efficacy in the treatment of primary or secondary central nervous system lymphoma, and the combination of zanubrutinib and pomalidomide can further improve the response rate and remission time. However, due to the limited cases, the strength of relevant clinical suggestions needs to be further confirmed by expanding the sample size and multi-center studies. Keywords: Immunomodulation, Lymphoma therapy, Bruton’s tyrosine kinase inhibitor (BTKi)

Background: The tumor microenvironment and tumor immunity have become the focus of research on tumor diagnosis and treatment. Lymphocyte activation gene-3 (LAG-3, CD223) is a newly discovered immunosuppressive receptor that is abnormally expressed in various tumor microenvironments and plays an important role as an immune checkpoint in the tumor immune response. Objective: We developed a novel enzyme-linked immunosorbent assay kit, examined the levels of soluble LAG-3 (sLAG-3) in the serum of patients with cervical cancer, and identified new biomarkers for cervical cancer development. Methods: To investigate the potential biological function of sLAG-3, we generated and characterized 2 novel anti-LAG-3 monoclonal antibodies, namely 4F4 and 4E12. We performed western blotting, immunofluorescence, and immunohistochemistry using hybridoma technology and an enzyme-linked immunosorbent assay kit for detecting human sLAG-3 based on an improved double-antibody sandwich enzyme-linked immunosorbent assay method. The stability and sensitivity of these kits were also assessed. Results: We screened and characterized 2 novel monoclonal antibodies against human LAG-3. The enzyme-linked immunosorbent assay kit also includes a wide range of tests. Using this enzyme-linked immunosorbent assay system, we found that the expression level of sLAG-3 in the peripheral blood of patients with cervical cancer significantly decreased as the disease progressed ( P < .0001). Multivariate logistic regression analysis revealed that low sLAG-3 expression was an independent predictor of cervical cancer and related diseases ( P < .05). Furthermore, receiver operating characteristic curve analysis showed that sLAG-3 had diagnostic value for cervical cancer metastasis ( P < .0001). Conclusion: These data suggest that sLAG-3 is a potential biomarker for cervical cancer development. Therefore, this kit has a certain application value in the diagnosis of cervical cancer.

Depression is one of the common non-motor symptoms of Parkinson’s disease (PD). In the clinic, botulinum neurotoxin A (BoNT/A) has been used to treat depression. In this study, we investigated the mechanisms underlying the anti-depressive effect of BoNT/A in a PD mouse model. Mice were administered reserpine (3 μg/mL in the drinking water) for 10 weeks. From the 10 th week, BoNT/A (10 U·kg −1 ·d −1 ) was injected into the cheek for 3 consecutive days. We showed that chronic administration of reserpine produced the behavioral phenotypes of depression and neurochemical changes in the substantia nigra pars compacta (SNpc) and striatum. BoNT/A treatment significantly ameliorated the depressive-like behaviors, but did not improve TH activity in SNpc of reserpine-treated mice. We demonstrated that BoNT/A treatment reversed reserpine-induced complement and microglia activation in the hippocampal CA1 region. Furthermore, BoNT/A treatment significantly attenuated the microglial engulfment of presynaptic synapses, thus ameliorating the apparent synapse and spine loss in the hippocampus in the reserpine-treated mice. Moreover, BoNT/A treatment suppressed microglia-mediated expression of pro-inflammatory cytokines TNF-α and IL-1β in reserpine-treated mice. In addition, we showed that BoNT/A (0.1 U/mL) ameliorated reserpine-induced complement and microglia activation in mouse BV2 microglial cells in vitro. We conclude that BoNT/A ameliorates depressive-like behavior in a reserpine-induced PD mouse model through reversing the synapse loss mediated by classical complement induced-microglial engulfment as well as alleviating microglia-mediated proinflammatory responses. BoNT/A ameliorates depressive-like behavior, and reverses synapse loss mediated by classical complement pathway-initiated microglia engulfment as well as alleviates microglia-mediated proinflammatory response in the reserpine-induced Parkinson’s disease mouse model.

Introduction: Relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (R/R T-ALL/LBL) is highly heterogeneous. The available salvage treatment options for relapsed patients showed remission rates of less than 50% and a 5-year overall survival (OS) rate of less than 25%. Venetoclax, a Bcl-2 inhibitor, in combination with azacitidine, has demonstrated a high remission rate in 5 patients with R/R T-ALL/LBL in our previous report. Here, we report the interim analysis of a phase 2 study (NCT05149378) for the treatment of venetoclax combined with azacitidine for R/R T-ALL/LBL. Methods: From November 2021 to May 2023, a total of 18 R/R T-ALL/LBL patients were enrolled in the study. Among them, 11 were male and 7 were female. These patients were from seven hospitals, including the central hospital of the First Affiliated Hospital of Soochow University. All patients received salvage treatment with venetoclax (orally, 100mg on day 1, 200mg on day 2, and 400mg on days 3-21) and azacitidine（75mg/m 2/d on days 1-7, subcutaneously). Bone marrow evaluation was performed after the blood cell count recovery or within 42 days since the initiation of the treatment. Results: Among the 18 patients enrolled, 8 were diagnosed with T-ALL, 7 with ETP-ALL, and 3 with T-LBL (Table). 5/18 patients were relapsed T-ALL/LBL, 13/18 patients were refractory to previous treatments. The median age of the patients was 39 years (range: 30-53). After 1-2 courses of venetoclax in combination with azacitidine regimen. 4 (22.2%) achieved CR, 1 patient (5.6%) achieved CRh, 9 (50.0%) patients achieved CRi and 2 (11.1%) achieved MLFS. The overall response rate was 88.9%. With a median follow-up time of 24.1 months (95% CI: 6.8-41.4), the estimated median OS was 24.1 months (95% CI: 6.8-41.4) (Figure a) and the median relapse-free survival was 14.0 (95% CI: 3.8-24.2) months (Figure b). After the treatment, 12/18 (66.7%) patients underwent allogeneic hematopoietic stem cell transplantation. Five patients experienced relapse between 6 to 19 months after the venetoclax and azacitidine treatment. Four patients died because of relapse after the regimen, two patients died because of COVID-19. Grade 3 or higher treatment-related hematologic AE included neutropenia (15/18, 83.3%), anemia (6/18, 33.3%), and thrombocytopenia (4/18, 22.2%). Treatment-related non-hematologic AE included infections (6/18, 33.3%. 4 patients developed pneumonia, 1 patient had perianal infection, 1 patient developed sepsis), elevation of ALT and AST (5/18, 27.8%), and renal function impairment (2/18, 11.1%). There was no other grade 3 or higher non-hematologic AE and no treatment-related death was observed. Conclusion: Our results showed that venetoclax in combination with azacitidine was an effective salvage regimen for R/R T-ALL/LBL patients. The benefit of this regimen for distinct cytogenetic groups in R/R T-ALL/LBL needs to be analyzed in more cases.

INTRODUCTION:Diabetic foot infection is a serious and painful process for patients with diabetes, and the considerable morbidity associated with the condition warrants attention. Effective inflammatory markers may become important in the detection of diabetic foot infection.OBJECTIVE:The goal of the research was to systematically assess the function of inflammatory markers in the detection of diabetic foot infection.METHODS:Online databases including PubMed, SpringerLink, and Web of Science were searched. The quality of research and data was assessed using the Newcastle-Ottawa Scale. A random-effects model was used to compare changes in inflammatory markers between patients with infected diabetic foot (IDF) and patients with non-infected diabetic foot.RESULTS:Ten studies with 785 participants were included in the systematic review. The study analyzed 3 inflammatory markers: white blood cell (WBC) count, C-reactive protein (CRP) level, and procalcitonin (PCT) level. The meta-analysis indicated that mean WBC count (standardized mean differences [SMD]: 0.51, 95% CI: 0.23, 0.79; P < .0001), mean CRP level (SMD: 1.05, 95% CI: 0.60, 1.50; P < .0001) and mean PCT level (SMD: 0.80, 95% CI: 0.36, 1.24; P < .0001) were higher in patients with IDF. The differences were statistically significant, but the funnel plots indicated the existence of publication bias.CONCLUSIONS:The meta-analysis further confirmed the significant association between inflammatory markers and diabetic foot infection. It also confirmed that WBC count, CRP level, and PCT level can be used as laboratory auxiliary indexes in the detection of diabetic foot infection, providing information for improved diagnosis and prevention.

Objective. To systematically evaluate the clinical value of tenofovir combined with recombinant human interferon α-2b in the treatment of chronic hepatitis B and to provide evidence-based medicine for its popularization and use. Methods. The randomized controlled trials (RCTs) of tenofovir combined with recombinant human interferon α-2b in the online database of PubMed, EMBASE, ScienceDirect, Cochrane Library, China knowledge Network (CNKI), China VIP database, Wanfang database, and China Biomedical Literature Database (CBM) were searched. The data included in this study were extracted by two independent researchers. After extracting the data of the study, the Cochrane manual 5.1.0 standard was used to evaluate the bias risk of all the literature included in this study. RevMan5.4 statistical software was used to analyze the collected data by meta. Results. Entecavir combined with recombinant human interferon α-2b can inhibit the activity of HBV polymerase and improve the inflammatory response of the liver. Recombinant human interferon α-2b can regulate immune function by inducing T cell differentiation and maturation and enhancing the production of cytokines. The systematic evaluation showed that entecavir combined with recombinant human interferon α-2b had higher serum HBeAg negative conversion rate, higher drug safety compared with entecavir alone, and improved liver function and immune status. Conclusion. Tenofovir combined with recombinant human interferon alpha-2b has a high serum HBeAg negative rate and safety profile for the treatment of chronic hepatitis B. The combination treatment can improve liver function and immune status in patients, but more studies with higher methodological quality and longer duration of intervention are needed for further validation.

OBJECTIVE:To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane. METHODS:The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet. RESULTS:The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05). CONCLUSION:A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Atherosclerosis is the leading cause of coronary heart disease. In recent years, circ_0029589 (circCHFR) has been found to be associated with atherosclerosis development. However, the molecular mechanism of circCHFR action in atherosclerosis development is unknown. This study was aimed to investigate the function and action mechanism of circCHFR in atherosclerosis development. An atherosclerosis cell model was created by exposing human vascular endothelial cells (HUVECs) to oxidized low-density lipoprotein. The expression of circCHFR, microRNA(miR)-15b-5p, growth arrest and DNA damage inducible gamma (GADD45G), and their associated proteins was evaluated using quantitative reverse transcription-polymerase chain reaction and Western blotting. Additionally, cell viability, apoptosis, and cytokine levels were determined using Cell Counting Kit-8 (CCK8) assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. circCHFR expression was upregulated in patients with atherosclerosis and oxidized low-density lipoprotein (ox-LDL)-exposed HUVECs, whereas miR-15b-5p expression was downregulated. circCHFR silencing significantly improved viability and reduced apoptosis of HUVECs. In addition, the pro-apoptotic protein Bax and atherosclerosis-associated cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) were significantly downregulated, whereas the anti-apoptotic protein Bcl-2 was upregulated. Further, we discovered that circCHFR serves as a molecular sponge of miR-15b-5p. GADD45G was found to be an important target of miR-15b-5p; miR-15b-5p mimic inhibited GADD45G expression, reduced apoptosis and proinflammatory cytokine secretion, and improved cell survival. However, these effects of miR-15b-5p on (ox-LDL) induced HUVECs were reversed with GADD45G plasmid co-transfection. In conclusion, circCHFR promotes atherosclerosis progression via the miR-15b-5p/GADD45G axis and may be an important target for atherosclerosis treatment.

Abstract Background: Pleural effusion (PE) is a common disease in clinical practice. Cholesterol PE or pseudochylothorax is a special type of exudative PE. For the lack of deep understanding of cholesterol PE, it is easy to misdiagnose in clinical practice. Case presentation: A 65-year-old male patient was diagnosed with Secondary tuberculosis (both lungs, smear positive, initial treatment), Tuberculous pleurisy, Cholesterol Pleural Effusion. 800 ml yellow pleural effusion (“Motor-oil” appearance) was drained from the patient’s pleural space after admission. A large number of crystals were observed from the patients’ pleural effusion. The level of Cholesterol (CHOL) of the patients’ PE was 11.41mmol/L. According to the weight of the patients, Isoniazid (0.3g/d), Rifampicin (0.45g/d), Pyrazinamide (2g/d), and Ethambutol (0.75g/d) were used to treat tuberculosis. And small doses of glucocorticoids (start with 32 mg of methylprednisolone, then decrease by 8 mg every week, and stop after 4 weeks) were used to inhibit pleural effusion. The pleural effusion was obviously absorbed, and the sputum smear was negative of the patient subsequent to his visit On May 22, 2021 Conclusions: Cholesterol PE is a rare condition that mainly results from tuberculosis or rheumatoid diseases. “Motor-oil” appearance, numerous rhomboid-shaped cholesterol crystals, and pleural fluid cholesterol (PFCHOL) higher than 200 mg/dL are the key characteristics of Cholesterol PE. The treatment of Cholesterol PE is dependent upon the underlying disease. Glucocorticoid seemed to be an effective adjunctive therapy for Cholesterol PE.

Reserpine is an effective drug for the clinical treatment of hypertension. It also induces Parkinson's disease (PD)-like symptoms in humans and animals possible through the inhibition of monoamine vesicular transporters, thus decreasing the levels of monoamine neurotransmitters in the brain. However, the precise mechanisms remain unclear. Herein, we aimed to develop a preclinical reserpine model recapitulating the non-motor and motor symptoms of PD and investigate the underlying potential cellular mechanisms. Incubation of reserpine induced apoptosis, led to the accumulation of intracellular reactive oxygen species (ROS), lowered DNA methylation of alpha-synuclein gene, resulted in alpha-synuclein protein deposition, and elevated the ratio of LC3-II/LC3-Ⅰ and p62 in cultured SH-SY5Y cells. Feeding reserpine dose-dependently shortened the lifespan and caused impairment of motor functions in male and female Drosophila. Moreover, long-term oral administration of reserpine led to multiple motor and non-motor symptoms, including constipation, pain hypersensitivity, olfactory impairment, and depression-like behaviors in mice. The mechanistic studies showed that chronic reserpine exposure caused hypomethylation of the alpha-synuclein gene and up-regulated its expression and elevated the ratio of LC3-II/LC3-Ⅰ and expression of p62 in the substantia nigra of mice. Thus, we established preclinical animal models using reserpine to recapitulate the motor and non-motor symptoms of PD. Chronic reserpine exposure epigenetically elevated the levels of alpha-synuclein expression possible by lowering the DNA methylation status and inducing autophagic impairment in vitro and in vivo.

BACKGROUND:Depression is characterized by low moods, anhedonia, and social avoidance. Effective and acceptable treatments are required for depression. Positive effects on mood have been observed in patients with depression after treatment with botulinum toxin A (BoNT/A).METHODS:A total of 88 patients with depression were randomly assigned to BoNT/A (n = 56) and placebo (saline, n = 22) groups. The primary objective was to determine the change in the 17-item version of the Hamilton Depression Rating Scale (HAMD), 12 weeks after the treatments when compared with the baseline.RESULTS:The BoNT/A and placebo groups did not differ significantly in all the collected baseline characteristics. However, there was a significant improvement in the depressive symptoms of the BoNT/A group compared to those of the placebo group throughout the 12-week follow-up period. This was according to the measurements of HAMD (F (1, 370) = 9.094, P = 0.0027), Self-rating Depression Scale (SDS) (F (1, 370) = 11.26, P < 0.001), Hamilton Anxiety Scale (HAMA) (F (1, 410) = 8.673, P = 0.0034) and Self-rating Anxiety Scale (SAS) (F (1, 379) = 5.788, P = 0.017). Furthermore, the effectiveness was even higher at the end of the study period.LIMITATIONS:The limitations include the absence of a multicenter study and an inadequate number of cases. Additionally, the mechanism of BoNT/A antidepression was not studied.CONCLUSION:This study showed that a single treatment with BoNT/A may accomplish a strong and sustained alleviation of depression in patients.

Background Diabetic foot (DF) is a dangerous complication of diabetes. The aim of the study was to synthesize all the published single nucleotide polymorphisms (SNPs) of DF to objectively evaluate the relationship of SNPs and DF risks. Methods The HuGE database and CNKI were searched for eligible publications on genetic polymorphisms and the risk of DF systematically. The quality of literatures was evaluated by the Newcastle-Ottawa scale. Pooled odds ratios with a 95% confidence interval for SNPs were evaluated through 3 genetic models. Results Citing 29 different polymorphisms from 24 articles and the study met our selection criteria. There were 24 polymorphisms summarized systematically, and 5 merged polymorphisms for a meta-analysis: 9 positively associated with DF: HIF-1α rs11549465, TNF-α rs1800629, TLR-9 rs5743836, FIB rs6056, HSP70-2437C/T, VDR rs2228570, LOX rs1800449, ITLN1 rs2274907, and OPG rs2073617, but OPG rs3134069 was not a risk factor in DF; 6 negatively associated with DF: VEGF rs833061 and rs2010963, MCP-1 rs1024611, SDF-1 rs1801157, SIRT1 rs12778366, and OPG rs2073617. In addition, 13 polymorphisms were not associated with DF: MMP-9 rs3918242, eNOS rs1799983, VEGF rs3025039, -7C/T, rs1570360, rs13207351, and rs699947, IL-6 rs1800795, HIF-1α rs11549467, TNF-α rs361525, TLR-2 rs3804100, SIRT1 rs3758391, and TIMP-1 rs2070584. Conclusions The study provided some evidence for SNPs to the development of diabetic foot. The meta-analysis showed that rs1024611 of MCP-1 may be regarded as a protective factor, especially in Asian populations. Other loci indicated inconsistent results.

Background: Long intergenic noncoding RNA regulator of reprogramming (linc-ROR) is a novel long noncoding RNA that exhibits significant effects on cancer progression. This research presented that linc-ROR had a crucial part in promoting biological characteristics associated with worse prognosis in colon cancer. Method: Bioinformatics analysis was performed to predict signaling pathways related to linc-ROR. In addition, western blot, quantitative reverse transcription-polymerase chain reaction, RNA-pulldown, cell proliferation assays, colony formation assays, wound healing assays, and transwell assays were applied to detect the role and regulation of particular molecules. Results: Our results showed that the knockdown of linc-ROR reduced cell invasion, proliferative ability, and migration in colon cancer. Further evaluation verified that downregulating linc-ROR inhibited the activation of epidermal growth factor receptor (EGFR) signaling. In addition, cbl-b, a kind of E3 ubiquitin ligase that increases the degradation of EGFR, was found to be a potential linc-ROR target. Conclusions: Based on our findings, it was presented that linc-ROR served a role as a tumor-promoting factor via repressing the ubiquitination and degradation of EGFR signaling, which indicated that it could be a possible prognostic marker and therapeutic target for colon cancer.

Background: Timely and effective removal of respiratory secretions is of great significance for tracheotomized patients. The purpose of this study is to investigate the effectiveness of capsaicin nebulization to stimulate cough to promote early clearance of respiratory secretions in tracheotomized patients after hemorrhagic stroke. Method: This study implemented a randomized controlled design. Sixty-three patients who were tracheotomized following a hemorrhagic stroke completed this randomized controlled trial. In the control group, 33 cases were given a routine care after tracheotomy. In the intervention group, 30 cases were given a capsaicin solution nebulization in addition to the routine care. The daily sputum output and the number of sputum suctioning were observed. The differences in sputum viscosity, cough function, and Clinical Pulmonary Infection Score (CPIS) were compared between the two groups before and after the intervention. Vital sign changes during capsaicin nebulization and suctioning were compared between the two groups in a pilot study. Results: The daily sputum output of the capsaicin intervention group was significantly higher than that of the control group (p < .05). The number of sputum suctioning of capsaicin group was less than that of the control group after intervention (p < .05). The CPIS score of the capsaicin group was lower than that of the control group (p < .05) after a 1-week intervention. Patients' heart rate, respiratory rate, and oxygen saturation during capsaicin nebulization were not statistically different from those during routine sputum suctioning (p > .05). Conclusions: Capsaicin atomization-induced cough can effectively promote sputum excretion of hemorrhagic stroke patients undergoing tracheotomy and has a good safety profile. The Clinical Trial registration number of this study is ChiCTR2000037772 (http://www.chictr.org.cns). Supplemental Material: https://doi.org/10.23641/asha. 16821352

BACKGROUND: Osteomyelitis of the foot is a risk factor for amputation in persons with diabetes mellitus. There is some evidence to suggest that patient sex affects the risk of diabetes-related foot complications. PURPOSE: To examine the effect of sex on osteomyelitis risk in patients with diabetic foot disease. METHODS: Systematic searches of PubMed and the China National Knowledge Infrastructure were performed from inception through May 2020 using the terms "diabetic foot" and "osteomyelitis." Original research studies including persons with diabetes mellitus, diabetic foot disease, or ulcers as well as reports of osteomyelitis were included. Study quality was assessed according to the Newcastle-Ottawa Scale. The pooled odds ratio (OR) and 95% confidence interval (CI) for osteomyelitis were calculated by sex. RESULTS: Nine (9) studies from 6 countries involving 2583 patients met the inclusion criteria for analysis. No significant publication bias was observed. The average age of patients was 65.2 years, and 32.03% of men and 30.0% of women were diagnosed with osteomyelitis. The pooled OR was 1.14 (95% CI, 0.94-1.38; P =.76). Regression analysis (t = -0.61; P >.561) showed no association between the incidence of osteomyelitis and ORs. CONCLUSION: This meta-analysis suggests that patient sex does not affect the odds of having osteomyelitis among persons with diabetes and diabetic foot disease or ulcers.