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Systematic immune responses have been identified in patients with acute spontaneous intracerebral hemorrhage (ICH). T cells have been established to participate in central nervous system damage and repair following brain injury. However, their contribution to the prognosis of patients with ICH remains to be elucidated. In this study, peripheral blood mononuclear cells (PBMCs) were collected from 45 patients with acute spontaneous ICH (

Abstract Background The cryptochromes (CRY) are specific blue light receptors of plants and animals, which play crucial roles in physiological processes of plant growth, development, and stress tolerance. Results In the present work, a systematic analysis of the CRY gene family was performed on twelve cotton species, resulting in 18, 17, 17, 17, and 17 CRYs identified in five alloteraploid cottons (Gossypium hirsutum, G. barbadense, G. tomentosum, G. mustelinum and G. darwinii), respectively, and five to nine CRY genes in the seven diploid species. Phylogenetic analysis of protein-coding sequences revealed that CRY genes from cottons and Arabidopsis thaliana could be classified into seven clades. Synteny analysis suggested that the homoeolog of G. hirsutum Gh_A02G0384 has undergone an evolutionary loss event in the other four allotetraploid cotton species. Cis-element analysis predicated the possible functions of CRY genes in G. hirsutum. RNA-seq data revealed that Gh_D09G2225, Gh_A09G2012 and Gh_A11G1040 had high expressions in fiber cells of different developmental states. In addition, the expression levels of one (Gh_A03G0120), 15 and nine GhCRY genes were down-regulated following the PEG, NaCl and high-temperature treatments, respectively. For the low-temperature treatment, five GhCRY genes were induced, and five were repressed. These results indicated that most GhCRY genes negatively regulate the abiotic stress treatments. Conclusion We report the structures, domains, divergence, synteny, and cis-elements analyses systematically of G. hirsutum CRY genes. Possible biological functions of GhCRY genes in differential tissues as well as in response to abiotic stress during the cotton plant life cycle were predicted.

AimWe sought to evaluate the efficacy and safety of conventional transcatheter arterial chemoembolization (cTACE) sequentially combined with systemic treatment by programmed cell death protein 1 (PD-1) inhibitor and anti-angiogenesis tyrosine kinase inhibitor (Anti-angiogenesis TKI) in patients with unresectable hepatocellular carcinoma (HCC).Materials and methodsOne hundred and forty-seven advanced HCC patients who received PD-1 inhibitors and TKIs as first-line systemic treatment between August 2019 and April 2021 were collected retrospectively. Fifty-four patients were finally included and divided into cTACE and no-cTACE groups, according to whether cTACE treatment was performed within 8 weeks before systemic treatment. The tumor objective response ratio (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared between the groups. Significant factors affecting PFS and OS were determined by Cox regression.ResultsThirty-one patients received cTACE followed by systemic treatment and 23 patients received systemic treatment only. The ORRs of the cTACE group were 48.4% (after two cycles of systemic treatment) and 51.6% (after four cycles of systemic treatment), while those of the no-cTACE group were only 17.4% and 21.7%. cTACE patients also had a longer median PFS (11.70 vs. 4.00 months, P = 0.031) and median OS (19.80 vs. 11.6 months, P = 0.006) than no-cTACE patients. Regression analyses indicated that cTACE therapy and Eastern Cooperative Oncology Group performance status were independent risk factors for PFS and OS. AEs by type were similar between the cTACE and no-cTACE groups, except for liver function injury, which was more common among cTACE patients. Fourteen patients suffered with grade 1-2 of rash in 21 patients with objective response, while only 10 patients suffered with rash in 33 patients without objective response, the adjusted hazard ratio (HR) was 4.382 (1.297–14.803).ConclusionsThe combination of cTACE and PD-1 inhibitors and anti-angiogenesis TKIs as therapy significantly improved markers of treatment efficacy, including ORR, PFS, and OS, in unresectable HCC patients, while no more serious AEs recorded in this population compared to those receiving systemic treatment alone. Skin rash might be a predict factor to the efficacy of PD-1 inhibitors and TKI treatment.

ObjectiveParkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is suspected as one of the pathogenic mechanisms of PD. Growth/differentiation Factor-15 (GDF15) has been reported to affect mitochondrial function in PD. However, the relationship between mitochondrial function and GDF15 induction has not been explained well. Hence, we aimed to reveal the effect of GDF15 induction on SH-SY5Y cells with rotenone toxicity, a cell model of PD.MethodsSH-SY5Y cells were exposed to 1 μM rotenone as a PD model. Cells were transfected with a GDF15-overexpression plasmid and empty vector. We then analyzed the expression level of GDF15, BCL-2/BAX, P53, PGC1-α, α-syn, and TH in GDF15-overexpressing cells by western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. The cytotoxicity of rotenone was measured by CCK-8 assays. Cell apoptosis was detected by flow cytometric and TUNEL assays. The effect of GDF15 on oxidative stress and mitochondrial function was revealed using DCFH-DA, mito-SOX, and JC-10 assays and a Seahorse XF Cell Mito Stress Test.ResultsGDF15 protected rotenone-treated SH-SY5Y cells from toxicity by preserving mitochondrial function and decreasing apoptosis, during which GDF15 might function by influencing PGC1α through the regulation of p53. In addition, GDF15 overexpression could improve Akt and mTOR phosphorylation, leading to PI3K/Akt/mTOR pathway activation. However, these protective effects were eliminated when cells were treated with the PI3K/Akt specific inhibitor LY294002.ConclusionOur findings suggest that GDF15 can protect mitochondrial function and inhibit apoptosis in SH-SY5Y cells after exposure to rotenone by upregulating PGC1α via p53. These properties might comprise its anti-apoptotic effects, mediated by the PI3K/Akt/mTOR signaling pathway.

The cytochrome c oxidase 20 (COX20) gene encodes a protein with a crucial role in the assembly of mitochondrial complex IV (CIV). Mutations in this gene can result in ataxia and muscle hypotonia. However, ophthalmoplegia and visual failure associated with COX20 mutation have not been examined previously. Moreover, the mechanism causing the phenotype of patients with COX20 variants to differ from that of patients with mutations in other genes impairing CIV assembly is unclear. In this investigation, the aim was to assess the relation between COX20 variants and CIV assembly. We performed detailed clinical, physical, and biochemical investigations of affected individuals. Western blotting, reverse transcription-polymerase chain reaction, and blue native-polyacrylamide gel electrophoresis were used to analyze the expression level of COX20 and oxidative phosphorylation. A Seahorse XF Cell Mito Stress Test and enzymatic activity analysis were performed to evaluate mitochondrial function. Whole-exome sequencing revealed the same compound heterozygous mutations (c.41A > G and c.222G > T, NM_198076) in COX20 in two siblings. This is the first description of ophthalmoplegia and visual failure associated with COX20 variants. In vitro analysis confirmed that the COX20 protein level was significantly decreased, impairing the assembly and activity of CIV in patients' fibroblast. Overexpression of COX20 using a transduced adenovirus partially restored the function of the patients' fibroblasts. Early-onset complex movement disorders may be closely related to COX20 variants. Our results broaden the clinical phenotypes of patients with COX20 variants showing ophthalmoplegia and visual failure. Additionally, dysfunction of COX20 protein can impair the assembly and activity of CIV.

This study explore the efficacy, toxic and side effects and survival impact of apatinib combined with capecitabine chemotherapy for the second-line treatment of advanced esophageal cancer. The clinical data of 76 patients with advanced esophageal cancer treated from January 2015 to April 2020 have been retrospectively analyzed. They are divided into experimental and control groups according to different treatment methods. The experimental group (n=29) underwent oral apatinib targeted therapy (250 mg/once/d) combined with oral capecitabine chemotherapy (1000 mg/m² according to the body surface area on D1-14). Maintenance therapy with apatinib has been conducted after 4-6 cycles. The control group (n=47) received the second-line chemotherapy. After more than 2 cycles of chemotherapy, complete response is achieved in 0 cases, partial response in 19 cases, stable disease in 6 cases, and progressive disease in 3 cases. Overall response rate (ORR) is found to be 67.86% and the disease control rate is 89.28%. The median progression-free survival (mPFS) and the median overall survival (mOS) are 6.7 months and 8.9 months, respectively. Karnofsky Performance Status score of 2 points, liver metastasis, elevation of tumor marker squamous cell carcinoma and unsatisfactory efficacy are independent prognostic factors. In control group, ORR was 34.04%, and mPFS and mOS are 3.9 months and 7.4 months, respectively. No severe drug-related toxic and side effects have been observed, except for 1 patient who voluntarily discontinued treatment due to grade III hypertension. Apatinib combined with capecitabine chemotherapy shows good overall efficacy with satisfactory safety and tolerance for the second-line treatment of advanced esophageal cancer. [ABSTRACT FROM AUTHOR]

Background Targeted therapies and immunotherapies, represented by programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have demonstrated high efficacies in multiple cancers. China-produced PD-1/PD-L1 inhibitors have been approved for use recently. Objective To investigate the efficacy and safety of China-produced camrelizumab, a PD-1 inhibitor, in combination with apatinib in the first-line treatment of middle and advanced stages of primary liver cancer. Methods Eighty-six patients with middle and advanced stages of primary liver cancer were selected from the oncology department of four hospitals in Chizhou (the People's Hospital of Chizhou, Chizhou Second People's Hospital, Dongzhi County People's Hospital, Shitai County People's Hospital) from June 2018 to January 2021. All patients were initially treated with apatinib mesylate tablets and intravenous infusion of China-produced camrelizumab, and followed up till August 31, 2021 with disease progression or all-cause death as the endpoint. Clinical efficacies were assessed at the end of the first and third months of treatment. The treatment-emergent adverse events were counted. Results There were no dropouts due to serious treatment-emergent adverse events. The overall response rate (ORR) and disease control rate (DCR) in the patients were 58.14% (50/86) and 65.12% (56/86) , respectively, at the end of the first month of treatment, and were 76.74% (66/86) and 82.56% (68/86) , respectively, at the end of the third month of treatment. The follow-up period for them ranged from four to 26 months, with a mean value follow-up time of (12±6) months. A total of 35 patients died during the follow-up. The median progression-free survival was 8〔95%CI (5.18, 11.89) 〕 months, and the median overall survival was 12〔95%CI (8.97, 15.97) 〕 months in all patients. The major treatment-emergent adverse events included gastrointestinal reactions〔52 (60.47%) 〕, secondary hypertension〔31 (36.05%) 〕, hand-foot syndrome〔18 (20.93%) 〕 and proteinuria〔12 (13.95%) 〕, among which gastrointestinal reactions (6.98%) in six cases, secondary hypertension (2.33%) in two cases and hand-foot syndrome (1.16%) in one case were grade 3-5 adverse events. Conclusion For middle and advanced stages of primary liver cancer, China-produced camrelizumab with apatinib as the first-line treatment has good effect with controllable adverse events.