Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity.

OBJECTIVE: Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action. METHODS: Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence. RESULTS: Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity. CONCLUSION: SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6. Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; 21(5): 464-473.

MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription.

Epilepsy is considered to result from an imbalance between excitation and inhibition of the central nervous system. Pathogenic mutations in the methyl-CpG binding domain protein 5 gene (MBD5) are known to cause epilepsy. However, the function and mechanism of MBD5 in epilepsy remain elusive. Here, we found that MBD5 was mainly localized in the pyramidal cells and granular cells of mouse hippocampus, and its expression was increased in the brain tissues of mouse models of epilepsy. Exogenous overexpression of MBD5 inhibited the transcription of the signal transducer and activator of transcription 1 gene (Stat1), resulting in increased expression of N-methyl-d-aspartate receptor (NMDAR) subunit 1 (GluN1), 2A (GluN2A) and 2B (GluN2B), leading to aggravation of the epileptic behaviour phenotype in mice. The epileptic behavioural phenotype was alleviated by overexpression of STAT1 which reduced the expression of NMDARs, and by the NMDAR antagonist memantine. These results indicate that MBD5 accumulation affects seizures through STAT1-mediated inhibition of NMDAR expression in mice. Collectively, our findings suggest that the MBD5-STAT1-NMDAR pathway may be a new pathway that regulates the epileptic behavioural phenotype and may represent a new treatment target.

Copper-Catalyzed Annulation of O-Acyl Oximes with Cyclic 1,3-Diones for the Synthesis of 7,8-Dihydroindolizin-5(6H)-ones and Cyclohexanone-Fused Furans.

A copper-catalyzed annulation of O-acyl oximes with cyclic 1,3-diones has been developed for the concise synthesis of 7,8-dihydroindolizin-5(6H)-ones and cyclohexanone-fused furans through the substituent-controlled selective radical coupling process. 2-Alkyl cyclic 1,3-diones undergo C-C radical coupling, while 2-unsubstituted cyclic 1,3-diones undergo C-O radical coupling.

The Effect of Arthroscopic Extra-Articular Entire Coracohumeral Ligament Release for Patients with Recalcitrant Frozen Shoulder.

OBJECTIVE: The thickened coracohumeral ligament (CHL) is an important part of the typical manifestations and magnetic resonance imaging of frozen shoulder. However, only a few clinical studies with limited cases on arthroscopic extra-articular entire CHL release exist in the literature. This study was to evaluate the effect of arthroscopic extra-articular entire CHL release for patients with recalcitrant frozen shoulder. METHODS: From February 2014 to February 2020, 81 cases of recalcitrant frozen shoulder patients treated with surgery in a single-center shoulder department and followed for more than 2 years were analyzed. Arthroscopic 360° capsular release was performed with intra-articular partial release (IPR group) or additional extra-articular entire release (IPR + EER group) of CHL. The same rehabilitation program was performed after surgery in both groups. Visual analogue scale (VAS) for pain, range of motion (ROM), and the Constant-Murley scoring system was evaluated before operation, at 3 months after operation, 6 months after operation, and the final follow-up. T-test, Mann-Whitney U-test and chi-squared test were used to compared data. RESULTS: There were 39 patients in the IPR group, with an average follow-up of 29.2 months. A total of Forty-two patients in the IPR + EER group completed a mean follow-up of 25.7 months. All incisions healed in stages. There were significant differences in Constant-Murley shoulder score, VAS score, and ROM before operation and at the final follow-up in both groups (both P < 0.001). The VAS score of the IPR + EER group was lower than that of the IPR group at 3 months after surgery (P < 0.05), and 6 months after operation (P < 0.05). External rotation, internal rotation, and abduction of ROMs and Constant-Murley shoulder score were significantly greater in the IPR + EER group at 3 months (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively) and 6 months after operation (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively). At the last follow-up, there was no significant difference in forward flexion, internal rotation, and abduction of ROMs, VAS, and the Constant-Murley shoulder score between the IPR and IPR + EER groups. The external rotation of the IPR + EER group was still greater than that of the IPR group at the last follow-up (P < 0.001). CONCLUSION: Arthroscopic extra-articular entire coracohumeral ligament release could solve early pain of shoulder joint, recover shoulder joint functions effectively, and achieve a satisfactory efficacy in the treatment of recalcitrant frozen shoulder.

Dose estimation in etiology of occupational radiogenic neoplasms: A case analysis / 中国辐射卫生

Objective To analyze the problems and solutions in the diagnosis of a patient with occupational radiogenic neoplasms. Methods The dose conversion method was selected in dose estimation. Personal dose equivalent, skin absorbed dose, and reported detection data were converted into red bone marrow absorbed dose. The upper 95% confidence limit of the probability of causation (PC 95%) was calculated. Results The PC 95% of cancer due to radiation in the worker was 66.38%, which suggested occupational radiogenic neoplasms. Personal dose data were missing in dose estimation. The current dose estimation standard lacked bedside radiography and CT operation type, and the dose conversion formula was not perfect. Conclusion In the judgment of occupational radiogenic neoplasms, the estimated dose showed uncertainty. There is an urgent need to formulate and promulgate dose estimation standards that are operational and in line with the current development of radiological diagnosis and treatment technology and equipment.

Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity / 中西医结合学报

OBJECTIVE@#Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.@*METHODS@#Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence.@*RESULTS@#Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.@*CONCLUSION@#SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6. Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; 21(5): 464-473.

Exploring the Accessibility by Using the Hydroxycobalamin Preparations of High Concentration in Treating Methylmalonic Acidemia / 罕见病研究

Methylmalonic acidemia(MMA) is one of the common diseases in hereditary organic acid metabolism disorder. The disorder is mainly treated by using vitamin B12 which comes in various forms.The use of the methylcobalamin and adenosylcobalamin in China cannot meet the needs of children with MMA. Parenteral use of hydroxocobalamin of high concentration has significant advantages in the treatment of MMA. But, the accessibility to hydroxocobalamin is challenging now.Through the supervision and adjustment of hydroxocobalamin, we explored the strategy of using the drugs. Meanwhile, we are considering the oral use of the hydroxocobalamin as supplement to treatment. Solving the challenges of the hydrococobalamin is helpful to meet the treatment of MMA and to provide a new possibility for the use of medication for rare diseases. The improvement in policy and supervision measures will facilitate the development, involvement, and production of hydroxocobalamin, so that the patients will have a good chance of access to the treatment.

Interventions for non-alcoholic liver disease: a gut microbial metabolites perspective.

Over the past two decades, non-alcoholic fatty liver disease (NAFLD) has become a leading burden of hepatocellular carcinoma and liver transplantation. Although the exact pathogenesis of NAFLD has not been fully elucidated, recent hypotheses placed more emphasis on the crucial role of the gut microbiome and its derivatives. Reportedly, microbial metabolites such as short-chain fatty acids, amino acid metabolites (indole and its derivatives), bile acids (BAs), trimethylamine N-oxide (TMAO), and endogenous ethanol exhibit sophisticated bioactive properties. These molecules regulate host lipid, glucose, and BAs metabolic homeostasis via modulating nutrient absorption, energy expenditure, inflammation, and the neuroendocrine axis. Consequently, a broad range of research has studied the therapeutic effects of microbiota-derived metabolites. In this review, we explore the interaction of microbial products and NAFLD. We also discuss the regulatory role of existing NAFLD therapies on metabolite levels and investigate the potential of targeting those metabolites to relieve NAFLD.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation.

Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation's pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

Linezolid-Induced Pure Red Cell Aplasia: A Case Report.

Linezolid (LZD) has been widely used for treating the infections of multidrug-resistant gram-positive organisms. As we know, anemias induced by Linezolid (LZD) are common. However, LZD-induced pure red cell aplasia (PRCA) is very rare. In this paper, we report on a 68-year-old woman with intravascular stent infection who developed PRCA after treatment with LZD. The patient presented to our hospital with a 6-month history of fever after stent implantation for aneurysms in both lower limbs. Bone culture grew methicillin-resistant Staphylococcus hemolyticus (MRSH). She received LZD after developing adverse reactions to initial antibiotics. Although her infective symptoms were improved by LZD, progressive thrombocytopenia was observed 23 days after LZD therapy. Her platelets declined to 66*109/L and hemoglobin level was 10.1 g/dL. Thrombocytopenia recovered 12 days after cessation of LZD. LZD was administered again due to recovered fever. 57 days after LZD administration, her hemoglobin level was 4.1 g/dL and reticulocytes were 0.2%. Bone marrow smear revealed active granulocyte proliferation and markedly decreased erythropoiesis with vacuolar degeneration. 12 days after cessation of LZD, her hemoglobin and reticulocyte levels rose to 9.6 g/dL and 5.1%, respectively. LZD was used for the third time as fever and inflammatory markers progressively increased, but Hb was reduced to 6.7g/dL 15 days after LZD therapy. 12 days after cessation of LZD, the hemoglobin level rose to 11.9 g/dL. In summary, we suggest complete blood count and reticulocyte count should be monitored to detect bone marrow suppression during long-term LZD therapy, especially in patients aged over 58 and/or with pre-existing anemia, chronic infections, and renal insufficiency.

[Psychological Status and Influencing Factors of Staff at Centers for Disease Control and Prevention in Sichuan Province during the Outbreak of Coronavirus Disease 2019].

Objective To assess the psychological status of staff at the centers for disease control and prevention(CDC) in Sichuan during the outbreak of coronavirus disease 2019(COVID-19) and explore the influencing factors. Methods The staff at Sichuan provincial,municipal,and county(district)-level CDC were selected by convenience sampling.Their basic information,work status,training status,work difficulties,and support from the work group were collected from the self-filled questionnaires online.The Generalized Anxiety Disorder Scale and the 9-question Patient Health Questionnaire were respectively employed to measure the anxiety and depression of the staff.The stepwise Logistic regression was carried out to analyze the influencing factors of anxiety and depression in CDC staff. Results Among the 653 staff,58.35% and 50.06% presented anxiety and depression,respectively.The regression results showed that age(OR=0.95,95%CI=0.92-0.97) and mental support from the work group(OR=0.61,95%CI=0.45-0.82) were the protective factors while physical fatigue(OR=1.82,95%CI=1.20-2.74),work pressure(OR=1.61,95%CI=1.21-2.12),and insufficient protective equipment(OR=1.92,95%CI=1.06-3.49) were the risk factors for depression of CDC staff.Age(OR=0.97,95%CI=0.94-0.99),length of sleep per day(OR=0.74,95%CI=0.56-0.96),and participation in technical training(OR=0.33,95%CI=0.12-0.95) were the protective factors while mental fatigue(OR=1.68,95%CI=1.18-2.41),work pressure(OR=2.94,95%CI=2.08-4.17),and unclear incentive system for overtime(OR=1.99,95%CI=1.23-3.23) were the risk factors for the anxiety of CDC staff. Conclusion The anxiety and depression status of CDC staff during the COVID-19 outbreak were worrying,which were mainly affected by age,sleep,supply of protective equipment,incentive system,fatigue,and work pressure.

Psychological Status and Influencing Factors of Staff at Centers for Disease Control and Prevention in Sichuan Province during the Outbreak of Coronavirus Disease 2019 / 中国医学科学院学报

Objective To assess the psychological status of staff at the centers for disease control and prevention(CDC) in Sichuan during the outbreak of coronavirus disease 2019(COVID-19) and explore the influencing factors. Methods The staff at Sichuan provincial,municipal,and county(district)-level CDC were selected by convenience sampling.Their basic information,work status,training status,work difficulties,and support from the work group were collected from the self-filled questionnaires online.The Generalized Anxiety Disorder Scale and the 9-question Patient Health Questionnaire were respectively employed to measure the anxiety and depression of the staff.The stepwise Logistic regression was carried out to analyze the influencing factors of anxiety and depression in CDC staff. Results Among the 653 staff,58.35% and 50.06% presented anxiety and depression,respectively.The regression results showed that age(OR=0.95,95%CI=0.92-0.97) and mental support from the work group(OR=0.61,95%CI=0.45-0.82) were the protective factors while physical fatigue(OR=1.82,95%CI=1.20-2.74),work pressure(OR=1.61,95%CI=1.21-2.12),and insufficient protective equipment(OR=1.92,95%CI=1.06-3.49) were the risk factors for depression of CDC staff.Age(OR=0.97,95%CI=0.94-0.99),length of sleep per day(OR=0.74,95%CI=0.56-0.96),and participation in technical training(OR=0.33,95%CI=0.12-0.95) were the protective factors while mental fatigue(OR=1.68,95%CI=1.18-2.41),work pressure(OR=2.94,95%CI=2.08-4.17),and unclear incentive system for overtime(OR=1.99,95%CI=1.23-3.23) were the risk factors for the anxiety of CDC staff. Conclusion The anxiety and depression status of CDC staff during the COVID-19 outbreak were worrying,which were mainly affected by age,sleep,supply of protective equipment,incentive system,fatigue,and work pressure.

Efficacy of sintilimab combined with apatinib in treatment of advanced non-small cell lung cancer / 肿瘤研究与临床

Objective:To observe the efficacy of sintilimab combined with apatinib in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Eighty-two patients with advanced NSCLC who were admitted to Nantong Cancer Hospital from October 2019 to September 2020 were selected for a prospective controlled study. They were divided into control group (treated with apatinib) and combination group (treated with sintilimab + apatinib) using the random number table method, with 41 cases in each group. The short-term clinical efficacy, tumor markers [neuron specific enolase (NSE), cytokeratin 19 fragment antigen (CYFRA21-1)], adverse reactions during treatment and survival were compared between the two groups.Results:The objective remission rate and clinical control rate in the combination group were higher than those in the control group [41.46% (17/41) vs. 19.51% (8/41), 85.37% (35/41) vs. 58.54% (24/41)], and the differences were statistically significant ( χ2 values were 4.66 and 7.31, both P < 0.05). The levels of NSE and CYFRA21-1 in the combination group were lower than those in the control group after treatment [(19.04±2.54) ng/ml vs. (21.35±3.11) ng/ml, (4.58±1.02) μg/L vs. (6.07±1.84) μg/L], and the differences were statistically significant ( t values were 3.68 and 4.54, both P < 0.001). There were no statistical differences in the incidence rates of gastrointestinal reaction, bone marrow depression, fatigue, and liver and kidney function damage between the combination group and the control group during treatment (all P > 0.05). The survival rate of the combination group was higher than that of the control group (71.79% vs. 47.50%), and the difference was statistically significant ( χ2 = 4.84, P = 0.028). Conclusions:Sintilimab combined with apatinib may improve clinical efficacy, reduce tumor marker levels, and improve short-term survival rate of advanced NSCLC patients.

Pre- and postoperative heart rate variability and vagus nerve stimulation in patients with drug-resistant epilepsy - A meta-analysis.

OBJECTIVE: The effect of vagus nerve stimulation (VNS), an important auxiliary therapy for treating drug-resistant epilepsy (DRE), on autonomic nerve function is still controversial. Heart rate variability is a widely used indicator of autonomic nerve function. To clarify the relationship between VNS and heart rate variability (HRV), we performed a meta-analysis to systematically evaluate the effect of VNS on HRV in patients with epilepsy. METHODS: We performed a systematic review by searching the following online databases: PubMed, Web of Science, EMBASE and the Cochrane Library. The key search terms were "vagal nerve stimulation," "epilepsy" and "heart rate variability". Other features of VNS in patients with epilepsy include postoperative changes in low-frequency (LF), high-frequency (HF) and low-frequency/high-frequency (LF/HF) heart rate variability, which were used as evaluation indices, and the Newcastle-Ottawa Quality Assessment Scale and Stata 14.0 statistical software were used for literature quality evaluation and meta-analysis. RESULTS: Twelve studies published in English were obtained, and 229 patients with epilepsy who underwent VNS were ultimately included after elimination of duplicate articles and those that did not meet the inclusion criteria. Regarding LF heart rate variability, in the response subgroup, patients with DRE with VNS presented a lower value (-0.58) before surgery than after surgery, with a 95% confidence interval (CI) ranging from -1.00 to -0.15. For HF heart rate variability, patients with DRE with VNS had a lower value (-0.45) before surgery than after surgery in the response subgroup, with a 95% CI ranging from -0.74 to -0.17. No differences were found for LF/HF values or the LF and HF values of other subgroups. CONCLUSION: VNS has little effect on the balance of sympathetic and parasympathetic nerve activity and would not be expected to cause cardiovascular autonomic dysfunction in patients with DRE. For patients with DRE, VNS can control seizures and has little effect on autonomic nervous function.

Phylogeny and Comparative Analysis for the Plastid Genomes of Five Tulipa (Liliaceae).

Species of Tulipa (Liliaceae) are of great horticultural importance and are distributed across Europe, North Africa, and Asia. The Tien Shan Mountain is one of the primary diversity centres of Tulipa, but the molecular studies of Tulipa species from this location are lacking. In our study, we assembled four Tulipa plastid genomes from the Tien Shan Mountains, T. altaica, T. iliensis, T. patens, and T. thianschanica, combined with the plastid genome of T. sylvestris to compare against other Liliaceae plastid genomes. We focussed on the species diversity and evolution of their plastid genomes. The five Tulipa plastid genomes proved highly similar in overall size (151,691-152,088 bp), structure, gene order, and content. With comparative analysis, we chose 7 mononucleotide SSRs from the Tulipa species that could be used in further population studies. Phylogenetic analyses based on 24 plastid genomes robustly supported the monophyly of Tulipa and the sister relationship between Tulipa and Amana, Erythronium. T. iliensis, T. thianschanica, and T. altaica were clustered together, and T. patens was clustered with T. sylvestris, with our results clearly demonstrating the relationships between these five Tulipa species. Our results provide a more comprehensive understanding of the phylogenomics and comparative genomics of Tulipa.

Clinical and Microbiological Characteristics of a Community-Acquired Carbapenem-Resistant Escherichia coli ST410 Isolate Harbouring blaNDM-5-Encoding IncX3-Type Plasmid From Blood.

Objectives: The aim of this research was to investigate the clinical and microbiological characteristics of a case of community-acquired carbapenem-resistant Escherichia coli isolated from a patient with a bloodstream infection in China. Methods: Escherichia coli Huamei202001 was recovered from the first blood culture from a patient hospitalised in China. An antimicrobial susceptibility test was performed, and the genome was sequenced on an Illumina HiSeq X 10 platform with a 150-bp paired-end approach. The generated sequence reads were assembled using Unicycler, and the whole genome sequence data were analysed using bioinformatics tools. Moreover, the patient and her main family members obtained a faecal sample screening test for CRE, the positive strain was further isolated and the identification and antimicrobial susceptibility testing was performed. Results: Escherichia coli Huamei202001 belonged to sequence type 410. In addition, a blaNDM-5-encoding IncX3-type plasmid was responsible for the spreading of carbapenem resistance. Only the patient was detected as having a positive faecal sample screening test for CRE. Strain Fec01 was identified as E. coli, and the antibiotic susceptibility profile was the same as that of E. coli Huamei202001. Conclusions: Escherichia coli Huamei202001 is defined as community-acquired carbapenem-resistant Enterobacteriaceae. The clone ST410 that harbours the blaNDM-5-encoding IncX3-type plasmid is causing new high-risk clones globally. Thus, infection control measures should be strengthened to curb the dissemination of IncX3.