Noncoding SNPs influence a distinct phase of Polycomb silencing to destabilize long-term epigenetic memory at Arabidopsis FLC.

In Arabidopsis thaliana, the cold-induced epigenetic regulation of FLOWERING LOCUS C (FLC) involves distinct phases of Polycomb repressive complex 2 (PRC2) silencing. During cold, a PHD-PRC2 complex metastably and digitally nucleates H3K27me3 within FLC On return to warm, PHD-PRC2 spreads across the locus delivering H3K27me3 to maintain long-term silencing. Here, we studied natural variation in this process in Arabidopsis accessions, exploring Lov-1, which shows FLC reactivation on return to warm, a feature characteristic of FLC in perennial Brassicaceae This analysis identifies an additional phase in this Polycomb silencing mechanism downstream from H3K27me3 spreading. In this long-term silencing (perpetuated) phase, the PHD proteins are lost from the nucleation region and silencing is likely maintained by the read-write feedbacks associated with H3K27me3. A combination of noncoding SNPs in the nucleation region mediates instability in this long-term silencing phase with the result that Lov-1 FLC frequently digitally reactivates in individual cells, with a probability that diminishes with increasing cold duration. We propose that this decrease in reactivation probability is due to reduced DNA replication after flowering. Overall, this work defines an additional phase in the Polycomb mechanism instrumental in natural variation of silencing, and provides avenues to dissect broader evolutionary changes at FLC.

The P-body component DECAPPING5 and the floral repressor SISTER OF FCA regulate FLOWERING LOCUS C transcription in Arabidopsis.

Flowering is the transition from vegetative to reproductive growth and is critical for plant adaptation and reproduction. FLOWERING LOCUS C (FLC) plays a central role in flowering time control, and dissecting its regulation mechanism provides essential information for crop improvement. Here, we report that DECAPPING5 (DCP5), a component of processing bodies (P-bodies), regulates FLC transcription and flowering time in Arabidopsis (Arabidopsis thaliana). DCP5 and its interacting partner SISTER OF FCA (SSF) undergo liquid-liquid phase separation (LLPS) that is mediated by their prion-like domains (PrDs). Enhancing or attenuating the LLPS of both proteins using transgenic methods greatly affects their ability to regulate FLC and flowering time. DCP5 regulates FLC transcription by modulating RNA polymerase II enrichment at the FLC locus. DCP5 requires SSF for FLC regulation, and loss of SSF or its PrD disrupts DCP5 function. Our results reveal that DCP5 interacts with SSF, and the nuclear DCP5-SSF complex regulates FLC expression at the transcriptional level.

SISTER OF FCA physically associates with SKB1 to regulate flowering time in Arabidopsis thaliana.

BACKGROUND: Proper flowering time is important for the growth and development of plants, and both too early and too late flowering impose strong negative influences on plant adaptation and seed yield. Thus, it is vitally important to study the mechanism underlying flowering time control in plants. In a previous study by the authors, genome-wide association analysis was used to screen the candidate gene SISTER OF FCA (SSF) that regulates FLOWERING LOCUS C (FLC), a central gene encoding a flowering suppressor in Arabidopsis thaliana. RESULTS: SSF physically interacts with Protein arginine methyltransferase 5 (PRMT5, SKB1). Subcellular co-localization analysis showed that SSF and SKB1 interact in the nucleus. Genetically, SSF and SKB1 exist in the same regulatory pathway that controls FLC expression. Furthermore, RNA-sequencing analysis showed that both SSF and SKB1 regulate certain common pathways. CONCLUSIONS: This study shows that PRMT5 interacts with SSF, thus controlling FLC expression and facilitating flowering time control.

Inactivation of RPX1 in Arabidopsis confers resistance to Plutella xylostella through the accumulation of the homoterpene DMNT.

The lepidopteran crop pest Plutella xylostella causes severe constraints on Brassica cultivation. Here, we report a novel role for RPX1 (resistance to P. xylostella) in resistance to this pest in Arabidopsis thaliana. The rpx1-1 mutant repels P. xylostella larvae, and feeding on the rpx1-1 mutant severely damages the peritrophic matrix structure in the midgut of the larvae, thereby negatively affecting larval growth and pupation. This resistance results from the accumulation of defence compounds, including the homoterpene (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), due to the upregulation of PENTACYCLIC TRITERPENE SYNTHASE 1 (PEN1), which encodes a key DMNT biosynthetic enzyme. P. xylostella infestation and wounding induce RPX1 protein degradation, which may confer a rapid response to insect infestation. RPX1 inactivation and PEN1 overexpression are not associated with negative trade-offs for plant growth but have much higher seed production than the wild-type in the presence of P. xylostella infestation. This study offers a new strategy for plant molecular breeding against P. xylostella.

Combining quantitative trait locus mapping with multiomics profiling reveals genetic control of corn leaf aphid (Rhopalosiphum maidis) resistance in maize.

The corn leaf aphid (Rhopalosiphum maidis) is a major maize pest that frequently causes substantial yield losses. Exploring the genetic basis of resistance to aphids is important for improving maize yield and quality. Here, we used a maize recombinant inbred line population derived from two parents with different susceptibility to aphids, B73 (susceptible) and Abe2 (resistant), and performed quantitative trait locus (QTL) mapping using aphid resistance scores as an indicator. We mapped a stable QTL, qRTA6, to chromosome 6 using data from 2 years of field trials, which explained 40.12-55.17% of the phenotypic variation. To further investigate the mechanism of aphid resistance in Abe2, we constructed transcriptome and metabolome libraries from Abe2 and B73 leaves with or without aphid infestation at different time points. Integrating QTL mapping and transcriptome data revealed three aphid resistance candidate genes (Zm00001d035736, Zm00001d035751, and Zm00001d035767) associated with the hypersensitive response, the jasmonic acid pathway, and protein ubiquitination. Integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes and metabolites were enriched in flavonoid biosynthesis. These findings extend our understanding of the molecular mechanisms controlling aphid resistance in maize, and the QTL and candidate genes are valuable resources for increasing this resistance.

Phenotypic evolution through variation in splicing of the noncoding RNA COOLAIR.

The extent to which natural polymorphisms in noncoding sequences have functional consequences is still unknown. A large proportion of the natural variation in flowering in Arabidopsis thaliana accessions is due to noncoding cis polymorphisms that define distinct haplotypes of FLOWERING LOCUS C (FLC). Here, we show that a single natural intronic polymorphism in one haplotype affects FLC expression and thus flowering by specifically changing splicing of the FLC antisense transcript COOLAIR. Altered antisense splicing increases FLC expression via a cotranscriptional mechanism involving capping of the FLC nascent transcript. Single noncoding polymorphisms can therefore be a major contributor to phenotypic evolution through modulation of noncoding transcripts.

Linkage mapping combined with GWAS revealed the genetic structural relationship and candidate genes of maize flowering time-related traits.

BACKGROUND: Flowering time is an important agronomic trait of crops and significantly affects plant adaptation and seed production. Flowering time varies greatly among maize (Zea mays) inbred lines, but the genetic basis of this variation is not well understood. Here, we report the comprehensive genetic architecture of six flowering time-related traits using a recombinant inbred line (RIL) population obtained from a cross between two maize genotypes, B73 and Abe2, and combined with genome-wide association studies to identify candidate genes that affect flowering time. RESULTS: Our results indicate that these six traits showed extensive phenotypic variation and high heritability in the RIL population. The flowering time of this RIL population showed little correlation with the leaf number under different environmental conditions. A genetic linkage map was constructed by 10,114 polymorphic markers covering the whole maize genome, which was applied to QTL mapping for these traits, and identified a total of 82 QTLs that contain 13 flowering genes. Furthermore, a combined genome-wide association study and linkage mapping analysis revealed 17 new candidate genes associated with flowering time. CONCLUSIONS: In the present study, by using genetic mapping and GWAS approaches with the RIL population, we revealed a list of genomic regions and candidate genes that were significantly associated with flowering time. This work provides an important resource for the breeding of flowering time traits in maize.

Multiple FLC haplotypes defined by independent cis-regulatory variation underpin life history diversity in Arabidopsis thaliana.

Relating molecular variation to phenotypic diversity is a central goal in evolutionary biology. In Arabidopsis thaliana, FLOWERING LOCUS C (FLC) is a major determinant of variation in vernalization--the acceleration of flowering by prolonged cold. Here, through analysis of 1307 A. thaliana accessions, we identify five predominant FLC haplotypes defined by noncoding sequence variation. Genetic and transgenic experiments show that they are functionally distinct, varying in FLC expression level and rate of epigenetic silencing. Allelic heterogeneity at this single locus accounts for a large proportion of natural variation in vernalization that contributes to adaptation of A. thaliana.

Identification of a genomic region controlling thermotolerance at flowering in maize using a combination of whole genomic re-sequencing and bulked segregant analysis.

KEY MESSAGE: A novel genomic region controlling thermotolerance at flowering was identified by the combination of whole genomic re-sequencing and bulked segregant analysis in maize. The increasing frequency of extreme high temperature has brought a great threat to the development of maize throughout its life cycle, especially during the flowering phase. However, the genetic basis of thermotolerance at flowering in maize remains poorly understood. Here, we characterized a thermotolerant maize ecotype Abe2 and dissected its genetic basis using a F2:8 recombinant inbred line (RIL) population generated from a cross between Abe2 and B73. After continuous high temperature stress above 35 °C for 17 days, Abe2 and B73 show distinct leaf scorching phenotype under field conditions. To identify the genomic regions associated with the phenotypic variation, we applied a combination of whole genomic re-sequencing and bulked segregant analysis, and revealed 10,316,744 SNPs and 1,488,302 InDels between the two parental lines, and 2,693,054 SNPs and 313,757 InDels between the two DNA pools generated from the thermos-tolerant and the sensitive individuals of the RIL, of which, 108,655 and 17,853 SNPs may cause nonsynonymous variations. Finally, a 7.41 Mb genomic region on chromosome 1 was identified, and 7 candidate genes were annotated to participate in high temperature-related stress response. A candidate gene Zm00001d033339 encoding a serine/threonine protein kinase was proposed to be the most likely causative gene contributing to the thermotolerance at flowering by involving in stomatal movement (GO: 0010119) via Abscisic acid (ABA) pathway (KO04075). This work could provide an opportunity for gene cloning and pyramiding breeding to improve thermotolerance at flowering in maize.

A robust LC-MS/MS method for the simultaneous determination of docetaxel and voriconazole in rat plasma and its application to pharmacokinetic studies.

Opportunistic fungal infections are common in immunocompromised cancer patients, especially patients undergoing chemotherapy. Because antitumor agents are possible to combine with antifungal agents in clinical, it is necessary to study drug-drug interaction between antitumor agents and antifungal agents. The aim of the study was to explore a method for the simultaneous determination of voriconazole and docetaxel in plasma and investigate pharmacokinetic interaction of voriconazole and docetaxel in rats. A precise and reliable method using liquid chromatography tandem mass spectrometry (LC-MS/MS) was established for the simultaneous measure of docetaxel and voriconazole in rat plasma after liquid-liquid extraction with ethyl acetate. The method was fully validated and successfully applied to a pharmacokinetic interaction study of docetaxel and voriconazole in rats after single or combined administration. We found that the AUC of each drug after coadministration increased compared with that after the single administration, which might be caused by interaction at the absorption stage or the competitive inhibition on the metabolic enzymes. This established method can be utilized to study the detailed mechanism of the drug-drug interaction and guide rational drug use in the clinic.

Bibliometric and visualization analyses of cancer-related fatigue research published worldwide from 2001 to 2023.

Objective: Cancer seriously endangers human health and represents a global public health issue. Cancer-related fatigue (CRF) is a distressing and persistent sense of exhaustion caused by cancer or cancer treatment, widely prevalent among cancer patients. This study aims to summarize emerging trends and provide directions for future research of CRF through bibliometric and visualization analyses. Methods: A systematic search in the Web of Science Core Collection database from 2001-01-01 to 2023-05-18 were conducted. Only reviews and articles written in English were considered. CiteSpace and the R were used for bibliometric and visualization analyses. Results: The analysis revealed that 2,566 studies on CRF have been published by 1,041 institutions in 70 countries so far. The number of articles published and cited annually have been steadily increasing. Eduardo Bruera published the most articles, and Julienne E Bower is the most co-cited author. The University of Texas System is the leading institution in cancer-related fatigue research. The United States and China have the largest number of publications. Supportive Care in Cancer published the most articles, and Journal of Clinical Oncology is the most co-cited journal. "Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis", authored by Mustian KM et al. and published in JAMA Oncology was the most co-cited document. Keyword analysis indicated that research focus had shifted from "epoetin alpha" and "anemia" to "risk factors", "systematic review", "acupuncture", "anxiety", "traditional Chinese medicine" and "guidelines". Conclusion: In conclusion, this analysis provides comprehensive research trends and knowledge network maps of CRF. Clinical physicians should concurrently focus on the anemia, insomnia, anxiety, and depression status of patients when assessing or managing CRF. Improvements in related risk factors also contribute to alleviating fatigue. Furthermore, it is essential to pay attention to authoritative CRF guidelines. Acupuncture and traditional Chinese medicine also have therapeutic potential, which merits further investigation. Researchers should draw attention to the crucial roles of inflammation, hypoxia, and mitochondrial dysfunction, which could be the frontiers.

Global research landscape and emerging trends in Graves' disease: A bibliometric analysis.

BACKGROUND: Graves' disease is a prevalent thyroid disorder and is the primary cause of hyperthyroidism. Significant progress has been made in understanding the epidemiology, pathogenesis, diagnosis, treatment, and prognosis of this disease. However, bibliometric analyses on Graves' disease are lacking. We aimed to comprehensively summarize the research, progression, and focal points of Graves' disease through data mining and integrated analysis of the existing literature. METHODS: We retrieved relevant literature on Graves' disease from 2003 to 2023 from the Web of Science database. We performed bibliometric analysis using CiteSpace and the R package Bibliometrix. RESULTS: We identified 10,901 publications from 132 countries, with a steady rise in the number of publications over the past 5 years. The US leads in publication volume, with the University of California System being the primary contributing institution. The journal Thyroid had the highest publication output, while the Journal of Clinical Endocrinology and Metabolism was the most frequently cited. These publications involved 2305 authors, with Antonelli Alessandro and Smith Terry being the most prolific. The most frequently cited articles were the "2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis" and the "Thyroid Association/European Group on Graves' orbitopathy guidelines for the management of Graves' orbitopathy." Analysis of the bursts of cited references, keywords, and their clustering revealed that research on Graves' disease predominantly centers on clinical management, thyroid-stimulating hormone receptors, thyroid hormones, autoimmunity and inflammation, Graves' ophthalmopathy, thyroid nodules, and thyroid cancer. CONCLUSION: This is the first comprehensive bibliometric study to summarize progress and trends in Graves' disease research. These results highlight recent research hotspots and promising directions, thereby providing a valuable reference for other scholars.

The burden and management competency of cardiomyopathies in China: a nationwide survey study.

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Borderline personality disorder and thyroid diseases: a Mendelian randomization study.

Background: Previous studies have shown that there is a correlation between diseases of the thyroid gland and mental illnesses; however, any causal relationship between them remains unclear. This study aimed to evaluate the causal relationship between borderline personality disorder and four thyroid diseases. Methods: The causal relationship was inferred using double-sample Mendelian randomization analysis of appropriate instrumental variables from genome-wide association studies. We calculated the estimated value of the effect using various statistical methods. Results: Borderline personality disorder was a risk factor for non-toxic single thyroid nodules with each increase in standard deviation increasing the risk of a non-toxic single thyroid nodule by 1.13 times (odds ratio = 1.131; 95% confidence interval, 1.006-1.270; P=0.039). There was no evidence of a correlation between borderline personality disorder and hyperthyroidism/thyrotoxicosis, hypothyroidism, and autoimmune thyroiditis. Conclusion: This study showed that there is a positive causal correlation between borderline personality disorder and non-toxic single thyroid nodules but not with other thyroid diseases. This means that thyroid status should be monitored in patients with borderline personality disorder. However, the possibility of a causal relationship between other mental illnesses and thyroid diseases requires further research.

The Role of Complementary and Alternative Medicine on Cancer-Related Fatigue in Adults: An Overview of Systematic Reviews.

BACKGROUND: Cancer-related fatigue (CRF) has an enormous adverse impact on quality of life and subsequent therapy of cancer patients. Complementary and alternative medicine (CAM) is reported to improve CRF in many systematic reviews (SRs), but the effects are controversial because of variations in the quality and outcomes. METHODS: Thirteen databases were searched from inception to September 2022. Only SRs of randomized controlled trials (RCTs) were included. We assessed the quality of included SRs with the AMSTAR-2 tool, the strength of evidence with the GRADE system, the risk of bias with the ROBIS tool, and the integrity of SRs with the PRISMA checklist. RESULTS: We included 30 eligible SRs (27 meta-analyses). Based on the AMSTAR-2 tool, 29 SRs were rated as "critically low" quality, and only one was rated as "low" quality. With the ROBIS tool, 19 SRs demonstrated a low risk of bias. According to the PRISMA checklist, no SRs reported all the items, and 10 SRs sufficiently reported over 70%. Based on the GRADE system, 7 outcomes were assessed as high-quality evidence. CONCLUSION: This overview demonstrates promising evidence for the effectiveness of CAM interventions in the treatment of CRF in adults. The roles of qigong, music, auricular point therapy, and dietary supplements in CRF need further evaluation. Although findings are mixed, it is recommend to select appropriate CAM to manage cancer-related fatigue under the guidance of physicians. More studies with rigorous methodological designs and sufficient sample sizes are needed.

Chinese Medicine Enhancing Response Rates to Immunosuppressant PD-L1 Inhibitor and Improving the Quality of Life of Hepatocellular Carcinoma-Bearing Mice.

Background: Malignant tumors are a significant disease endangering human health. Chinese Medicine (CM) plays an important role in comprehensive and holistic tumor treatment. Objectives: We aimed to investigate whether CM combined with the immunosuppressant PD-1/PD-L1 inhibitor has a good synergistic effect and can significantly improve response rates for the immunosuppressant. Methods: We combined CM with immunosuppressant in treating six-week-old hepatocellular carcinoma-bearing mice and compared the outcomes of groups undergoing different interventions: blank group, control group, CM group, PD-L1 inhibitor group, and CM + PD-L1 inhibitor group, with ten mice in each group. The quality of life was evaluated along with the tumor inhibition effects and growth rates. Results: CM significantly reduced tumor load and improved the quality of life of cancer-bearing mice. The survival rate was 81.8% in the control group, 100% in the CM group, 90.9% in the PD-L1 inhibitor group, and 100% in the combined group in the first week. The survival rate was 45.5% in the control group, 54.5% in the CM group, 81.8% in the PD-L1 inhibitor group, and 81.8% in the combined group in the second week. 38% mice in the CM+PD-L1 inhibitor group with smaller tumor size than the average of the control group, which was much higher than other treatment groups. CM also reduced the expression of JAK2 mRNA and STAT3 mRNA, although not significantly (P > 0.05), and reduced PD-L1 mRNA in tumor tissue compared to the control group (P < 0.05). Conclusions: CM had a synergistic effect on PD-L1 inhibitors and increased response rates to PD-L1 inhibitor treatment.

Structural modification of (3E)-4,8-dimethyl-1,3,7-nontriene enhances its ability to kill Plutella xylostella insect pests.

BACKGROUND: Plant secondary metabolites and their modified derivatives play an important role in the discovery and development of novel insecticides. The natural plant product (3E)-4,8-dimethyl-1,3,7-nontriene (DMNT) has been proven to be able to effectively repel and kill the lepidopteran insect pest Plutella xylostella. RESULTS: In this study, four oxygenated derivatives of DMNT were synthesized by allylic hydroxylation and subsequent etherification or esterification. Bioassays on P. xylostella larvae showed that the compounds DMNT-OCH3 (2), DMNT-OCy (3) and DMNT-OAc (4) were more toxic to the larvae than DMNT alone. The most pronounced effect was observed for compound 2, which showed a 22.23% increase in lethality at a concentration of 0.25 µm. Moreover, the peritrophic matrix (PM) barrier in the insect midgut was more severely damaged by compounds 2, 3 and 4 than by DMNT. The median lethal concentration (LC50 , 48 h) of compounds 2, 3 and 4 on P. xylostella was determined to be 0.98, 1.13 and 1.11 mg mL-1 , respectively, which is much lower than the commercial insecticides eucalyptol (2.89 mg mL-1 ) and thymol (2.45 mg mL-1 ). CONCLUSION: These results suggested that oxygenated DMNT derivatives offer a significantly improved killing effect over DMNT on P. xylostella. This work has provided a basis for further design, structural modification and development of DMNT as botanical insecticides. © 2023 Society of Chemical Industry.

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.

Efficacy and safety of oral Chinese medicine on cancer-related fatigue for lung cancer patients after chemotherapy: Protocol for systematic review and meta-analysis.

INTRODUCTION: Lung cancer has the highest mortality rate of about 18.0% among malignant tumors worldwide, and chemotherapy is the main treatment. 80% of patients receiving chemotherapy suffers from cancer-related fatigue, which is the most severe symptom, with a large effect on quality of life as well as prognosis. Oral Chinese medicine, a kind of complementary and alternative medicine, has been proved to benefit lung cancer patients. However, no studies have reviewed whether it can reduce fatigue in lung cancer patients after chemotherapy, which is the purpose of our study. METHODS: Two reviewers will systematically and independently retrieve papers, select studies for inclusion, extract data, and assess risk of bias. The following nine databases will be searched: China National Knowledge Infrastructure, Wan Fang database, Chinese Scientific Journals Database, Chinese biomedical literature service system, PubMed, Web of Science, OVID, Scopus, and EMBASE from inception to February, 2022. Included studies will only be randomized controlled trials. Primary outcome is cancer-related fatigue. Secondary outcomes are quality of life, immunologic function, and the incidence of adverse events. We will use RoB 2 tool to assess the risk of bias and RevMan to analyze data. Risk ratios will be calculated for dichotomous data and mean differences for continuous data. Random-effect model will be used to integrate statistical effects. Meta-regression, subgroup and sensitivity analyses will be carried out. We will evaluate the strength and overall quality of evidence with four levels: very low, low, moderate, and high. RESULTS: The review of current evidence of oral Chinese medicine on cancer-related fatigue for lung cancer patients after chemotherapy will be narratively summarized and quantitatively analyzed. CONCLUSION: The definitive conclusion will help physicians to determine whether oral Chinese medicine is an effective treatment for reducing fatigue in lung cancer patients after chemotherapy in clinical settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021292576.

Midterm Outcome After Septal Myectomy and Medical Therapy in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy.

Objective: The purpose of this study was mainly to determine the midterm outcome of septal myectomy (SM) and medical therapy (MT) in mildly symptomatic patients (NYHA class II) with hypertrophic obstructive cardiomyopathy (HOCM). Methods: The study cohort consisted of 184 mildly symptomatic patients with HOCM evaluated in Beijing Anzhen Hospital, Capital Medical University between March 2001 and December 2017, including 82 patients in the SM group and 102 patients in the MT group. Overall survival and HCM-related survival were mainly observed. Results: The average follow-up time was 5.0 years. Compared to patients accepting MT, patients treated with SM were associated with comparable overall survival (96.5% and 93.1% vs. 92.9% and 83.0% at 5 and 10 years, respectively; P = 0.197) and HCM-related survival (98.7% and 98.7% vs. 94.2% and 86.1% at 5 and 10 years, respectively; P = 0.063). However, compared to MT, SM was superior at improvement of NYHA class (1.3 ± 0.6 vs. 2.1 ± 0.5, P < 0.001) and mean reduction of resting left ventricular outflow (LVOT) gradient (78.5 ± 18.6% vs. 28.3 ± 18.4%, P < 0.001). Multivariate analysis suggested that resting LVOT gradient in the last clinical examination was an independent predictor of all-cause mortality (HR = 1.017, 95%CI: 1.000-1.034, P = 0.045) and HCM-related mortality (HR = 1.024, 95%CI: 1.005-1.043, P = 0.012) in the entire cohort. Conclusion: Compared with MT, SM had comparable overall survival and HCM-related survival in mildly symptomatic HOCM patients, but SM had advantages on improving clinical symptoms and reducing resting LVOT gradient. Resting LVOT gradient in the last clinical examination was an independent predictor of all-cause mortality and HCM-related mortality.