Morinda officinalis is one of the “Four Great Southern Medicines” and is commonly used in clinical practice to treat erectile dysfunction and nocturnal emissions caused by kidney yang deficiency， uterine cold infertility， menstrual disorders， low abdominal pain， rheumatism， and muscle and bone weakness. Based on the principle of “treating raw and cooked differently”， this article summarizes the effects of different processing methods on the chemical constituents and pharmacological effects of M. officinalis . Research has found that processing can affect the content and structure of sugars， iridoids， and anthraquinones in M. officinalis ， thereby regulating its pharmacological effects such as anti-osteoporosis， immune regulation， anti-fatigue， and anti-depression. Among them， salt M. officinalis shows outstanding performance in anti-osteoporosis and enhancing immunity. Although previous studies have preliminarily elucidated the major chemical constituents of M. officinalis and their pharmacological characteristics， the dynamic transformation paths of constituents during the processing remain to be further clarified， especially the es tablishment of a quality marker system associated with the processing technology， to achieve the precision and intelligent development of the processing.

Morinda officinalis is one of the “Four Great Southern Medicines” and is commonly used in clinical practice to treat erectile dysfunction and nocturnal emissions caused by kidney yang deficiency， uterine cold infertility， menstrual disorders， low abdominal pain， rheumatism， and muscle and bone weakness. Based on the principle of “treating raw and cooked differently”， this article summarizes the effects of different processing methods on the chemical constituents and pharmacological effects of M. officinalis . Research has found that processing can affect the content and structure of sugars， iridoids， and anthraquinones in M. officinalis ， thereby regulating its pharmacological effects such as anti-osteoporosis， immune regulation， anti-fatigue， and anti-depression. Among them， salt M. officinalis shows outstanding performance in anti-osteoporosis and enhancing immunity. Although previous studies have preliminarily elucidated the major chemical constituents of M. officinalis and their pharmacological characteristics， the dynamic transformation paths of constituents during the processing remain to be further clarified， especially the es tablishment of a quality marker system associated with the processing technology， to achieve the precision and intelligent development of the processing.

ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology and pharmacodynamics， to investigate the pharmacodynamic material basis and mechanism of Hei Xiaoyaosan in improving learning and memory ability of insomnia rats. MethodUPLC-Q-TOF-MS was used to characterize the chemical constituents of Hei Xiaoyaosan. Network pharmacology was applied to construct the network of active ingredients-intersecting targets-pathways， and molecular docking was performed on key ingredients and core targets. Sixty 8-week-old male SD rats were selected and randomly divided into blank group， model group， Hei Xiaoyaosan low， medium， and high dose groups（3.82， 7.65， 15.30 g·kg^-1）， and zolpidem tartrate group（0.5 mg·kg^-1）， with 10 rats in each group. Except for the blank group， the insomnia model was induced by intraperitoneal injection of p-chlorophenylalanine（PCPA） for 4 consecutive days. Rats in each dosing group were administered the corresponding dose by gavage， once a day for 14 consecutive days. Morris water maze test was utilized to assess the learning and memory ability of rats， transmission electron microscopy was employed to examine the ultrastructure of hippocampal synapses， enzyme-linked immunosorbent assay（ELISA） was conducted to analyze the levels of 5-hydroxytryptamine（5-HT）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in hippocampal tissues， and Western blot was performed to detect the expression levels of tumor suppressor protein p53（TP53）， rat sarcoma virus（RAS）， epidermal growth factor receptor（EGFR）， cyclic adenosine monophosphate（cAMP）-response element binding protein（CREB） binding protein（CREBBP）， glycogen synthase kinase-3β（GSK-3β）， protein kinase B1（Akt1）， nitric oxide synthase 1（NOS1）， phosphorylated（p）-Akt1， and p-GSK-3β in hippocampal tissues. Additionally， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to assess the mRNA expression levels of TP53， RAS， EGFR， CREBBP， GSK-3β， Akt1 and NOS1. ResultA total of 176 components were identified in Hei Xiaoyaosan， mainly flavonoids， triterpene saponins， phenylpropanoids and other compounds. Network pharmacological analysis revealed that TP53， V-Ha-Ras Harvey Rat sarcoma viral oncogene homolog（HRAS）， neuroblastoma sarcoma viral oncogene homolog（NRAS）， EGFR， CREBBP， GSK-3β， Akt1 and NOS1 were the key targets of Hei Xiaoyaosan in treating insomnia. The core targets were predominantly associated with cAMP， RAS， Ras-associated protein 1（Rap1）， advanced glycation end products（AGE）/receptor for AGE（RAGE）， and EGFR signaling pathways， and the key active ingredients of Hei Xiaoyaosan in treating insomnia were 8-shogaol， ligustilide F， 6-gingerol， levistilide A and senkyunolide E. Animal experiment results demonstrated that Hei Xiaoyaosan medium and high dose groups significantly increased body weight， shortened sleep latency and prolonged sleep duration in insomnia rats（P<0.01）， significantly decreased escape latency and increased platform crossing frequency（P<0.01）， and improved the pathological changes of hippocampal synaptic ultrastructure. Meanwhile， the two groups could significantly elevate 5-HT level， Akt1 mRNA expression， Akt1 and p-Akt1 protein expression（P<0.01）， reduce inflammatory factor levels（P<0.01）， and down-regulate protein expression levels of TP53， RAS， NOS1， EGFR， CREBBP， GSK-3β and p-GSK-3β（P<0.01）， as well as mRNA expression levels of TP53， RAS， NOS1， EGFR， CREBBP and GSK-3β in hippocampal tissues（P<0.01）. ConclusionThis study determined that the five key active ingredients（8-shogaol， ligustilide F， 6-gingerol， levistilide A and senkyunolide E） in Hei Xiaoyaosan may improve the learning and memory ability of insomnia rats by regulating signaling pathways such as cAMP， RAS， and EGFR， providing an important reference for its mechanism research and clinical application.

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

INTRODUCTION: Amid the COVID-19 pandemic, many rumours have emerged. Given prior research linking rumour exposure to mental well-being, we conducted a nationwide survey to document the base rate of rumour exposure and factors associated with rumour vulnerability. METHODS: Between March and July 2020, 1,237 participants were surveyed on 5 widely disseminated COVID-19 rumours (drinking water frequently could be preventive, eating garlic could be preventive, the outbreak arose because of bat soup consumption, the virus was created in an American lab, and the virus was created in a Chinese lab). For each rumour, participants reported whether they had heard, shared or believed each rumour. RESULTS: Although most participants had been exposed to COVID-19 rumours, few shared or believed these. Sharing behaviours sometimes occurred in the absence of belief; however, education emerged as a protective factor for both sharing and belief. CONCLUSION Our results suggest that campaigns targeting skills associated with higher education (e.g. epistemology) may prove more effective than counter-rumour messages.
Adult ; Aged ; Aged, 80 and over ; COVID-19/psychology* ; Communication ; Consumer Health Information ; Culture ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Self Report ; Singapore/epidemiology* ; Social Environment ; Social Media ; Surveys and Questionnaires

Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations. Prostate cancer (PCa) is characterized by variable clinical manifestations and frequently unpredictable outcomes. We performed an expression quantitative trait loci (eQTL) analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information. Using multi-level information published in The Cancer Genome Atlas, we performed eQTL-based analyses on DNA methylation and gene expression. To better interpret these data, we correlated loci and clinical indexes to identify the important loci for both PCa development and progression. Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa, these genes are enriched in important cancer-related groups. In addition, single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci, including the 19q13.2-q13.43 and 16q22.2-q23.1 loci. Further, an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation. Although DNA methylation-regulated genes across PCa samples are a small proportion, the associated genes play important roles in PCa carcinogenesis.

OBJECTIVE: To provide evidence on the efficacy and safety of Chinese herbal medicine (CHM) as interventions for systemic lupus erythematosus (SLE). METHODS: Seven electronic databases, including the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, Embase, and PubMed, were comprehensively searched, from their inception to August 16, 2020, for all randomized controlled trials (RCTs) that focused on CHM used alone or in combination with conventional medicine for SLE. Outcomes were SLE activity index (SLEDAI), traditional Chinese medicine symptom/syndrome score (TCMSS), dosage of glucocorticoids, main serological testing, and incidence of adverse events. Data were extracted and pooled using Review Manager 5.3 software. RESULTS: A total of 13 RCTs enrolling 856 participants met our inclusion criteria. Meta-analyses showed that, compared to placebo, CHM had statistically significant effect on reducing SLEDAI score (MD=-1.74, 95% CI: -2.29 to -1.18), diminishing TCMSS (SMD=-0.89, 95% CI: -1.16 to -0.62), decreasing dosage of glucocorticoids (MD=-2.41 mg/d, 95% CI: -3.34 to -1.48), lowering erythrocyte sedimentation rate (MD=-4.78 mm/h, 95% CI: -8.86 to -0.71), and increasing serum complement C4 level (MD=0.03 mg/dL, 95% CI: 0.00 to 0.06). No significant difference was found between CHM and placebo on adverse events. CONCLUSIONS CHM provided significant beneficial effect on controlling disease activity and reducing dose of glucocorticoids used among SLE patients. Future advanced designed RCTs for CHM treating moderate to severe SLE with multicenter and longer follow-up are urgently needed.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Lupus Erythematosus, Systemic/drug therapy* ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic

Transcriptional regulators (TRs) participate in essential processes in cancer pathogenesis and are critical therapeutic targets. Identification of drug response-related TRs from cell line-based compound screening data is often challenging due to low mRNA abundance of TRs, protein modifications, and other confounders (CFs). In this study, we developed a regression-based pharmacogenomic and ChIP-seq data integration method (RePhine) to infer the impact of TRs on drug response through integrative analyses of pharmacogenomic and ChIP-seq data. RePhine was evaluated in simulation and pharmacogenomic data and was applied to pan-cancer datasets with the goal of biological discovery. In simulation data with added noises or CFs and in pharmacogenomic data, RePhine demonstrated an improved performance in comparison with three commonly used methods (including Pearson correlation analysis, logistic regression model, and gene set enrichment analysis). Utilizing RePhine and Cancer Cell Line Encyclopedia data, we observed that RePhine-derived TR signatures could effectively cluster drugs with different mechanisms of action. RePhine predicted that loss-of-function of EZH2/PRC2 reduces cancer cell sensitivity toward the BRAF inhibitor PLX4720. Experimental validation confirmed that pharmacological EZH2 inhibition increases the resistance of cancer cells to PLX4720 treatment. Our results support that RePhine is a useful tool for inferring drug response-related TRs and for potential therapeutic applications. The source code for RePhine is freely available at https://github.com/coexps/RePhine.

Objective:To analyze the epidemiological and etiological characteristics of a dengue fever outbreak in Hunan province in 2018.Methods:Real-time PCR assay was performed for the laboratory diagnosis of 8 suspected dengue fever cases. Etiological surveillance was performed in 186 suspected dengue fever cases and fever cases who had close contacts with dengue fever patients. C6/36 cells was used for the virus isolation from acute phase serum. By sequencing the full length of E genes of 15 dengue virus strains, phylogenetic analysis was performed based on the sequences obtained, including reference sequences from the NCBI GenBank database, the serotypes and gene subtypes of the virus were analyzed to trace the possible source of transmission. An emergency monitoring of vector density and a retrospective survey of sero-epidemiology in healthy population were conducted in the epidemic area.Results:In the serum samples of 8 suspected patients, 6 were dengue virus RNA positive, and 4 were NS1 antigen positive. In 186 suspected patients, 96 were dengue virus nucleic acid, NS1 antigen or antibody positive in etiological test. A total of 64 dengue virus strains were isolated. The phylogenetic analysis showed that all the dengue virus strains belonged to type 2, which might be from Guangdong or Zhejiang provinces. The Bretub index was up to 65, indicating an extremely high risk of transmission. The positive rate of the dengue virus IgG antibody was 0.53%(2/377) in retrospective survey of 377 healthy people.Conclusion:The field epidemiologic and the molecular genetics analyses showed the outbreak of dengue fever in Hunan in 2018 was caused by imported cases and dengue virus 2.