Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective To summarize the experience of integrative palliative care at Peking Union Medi-cal College Hospital and provide a reference for promoting the integrative palliative care model.Methods Twenty cases receiving integrative palliative care at Peking Union Medical College Hospital were collected.The clinical characteristics,reasons for initiating integrative palliative care,the process of integrative palliative care,and feedback from these cases were summarized.Results Insomnia(11 cases,55％)and pain(9 cases,45％)were the most common symptoms requiring control in the 20 cases.The integrative palliative care team assisted in medical decision-making for 17 cases(85％),prepared end-of-life for 9 cases(45％),assisted in the transfer for 3 cases(15％),and provided comfort care for all the 20 cases(100％).Conclusions The integrative palliative care model can help alleviate suffering in end-of-life patients and provide support to patients'families and the original medical teams.This model is worth further promotion within class A tertiary hospitals.

Objective The goals of this study were to identify early warning markers of severe dengue based on bioinformatics com-bined with machine learning,and explore the evaluation system of the risk of occurrence of severe dengue.Methods Based on the Gene Expression Omnibus database,the differentially expressed genes between dengue and severe dengue were analyzed,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted.Early warning genes of severe dengue were screened using a random forest model,and the accuracy of the genes was verified using receiver operating characteristic(ROC)curves.Finally,nomograms were constructed to quantify the warning genes and predict the risk of progression from dengue to severe dengue based on the expression level of these genes.Results A total of 817 differentially expressed genes were identified,along with the associated biolo-gical processes that may be closely related to the occurrence and development of severe dengue,namely,antimicrobial humoral response,humoral immune response,serine hydrolase activity,and arachidonic acid metabolism.Based on this analysis,five early warning genes were isolated:AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A.Among these,ATP4A,COL4A3BP,and TRPM4 showed low expression levels,whereas AZU1and PDCD4were highly expressed.The ROC curves indicated that these genes were accurate pre-dictors of severe dengue.The nomograms indicated good predictive accuracy,clinical benefit rate,and clinical effectiveness of the model.Conclusion Measuring the expression levels of five warning genes(AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A)may help to evaluate the risk of severe dengue.

Objective To evaluate the clinical efficacy and safety of modified Weijing Decoction in the treatment of stable stage of bronchiectasis(phlegm heat accumulating in the lung pattern).Methods A series of N-of-1 trials using bronchiectasis patients in stable stage with phlegm heat accumulation in the lung pattern were performed.Participants meeting inclusion criteria underwent two distinct treatment protocols during a therapy period.Modified Weijing Decoction was used in the experimental period and ambroxol tablets were used in the control period,washout periods were set.The medication-use order in the control period and experimental period is random.The visual analog scale(VAS)was used to assess symptom changes before and after treatment.24-hour sputum volume and COPD self-assessment test(CAT)scores were recorded,while adverse reactions were monitored during the study period.Statistical analysis and drawing were performed on SPSS 25.0 and GraphPad Prism 8.Comparison of inter-group differences before grouping was assessed by independent samples t-test.Analysis of symptom score,24-hour sputum volume and CAT scores in the experimental and control periods,as well as comparison of differences between the above two groups before and after treatment were performed using paired t-test,which enabled comprehensive exploration of clinical and statistical distinctions.Results A total of 9 patients participated in 16 rounds of analysis.Statistically significant differences(P＜0.05)before and after the treatment in the experimental period were noted in total Traditional Chinese Medicine(TCM)symptom scores,cough,sputum,sputum color,chest tightness and chest pain,bitter and dry mouth,fatigue and tiredness,24-hour sputum volume,and CAT score.Paired t-tests revealed significant variations(P＜0.05)in the total TCM symptom scores,sputum color scores,scores of chest tightness and pain,and 24-hour sputum volume between experimental and control periods.No adverse events related to the test methods or drugs occurred during the observation period.Conclusion Modified Weijing Decoction could comprehensively improve clinical symptoms of bronchiectasis patients in stable stage.It exhibits superior efficacy compared to ambroxol,and maintains a favorable safety profile.

Objective:To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen.Methods:The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy.Results:A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021.Conclusions:Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.

OBJECTIVE：To provide reference for improving TCM treatment of pulmonary nodule. METHODS ：The experience of famous TCM doctors in the TCM treatment of pulmonary nodule was searched by computer ，the formulations of the cases were sorted out ，and the data were recorded into the TCMISS V 2.5 for data analysis ，and the medicine frequency was counted. Apriori algorithm and association rules were used for statistical analysis of core combination of formulations （support degree was 16，confidence degree was 0.65）. Inner core combination and new combination were extracted according to the entropy clustering method of complex system （correlation was 6，penalty was 2）. RESULTS ：A total of 25 literatures were input ，including 64 formulations in total ，166 medicinal materials. For the prescriptions of pulmonary nodule ，the frequency of single ingredient from high to low was Bolbostemma paniculatum ，Glycyrrhiza uralensis ，Astragalus membranaceus ，Prunella vulgaris ，Ostrea gigas，Angelica sinensis ，Pinellia ternate ，Ligusticum chuanxiong ，Mori Corlex ，etc. The main compatibility of the drug model is to invigorate Qi ，dissipate phlegm ，invigorate Qi and activate blood circulation ，and promote Qi and softness ，such as “G. uralensis，B. paniculatum ”“A. membranaceus ，B. paniculatum ”“A. membranaceus ，G. uralensis ”，etc；10 core combinations of the drug were found out ， such as Begonia fimbristipula-Rhodiola rosea-Bupleurum Chinense ， Cervus elaphus Clematis chinensis-Buffalo Horn，etc. There were 5 new prescriptions ，i.e. B. fimbristipula-R. rosea-B. chinense-Setaria italic ，C. elaphus-C. chinensis-Buffalo Horn-French chalk ，A. sinensis-L. chuanxiong-Morus alba- Mori Corlex -P. vulgaris-Ganoderma lucidum ，Hedyotis diffusa-Prunus persica-Trichosanthes kirilowii-Achyranthes bidentata-Eupolyphaga sinensis- Cinnamomi Ramulus ，A. bidentata-E. sinensis-Ephedra sinica-Curcuma aromatica-Curcuma longa-Concretio silicea . CONCLUSIONS ：Most modern doctors believe that the interaction of phlegm and blood stasis is the main pathogenesis of pulmonary nodule ，and the treatment is mainly based on the treatment of lung ，spleen，liver and kidney ，focus on the elimination of symptoms and phlegm ，the elimination of blood stasis and the soft and hard treatment ，pay attention to the weak body of the patient. TCM treatment of pulmonary nodule has a good prospect.

Objective: To analyze the molecular characteristics of Listeria monocytogenes strains from ready-to eat food in China. Methods: A total of 239 Listeria monocytogenes strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. Results: All strains were categorized into three different lineages, lineage Ⅱ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Conclusion Ⅱa was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.

Objective:To explore the differences of attention bias performance between patients with heroin dependence in methadone maintenance treatment(MMT) and healthy controls.Methods:A total of 38 heroin dependent patients in the Fourth People's Hospital of Huainan from January 2018 to September 2018 were selected as MMTgroup, and 32 gender-and age-matched healthy controls were selected as healthy control(HC) group.The attention bias was evaluated by Emotional Stroop Task, and the difference between the two groups was compared.Results:The error number of the herion-related words in Emotional Stroop Task of MMT group was lower than that of HC group[0.75(2, 5) vs.1(0, 2)], the difference was statistically significant( Z=-2.184, P=0.029). The number of errors in point and neutral words and reaction time of point, neutral word and clue word had no statistically significant differences between MMT group and HC group[1(0, 4) vs.1(0, 2); 3(2, 5) vs.2(2, 3); (1 055.14±303.50)ms vs.(985.40±173.71)ms, (1 126.89±347.82)ms vs.(1 022.76± 173.62)ms; (1 188.53±371.80)ms vs.(1 113.23±225.11)ms]( Z=-1.331, P=0.183; Z=-1.723, P=0.085; t=1.150, P=0.254; t=1.539, P=0.129; t=1.001, P=0.320). There were no statistically significant differences in attention bias influenced by the dosage and duration of methadone between MMT group and HC group(all P>0.05). Conclusion:These results demonstrate that heroin dependence patients in MMT have attentional bias in heroin-related words.Methadone has no effect on attention bias in patients with heroin dependence during maintenance treatment intervention.

To investigate the association of preoperative clinical and sonographic characteristics of clinically node‐negative ( cN0) papillary thyroid carcinoma ( PTC) with central lymph node metastasis ( CLNM ) . Methods A total of 514 patients with PTC confirmed by pathology in our hospital were included in the retrospective analysis . Clinical and sonographic characteristics were assessed including age ,gender ,tumor size ,and the distance between the tumor and the capsule . These cases were all diagnosed as cN0 according to clinical and sonography examinations . And the cases were divided into CLNM ( + ) group and CLNM ( －) group based on the pathological results . T hen statistical analysis was used to evaluate the correlation between CLNM and risk factors of cN 0 PTCs . Results ① Of the 514 cN0 PTC cases ,211 cases ( 41 .1% ) were CLNM ( + ) and 303 cases ( 58 .9% ) were CLNM ( －) . ② With the presence of capsule invasion in the ultrasound examination ,the probability of CLNM ( + ) group was higher than that of CLNM ( －) group ( 62 .1% vs 37 .9% ) . ③ In the 364 cases without capsule invasion ,the probability of CLNM ( + ) was significantly increased when the distance between the tumor and the capsule was ＜ 1 .5 mm ( 88 .8% vs 11 .2% ) . ④ M ultivariate analysis showed that risk factors independently associated with CLNM included age ＜45 years old ,tumor maximum diameter ≥10 mm ,and the distance between the tumor and the capsule ＜ 1 .5 mm ,among w hich the distance between the tumor and the capsule ＜1 .5 mm had the highest OR value . Conclusions In cN0 PTC patients ,CLNM is associated with age ,size and the distance between the tumor and the capsule .