Phylogenomics and biogeographical diversification of Collabieae (Orchidaceae) and its implication in the reconstruction of the dynamic history of Asian evergreen broadleaved forests.

The tribe Collabieae (Epidendroideae, Orchidaceae) comprises approximately 500 species. Generic delimitation within Collabieae are confusing and phylogenetic interrelationships within the Collabieae have not been well resolved. Plastid genomes and nuclear internal transcribed spacer (ITS) sequences were used to estimate the phylogenetic relationships, ancestral ranges, and diversification rates of Collabieae. The results showed that Collabieae was subdivided into nine clades with high support. We proposed to combine Ancistrochilus and Pachystoma into Spathoglottis, merge Collabium and Chrysoglossum into Diglyphosa, and separate Pilophyllum and Hancockia as distinctive genera. The diversification of the nine clades of Collabieae might be associated with the uplift of the Himalayas during the Late Oligocene/Early Miocene. The enhanced East Asian summer monsoon in the Late Miocene may have promoted the rapid diversification of Collabieae at a sustained high diversification rate. The increased size of terrestrial pseudobulbs may be one of the drivers of Collabieae diversification. Our results suggest that the establishment and development of evergreen broadleaved forests facilitated the diversification of Collabieae.

Occurrence, distribution, and risk assessment of antibiotics in a typical aquaculture area around the Dongzhai Harbor mangrove forest on Hainan Island.

The trees of the Dongzhai Harbor mangrove forest suffer from antibiotic contamination from surrounding aquaculture areas. Despite this being one of the largest mangrove forests in China, few studies have focused on the antibiotic pollution status in these aquaculture areas. In the present study, the occurrence, distribution, and risk assessment of 37 antibiotics in surface water and sediment samples from aquaculture areas around Dongzhai Harbor mangrove forests were analyzed. The concentration of total antibiotics (∑antibiotics) ranged from 78.4 ng/L to 225.6 ng/L in surface water (except S14-A2) and from 19.5 ng/g dry weight (dw) to 229 ng/g dw in sediment. In the sediment, the concentrations of ∑antibiotics were relatively low (19.5-52.3 ng/g dw) at 75 % of the sampling sites, while they were high (95.7-229.0 ng/g dw) at a few sampling sites (S13-A1, S13D, S8D). The correlation analysis results showed that the Kd values of the 9 antibiotics were significantly positively correlated with molecular weight (MW), Kow, and LogKow. Risk assessment revealed that sulfamethoxazole (SMX) in surface water and SMX, enoxacin (ENX), ciprofloxacin (CFX), enrofloxacin (EFX), ofloxacin (OFX), and norfloxacin (NFX) in sediment had medium/high risk quotients (RQs) at 62.5 % and 25-100 %, respectively, of the sampling sites. The antibiotic mixture in surface water (0.06-3.36) and sediment (0.43-309) posed a high risk at 37.5 % and 66.7 %, respectively, of the sampling sites. SMX was selected as an indicator of antibiotic pollution in surface water to assist regulatory authorities in monitoring and managing antibiotic pollution in the aquaculture zone of Dongzhai Harbor. Overall, the results of the present study provide a comprehensive and detailed analysis of the characteristics of antibiotics in the aquaculture environment around the Dongzhai Harbor mangrove system and provide a theoretical basis for the source control of antibiotics in mangrove systems.

Genome-Wide Identification and Expression Analysis of WNK Kinase Gene Family in Acorus.

WNK (With No Lysine) kinases are members of serine/threonine protein kinase family, which lack conserved a catalytic lysine (K) residue in protein kinase subdomain II and this residue is replaced by either asparagine, serine, or glycine residues. They are involved in various physiological regulations of flowering time, circadian rhythms, and abiotic stresses in plants. In this study, we identified the WNK gene family in two species of Acorus, and analyzed their phylogenetic relationship, physiochemical properties, subcellular localization, collinearity, and cis-elements. The results showed twenty-two WNKs in two Acorus (seven in Ac. gramineus and fifteen in Ac. calamus) have been identified and clustered into five main clades phylogenetically. Gene structure analysis showed all WNKs possessed essential STKc_WNK or PKc_like superfamily domains, and the gene structures and conserved motifs of the same clade were similar. All the WNKs harbored a large number of light response elements, plant hormone signaling elements, and stress resistance elements. Through a collinearity analysis, two and fourteen segmental duplicated gene pairs were identified in the Ac. gramineus and Ac. calamus, respectively. Moreover, we observed tissue-specificity of WNKs in Acorus using transcriptomic data, and their expressions in response to salt stress and cold stress were analyzed by qRT-PCR. The results showed WNKs are involved in the regulation of abiotic stresses. There were significant differences in the expression levels of most of the WNKs in the leaves and roots of Acorus under salt stress and cold stress, among which two members in Ac. gramineus (AgWNK3 and AgWNK4) and two members in Ac. calamus (AcWNK8 and AcWNK12) were most sensitive to stress. In summary, this paper will significantly contribute to the understanding of WNKs in monocots and thus provide a set up for functional genomics studies of WNK protein kinases.

Origin and diversification of a Himalayan orchid genus Pleione.

Pleione is an orchid endemically distributed in high mountain areas across the Hengduan Mountains (HDM), Himalayas, Southeast Asia and South of China. The unique flower shapes, rich colors and immense medicinal importance of Pleione are valuable ornamental and economic resources. However, the phylogenetic relationships and evolutionary history of the genus have not yet been comprehensively resolved. Here, the evolutionary history of Pleione was investigated using single-copy gene single nucleotide polymorphisms and chloroplast genome datasets. The data revealed that Pleione could be divided into five clades. Discordance in topology between the two phylogenetic trees and network and D-statistic analyses indicated the occurrence of reticulate evolution in the genus. The evolution could be attributed to introgression and incomplete lineage sorting. Ancestral area reconstruction suggested that Pleione was originated from the HDM. Uplifting of the HDM drove rapid diversification by creating conditions favoring rapid speciation. This coincided with two periods of consolidation of the Asian monsoon climate, which caused the first rapid diversification of Pleione from 8.87 to 7.83 Mya, and a second rapid diversification started at around 4.05 Mya to Pleistocene. The interaction between Pleione and climate changes, especially the monsoons, led to the current distribution pattern and shaped the dormancy characteristic of the different clades. In addition to revealing the evolutionary relationship of Pleione with orogeny and climate changes, the findings of this study provide insights into the speciation and diversification mechanisms of plants in the East Asian flora.

Potential mechanisms of Shenmai injection against POCD based on network pharmacology and molecular docking.

BACKGROUND: As the population ages, the number of patients with postoperative cognitive dysfunction increases. This study aims to investigate the mechanisms of Shenmai injection as a therapeutic strategy for postoperative cognitive dysfunction using a network pharmacology approach. METHODS: Shenmai injection and its targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Postoperative cognitive dysfunction-associated protein targets were identified using the GeneCards and DisGeNET databases. Subsequently, a protein-protein interaction network was constructed using the String database. For treating postoperative cognitive dysfunction, the core targets of Shenmai injection were identified through topological analysis, followed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses performed for annotation. Molecular docking was performed on the screened core targets and components. RESULTS: One hundred and eighty-two related targets of Shenmai injection in treating postoperative cognitive dysfunction were identified. Eleven active ingredients in Shenmai injection were detected to have a close connection with postoperative cognitive dysfunction-related targets. Additionally, Gene Ontology analysis revealed 10 biological processes, 10 cellular components and 10 molecular functions. The Kyoto Encyclopedia of Genes and Genomes analysis identified 20 signaling pathways. The docking results indicated five active ingredients from Shenmai injection can fit in the binding pockets of all three candidate targets. CONCLUSIONS: Thus, the present work systematically explored the anti-postoperative cognitive dysfunction mechanism of potential targets and signaling pathways of Shenmai injection. These results provide an important reference for subsequent basic research on postoperative cognitive dysfunction.

Correlation of serum 25-hydroxyvitamin D level with Thyrotropin receptor antibody and bone metabolism markers in patients with Graves' disease / 中华临床营养杂志

Objective:To investigate the serum 25-hydroxyvitamin D [25(OH)D] level in patients with Graves' disease (GD) and its correlation with thyrotropin receptor antibody (TRAb) and bone metabolism markers.Methods:A total of 124 patients with newly diagnosed or relapsed GD were selected and divided into three groups according to serum 25(OH)D level, namely vitamin D deficiency group with 25(OH)D <12 μg/L, vitamin D insufficiency group with 25(OH)D of 12 to 20 μg/L, and vitamin D sufficiency group with 25(OH)D ≥ 20 μg/L. The levels of serum 25(OH)D, TRAb, type I procollagen N-terminal pro-peptide (PINP), type I collagen cross-linked C-terminal peptide (S-CTX), parathyroid hormone (PTH), total triiodothyronine (TT 3), total thyroxine (TT 4) and thyroid-stimulating hormone (TSH) were measured in all patients, and the differences of these biochemical indices were compared across groups. Oneway analysis of variance or Kruskal-Wallis test was used for comparison between groups, and Pearson or Spearman correlation analysis was applied for correlation test. Results:The levels of serum TT 3, TT 4, PINP, and S-CTX significantly increased ( P < 0.01) and the level of phosphorus (P) decreased ( P < 0.01) with the decreased vitamin D levels. The levels of PTH and calcium (Ca) were significantly lower in the vitamin D sufficiency group compared with the vitamin D insufficiency group and vitamin D deficiency group ( P < 0.01). Correlation analysis showed that serum 25(OH)D level was negatively correlated with the levels of TT 3, TT 4, PINP, S-CTX, PTH and Ca ( P < 0.01), and positively correlated with the levels of P and TSH ( P < 0.01). Conclusions:Decreased serum 25(OH)D level is closely related with increased bone turnover, PTH, and thyroid hormone levels in patients with GD, but not related with TRAb. Thyroid hormone levels have a certain predictive value regarding vitamin D deficiency in GD patients. It is necessary to monitor the vitamin D levels in patients with GD and provide vitamin D supplementation to reduce the incidence of osteoporosis, improve the effectiveness of antithyroid treatment and reduce the recurrence of GD.

Analysis on mechanisms of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstones and cholecystitis based on network pharmacology / 国际中医中药杂志

Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

Research progress of nutrition literacy assessment for children and adolescents / 中国学校卫生

Abstract@#Children and adolescents are at an important stage in the development of eating habits and food skills. Nutrition literacy is inseparable from healthy eating behaviors and higher nutritional quality, and improving nutrition literacy is an important pathway to better nutrition. The paper summarizes domestic and international research on nutrition literacy from the perspectives of definition and assessment tools in children and adolescents. It is found that there is no universal definition of nutritional literacy. Adult nutrition literacy or with appropriate adjustments are widely used in children and adolescents, without taking into account the unique developmental characteristics and nutritional needs of children and adolescents; the measurement tools of nutritional literacy are diverse, and there is no unified assessment tools, so it is difficult to compare and analyze research findings and draw reliable conclusions. In the future, authoritative definitions, and standardized evaluation tools are in great need.

Variations of glucose content in Massa Medicata Fermentata during processing based on quantitative proton nuclear magnetic resonance / 中国中药杂志

A quantitative proton nuclear magnetic resonance(qHNMR) method was established to determine the glucose content in commercially available Massa Medicata Fermentata(MMF) products and explore the variations of glucose content in MMF products during processing. The qHNMR spectrum of MMF in deuterium oxide was obtained with 2,2,3,3-d_4-3-(trimethylsilyl) propionate sodium salt as the internal standard substance. With the doublet peaks of terminal hydrogen of glucose with chemical shift at δ 4.65 and δ 5.24 as quantitative peaks, the content of glucose in MMF samples was determined. The glucose content showed a good linear relationship within the range of 0.10-6.44 mg·mL~(-1). The relative standard deviations(RSDs) of precision, stability, repeatability, and recovery for determination were all less than 2.3%. The glucose content varied in different commercially available MMF samples, which were associated with the different fermentation days, wheat bran-to-flour ratios, and processing methods. The glucose content in MMF first increased and then decreased over the fermentation time. Compared with the MMF products fermented with wheat bran or flour alone, the products fermented with both wheat bran and flour had increased glucose. The glucose content of bran-fried MMF was slightly lower than that of raw MMF, while the glucose content in charred MMF was extremely low. In conclusion, the qHNMR method established in this study is simple, fast, and accurate, serving as a new method for determining the glucose content in MMF. Furthermore, this study clarifies the variations of glucose content in MMF during processing, which can not only indicate the processing degree but also provide a scientific basis for revealing the fermentation mechanism and improving the quality control of MMF.

The effect of Jiegeng decoction on lipopolysaccharide-induced acute lung injury in mice based on metabolomics / 药学学报

One of the traditional prescriptions for treating lung diseases, Jiegeng decoction (JGT), is still unknown in terms of its chemical makeup and mechanism. In this study, Q-Exactive-Orbitrap MS technology was used to identify the chemical constituents of JGT, and metabolomics was used to examine the effect of JGT on metabolites in the lung tissue of mice with acute lung injury (ALI) model. The potential biomarkers were screened by fold change (FC) > 1.5 or FC < 0.67 and P < 0.05, and enriched for metabolic pathways. A total of 40 compounds, including triterpenoid saponins, flavonoids and glycosides, were identified by mass spectrometry analysis of JGT. All animal experiments were approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2021106). The results showed that JGT improved the lung coefficient, and lung tissue morphology of mice with ALI, lowered the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in bronchoalveolar lavage fluid (BALF), and reduced myeloperoxidase (MPO) content in lung tissue. The metabolomic results showed that JGT could regulate 22 metabolites associated with ALI, among which leukotriene D4, docosapentaenoic acid, hypoxanthine, L-5-oxoproline, and other metabolites were mainly associated with the body′s inflammatory response and oxidative stress, and were enriched in the pathways of glutathione metabolism, purine metabolism, and primary bile acid biosynthesis. This study analyzed the potential mechanism of JGT in the treatment of ALI through metabolomics, providing an important theoretical basis for the clinical application of JGT.

Advances in electrochemically active biofilm of Shewanella oneidensis MR-1 / 生物工程学报

Facing the increasingly severe energy shortage and environmental pollution, electrocatalytic processes using electroactive microorganisms provide a new alternative for achieving environmental-friendly production. Because of its unique respiratory mode and electron transfer ability, Shewanella oneidensis MR-1 has been widely used in the fields of microbial fuel cell, bioelectrosynthesis of value-added chemicals, metal waste treatment and environmental remediation system. The electrochemically active biofilm of S. oneidensis MR-1 is an excellent carrier for transferring the electrons of the electroactive microorganisms. The formation of electrochemically active biofilm is a dynamic and complex process, which is affected by many factors, such as electrode materials, culture conditions, strains and their metabolism. The electrochemically active biofilm plays a very important role in enhancing bacterial environmental stress resistance, improving nutrient uptake and electron transfer efficiency. This paper reviewed the formation process, influencing factors and applications of S. oneidensis MR-1 biofilm in bio-energy, bioremediation and biosensing, with the aim to facilitate and expand its further application.

Identification of the Key Functional Domains of Bombyx mori Nucleopolyhedrovirus IE1 Protein.

The immediate early protein 1 (IE1) acts as a transcriptional activator and is essential for viral gene transcription and viral DNA replication. However, the key regulatory domains of IE1 remain poorly understood. Here, we analyzed the sequence characteristics of Bombyx mori nucleopolyhedrovirus (BmNPV) IE1 and identified the key functional domains of BmNPV IE1 by stepwise truncation. Our results showed that BmNPV IE1 was highly similar to Autographa californica nucleopolyhedrovirus (AcMNPV) IE1, but was less conserved with IE1 of other baculoviruses, the C-terminus of IE1 was more conserved than the N-terminus, and BmNPV IE1 was also necessary for BmNPV proliferation. Moreover, we found that IE1158-208 was a major nuclear localization element, and IE11-157 and IE1539-559 were minor nuclear localization elements, but the combination of these two minor elements was equally sufficient to fully mediate the nuclear entry of IE1. Meanwhile, IE11-258, IE1560-584, and the association of amino acids 258 and 259 were indispensable for the transactivation activity of BmNPV IE1. These results systematically resolve the functional domains of BmNPV IE1, which contribute to the understanding of the mechanism of baculovirus infection and provide a possibility to synthesize a small molecule IE1-truncated mutant as an agonist or antagonist.

Self-Reported Use of COVID-19 Immunologic Test Results to Inform Decisions About Daily Activities and COVID-19 Vaccination

ImportanceDespite widespread use of clinical diagnostic tests to assess prior exposure to SARS-CoV-2, limited evidence exists regarding how test results affect patient behaviors and decision-making. ObjectiveTo understand the rationale behind ordering diagnostic T-cell receptor (TCR) immunosequencing for assessment of prior SARS-CoV-2 infection and evaluate how test results affect patient behaviors, including day-to-day activities and decisions about vaccination. DesignMandatory demographic information and clinical characteristics were collected for all individuals ordering T-Detect COVID. Study participants completed a one-time survey that included additional questions about demographics and clinical characteristics, relevant interactions with healthcare providers, reasons for ordering diagnostic TCR immunosequencing, and the utility of test results. SettingUS participants ordering T-Detect COVID between February 2021 and March 2022. ParticipantsOf the 806 individuals who underwent diagnostic TCR immunosequencing, provided informed consent, and were sent the email survey, 718 completed the survey (response rate, 89.1%). At the time of receiving the test report, 25.5% of participants had been vaccinated against COVID-19, 29.7% reported a previous COVID-19 infection, and 25.6% were immunocompromised. Main Outcome(s) and Measure(s)Patient demographics and clinical characteristics were reported using descriptive statistics. Additional analyses explored trends in reported data over time and evaluated reasons for ordering diagnostic TCR immunosequencing and behaviors among participant subgroups (vaccinated or unvaccinated individuals and those with positive or negative test results). Logistic regression analysis evaluated factors that increased the likelihood of post-test vaccination. ResultsStudy participants ordered diagnostic TCR immunosequencing to understand their health status (55.0%) and to inform decision-making about daily activities (43.6%) and vaccination (38.3%). Most participants (92.1%) ordered diagnostic TCR immunosequencing for themselves without consulting their physician. Testing negative for prior SARS-CoV-2 infection was associated with increased likelihood of subsequent COVID-19 vaccination (31.0% vs 6.9%; median time to vaccination, 17.0 days vs 47.5 days), which was confirmed by logistic regression analysis. Conclusions and RelevanceThis report presents patient-reported clinical utility of a commercial COVID-19 assay based on an immune response readout. Our findings suggest that participants used diagnostic TCR immunosequencing results to inform decisions about daily activities and COVID-19 vaccination. Trial RegistrationNot applicable. KEY POINTSO_LIWe aimed to understand the factors driving immunologic testing for SARS-CoV-2 and characterize the actions and decisions spurred by test results. C_LIO_LIResults of this study suggest that individuals frequently ordered immunologic testing for themselves to understand their health status and to inform decision-making about daily activities and vaccination. C_LIO_LIAmong unvaccinated participants, testing negative for prior SARS-CoV-2 infection was associated with increased likelihood of undergoing vaccination and shorter time to vaccination. C_LIO_LIThis study provides the first real-world evidence of patient-perceived utility of a COVID-19 immunologic test for decision-making related to vaccination and lifestyle. C_LI

Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology / 中国实验血液学杂志

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Research Progress on the Mechanism of Tubulin in Megakaryopoiesis and Regulation of Platelet Count--Review / 中国实验血液学杂志

Tubulin affects platelets count through the control of mitosis and the formation of pro-platelets during the maturation of megakaryoblast to platelets. Tubulin is involved in maintaining the integrity of platelet skeleton, and also participates in the change of platelet morphology during platelet activation. Some new anti-tumor drugs targeting cell mitosis are trying to reduce the effect on tubulin in order to reduce the side effect of drugs on platelet formation. In some patients with thrombocytopenia, the variation and polymorphism of the tubulin gene affect the structure of microtubule multimers, which leads to the decrease of platelet formation. This review summarized the latest progresses of tubulin in the regulation of megakaryopoiesis and thrombopoiesis.

Ameliorative Effect of Gramine on 2，4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of gramine on 2，4-dinitrochlorobenzene （DNCB）-induced atopic dermatitis （AD） in mice and its potential mechanism. MethodThe mice were divided into the normal control group， model group， dexamethasone （0.05 g·kg-1） group， and high- and low-dose （0.12，0.06 g·kg-1） gramine groups. Mice in all groups except for the normal control group were stimulated with DNCB， followed by medication 13 d later. The changes in skin lesions were then observed， and the skin thickness， moisture content， and transepidermal water loss （TWEL） in each group were measured. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining， and the effects of drugs on CD4+/CD8+T-cell ratio in the spleen were detected by flow cytometry. The levels of immunoglobulin E （IgE）， interleukin （IL）-4， and IL-6 in serum were detected by enzyme-linked immunosorbent assay （ELISA）， and the changes in serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （CRE） by microplate method. The mRNA expression levels of inflammatory cytokines γ-interferon（IFN-γ）， IL-13， IL-17， IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in skin lesions were assayed by real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of nuclear transcription factor -κB (NF-κB) and NF-κB inhibitory protein α (IκBα) in skin lesions by Western blot. ResultCompared with the normal control group， the model group showed skin edema， erythema， scab， scratch， and lymphocyte and neutrophil infiltration， decreased skin moisture content， as well as increased skin thickness， TWEL （P<0.01）， spleen index， CD4+/CD8+ T-cell ratio in the spleen （P<0.05）， mRNA expression of IFN-γ， IL-13， IL-17， IL-1β， IL-6， and TNF-α in the skin lesions （P<0.05）， serum contents of IgE， IL-4， and IL-6 （P<0.05）， and protein expression of IκBα and NF-κB in skin lesions （P<0.05）. Compared with the model group， dexamethasone and gramine at different doses alleviated skin erythema， scale， scab， and inflammatory cell infiltration， elevated skin moisture content， inhibited skin thickening and TWEL， and decreased spleen index， CD4+/CD8+T-cell ratio in the spleen， mRNA expression of inflammatory factors in the skin lesions， serum contents of IgE and inflammatory factors， and protein expression of IκBα and NF-κB in skin lesions， especially in the dexamethasone group and the high- dose gramine group（P<0.05，P<0.01）. ConclusionGramine can inhibit the expression of related inflammatory factors and regulate the immune function of AD mice via the IκBα/NF-κB pathway， enabling it become a potential drug for treating AD.

Oral Chinese Patent Mediciens for Lung Cancer：A Scoping Review of Clinical Evidence / 中国实验方剂学杂志

This scoping review aimed to summarize the application information and clinical studies of oral Chinese patent medicines. The oral Chinese patent medicines in treating lung cancer were screened out by searching pf the drug directory， related guidelines， and medical information websites. The data including functions， application， ingredients， and prices of these medicines were collected. Six public databases were searched with the time interval of establishment to August 22， 2021 for collection of the clinical studies of oral Chinese patent medicines in the treatment of lung cancer. The expert consensuses， systematic reviews， randomized controlled trials， non-randomized controlled trials， and non-controlled trials were selected for analysis. A total of 104 oral Chinese patent medicines were screened out， including 31 capsules， 16 granules， 20 oral liquids， 17 tablets， 17 pills， and 3 ointments， in which altogether 198 herbal medicines were involved. The single-dose prices of 2， 36， and 66 medicines were > CNY 100， CNY 10-100， and < CNY 10， respectively. There were 410 clinical studies associated with 48 oral Chinese patent medicines， which were published from 1986 to 2021. These publications included 1 expert consensus， 21 systematic reviews， 277 randomized controlled trials， 87 non-randomized controlled trials， and 24 non-controlled trials. In the clinical studies， the Chinese patent medicines were usually applied in combination with radiotherapy and chemotherapy. The evaluation of primary outcomes focused on 9 indicators including clinical efficacy， quality of life， and incidence of side effects. In conclusion， the oral Chinese patent medicines demonstrated significant advantages in the treatment of lung cancer， and the relevant clinical trials were increasing year by year， with multiple outcome indicators being evaluated. More comprehensive and standardized clinical studies need to be designed for oral Chinese patent medicines in treating lung cancer in the future.

Standardized manipulations for pediatric Tuina in medical institutions / 国际中医中药杂志

The standardization of pediatric Tuina is beneficial to pediatric Tuina practitioners in a norm practices. The paper collects the content from teaching textbooks, TCM ancient books and database literature, and tries to develop the technical specifications of pediatric Tuina by four rounds Delphi surveys and expert consensus. This specification covers the manipulation of pediatric Tuina, the position of acupoints, the effects of acupoints and the diagnosis and treatment of pediatric Tuina, including indications, contraindications, cautious use, operation steps and methods.

The Therapeutic Effects of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells on Scleroderma

BACKGROUND@#Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. @*METHODS@#Mice with scleroderma received a single 50 lg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. @*RESULTS@#HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages. @*CONCLUSION@#We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycininduced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.

Genetic and Clinical Characteristics of A Family with Combined PROC and PROS1 Genetic Variants / 中国实验血液学杂志

OBJECTIVE@#To test the anticoagulation functions, perform the genetic diagnosis and analyze the clinical characteristics in a family with combined heterozygous genetic variants of PROC and PROS1.@*METHODS@#Peripheral blood was collected from all the family members. Hematological phenotypes and activity of anticoagulant factors were analyzed. Target genes were amplified by PCR from DNA isolated from peripheral blood, and then were analyzed by Sanger DNA sequencing.@*RESULTS@#Many members in the family displayed the combined genetic variants in protein C and protein S, and six family members accompanied by deep venous thrombosis (DVT). The influences of genetic and secondary factors on the incidence of venous thrombosis in the family members were analyzed. The results showed that in this family, carriers of combined protein C and protein S gene defects had a higher incidence of VTE, but acquired factors still played a key role in the eventual thrombotic symptoms.@*CONCLUSION@#Venous thromboembolism (VTE) is a multifactorial disease, the combined genetic heterozygous mutations of protein C and S is an important genetic factor, and the clinical phenotype show a high heterogenicity, the secondary factors contribute to the VTE incidence.