Through literature research and standard retrieval, Corydalis-derived medicinal materials, the origins, and related standards were summarized. Finally, 27 medicinal materials were screened out, involving 71 species(varieties). Among them, only 11 are recorded in Chinese Pharmacopoeia(2020), National Standard for Chinese Patent Drugs·Tibetan Medicine, Tibetan Medicine Standards, and other local standards, including Corydalis Bungeanae Herba and Corydalis Herba. The names and original plants of the medicinal materials are different in different standards, and the phenomena of "same medicinal material with different names" and "same name for different medicinal materials" are prominent. Most standards only include the traits, microscopic identification, and physico-chemical property identification, with unsound quality criteria. Thus, efforts should be made to strengthen the sorting of Corydalis medicinal plants, herbal textual research, and investigation of the resources and utilization. Moreover, via modern techniques, the chemical components and medicinal material basis of different original plants should be explored and sound quality standards should be established to improve the safety and quality of Corydalis-derived medicinal materials. Summarizing Corydalis medicinal plants, Corydalis-derived medicinal materials, and related standards, this study is expected to provide a reference for the standard formulation, quality evaluation, expansion of drug sources, and rational development and utilization of Corydalis resources.
Corydalis ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional ; Medicine, Tibetan Traditional ; Plants, Medicinal/chemistry* ; Reference Standards

AIM:To analyze the correlation between optical coherence tomography(OCT)parameters and central retinal vein occlusion of macular edema secondary(CRVO-ME), and compare the clinical efficacy of ranibizumab combined with laser photocoagulation and ranibizumab alone in the treatment of CRVO-ME.METHODS:There were 43 case with 43 eyes of patients in CRVO-ME diagnosed in our hospital from January 2020 to December 2020 included in the present study and divided into two groups, namely A and B. Patients in group A were treated with ranibizumab combined with laser photocoagulation, while patients in group B were treated with ranibizumab alone. The structure of outer retina and “SAVE” scores were observed and estimated using OCT and fluorescein angiography(FFA)examination before and after the treatment at 1, 3, 6, 12mo, and then analyzed their correlation with best corrected visual acuity(BCVA, LogMAR). The BCVA, central macular thickness(CMT), intraocular pressure and average number of drug injections were also compared between the two groups before and after treatment.RESULTS:At 12mo after treatment, the BCVA in the OCT baseline external limiting membrane(ELM)intact group and baseline ellipsoid zone(EZ)intact group before and after treatment were significantly improved than those of the fracture group(0.47±0.16 vs 0.21±0.15, P=0.013; 0.44±0.20 vs 0.25±0.17, P=0.008). There was no statistically significant difference in BCVA changes between baseline RPE fracture group and RPE intact group(P>0.05). The number of patients with “S” and “A” at 1 score decreased significantly at 12mo after treatment in both groups, the BCVA of patients with “V” and “E” at 0 score before treatment was significantly improved than those patients at 1 score(all P<0.05). The BCVA and CMT of patients after treatment in groups A and B were both significant improved compared with before treatment(P<0.05). There were no significant differences in the BCVA and CMT in the number of drug injections between the two groups(P>0.05). In addition, there were no severe complications such as secondary glaucoma and endophthalmitis in both groups.CONCLUSION: Baseline status of ELM and EZ, presence or absence of vitreoretinal abnormalities(V), and focal leakage(E)could suggest the treatment efficacy of CRVO-ME. Ranibizumab in the treatment of CRVO-ME demonstrates prominent efficacy and great safety, and there was no better effect was observed when combined with laser photocoagulation.

AIM: To evaluate the clinical efficacy of adalimumab(ADA)with dose-reduced glucocorticoid for the treatment of Vogt-Koyanagi-Harada disease(VKH).METHODS: A total of 21 patients(37 eyes)with VKH who received ADA therapy in the Department of Ophthalmology of our hospital from August 2020 to December 2021 were included. The interval of ADA administration was progressively extended after intraocular inflammation controlled and lasted for 3mo, and it returned to the initial treatment interval once the inflammation recurred. After follow-up for 12mo, anterior chamber cell(ACC)grade, vitreous haze(VH)grade, retinal/choroidal lesions, serous retinal detachment(SRD), best corrected visual acuity(BCVA), central macular thickness(CMT)and doses of glucocorticoid and immunosuppressant were compared before and after the first ADA injection. Treatment failure events and adverse reactions were recorded.RESULTS: Compared with baseline, the proportion of eyes with ACC grade ≤1+ and VH grade ≤1+ increased(P<0.05), the proportion of eyes with retinal/choroidal lesions decreased significantly(P<0.01), BCVA and CMT were significantly improved(P<0.01), and the average dose of glucocorticoid reduced significantly(P<0.01)at 2wk, 1, 3 and 6mo after treatment. At the final follow-up, 82% of patients received glucocorticoid ≤5 mg, and all patients stopped using immunosuppressant. There were 13 treatment failure events during the follow-up period, and 12 patients(57%)extended the ADA treatment interval, with no serious adverse events related to ADA treatment observed.CONCLUSION: ADA is effective and safe for the treatment of VKH, reducing the need for glucocorticoid and immunosuppressant. In addition, extending the interval of ADA treatment is effective, which has a lower recurrence rate.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

R2 R3-MYB transcription factors are ubiquitous in plants, playing a role in the regulation of plant growth, development, and secondary metabolism. In this paper, the R2 R3-MYB transcription factors were identified by bioinformatics analysis of the genomic data of Erigeron breviscapus, and their gene sequences, structures, physical and chemical properties were analyzed. The functions of R2 R3-MYB transcription factors were predicted by cluster analysis. Meanwhile, the expression patterns of R2 R3-MYB transcription factors in response to hormone treatments were analyzed. A total of 108 R2 R3-MYB transcription factors, named EbMYB1-EbMYB108, were identified from the genome of E. breviscapus. Most of the R2 R3-MYB genes carried 2-4 exons. The phylogenetic tree of MYBs in E. breviscapus and Arabidopsis thaliala was constructed, which classified 234 MYBs into 30 subfamilies. The MYBs in the five MYB subfamilies of A.thaliala were clustered into independent clades, and those in E. breviscapus were clustered into four clades. The transcriptome data showed that MYB genes were differentially expressed in different tissues of E. breviscapus and in response to the treatments with exogenous hormones such as ABA, SA, and GA for different time. The transcription of 13 R2 R3-MYB genes did not change significantly, and the expression patterns of some genes were up-regulated or down-regulated with the extension of hormone treatment time. This study provides a theoretical basis for revealing the mechanisms of R2 R3-MYB transcription factors in regulating the growth and development, stress(hormone) response, and active ingredient accumulation in E. breviscapus.
Erigeron/genetics* ; Gene Expression Regulation, Plant ; Genes, myb ; Phylogeny ; Plant Proteins/metabolism* ; Transcription Factors/metabolism*

Codonopsis Radix， one of the bulk commodities， has been commonly used for tonification in clinical practice. Apart from the medicinal purpose， it can also be utilized as food. Among the multiple local varieties， the ones called "Luduiduoji" in Tibetan medicine cannot be neglected， which have frequently been adopted for diminishing inflammation and swelling， invigorating spleen and stomach， and tonifying Qi， etc. Considering its complex origins and frequent substitution by or confusion with other medicinal materials， this paper reviewed the Si Bu Yi Dian， Jingzhu Bencao， ministerial and local standards， modern literature on Tibetan medicine， and the results of field investigation in major Tibetan medicine hospitals and medicinal material markets of Sichuan， Qinghai and Tibet to figure out the name， original plants， medicinal parts， effects， and local varieties of Codonopsis Radix in Tibetan medicine. The results showed that the names of local varieties were diverse， many of which were transliterated into Tibetan， with "Luduiduoji" being most well-known. It was derived from 14 species in genus Codonopsis and one in Adenophora of family Campanulaceae， with Codonopsis foetens subsp. nervosa， C. thalictrifolia var. mollis， C. canescens， C. alpina， and C. pilosula being the main species. According to literature records， the roots， aerial parts， and whole plants could all be employed as medicine， but there were certain differences in their clinical applications. At present， in order to protect the medicinal resources， Tibetan medical workers mostly collect the aerial parts， which are applicable to patients with yellow water， rheumatism， Gamba disease， and leprosy. This literature review of local varieties for Codonopsis Radix and textual research on their original plants are of great significance for elevating the standard， accelerating the pharmacodynamic research， expanding the sources and promoting the rational use of Codonopsis Radix.

BACKGROUND: TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL. METHODS: We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons. RESULTS: From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P < 0.05 for both). The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells. In addition, we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis, and vice versa in the cell line. CONCLUSIONS TOSO might be involved in the pathogenesis of CLL by interacting with SYK, enhancing the BCR signaling pathway, and inducing apoptosis resistance.

ObjectiveTo investigate the drug-resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province. MethodsFrom 2015 to 2016, blood samples were collected from imported P. falciparum malaria patients returning from Equatorial Guinea to Shandong Province, and genome DNA of the malaria parasite was extracted. The drug-resistant Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum were amplified using a PCR assay, followed by DNA sequencing, and the sequences were aligned. Results The target fragments of all 5 drug-resistant genes of P. falciparum were successfully amplified and sequenced. There were 72.8%, 18.6%, and 8.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfcrt gene, respectively, and all mutant haplotypes were CVIET (the underline indicates the mutation site). There were 20.0%, 61.4% and 18.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfmdr1 gene, respectively, and the mutant haplotypes mainly included YF and NF (the underlines indicate the mutation sites). There were 1.4%, 98.6%, and 0 of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhfr gene, respectively, and AIRNI was the predominant mutant haplotype (the underline indicates the mutation site). There were 1.4%, 94.3%, and 4.3% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhps gene, respectively, and SGKAA was the predominant mutant haplotype (the underline indicates the mutation site). The complete drug-resistant IRNGE genotype consisted of 8.6% of the Pfdhfr and Pfdhps genes, and the K13 gene A578S mutation occurred in 1.4% of the parasite samples. Conclusions There are mutations in the Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum imported from Equatorial Guinea to Shandong Province, with a low frequency in the Pfcrt gene mutation and a high frequency in the Pfmdr1, Pfdhfr, and Pfdhps gene mutations, and the K13 gene A578S mutation is detected in the parasite samples.

The application of traditional Chinese medicine(TCM) formula granules in clinical practice is gradually extensive. However, TCM formula granules is still lacking rapid and simple quality control standards. In this study, allele-specific PCR and enzyme-linked immunoassay(ELISA) was used for rapid detection of the quality of Lonicerae Japonicae Flos formula granules. The authenticity of Lonicerae Japonicae Flos formula granules was identified by allele-specific PCR and index component was detected by ELISA. Thus, it lays a foundation for the establishment of rapid quality detection standard for Lonicerae Japonicae Flos formula granules, and also provides reference for other studies on the quality standard of traditional Chinese medicine formula granules.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/analysis* ; Enzyme-Linked Immunosorbent Assay ; Lonicera/chemistry* ; Medicine, Chinese Traditional ; Polymerase Chain Reaction ; Quality Control

Background: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. Methods: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. Results: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios⁺ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. Conclusion Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.