ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi， so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） combined with Smart aroma database and National Institute of Standards and Technology（NIST） database were used to characterize the aroma components in different parts of N. jatamansi， and the aroma components were quantified according to relative response factor（RRF） and three internal standards， and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis（OPLS-DA） and cluster thermal analysis based on variable importance in the projection（VIP） value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose， and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data， and the rapid identification model of different parts of N. jatamansi was established by principal component analysis（PCA）， discriminant factor alysis（DFA）， soft independent modeling of class analogies（SIMCA） and statistical quality control analysis（SQCA）. ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi， of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components， the contents of five components（ethyl isovalerate， 2-pentylfuran， benzyl alcohol， nonanal and glacial acetic acid，） in the aboveground part of N. jatamansi were significantly higher than those in the underground part（P<0.01）， the contents of β-ionone， patchouli alcohol， α-caryophyllene， linalyl butyrate， valencene， 1，8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part（P<0.01）. Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82， and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted， respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%， the validation score of the SIMCA model for discrimination of the two parts was 99， and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose（PCA， DFA， SIMCA and SQCA） can realize the rapid identification of different parts of N. jatamansi. Combining the two results， it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.

OBJECTIVE: To observe the effects of moxibustion at different temperatures on cognitive function and blood glucose levels in patients with cognitive impairment associated with type 2 diabetes mellitus (T2DM). METHODS: A total of 66 T2DM patients with cognitive impairment were randomly assigned to a high-temperature group (22 cases, 1 case dropped out, 1 case was eliminated), a medium-temperature group (22 cases, 2 cases were eliminated), and a low-temperature group (22 cases, 2 cases were eliminated). All groups received moxibustion at Baihui (GV20), Dazhui (GV14), and Shenting (GV24) based on their existing glycemic control treatment. Moxibustion temperatures were maintained at 44-46 ℃ (high-temperature group), 41-43 ℃ (medium-temperature group), and 38-40 ℃ (low-temperature group), respectively, for 20 min per session, every other day, 3 times a week for 3 months. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, short-term memory (STM) accuracy and average reaction time, Rey-Osterrieth complex figure (ROCF) score, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were assessed before and after treatment. Clinical efficacy was evaluated after treatment. RESULTS: After treatment, MMSE scores in all three groups were higher than those before treatment (P<0.05). In the high-temperature group, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, naming, language, and abstraction were higher than those before treatment (P<0.05); the scores of ROCF copy, immediate recall, and delayed recall were higher than those before treatment (P<0.05); the HbA1c level was lower than that before treatment (P<0.05). In the medium-temperature group, the total MoCA score and the scores of memory and delayed recall, attention, and language were higher than those before treatment (P<0.05). STM accuracy was higher than before treatment (P<0.05), and STM average reaction time was shorter than before treatment (P<0.05) in both the high-temperature and medium-temperature groups. After treatment, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, and language in the high-temperature group were higher than those in the medium- and low-temperature groups (P<0.05); MMSE score, STM accuracy, and ROCF immediate recall and delayed recall scores were higher than those in the medium- and low-temperature groups (P<0.05); STM average reaction time was shorter than that in the medium- and low-temperature groups (P<0.05); HbA1c level was lower than that in the low-temperature group (P<0.05). The total MoCA score, attention score, and MMSE score in the medium-temperature group were higher than those in the low-temperature group (P<0.05), and STM average reaction time was shorter than that in the low-temperature group (P<0.05). There were no statistically significant differences in FPG within or between the three groups before and after treatment (P>0.05). The total effective rates were 75.0% (15/20) in the high-temperature group, 50.0% (10/20) in the medium-temperature group, and 15.0% (3/20) in the low-temperature group; the total effective rate in the high-temperature group was significantly higher than that in the low-temperature group (P<0.05). CONCLUSION Moxibustion at different temperatures has a dose-effect relationship in treating cognitive impairment in T2DM patients. A temperature range of 44-46 ℃ is more effective in improving cognitive function and stabilizing average blood glucose levels over 2-3 months.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognitive Dysfunction/psychology* ; Cognition ; Temperature ; Blood Glucose/metabolism* ; Adult ; Acupuncture Points

At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*

The AP2/ERF transcription factor family is a class of transcription factors widely present in plants, playing a crucial role in regulating flowering, flower development, flower opening, and flower senescence. Based on transcriptome data from flower, leaf, and stem samples of two Lonicera macranthoides varieties, 117 L. macranthoides AP2/ERF family members were identified, including 14 AP2 subfamily members, 61 ERF subfamily members, 40 DREB subfamily members, and 2 RAV subfamily members. Bioinformatics and differential gene expression analyses were performed using NCBI, ExPASy, SOMPA, and other platforms, and the expression patterns of L. macranthoides AP2/ERF transcription factors were validated via qRT-PCR. The results indicated that the 117 LmAP2/ERF members exhibited both similarities and variations in protein physicochemical properties, AP2 domains, family evolution, and protein functions. Differential gene expression analysis revealed that AP2/ERF transcription factors were primarily differentially expressed in the flowers of the two L. macranthoides varieties, with the differentially expressed genes mainly belonging to the ERF and DREB subfamilies. Further analysis identified three AP2 subfamily genes and two ERF subfamily genes as potential regulators of flower development, two ERF subfamily genes involved in flower opening, and two ERF subfamily genes along with one DREB subfamily gene involved in flower senescence. Based on family evolution and expression analyses, it is speculated that AP2/ERF transcription factors can regulate flower development, opening, and senescence in L. macranthoides, with ERF subfamily genes potentially serving as key regulators of flowering duration. These findings provide a theoretical foundation for further research into the specific functions of the AP2/ERF transcription factor family in L. macranthoides and offer important theoretical insights into the molecular mechanisms underlying floral phenotypic differences among its varieties.
Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Transcription Factors/chemistry* ; Lonicera/classification* ; Flowers/metabolism* ; Phylogeny ; Gene Expression Profiling ; Multigene Family

OBJECTIVE: To analyze two families with inherited dysfibrinogenemia, and explore the molecular pathogenic mechanisms. METHODS: The coagulation indexes of the probands and their family members were detected. The FGA, FGB, and FGG exons and their flanking sequences were amplified by PCR, and the mutation sites were identified by sequencing. SIFT, PolyPhen2, LRT, ReVe, MutationTaster, phyloP, and phastCons bioinformatics software were used to predict the functional impact of the mutation sites. Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software. RESULTS: The thrombin time (TT) of the proband in family 1 was prolonged to 37.00 s, and Fg∶C decreased to 0.52 g/L. The TT of the proband in family 2 was 20.30 s, and Fg∶C was 1.00 g/L, which was lower than the normal range. Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T>C in FGA, resulting in the substitution of phenylalanine 27 with serine (Phe27Ser). The proband in family 2 had a heterozygous mutation c.1007T>A in FGG, resulting in the substitution of methionine 336 with lysine (Met336Lys). Bioinformatics software prediction analysis indicated that both mutations were deleterious variants. PyMOL mutation models revealed that the Aα chain mutation (Phe27Ser) in family 1 and γ chain mutation (Met336Lys) in family 2 resulted in alterations in spatial structure and reduced protein stability. Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species. CONCLUSION Heterozygous mutations of FGA gene c.80T>C and FGG gene c.1007T>A are both pathogenic variants, causing inherited dysfibrinogenemia.
Female ; Humans ; Male ; Afibrinogenemia/genetics* ; Fibrinogen/genetics* ; Heterozygote ; Mutation ; Pedigree

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder(CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD.Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA,FGB,and FGG genes,and sequencing was performed to analyze mutation characteristics.Results Among the 16 children,there were 9 boys(56%)and 7 girls(44%),with a median age of 4 years at the time of attending the hospital.Among these children,9(56%)attended the hospital due to bleeding events,and 7(44%)were diagnosed based on preoperative examination.The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events(P<0.05).Genetic testing was conducted on 12 children and revealed a total of 12 mutations,among which there were 4 novel mutations,i.e.,c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene.There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene,with relatively severe bleeding symptoms.There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes,and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous,and the severity of bleeding is associated with the level of fibrinogen activity,but there is a weak association between clinical phenotype and genotype.

The changes in epigenetic modifications of histones are one of the important factors in cancer development and metastasis,and the development of epigenetic therapies for cancer treatment has led to epigenetic drug screening as a research focus. In this work,the common methylation and acetylation modifications at the N-terminal of cellular histones H3 were quantified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method,and a throughput assay for screening and assessment of epigenetic drug was established. A total of 39 kinds of modification combinations containing common methylation and acetylation sites of H3 peptides were simultaneously monitored by triple quadrupole mass spectrometry in multiple reaction monitoring (MRM) mode. The developed method was applied to analyze HepG2 cells exposed for 24 h to 28 kinds of epigenetic drugs that could modulate the level of methylation or acetylation modifications. Results showed that 25 of these drugs,such as deacetylase inhibitors Abexinostat,Valproic acid and AGK7,induced histone H3 modification changes in the exposed cells that were consistent with those reported in the literature,while other modification changes were also detectable. Three of these drugs,including demethylase inhibitors IOX1,GSK-j1 and acetyltransferase inhibitor L002,however,induced modification changes different from those reported in the literature. An overall test match rate of 89.3％ was achieved. The established LC-MS/MS method could quantitatively analyze histone H3 modification sites and their changes in cells in a high-throughput and highly sensitive manner,and could be applied to the evaluation of epigenetic drugs with known activities,with good specificity and rich modification information,which was expected to provide a new technological tool for screening and evaluation of epigenetically active compounds and exploration of their mechanism of action.

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.
Humans ; Aged ; Methotrexate/adverse effects* ; Retrospective Studies ; Temozolomide/therapeutic use* ; Central Nervous System Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Central Nervous System