ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

Sustained and controlled release preparation is ideal for reducing the side effects of drugs, improving patient compliance and enhancing efficacy, among which oral sustained-release tablets are the most widely used. The in vitro release of the preparation is closely related to the in vivo absorption of the drug. However, current in vitro release experiments are labor-intensive and destructive, and the lack of big data also makes it difficult to establish good in vivo and in vitro correlations. Computer modeling, as a technical means that can transform objective principles into mathematical models, has great prospects in data prediction. This review explores the existing computer modeling methods that can be used to predict in vitro release profiles of oral sustained-release tablets, and further discusses auxiliary technologies that can improve the accuracy of the models, providing new ideas for drug development.

Antisense oligonucleotides are a type of gene therapy that targets mRNA and inhibits gene expression. They have been applied in the treatment of various diseases, but there are still problems with poor enzyme stability and high dosage in vivo, due to the shortage of appropriate delivery system. Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor with tyrosine kinase activity. Its expression is abnormal in a variety of malignant tumors. It mediates the malignant proliferation, migration and invasion of tumor cells through a variety of ways. In this study, an antisense oligonucleotide (ASO, N04) targeting IGF1R mRNA was designed and chemically modified (PS, 2'-OMOE), then neutral cytidine lipid DNCA and cystine backbone cationic lipid CLD (Mix) were used to encapsulate ASOs. The particle size, polymer dispersity index and ζ potential of the formulations were 151 nm, 0.18 and -3.9 mV. The nanoparticles entered liver cancer cells (HepG-2, Huh-7), silenced target mRNA, arrested cell cycle in S phase, promoted apoptosis, and inhibited the proliferation efficiently. These results indicate that Mix/N04_MOE5 has great potential in tumor treatment, which provides a basis for further research on novel agents against hepatocellular carcinoma.

Objective To establish a high performance liquid chromatography(HPLC)characteristic chromatogram and multi-component content determination method for the substance benchmark of Fuzi Decoction.Methods The characteristic chromatogram method of Fuzi Decoction substance benchmark was established,and the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition)was used to analyze the characteristic chromatograms of 15 batches of Fuzi Decoction substance benchmark samples.The HPLC content determination methods of 1 1 components in the Fuzi Decoction substance benchmark samples were established respectively,and the dry extract rate of 15 batches of Fuzi Decoction substance benchmark samples was determined.Results The similarity of characteristic chromatograms of 15 batches of Fuzi Decoction substance benchmark samples was greater than 0.9,and 12 common peaks were selected and eight of them were identified.The results showed that the contents of benzoylmesaconine,benzoylhypaconine,atractylenolide Ⅲ,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,gallic acid,albiflorin,paeoniflorin,1,2,3,4,6-penta-galloyl glucose and benzoyl paeoniflorin were 0.050 3-0.191 1,0.026 7-0.047 0,0.043 0-0.127 6,0.554 6-1.006 8,0.568 7-0.979 5,0.929 9-1.726 1,1.058 9-2.118 4,1.430 3-4.965 5,6.882 9-9.511 1,0.056 1-0.262 5,0.160 6-0.369 0 mg/g,respectively.The average dry extract rate of the 15 batches of Fuzi Decoction substance benchmark samples was 29.54％.Conclusion The established characteristic chromatogram and multi-index content determination method are accurate and stable,which provides a basis for the quality control of the substance benchmark and related preparations of Fuzi Decoction.

Objective To explore the application effect of multi-disciplinary team(MDT)model in hospital antimi-crobial management.Methods Relevant data on antimicrobial use in hospitalized patients in a hospital from January 2021 to December 2022 were analyzed retrospectively,January-December 2021 adopted conventional management mode and was as the control group,January-December 2022 adopted MDT management model and was as the inter-vention group.Antimicrobial therapy relevant indicators between two groups of patients were compared.Results After adopting the MDT management model,pathogen detection rate before the therapeutic antimicrobial use in the intervention group(73.62％)was higher than that in the control group(70.56％),difference was statistically sig-nificant(P＜0.001).Pathogen detection rate related to healthcare-associated infection diagnosis was 87.98％in the control group and 88.89％in the intervention group,with no statistically significant difference between two groups(P＞0.05).Pathogen detection rate before combined use of key antimicrobial agents in the intervention group(93.94％)was higher than that in the control group(92.00％),difference was statistically significant(P＜0.05).Antimicro-bial use rate in hospitalized patients and use rate of prophylactic antimicrobial agents in class Ⅰ incision surgery de-creased from 38.03％and 21.03％to 32.78％and 10.30％,respectively,with statistically significant differences(both P＜0.05).The amount and intensity of antimicrobial use in hospitalized patients in the intervention group de-creased.The implementation rate of bundled prevention and control measures for multidrug-resistant organism(MDRO)after intervention was significantly higher than that of the control group,with statistically significant differences(all P＜0.05).MDRO detection rate decreased from 34.70％to 32.37％,difference was statistically significant(P=0.027).there was no significant change in the MDRO case infection rate.Conclusion The MDT model can effectively improve the standardized management of antimicrobial agents,promote the rational use of anti-microbial agents in clinical practice,and prevent bacterial resistance.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

A variety of full 2ʹ-F/OMe-modified siRNAs were designed and synthesized, and the activity against hepatocellular carcinoma Huh-7 and HepG2 cells was evaluated. K&A DNA/RNA H-8 synthesizer was used to synthesize siRNAs, and neutral cytidinyl lipid DNCA mixed with cationic lipid CLD were used to transfect siRNA. By RT-qPCR and CCK-8 assay, the target gene silence and the proliferation of Huh-7 and HepG2 cells were detected. The siRNAs loading into Ago2 protein was detected by RNA-binding protein immunoprecipitation. Drug uptake and cell apoptosis were detected by flow cytometry, and the expression of PLK1 protein was detected by Western blot. Partial full 2ʹ-F/OMe modified siRNAs, especial siPLK1A3, increased the uptake of Huh-7 cells, enhanced their binding to Ago2 and gene silencing activity, down-regulated PLK1 protein, as well as induced more Huh-7 cell apoptosis and proliferation inhibition activity. It provides important data for the development of novel siRNA modification patterns and anti-HCC formulations.

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans ; Bone Density ; Low Back Pain ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy*