Quality control is a key link in the modernization process of traditional Chinese medicine(TCM). Studies have shown that the effects of active components in TCM depend on not only their chemical composition but also their suitable physical forms and states. The physical phase structures, such as micelles, vesicles, gels, and nanoparticles, can improve the solubility, delivery efficiency, and targeting precision of active components. These structures significantly enhance the pharmacological activity while reducing the toxicity and side effects, demonstrating functional activity surpassing that of active components and highlighting the key effects of "structures" on "functions" of active components. Taking the physical phase structure as a breakthrough point, this paper outlines the common types of TCM physical phase structures. Furthermore, this paper explores how to realize the quality upgrading of TCM through the precise regulation of physical phase structures based on the current applications and potential of TCM physical phase structures in processing to increase the efficacy and reduce the toxicity, compounding and decocting processes, drug delivery systems, and quality control, aiming to provide novel insights for the future quality control of TCM.
Quality Control ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional/standards* ; Humans ; Drug Delivery Systems

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.

Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.

Objective:To observe the clinical efficacy and safety of venetoclax(VEN)combined with azacitidine(AZA)in the treatment of adult acute myeloid leukemia(AML)patients who are unfit for intensive chemotherapy.Methods:The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected,and the efficacy and safety were analyzed retrospectively.Results:After one course of treatment with VEN and AZA,16 out of 21 unfit AML patients reached complete remission(CR)/CR with incomplete hematologic recovery(CRi),2 patients reached partial remission(PR),the overall response rate(ORR)was 85.7％.Among the 16 patients with CR/CRi,13 achieved minimal residual disease(MRD)negativity.Among the 11 patients with adverse prognosis,8 achieved CR/CRi.By the deadline of follow-up,the median overall suivival(OS)of the entire cohort was not reached,with 1-year OS rate of 61.7％.The main adverse events of VEN combined with AZA were myelosuppression,gastrointestinal reactions and infections.There were 13 cases of leukopenia,7 cases of neutropenia,7 cases of anemia,4 cases of thrombocytopenia,and these hematologic adverse events were all grade 3-4.There were 11 cases with gastrointestinal reactions and 7 cases with infections.The above adverse events were controllable and tolerable.No tumor lysis syndrome or infection related death occurred.Conclusion:VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML,and it shows a good safety profile.

Objective To investigate the distribution of pathogens and change of homology of Acinetobacter bau-mannii(AB)in intensive care units(ICUs)of partial medical institutions in Shanghai before and after the pandemic of coronavirus disease 2019(COVID-19).Methods Pathogens were isolated and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),the whole genome of AB was sequenced using Illumina Miseq sequencing platform,and its genetic relationship was explored based on multilocus sequence typing(MLST)and core genome multilocus sequence typing(cgMLST).Results The total detection rate of patho-gens in ICU environment after the pandemic was lower than before the pandemic([6.10％,101/1 656]vs[10.77％,181/1 680];P＜0.05).Before and after the pandemic,the proportion of AB detected on the surface of bedding in the ICU environment remained at the highest level.After the pandemic,the ST types showed a diverse distribution.MLST_Pasteur results showed that 162 strains of AB were divided into 20 ST types,with ST2(80.25％,n=130)being the main type.MLST_Oxford results showed that there were 19 ST types among 162 strains,with ST208(37.04％,n=60)being the main type.The clustering analysis based on cgMLST showed that ST208_Oxford had closer genetic relationship with ST540_Oxford and ST369_Oxford after the pandemic.ST164_Pasteur clone changed from ST234_Oxford before the pandemic to ST1418_Oxford after the pandemic,and 2 new types of ST_Pasteurr and 11 new types of ST_Oxford were discovered.Conclusion The detection rate of pathogens from ICU environment after the pandemic is lower than before the pandemic,and the distribution of ST types is slightly different at the same detection sites before and after the pandemic.ST2_Pasteur/ST208_Oxford is still the dominant epidemic clone before and after the pandemic,but some alleles have changed.cgMLST is more accurate than MLST_Oxford and MLST_Pasteur in homology analysis,evolution,spread,and outbreak analysis.

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

It is generally believed that high-quality Bupleurum scorzonerifolium roots possess specific morphological characteristics, being red, robust, and long with strong odor. However, the scientific connotation of these characteristics has not been elucidated. According to the theory of "quality evaluation through morphological identification", we studied the correlations between appearance traits(the RGB value of root surface, root length, root diameter, dry weight, and ratio of phloem to xylem) and content of main chemical components(volatile oils, total saponins, total flavonoids, total polysaccharides, and seven saikosaponins) of B. scorzonerifolium roots. Epson Scanner and ImageJ were used to scan the root samples and measure the appearance traits. Ultraviolet spectrophotometry and HPLC were employed to determine the content of chemical components. The correlation, regression, and cluster analyses were performed to study the correlations between the appearance traits and the content of chemical components. The results showed that the content of volatile oils and saikosaponins were significantly correlated with RGB value, root length, and root diameter, indicating that within a certain range, the roots being redder, longer, and thicker had higher content of volatile oils and saikosaponins. According to the appearance traits and chemical component content, the 14 samples from different producing areas were classified into four grades, and the differences in morphological traits and chemical component content were consistent among different grades. The findings in this study demonstrate that appearance traits(RGB value, root length, and root diameter) can be used to evaluate the quality of B. scorzonerifolium roots. Meanwhile, this study lays a foundation for establishing an objective quality evaluation method for B. scorzonerifolium roots.
Bupleurum/chemistry* ; Saponins/analysis* ; Oleanolic Acid/analysis* ; Oils, Volatile/analysis* ; Plant Roots/chemistry*

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Adult ; Humans ; Retrospective Studies ; Neoplasm, Residual/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Recurrence ; Leukemia, Myeloid, Acute/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*