Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

The holistic view is the key in the study of traditional Chinese medicine(TCM). The component structure theory is based on the holistic view to investigate the correlation between material basis and efficiency, which enriches the holistic "component-effect" research of TCM. Gintonin is a newly isolated non-saponin component of ginseng. Compared to ginsenosides, gintonin has many different pharmacological activities, and it provides new knowledge for the holistic research of ginseng. Thus, taking the discovery of gintonin from ginseng as an example, this paper explored the linkage between ginsenosides and gintonin from the perspective of "component-effect" correlations and systematically sorted out the similarities and differences between them in terms of structural characteristics, modes of action, and pharmacological activities. Starting from the collaborative interaction of TCM compounds, the study discussed the application and value of the holistic view in TCM "component-effect" research in the light of the component structure theory to provide new thoughts for the development of modern TCM research.
Panax/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Humans ; Ginsenosides/pharmacology* ; Animals

To determine the optimal cultivation duration and harvest period for cultivated Notopterygium incisum and promote its industrial development, this study established a characteristic chromatographic profile of cultivated N. incisum and employed chemometrics combined with entropy-weighted grey correlation analysis to assess differences in agronomic traits and quality indicators across different cultivation years and harvest periods. By comparing with reference substances, ten common peaks were identified, including chlorogenic acid, p-coumaric acid, ferulic acid, marmesinin, nodakenin, isochlorogenic acid B, notopterol, phenethyl ferulate, isoimperatorin, and falcarindiol. The similarity between the characteristic chromatographic profiles of N. incisum at different cultivation years and the reference profile was all above 0.932. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) revealed that the quality of 1-to 3-year-old cultivated N. incisum was highly dispersed and unstable, whereas the quality of 4-year-old cultivated N. incisum remained relatively stable across different harvest periods. This suggests that the accumulation of relevant compounds in the medicinal material had reached a plateau, confirming that the optimal cultivation period for N. incisum is four years. Entropy-weighted grey correlation analysis indicated that the quality of 4-year-old cultivated N. incisum across different harvest periods ranked from highest to lowest as follows: November, December, October, August, July, and September, demonstrating that November is the optimal harvest time. The findings of this study establish the suitable cultivation duration and optimal harvest period for N. incisum, providing a scientific basis for cultivation guidance and quality standardization.
Chromatography, High Pressure Liquid/methods* ; Apiaceae/chemistry* ; Entropy ; Chemometrics/methods* ; Drugs, Chinese Herbal/chemistry* ; Principal Component Analysis ; Quality Control

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

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective:To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia,and to strengthen understanding of the disease.Methods:7 cases of acute leukemia(AL)patients diagnosed with mucormycosis by metagenomic next generation sequencing(mNGS)after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected,and their clinical data,including clinical characteristics,diagnosis,treatment,and prognosis,were retrospectively analyzed.Results:Among the 7 patients with AL complicated with mucormycosis,there were 3 males and 4 females,with a median age of 52(20-59)years.There were 6 cases of acute myeloid leukemia(AML)and 1 case of acute lymphocytic leukemia(ALL).Extrapulmonary involvement in 4 cases,including 1 case suspected of central nervous system involvement.The median time for the occurrence of mucor infection was 16(6-69)days after chemotherapy and 19(14-154)days after agranulocytosis.The main clinical manifestations of mucormycosis were fever(7/7),cough(3/7),chest pain(3/7)and dyspnea(1/7).The most common chest CT imaging findings were nodules,patchy or mass consolidation(6/7).All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase.5 patients died within 8 months,and the median time from diagnosis to death was 1 month.Conclusion:Although prophylactic antifungal therapy is adopted,patients with acute leukemia still have a risk of mucor infection during the neutropenia phase.Fever is the main manifestation in the early stage of mucor infection.The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.

Objective:To explore the risk factors for in-hospital mortality in patients with severe trauma and their predictive predictive value.Methods:A retrospective case-control study was used to analyze the data of 509 patients with severe trauma in the trauma database of the Trauma Center of the Second Affiliated Hospital of Soochow University from January 2017 to December 2021, including 377 males and 132 females, aged 18-94 years [53(42, 65)years]. Injury severity score (ISS) was 16-75 points [22(18, 29)points]. Injured parts included the head and neck in 409 patients (80.35%), the chest in 328(64.44%), the abdomen in 193(37.91%), the pelvis in 142(27.90%), the spine in 79(15.52%), and the limb in 247(48.53%). According to the clinical outcome during the hospital stay, the patients were divided into survival group ( n=390) and non-survival group ( n=119). Baseline and clinical data of the two groups were compared, including gender, age, cause of injury (traffic injury, fall from height, sharp instrument injury, etc.), injury site (head and neck, chest, abdomen, pelvis, spine, limb), vital signs on admission (temperature, systolic blood pressure, heart rate, respiratory rate), blood tests on admission [hemoglobin, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (FIB)], Glasgow coma scale (GCS) upon admission to the emergency room, revised trauma score (RTS) upon admission to the emergency room, ISS after whole-body CT examination, quick sequential organ failure assessment (qSOFA) score upon admission to the emergency room, and INR combined with qSOFA score. The baseline and clinical data of the survival group and the non-survival group were first compared with univariate analysis. Then, the independent risk factors of in-hospital mortality in patients with severe trauma were determined by multivariate Logistic stepwise regression (forward and backward). Based on the above data, receiver operating characteristic (ROC) curves were generated with Medcalc statistical software to analyze the efficacy of each risk factor in assessing in-hospital mortality in patients with severe trauma. Results:Univariate analysis showed that there were significant differences in age, injury site, temperature, systolic blood pressure, hemoglobin, platelet, PT, APTT, INR, FIB, GCS, RTS, ISS, qSOFA score, and INR combined with qSOFA score between the two groups ( P<0.05 or 0.01), while there were no significant differences in gender, cause of injury, heart rate, and respiratory rate between the two groups ( P>0.05). Multivariate Logistic stepwise regression analysis showed that age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score were significantly correlated with in-hospital mortality in patients with severe trauma ( P<0.01). ROC curve analysis results showed that the area under the curve (AUC) of in-hospital mortality in patients with severe trauma predicted by age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score were 0.63(95% CI 0.59, 0.68) and 0.60(95% CI 0.55, 0.64), 0.66(95% CI 0.62, 0.70), 0.73(95% CI 0.69, 0.77), and 0.75(95% CI 0.72, 0.80), respectively. Conclusions:Age, systolic blood pressure, APTT, ISS, and INR combined with qSOFA score are the independent risk factors for in-hospital mortality in patients with severe trauma. ISS and INR combined qSOFA score can better predict in-hospital mortality of patients with severe trauma than age, systolic blood pressure and APTT.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.