1.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
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.
2.Correlation between IL-6 , chemerin , lipid ratio and insulin resistance in obese patients with type 2 diabetes mellitus
Yili LUO ; Han CAO ; Lu LIU ; Lijuan ZHANG
Journal of Public Health and Preventive Medicine 2025;36(1):45-48
Objective To investigate the correlation between insulin resistance and interleukin-6 (IL-6), chemerin, total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low density lipoprotein cholesterol (LDL-C)/HDL-C ratio and insulin resistance in obese patients with type 2 diabetes mellitus (T2DM), and to provide scientific basis for T2DM prevention and control. Methods A total of 355 obese T2DM patients in Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine were selected from January 2021 to December 2023. IL-6, chemerin and lipids were detected, and the assessment of insulin resistance was conducted through the homeostasis model assessment of insulin resistance (HOMA-IR). Results Among the 355 obese T2DM patients, there were 280 cases of insulin resistance, with the incidence rate of 78.87%. The BMI, IL-6, chemerin, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C in the insulin resistance group were higher than those in the non-insulin resistance group (P<0.05). The above insulin resistant patients were divided into 4 subgroups by means of insulin resistance, and there were significant differences in BMI, IL-6, chemerin, and TG/HDL-C among the subgroups (P<0.05). IL-6, chemerin, and TG/HDL-C were positively correlated with HOMA-IR in obese T2DM patients (P<0.05), while TC/HDL-C and LDL-C/HDL-C had no significant correlation with HOMA-IR (P>0.05). BMI, IL-6, chemerin, and TG/HDL-C were all influencing factors of insulin resistance in obese T2DM patients (P<0.05). Conclusion IL-6, chemerin and TG/HDL-C are correlated with insulin resistance in obese patients with T2DM and are influencing factors for the occurrence of insulin resistance.
3.Advances in the application of digital technology in orthodontic monitoring
WANG Qi ; LUO Ting ; LU Wei ; ZHAO Tingting ; HE Hong ; HUA Fang
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(1):75-81
During orthodontic treatment, clinical monitoring of patients is a crucial factor in determining treatment success. It aids in timely problem detection and resolution, ensuring adherence to the intended treatment plan. In recent years, digital technology has increasingly permeated orthodontic clinical diagnosis and treatment, facilitating clinical decision-making, treatment planning, and follow-up monitoring. This review summarizes recent advancements in digital technology for monitoring orthodontic tooth movement, related complications, and appliance-wearing compliance. It aims to provide insights for researchers and clinicians to enhance the application of digital technology in orthodontics, improve treatment outcomes, and optimize patient experience. The digitization of diagnostic data and the visualization of dental models make chair-side follow-up monitoring more convenient, accurate, and efficient. At the same time, the emergence of remote monitoring technology allows orthodontists to promptly identify oral health issues in patients and take corresponding measures. Furthermore, the multimodal data fusion method offers valuable insights into the monitoring of the root-alveolar relationship. Artificial intelligence technology has made initial strides in automating the identification of orthodontic tooth movement, associated complications, and patient compliance evaluation. Sensors are effective tools for monitoring patient adherence and providing data-driven support for clinical decision-making. The application of digital technology in orthodontic monitoring holds great promise. However, challenges like technical bottlenecks, ethical considerations, and patient acceptance remain.
4.Application of Huangkui Capsules in Diabetic Kidney Disease: A Review
Jia LUO ; Beile JIANG ; Qiuxiang HE ; Shilong LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):314-324
Diabetic kidney disease (DKD) is a kidney disease caused by hyperglycemia,which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes,the incidence of DKD has also increased year by year,and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress,inflammation,renal fibrosis,and decreased mitophagy activity,which are developed under a variety of complex mechanisms. In traditional Chinese medicine,it is believed that the incidence of DKD is closely related to damp heat. Therefore,it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules (HKC) have the effect of clearing damp heat,detoxifying, and detumescence. Because of its unique curative effect on DKD,HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies,it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy,reducing mitochondrial damage,reducing renal fibrosis,controlling inflammatory response,and inhibiting oxidative stress,which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory,anti-oxidative stress,anti-renal fibrosis effects,as well as reduction of urinary protein. Since DKD is not a single injury of renal function,it is often accompanied by problems in blood pressure,blood lipids,blood circulation,body immunity, and other aspects. Therefore,the combination of HKC with other drugs can often achieve more comprehensive results,improve the advantages of various drugs,and improve the therapeutic effect. The combination of drugs such as antihypertensive,lipid-lowering, vascular circulation improvement,immunity inhibition,and anti-oxidative stress with HKC has achieved good results. In addition,HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress,but there are still many places worthy of further study,and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking,and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally,it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.
5.Application of Huangkui Capsules in Diabetic Kidney Disease: A Review
Jia LUO ; Beile JIANG ; Qiuxiang HE ; Shilong LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):314-324
Diabetic kidney disease (DKD) is a kidney disease caused by hyperglycemia,which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes,the incidence of DKD has also increased year by year,and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress,inflammation,renal fibrosis,and decreased mitophagy activity,which are developed under a variety of complex mechanisms. In traditional Chinese medicine,it is believed that the incidence of DKD is closely related to damp heat. Therefore,it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules (HKC) have the effect of clearing damp heat,detoxifying, and detumescence. Because of its unique curative effect on DKD,HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies,it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy,reducing mitochondrial damage,reducing renal fibrosis,controlling inflammatory response,and inhibiting oxidative stress,which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory,anti-oxidative stress,anti-renal fibrosis effects,as well as reduction of urinary protein. Since DKD is not a single injury of renal function,it is often accompanied by problems in blood pressure,blood lipids,blood circulation,body immunity, and other aspects. Therefore,the combination of HKC with other drugs can often achieve more comprehensive results,improve the advantages of various drugs,and improve the therapeutic effect. The combination of drugs such as antihypertensive,lipid-lowering, vascular circulation improvement,immunity inhibition,and anti-oxidative stress with HKC has achieved good results. In addition,HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress,but there are still many places worthy of further study,and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking,and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally,it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.
6.Effect of Modified Chaihu Shugansan on CaMKⅡ/CREB Signaling Pathway in Rats with Myocardial Ischemia and Depression
Fen WAN ; Xiaohong LI ; Ying CHEN ; Yangyu PAN ; Yanna LUO ; Fangge LU ; Chuncheng ZHENG ; Pengyun KONG ; Chengxiang WANG ; Liqiang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):1-11
ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/cAMP-response element binding protein (CREB) signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet, intraperitoneal injection of isoproterenol (ISO), and chronic unpredictable mild stress (CUMS). A total of 108 SD male rats were randomly divided into normal group, model group, high (23.4 g·kg-1), medium (11.7 g·kg-1), and low (5.85 g·kg-1) dose groups of modified Chaihu Shugansan, CaMKⅡ inhibitor (KN93) group, and KN93 + high, medium, and low dose groups of modified Chaihu Shugansan, with 12 rats in each group. From the first day of modeling to the end of modeling, drugs were administered once a day. In the seventh and eighth weeks, the KN93 group and the KN93 + high, medium, and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week, behavioral tests including sucrose preference, open field, and elevated plus maze were conducted. Electrocardiogram (ECG) lead Ⅱ changes were observed in each group of rats, and hematoxylin-eosin (HE) staining was performed to observe changes in heart tissue. Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lactate dehydrogenase (LDH) were measured by using an enzyme-labeled instrument. Creatine kinase (CK) and creatine kinase-MB (CK-MB) were detected by ultraviolet spectrophotometry, while serum monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue, and Western blot was performed to assess protein expression of CaMKⅡ, phosphorylated (p)-CaMKⅡ, CREB, and p-CREB. ResultsCompared to the normal group, the model group showed significant reductions in sucrose preference rate, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01). The ECG showed ST-segment elevation, and HE staining showed serious degeneration of myocardial fibers, disordered arrangement, and infiltration of a large number of inflammatory cells. In addition, serum TC and LDL levels increased (P<0.01), and HDL level decreased (P<0.01). CK, CK-MB, LDH, and MCP-1 levels significantly increased (P<0.05, P<0.01). The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue (P<0.05, P<0.01), but those increased in the heart tissue (P<0.01). Compared to the model group, the high, medium, and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01), as well as decreased serum CK, CK-MB, LDH, and MCP-1 levels (P<0.05, P<0.01). KN93 also reduced ST-segment elevation, alleviated the degeneration degree of myocardial fibrosis, and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced (P<0.05, P<0.01). The KN93 + high, medium, and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression, possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway, with the high-dose modified Chaihu Shugansan showing the best effects.
7.Manufacture and mechanical property on zirconia abutments with a titanium base in dental implant restoration
Huan WANG ; Jing LU ; Ying LI ; Maohua MENG ; Jiayu SHU ; Yuncai LUO ; Wenjie LI ; Qiang DONG
Chinese Journal of Tissue Engineering Research 2025;29(10):2171-2177
BACKGROUND:With the development of computer-aided design and computer-aided manufacturing technology,zirconia abutments with a titanium base are widely used in clinic due to its good application advantages,but there are still some problems and a lack of consensus design standards. OBJECTIVE:To review the fabrication methods of Ti-base zirconia abutment,and the effect of abutment connection,emergence design,abutment angle,and bonding on mechanical properties of Ti-base zirconia abutment. METHODS:Relevant literature published from 2010 to 2023 was searched in CNKI and PubMed databases with the search terms"zirconia abutment,titanium base"in Chinese and English,respectively.The search time limit was extended for some classical literature.The relevant literature was obtained through inclusion and exclusion criteria,and 57 eligible documents were included for review. RESULTS AND CONCLUSION:It is recommended that clinicians try to select antirotational titanium bases or rotational titanium bases with a Morse taper connection.Implants should be placed in the correct axial angulation of not more than 15° or with an inclination to the palatal side when using angled zirconia abutments.When a≥30° labial inclination is followed for implant placement,the bite force must be decreased effectively to reduce the risk of mechanical and biological complications of implants,abutments,and prostheses.Ti-base zirconia abutments with a higher gingival height should be selected,and its restorative angle should not exceed 40°.Multilink Hybrid Abutment could be the first choice for extraoral bonding of zirconia abutment to titanium bases.
8.Analysis of risk factors for piracetam-associated thrombocytopenia and the establishment of risk prediction model
Tianmin HUANG ; Xingming LU ; Mei ZHENG ; Guizong GUO ; Xin LU ; Yilin LUO ; Yingxia YANG
China Pharmacy 2025;36(10):1226-1231
OBJECTIVE To analyze the risk factors contributing to piracetam-associated thrombocytopenia and develop a predictive model for risk prediction. METHODS The electronic medical record information of inpatients treated with piracetam was collected retrospectively from the First Affiliated Hospital of Guangxi Medical University from January 2021 to December 2023, including gender, age, underlying diseases, combined medication, and laboratory data, etc. Patients were divided into the occurrence group and the non-occurrence group according to whether thrombocytopenia occurred, and the differences in clinical data between the two groups were compared. The independent risk factors were determined through univariate/multivariate Logistic regression analysis. A nomogram was drawn to visually present the independent risk factors, and a risk prediction model was constructed. The predictive efficacy of the model was evaluated using the receiver operating characteristic (ROC) curve, Bootstrap internal validation and calibration curve. RESULTS A total of 224 patients were included, among which 196 cases were in the non- occurrence group and 28 cases in the occurrence group. The incidence of thrombocytopenia was 12.50%. The results of the univariate Logistic regression analysis showed that the proportion of patients using three or more combined antibiotics and the level of serum creatinine in the occurrence group were significantly higher than those in the non-occurrence group, while the level of hemoglobin was significantly lower (P<0.05). The results of the multivariate Logistic regression analysis revealed that the use of three or more combined antibiotics, low hemoglobin level and high serum creatinine level were independent risk factors for piracetam-associated thrombocytopenia (P<0.05). The constructed risk prediction model was LogitP= -1.114+1.256×three or more combined antibiotics-0.017×hemoglobin level+0.009×serum creatinine level. The AUC of the ROC curve of this model was 0.757, and the optimal cut-off value was 0.474; the AUC of the ROC curve of the Bootstrap internal validation was 0.733; the apparent curve and the bias-corrected curve were close to the ideal curve. CONCLUSIONS The use of three or more antibiotics, along with low hemoglobin level and high serum creatinine level, are identified as independent risk factors for piracetam-associated thrombocytopenia. The developed risk prediction model demonstrates good predictive value.
9.Analysis of the management effect of community pharmacy outpatient service on patients with type 2 diabetes mellitus
Lanying WANG ; Gaofeng LU ; Meijuan YUAN ; Weiling LI ; Yingyi LUO ; Feng XU
Journal of Pharmaceutical Practice and Service 2025;43(7):357-361
Objective To explore the effect of community pharmacy outpatient service on patients with type 2 diabetes mellitus. Methods A non-randomized controlled study was conducted, and type 2 diabetes patients managed in the community were divided into an intervention group of 112 cases and a control group of 110 cases. The control group received routine medication guidance during general practice outpatient visits, while the intervention group received comprehensive pharmacy outpatient service intervention based on routine medication guidance in general practice. Follow-up visits were conducted every 3 months. Repeated measurement analysis of variance and multivariate linear regression analysis were used to evaluate the intervention effect of the pharmacy outpatient service. Results Fasting blood glucose and glycosylated hemoglobin levels in the intervention group showed a decreasing trend with the increase of intervention time compared to pre-intervention time (P<0.01), with increased duration of weekly exercise, decreased staple food intake, increased vegetable intake, and increased medication adherence score (P<0.01). After adjusting for confounding factors through multivariate linear regression model, pharmacy outpatient intervention was found to be an independent protective factor for fasting blood glucose level (β=−0.891, P<0.01) and glycosylated hemoglobin level (β=−0.760, P<0.01) in the study subjects. Conclusion The community pharmacy outpatient service could enhance the self-management ability of patients with type 2 diabetes mellitus, and effectively improve patients’ fasting blood glucose and glycosylated hemoglobin.
10.Research progress on the chemical composition and antidepressant mechanism of volatile oils of traditional Chinese medicine
Yifei ZHANG ; Lu CHENG ; Mingshi REN ; Dao GUO ; Fengjiao KUANG ; Zonghua KANG ; Jianguang LUO ; Feihua WU
Journal of China Pharmaceutical University 2025;56(1):22-30
Depressive disorder is a mental illness characterized by poor mood and cognitive dysfunction caused by a range of complicated factors. Antidepressants have strong short-term efficacy in clinical application, yet with significant adverse effects and resistance in long-term use. Essential oils are small molecular compounds mainly composed of monoterpenes and sesquiterpenes, most of which are characterized by aromatic odors, easy permeability through the blood-brain barrier, and low toxic side effects. Volatile oil from traditional Chinese medicine can regulate neurotransmitter monoamine, hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, neuroinflammation and oxidative stress, and intestinal microbiota-gut-brain axis to exert an antidepressant effect through multiple pathways and targets. This review summarizes the main antidepressant chemical components of essential oil of traditional Chinese medicine, their pharmacological mechanisms and clinical application, aiming to provide some reference for further development and clinical application of essential oil of traditional Chinese medicine.


Result Analysis
Print
Save
E-mail