1.Effect of Serum Containing Zhenwutang on Apoptosis of Myocardial Mast Cells and Mitochondrial Autophagy
Wei TANG ; Meiqun ZHENG ; Xiaolin WANG ; Zhiyong CHEN ; Chi CHE ; Zongqiong LU ; Jiashuai GUO ; Xiaomei ZOU ; Lili XU ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):11-21
ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ (AngⅡ) and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment, AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h, and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 (CCK-8) to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of B-type natriuretic peptide (BNP) in cell culture supernatant, and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently, the experiment was divided into a blank group (20% blank serum), a model group (20% blank serum + 5×10-5 mol·L-1 AngⅡ), low-, medium-, and high-dose (5%, 10% and 20%) serum containing Zhenwutang groups, an autophagy inhibitor group (1×10-4 mol·L-1 3-MA), and autophagy inducer group (1×10-7 mol·L-1 rapamycin). The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe (Lyso Tracker) and mitochondrial probe (Mito Tracker) co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect Caspase-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-related X protein (Bax), and cytochrome C (Cyt C) in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase (Parkin), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3, cleaved Caspase-9, Bax, Bcl-2, and Cyt C in apoptosis-related pathways, phosphorylated ubiquitin ligase (p-Parkin), phosphorylated PTEN-induced kinase 1 (p-PINK1), p62, and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways, and the change of microtubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10-5 mol·L-1, the cell activity was the lowest, and there was no cytotoxicity. At this concentration, the surface area of cardiomyocytes was significantly increased (P<0.01), and the content of BNP in the supernatant of culture medium was significantly increased (P<0.05). Therefore, AngⅡ with a concentration of 5×10-5 mol·L-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group, the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate (P<0.01) and significantly decreased mitochondrial membrane potential (P<0.01). The results of immunofluorescence co-localization showed that compared with the blank group, the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group, the relative mRNA expression of Bax, Caspase-3, Caspase-9, Cyt C, and p62 in the model group was significantly up-regulated (P<0.01), while the relative mRNA expression of Bcl-2, Parkin, and PINK1 was significantly down-regulated (P<0.01). In addition, the relative protein expression of Bax, cleaved Caspase-3, cleaved Caspase-9, Cyt C, and p62 was significantly up-regulated (P<0.01). The LC3Ⅱ/Ⅰ was significantly decreased, and the relative protein expression of Bcl-2, p-Parkin, p-PINK1, and Beclin1 was significantly down-regulated (P<0.01). Compared with the model group, the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate (P<0.01), and the decrease ratio of mitochondrial membrane potential is significantly lowered (P<0.01) in a dose-dependent manner. Additionally, both red and green fluorescence spots became more in these groups. In the 3-MA group, the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax, Caspase-3, Caspase-9, Cyt C, and p62 was significantly down-regulated (P<0.05, P<0.01), while that of Bcl-2, Parkin, and PINK1 was significantly up-regulated (P<0.01). In the serum containing Zhenwutang groups, the relative protein expression levels of Bax, cleaved Caspase-3, cleaved Caspase-9, Cyt C, and p62 were significantly down-regulated (P<0.05,P<0.01). The LC3Ⅱ/Ⅰ was significantly increased, and the relative protein expression levels of Bcl-2, p-Parkin, p-PINK1, and Beclin1 were significantly up-regulated (P<0.01). ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.
2.Early clinical efficacy of Yiqi Tongluo Decoction on ischemic cerebrovascular disease after interventional therapy
Qinghua WANG ; Gesheng WANG ; Ruiping LI ; Can ZHENG ; Wenjing LI ; Jiaqi CHEN ; Kaihang GUO ; Xiaobo DONG ; Wenxin WANG ; Rongjuan GUO ; Le WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):108-121
Objective:
To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention.
Methods:
From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated.
Results:
Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group.
Conclusion
Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.
3.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.
4.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.
5.Treatment of depression based on the theory of " liver disease affecting to the spleen"
Siyi WANG ; Jingchun LI ; Shaozhen JI ; Shuaihang HU ; Tianle ZHENG ; Fei WANG ; Qianqi WANG ; Jiaxiu LI ; Rongjuan GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):216-222
The " liver disease affecting to the spleen" theory first appeared in Nanjing and was further elaborated in Jingui Yaolue. This theory encapsulates the traditional Chinese medicine principles of the " unity of the five viscera" and the " preventive treatment of disease" . The theory emphasizes that the spleen is the pivotal point where depression may progress from a functional disorder to an organic disease. The liver governs the emotions and qi flow, whereas the spleen is responsible for qi, blood, and body. In the early stages of the disease, emotional disorders and qi flow disorders primarily affect the liver, manifesting as depression or low mood. As the condition progresses, the liver (Wood) overacts on the spleen (Earth), disrupting liver and spleen functions and causing qi and blood disharmony. This stage is marked by fatigue and psychomotor retardation. Prolonged illness depletes qi and blood, eventually involving all five viscera, disrupting the harmony of the five spirits, and affecting both body and spirit. At this advanced phase, intense emotional distress or agitation often arises, accompanied by a heightened risk of suicide. The disease progression follows a dynamic " qi-blood-spirit" pattern, in which depression begins in the liver, characterized by qi stagnation, then affects the spleen, involving blood disharmony. In later stages, the disease eventually affects all viscera, with profound effects on both physical and mental health. Treatment strategies should align with the disease stage. Early intervention should focus on regulating the flow of qi, treating the liver, and strengthening the spleen. In the middle stages, qi and blood should be harmonized while promoting the harmonized functions of the liver and spleen. In the later stages, treatment should harmonize the five viscera to restore balance between body and spirit. Guided by this theory, integrating modern medical understanding of the progression of depression from emotional to somatic symptoms and adopting a stage-based approach to treatment in clinical practice can yield effective therapeutic outcomes for managing depression and related disorders.
6.Effect of Xianglian Huazhuo Prescription on Hedgehog Signaling Pathway in Rats with Chronic Atrophic Gastritis
Jinye ZHOU ; Haofeng ZHANG ; Ziwei LIU ; Yican WANG ; Yanru CAI ; Yuxi GUO ; Jie WANG ; Zheng ZHI ; Qian YANG ; Bolin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):41-47
ObjectiveTo explore the therapeutic effect and mechanism of Xianglian Huazhuo prescription on chronic atrophic gastritis (CAG) in rats based on the Hedgehog signaling pathway. MethodsThe CAG rat model was established by sodium salicylate, N-methyl-N′-nitro-N-nitroguanidine (MNNG), and irregular feeding. The successfully modeled rats were randomly divided into a model group (180 mg·L-1), a moradan group (1.4 g·kg-1), and Xianglian Huazhuo Prescription groups with high, medium, and low doses (36, 9, 18 g·kg-1), followed by drug intervention. Hematoxylin-eosin (HE) staining was used to observe morphological changes in the gastric mucosa. Transmission electron microscopy was used to observe the ultrastructure of gastric mucosa cells. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of Sonic Hedgehog (Shh), Patched 1 (Ptch1), and Glioma-associated oncogene homolog 1 (Gli1). Western blot was used to detect the protein expression levels of Shh, Ptch1, and Gli1 in the gastric mucosa. Immunohistochemistry was used to observe the protein expression of the epithelial marker E-cadherin. ResultsCompared with the normal group, the CAG model group showed a reduction in gastric mucosal intrinsic glands and infiltration of inflammatory cells. The ultrastructure of gastric mucosal cells showed nuclear pyknosis, fewer mitochondria, and abnormal mitochondrial structure. The mRNA and protein expression of Shh, Ptch1, and Gli1 in the gastric mucosa were significantly decreased (P<0.05), and E-cadherin protein expression was decreased. Compared with the model group, the intervention groups showed varying degrees of improvement in histopathological morphology and cellular ultrastructure. The mRNA and protein expression of Shh, Ptch1, Gli1, and E-cadherin increased to varying degrees. Xianglian Huazhuo Prescription upregulated the expression of key Hedgehog pathway factors and E-cadherin at both the mRNA and protein levels (P<0.05). ConclusionXianglian Huazhuo prescription has a therapeutic effect on CAG in rats, and its mechanism may be related to activation of the Hedgehog signaling pathway and inhibition of epithelial-mesenchymal transition (EMT).
7.Effectss of persistent obesity on lung function in school age children
Chinese Journal of School Health 2024;45(4):549-553
Objective:
To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children.
Methods:
A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations.
Results:
The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05).
Conclusion
Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.
8.DNA Polymerase θ: a Multifunctional and Error-prone DNA End Repair Enzyme
Yao WANG ; Guo-Jiang CHEN ; Jian-Nan FENG ; Yan-Chun SHI ; Jing WANG ; Yuan-Qiang ZHENG
Progress in Biochemistry and Biophysics 2024;51(3):493-503
DNA polymerase theta (Polθ), also known as DNA polymerase θ, is the member of the DNA polymerase A family and plays a crucial role in the repair of DNA double-strand breaks (DSB). Polθ has 3 distinct structural domains: the N-terminal helicase-like domain with a conserved sequence, the C-terminal polymerase domain, and the central domain, which is a disordered sequence connecting these two regions. Notably, Polθ is the only known polymerase in eukaryotes that possesses helicase activity. However, it is also an error-prone polymerase. When DNA DSBs occur, a specialized network consisting of at least 4 pathways, including classical-non homologous end joining (C-NHEJ), homologous recombination (HR), single-strand annealing (SSA), and alternative-end joining (Alt-EJ), is responsible for repairing DNA damage caused by DSBs. In the absence of major DNA repair pathways like HR, cells rely on Alt-EJ pathway mediated by Polθ to repair damaged DNA and maintain genomic stability. Nevertheless, due to the low fidelity of Polθ, Alt-EJ repair often leads to errors. Depletion of Polθ has shown to increases DSB formation and compromise genomic stability. Conversely, overexpression of Polθ has been associated with increases DNA damage markers and impairs cell cycle progression. As a result, the impact of Polθ on genome stability remains controversial. Furthermore, overexpression of Polθ is frequently observed in cancer and is associated with a characteristic mutational signature and poor prognosis. Depleting Polθ in an HR-deficient background has been shown to impair cell viability, suggesting a synthetic lethal (SL) relationship between Polθ and HR factors. In recent years, targeted chemotherapy drugs that inhibit tumor growth have gained significant attention. However, off-target effects and drug resistance pose challenges for clinical application, particularly with poly-ADP-ribose polymerase inhibitor (PARPi). Blocking Polθ activity in HR-deficient tumor cells has been found to reverse PARPi resistance, making Polθ a very promising therapeutic target in cancer treatment. The availability of crystal structures for both helicase and polymerase domain has facilitated the design of potent inhibitors of Polθ. Currently, several highly specific and effective small molecule inhibitors targeting Polθ, such as Novobiocin, RP-6685, and ART558, have been reported to effectively block various cancers with HR deficiency. The initial success of these inhibitors points to new directions for treating BRCA1/2-mutated tumors. Additionally, reducing the Alt-EJ repair pathway mediated by Polθ can improve HR repair efficiency and increase the chance of exogenous gene target integration (TI), suggesting potential new applications for Polθ inhibitors. This article reviews the recent research progress on the molecular function of Polθ and its involvement in the Alt-EJ pathway modification mechanism, providing insights for a deeper understanding of this field.
9.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
10.Comparison of clinical characteristics between first-episode and relapse of major depressive disorder
Xiuyan ZHENG ; Chengxia TANG ; Zhaorui LIU ; Tingting ZHANG ; Yueqin HUANG ; Liang ZHOU ; Yuandong GONG ; Yan LIU ; Bo LIU ; Jie ZHANG ; Haiming WANG ; Zhengmin FENG ; Jun GUO ; Wenming CHEN ; Linling JIANG ; Defang CAI ; Jin LU
Chinese Mental Health Journal 2024;38(1):25-32
Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6%)were first-episode depression and 329(36.0%)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95%CI:1.00-4.44),more days out of role(OR=1.26,95%CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95%CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95%CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95%CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.


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