1.Hemin regulates mitochondrial pathway of oxidative stress in mouse chondrocytes
Guanghui HE ; Jie YUAN ; Yanqin KE ; Xiaoting QIU ; Xiaoling ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(6):1183-1191
BACKGROUND:Studies have shown that mitochondrial oxidative stress has an important role in the development of knee osteoarthritis,and Hemin can regulate the expression of mitochondria-related proteins. OBJECTIVE:To study the regulatory effect of Hemin on oxidative stress in mouse chondrocytes and its interventional effect and mechanism in knee osteoarthritis. METHODS:(1)In vitro cell experiment:Primary chondrocytes from C57BL/6 mice were extracted and induced with 10 ng/mL interleukin-1β to construct an in vitro chondrocyte model of osteoarthritis.The optimal concentration of Hemin(0,1,10,20,40,80,and 160 μmol/L)for the intervention in mouse chondrocytes was determined by cell counting kit-8 method.Chondrocytes were randomly divided into control group,model group(interleukin-1β)and Hemin group(interleukin-1β+Hemin).Reactive oxygen species,mitochondrial membrane potential and apoptosis of chondrocytes in each group were detected.(2)In vivo experiment:Adult C57BL/6 mice were randomly divided into normal group,model group(osteoarthritis)and Hemin group(osteoarthritis+Hemin),with eight mice in each group.After 4 weeks of Hemin treatment,the behavioral test and histopathological observation of the knee joint were performed in each group.Changes in extracellular matrix-related protein expression and apoptosis in chondrocytes and the expression level of Nrf2/HO-1 protein in cartilage tissue were detected. RESULTS AND CONCLUSION:In vitro experiment:the optimal concentration of Hemin on primary chondrocytes was 40 μmol/L.Compared with the model group,the level of reactive oxygen species was significantly reduced,the mitochondrial membrane potential was significantly improved,and the apoptosis of chondrocytes was reduced in the hemin-treated interleukin-1β-induced chondrocytes.In vivo experiment:After 4 weeks of treatment,compared with the model group,the lower limb function of mice in the Hemin group was significantly improved,the histopathological score was significantly improved,and the apoptosis of knee chondrocytes was significantly reduced.All these findings indicate that Hemin can alleviate oxidative stress,restore mitochondrial function and reduce apoptosis in mouse chondrocytes induced by interleukin-1β.Hemin can improve extracellular matrix degradation,promote chondrocyte anabolism,reduce catabolism and reduce chondrocyte apoptosis in knee osteoarthritis.It may act by activating the chondrocyte Nrf2/HO-1 signaling pathway in the inflammatory environment.
2.Academic Connotation and Practical Applications of Theory of Cancer Collaterals
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):245-255
The modernization of traditional Chinese medicine (TCM) in the field of oncology has led to the formation of a diversified theoretical system for tumor treatment. However, this system faces challenges such as significant differences between theoretical understanding and clinical treatment and lack of unified consensus and standardized protocols. The pathogenesis and treatment of collateral diseases, when summarized by the philosophy of Yin and Yang Qi transformation, offer a valuable academic perspective in the tumor theory by simplifying complexity and integrating knowledge. Building on the foundation of the collateral theory and modern research, our team has innovatively proposed the theory of cancer collaterals. From the Yin and Yang Qi transformation of collaterals, this theory emphasizes that the core pathogenesis of cancer collaterals is the dysfunction of Qi transformation in collaterals. Cancer collaterals are characterized by a Yin substance with a Yang function, representing the pathogenic Qi combining Yin and Yang. This theory outlines seven pathological characteristics (concealment, aggressive onset, toxin coagulation, obstruction and stasis, deficiency and damage, variable dispersion, and differences in Zang-organ collaterals) of cancer collaterals, five unique pathogeneses (latent toxin, stasis obstruction, damage, abnormal proliferation, and toxin dispersion in cancer collaterals) of cancer collaterals, and the full-cycle pathogenesis evolution through four stages (early, middle, late, and post-treatment stages) of tumors. In clinical practice, it is essential to differentiate the Yin and Yang Qi transformation states of body collaterals and cancer collaterals to restore the normal Qi transformation of collaterals and regulate the disordered Qi transformation of cancer collaterals. Therefore, the treatment method of regulating Qi and dredging collaterals in the theory of cancer collaterals is proposed. Regulating Qi involves adjusting the yang of cancer collaterals to promote Qi transformation, while dredging collaterals involves resolving the Yin of cancer collaterals to transform the formed cancer toxin. Finally, the practical value of the theory of cancer collaterals is discussed in terms of guiding clinical differentiation and treatment, promoting scientific research, and breaking down theoretical barriers. The aim is to perfect the theoretical system of malignant tumor differentiation and treatment.
3.Investigation on the current status and optimization strategies for the standardized on-the-job training for community clinical pharmacists in Shanghai
Yangjiayi XIANG ; Jing SHENG ; Liping WANG ; Lie LUO ; Yuan YUAN ; Xiaodan ZHANG ; Yan LI ; Bin WANG ; Guanghui LI
China Pharmacy 2025;36(13):1568-1573
OBJECTIVE To systematically investigate the current status and effectiveness of the standardized on-the-job training program for community clinical pharmacists in Shanghai, and to provide a scientific basis for optimizing the training scheme. METHODS A questionnaire survey was conducted to collect the data from trainees and mentor pharmacists who participated in the program between 2016 and 2024. The survey examined their basic information, evaluations of the training scheme, satisfaction with training outcomes, and suggestions for improvement. Statistical analyses were also conducted. RESULTS A total of 420 valid responses were collected, including 340 from trainees and 80 from mentor pharmacists. Before training, only 30.29% of trainees were engaged in clinical pharmacy-related work, whereas this proportion increased to 73.24% after training. Most mentor pharmacists had extensive experience in clinical pharmacy (76.25% with ≥5 years of experience) and mentoring (78.75% with ≥3 teaching sessions). Totally 65.59% of trainees and 55.00% of mentor pharmacists believed that blended training yielded the best learning outcomes. Over 80.00% of both trainees and mentor pharmacists considered the overall training duration, theoretical study time, and practical training time to be reasonable. More than 95.00% of trainees and mentor pharmacists agreed that the homework and assessment schemes were appropriate. Trainees rated the relevance of training content to their actual work highly (with an average relevance score >4.5), though they perceived the chronic disease medication therapy management module as significantly more challenging than the prescription review and evaluation module and the home-based pharmaceutical care module. The average satisfaction score of trainees and mentor pharmacists with the training effectiveness of each project was above 4 points, indicating a high overall satisfaction. Inadequate provision of teaching resources was unanimously recognized by trainees and mentor pharmacists as the key area requiring improvement. CONCLUSIONS The standardized on-the-job training program for community clinical pharmacists in Shanghai has contributed to improving pharmaceutical services in community healthcare settings. However, ongoing improvements must concentrate on content design, resource development, and faculty cultivation.
4.Postoperative Stage-based Functional Protection Strategies for Lung Cancer Based on Theory of "Lungs Governing Qi"
Luchang CAO ; Guanghui ZHU ; Ruike GAO ; Manman XU ; Xiaoyu ZHU ; Wei HOU ; Ying ZHANG ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):86-93
Lung cancer (LC) is a significant global public health issue, with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually, posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However, postoperative multidimensional functional impairments, including respiratory, mucosal, and psychological functions, are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration, but also negatively correlate with prognosis, facilitating disease recurrence and metastasis. At present, postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine (TCM) differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery, and guided by the classical TCM theory of "lungs governing Qi", this study, based on the core concept of the "five perspectives on treatment" theory, innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase, mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase, and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly, stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase, the strategy emphasizes tonifying Qi and uplifting sinking Qi, with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase, the approach focuses on nourishing Yin and uplifting Qi, with prescription combinations that integrate unblocking and tonification. In the consolidation phase, the strategy aims to resolve constraint and uplift Qi, with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation, clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM, offering a new approach for TCM differentiation and treatment in the full-cycle, stage-based, and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.
5.A Hierarchical Strategy for Differentiation and Treatment of Recurrent Aphthous Oral Ulcers Related to Targeted Therapy for Lung Cancer Based on Yin Deficiency and Qi Collapse
Luchang CAO ; Guanghui ZHU ; Ruike GAO ; Manman XU ; Xiaoyu ZHU ; Ming LIN ; Ying ZHANG ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):116-125
Tumor treatment-related adverse reactions are a major focus of clinical concern, among which recurrent aphthous oral ulcers (RAU) associated with targeted therapy for lung cancer (LC) are among the most painful and distressing for patients. Currently, modern medical interventions show limited efficacy, and there is an urgent need for more effective treatment strategies. This study differentiates RAU associated with targeted therapy for LC from chemotherapy-related and ordinary oral ulcers, elucidates the pathophysiological basis of such ulcers, and traces the theoretical origin of "Yin deficiency and Qi collapse". Based on the new system of "five perspectives on diagnosis and treatment" for tumor prevention and treatment, with a focus on the core and symptom perspectives and rooted in the traditional concept of "lung dominating Qi", we innovatively propose the concept of "medicine-induced ulcer" and are the first to introduce the theory of "Yin deficiency and Qi collapse" into the syndrome differentiation and treatment of RAU associated with targeted therapy for LC (i.e., medicine-induced ulcer). We propose that "Yin deficiency and Qi collapse" is the core pathogenesis of medicine-induced ulcers, in which the collapse of formless Qi is the key to their onset, while the deficiency and stasis of tangible Yin and blood constitute the root of recurrence. A hierarchical strategy for syndrome differentiation and treatment is established: first treating the collapse of formless Qi, then replenishing tangible deficiencies, and concurrently preventing recurrence. We emphasize that treatment should address both root and manifestation, with appropriate prioritization. In the acute phase, while relieving symptoms and promoting ulcer healing by nourishing Qi, uplifting collapse, and generating body fluids, attention should also be paid to nourishing spleen Yin, facilitating the circulation of nutritive Qi, and alleviating stasis to target the root pathogenesis and reduce recurrence. A verified case is presented to support this approach. This study enriches the theoretical framework and clinical methods of traditional Chinese medicine (TCM) in the treatment of RAU associated with targeted therapy for LC, promotes symptom management of treatment-related adverse reactions through integrated TCM and Western medicine, and provides theoretical support for the construction and development of a comprehensive differentiation and treatment system for lung cancer prevention, treatment, and rehabilitation.
6.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
7.Research progress in treatment principles for endometrial cancer and its postoperative and postoperative recurrent radiotherapy
Teng LIU ; Ning ZHANG ; Mingyuan HE ; Guanghui CHENG
Journal of Jilin University(Medicine Edition) 2025;51(6):1747-1754
Endometrial cancer is one of the common malignant tumors of the female reproductive system.Its incidence rate in China is second only to cervical cancer,posing a serious threat to women's life and health,and the onset shows a trend of affecting younger individuals.Currently,the primary treatment for endometrial cancer is surgical intervention,and some postoperative patients and those with postoperative recurrence require adjuvant radiotherapy.Pelvic external beam radiotherapy(EBRT)and vaginal brachytherapy(VBT)are two modalities of postoperative radiotherapy.The appropriate postoperative radiotherapy approach should be selected based on individual conditions and guideline recommendations.Most patients can achieve satisfactory treatment outcomes through surgery and postoperative adjuvant radiotherapy.However,the specific indications for postoperative radiotherapy in endometrial cancer patients and the radiotherapy principles for those with postoperative recurrence are relatively complex,and recommendations for radiotherapy modalities in postoperative patients vary slightly across different guidelines.This article reviews the treatment principles for endometrial cancer patients in recent years,as well as the indications for postoperative and post operative recurrent radiotherapy and the radiotherapy techniques,aiming to provide a reference for radiotherapy in the endometrial cancer patients.
8.Analysis on epidemiological characteristics of severe congenital heart disease in Chongqing city during 2007-2023
Fen WANG ; Guanghui YIN ; Jie ZHANG ; Miao FENG ; Jun LIU
Chongqing Medicine 2025;54(2):505-511
Objective To understand the epidemiological characteristics of severe congenital heart dis-ease in Chongqing City during 2007-2023 to provide a basis for its comprehensive prevention and control measures.Methods Based on hospital monitoring data,453 children patients with severe congenital heart dis-ease monitored by the birth defects monitoring institutions in Chongqing city from January 2007 to December 2023 were included in the study.They were grouped by year,perinatal infants gender,maternal permanent res-idence(urban/rural),maternal age,different regions and other categories.The χ2 test was used to analyze the difference in the incidence rate of different categories of severe congenital heart diseases,and the Joinpoint re-gression model was used to analyze the change trend.Results A total of 1 468 005 perinatal neonates were monitored in Chongqing City during 2007-2023 and 453 cases of severe congenital heart disease were found,with an incidence rate of 3.09/10 000,in which the incidence rate of atrioventricular septal defect was 2.16/10 000,the incidence rate of tetralogy of fallot was 0.66/10 000 and the incidence rate of transposition of great ar-teries was 0.27/10 000.The total incidence rate of cities and towns was higher than that in the countryside(χ2=64.08,P<0.001),the urban area was higher than the Chongqing southeast and Chongqing northeast towns cluster(χ2=49.34,P<0.001),the female was higher than the male(χ2=5.63,P=0.018).The inci-dence rates in different ages groups showed the U shape distribution(χ2=31.63,P<0.001).The incidence rate of the pregnant women<20 years old group and pregnant women≥35 years old group was higher,which of the 25-29 years old group was lower.The incidence rate of severe congenital heart disease in Chongqing City during 2007-2023 appeared the turning point,which during 2007-2016 was gradually increased(APC=-15.95),and which during 2016-2023 was gradually decreased(APC=-15.36).Conclusion The incidence rate of severe congenital heart disease in Chongqing city during 2007-2023 was increased first and then de-creased,moreover there were differences in time,region and population.
9.Epidemiology and risk factors for mortality in patients with postcraniotomy meningitis caused by Gram-negative bacteria
Siqi WANG ; Guanghui ZHENG ; Yijun SHI ; Jialu SUN ; Hong LYU ; Guojun ZHANG
International Journal of Laboratory Medicine 2025;46(6):664-669
Objective To investigate the epidemiological characteristics of patients with postcraniotomy meningitis(PM)caused by Gram-negative bacteria(GNB),and to evaluate the related risk factors for mortal-ity.Methods A total of 202 PM patients in Beijing Tiantan Hospital,Capital Medical University from May 2019 to December 2021 were retrospectively analyzed,including 54 cases in the death group and 148 cases in the survival group.The distribution of microorganisms in the two groups was analyzed,and Cox proportional hazards regression model was established to evaluate the risk factors of death.Results Among the 202 pa-tients with PM caused by GNB,with a mortality rate of 26.7%,Klebsiella pneumoniae(24.8%),Acinetobact-er baumannii(21.8%)and Escherichia coli(8.4%)were the top three isolated pathogens.The proportions of GNB distribution in the survival group and the death group were similar,but the bacteria distribution in the death group was more concentrate.Cox proportional hazards regression model results showed that hyperten-sion(HR=2.384,95%CI 1.229-4.626,P=0.010)and admission to ICU(HR=3.695,95%CI 1.412-9.670,P=0.008)were independent risk factors for death in patients with PM caused by GNB.Conclusion The mortality of PM caused by GNB is high.Hypertension and admission to ICU are independent risk factors for death of patients,and attention should be paid to prevention and treatment in clinical practice.
10.Postoperative Treatment and Rehabilitation of Malignant Tumor Based on the Theory of Qi Sinking in Traditional Chinese Medicine
Qianhui SUN ; Guanghui ZHU ; Bowen XU ; Ying ZHANG ; Jie LI
Journal of Traditional Chinese Medicine 2024;65(11):1120-1125
As an important concept in Chinese medicine theory, "qi sinking" is the inheritance and extension of the thought core of sinking of qi in whole body. This article explored the concept of sinking of pectoral qi, center qi, and kidney qi in the theory of qi sinking, and believed that sinking of pectoral qi, stagnation and sinking of center qi, deficiency and sinking of kidney qi were the core pathogenesis of postoperative injury in malignant tumours. Anchored to the method of reinforcing healthy qi and lifting the sunken, this article recommended to identify pattern and treat by guiding supplement and lifting the sunken. For lung gold impairment, heart yang depletion, and pectoral qi sinking, the treatment is to warm and supplement heart and lung, lift pectoral qi, and restore the respiratory function by modified Shengxian Decoction (升陷汤) plus Guizhi Decoction (桂枝汤); for spleen depletion and pathways blockage, liver failing to act freely, and center qi stagnation and sinking, the treatment is to warm and supplement center qi, raise yang and lift the sunken, and restore the digestive function by modified Buzhong Yiqi Decoction (补中益气汤); for source exhausted and essence deficiency, liver qi hiding, and kidney qi deficiency to inward invasion, the treatment is to nourish the kidney and astringe the liver, consolidate the original qi and lift qi, improve the pelvic floor dysfunction, and protect the kidney function by modified Liuwei Dihuang Pill (六味地黄丸) plus Shengma Chaihu Decoction (升麻柴胡汤). Modification need base on different disease patterns and stages, and new ideas for postoperative traditional Chinese medicine treatment and rehabilitation of malignant tumours were provided.

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