1.Immunotherapy for Colorectal Cancer
Hao-Ran XU ; Xiao-Yi ZHAO ; He NIE ; Hui WANG ; Qing-Lin ZHANG ; Qiang ZHAN
Progress in Biochemistry and Biophysics 2024;51(10):2570-2586
Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.
2.Advances in HIV-1 latency-regulating agents
Jiao-jiao DAI ; Xiang-yi JIANG ; Da FENG ; Hao LIN ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(4):840-852
At present, there is no cure for acquired immune deficiency syndrome (AIDS) due to HIV-1 latent reservoirs. Therefore, it urgently requires novel HIV-1 latency-regulating agents with high potency, low toxicity and favorable drug-like properties to achieve a functional cure for AIDS. Herein, we reviewed the advances in HIV-1 latency-regulating agents since 2019, including the drug discovery strategies, bioactivities, and mechanisms of these compounds. It is of great guiding significance in the development of latency-regulating agents with clinical value.
3.Study on the correlation between viral load and activation and exhaustion levels of CD8 +T cells in HIV/AIDS patients
Jieqiong ZHAN ; Lili SONG ; Yi LIN ; Yuan DONG ; Yu WANG ; Wei CHU
Chinese Journal of Preventive Medicine 2024;58(11):1690-1696
Objective:To investigate and analyze the correlation between the expression levels of CD38, HLA-DR and programmed cell death-1 (PD-1) on peripheral blood CD8 +T cells and HIV-1 RNA viral load, immune activation and exhaustion in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Methods:A total of 81 HIV/AIDS patients (64 without antiretroviral therapy and 17 with therapy) and 40 healthy donors in the same period were enrolled as the control group. Flow cytometry was used to analyze the CD4 +T lymphocyte count and the expression levels of activation markers CD38 and HLA-DR and apoptosis marker PD-1 on CD8 +T cells. HIV-1 RNA in the plasma of HIV-1 infected patients was quantitatively detected by real-time fluorescence quantitative polymerase chain reaction. Variance analysis was used to compare the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells between HIV/AIDS patients and healthy controls. Spearman correlation analysis was used to analyze the correlation between different T lymphocyte counts and HIV RNA viral load, and the correlation between HIV RNA viral load and peripheral blood CD8 +T cell CD38, HLA-DR and PD-1. Results:Among the 81 HIV/AIDS patients, 69 (85.19%) were males and 12 (14.81%) were females, with an age M ( Q1, Q3) of 58 (36.5, 65.0) years. There were 60 HIV/AIDS patients over 55 years old (74.07%) and 21 HIV/AIDS patients between 18 and 55 years old (25.93%). The results of variance analysis showed that compared with the healthy control group, the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells in HIV/AIDS patients increased, and the differences were statistically significant (all P<0.05). In addition, the expression of CD38, HLA-DR and PD-1 increased significantly in patients with CD4 +T cell count less than 350 cells/μl, and the differences were statistically significant (all P<0.05). Spearman correlation analysis showed that CD4 +and CD4 +/CD8 +were negatively correlated with viral load in HIV/AIDS patients ( r=-0.407 and -0.378, respectively, both P<0.05), and CD8 +was positively correlated with viral load ( r=0.356, P<0.05). When the HIV RNA level was≤10 5 CPs/ml, there was no correlation between the HIV RNA level and the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells (all P>0.05). However, when the level of HIV RNA was>10 5 CPs/ml, the level of HIV RNA was positively correlated with the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells ( r=0.412, 0.387, 0.395, respectively, all P<0.05). Conclusions:The activation levels of CD38 and HLA-DR and the expression of PD-1 on CD8 +T cells in the peripheral blood of HIV/AIDS patients are increased. When the viral load is high, the HIV RNA viral load is positively correlated with the activation and exhaustion levels of CD8 +T cells.
4.A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection
Zhan ZENG ; Mingfang ZHOU ; Yanjie LIN ; Xiaoyue BI ; Liu YANG ; Wen DENG ; Tingting JIANG ; Leiping HU ; Mengjiao XU ; Lu ZHANG ; Wei YI ; Minghui LI
Chinese Journal of Hepatology 2024;32(2):113-118
Objective:To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection.Methods:A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data.Results:A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z ?=?-1.981, P ?=?0.048), aspartate aminotransferase (AST, z ?=?-3.956, P ?0.001), HBV load ( z ?=?-15.292, P ?0.001), and HBeAg ( z ?=?-4.77, P ?0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion:Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.
5.Overview of Research on Qushi Tongmai Method in the Treatment of Rheumatoid Arthritis and Its Application
Chang-Song LIN ; Jing-Yi ZHAN ; Shu-Lin CHEN ; Yi-Fang ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2625-2630
The pathogenesis of rheumatoid arthritis patients exerts the features of wind-damp and stasis obstruction,sinew injury and bone damage,therefore,the therapy of dispelling wind and removing dampness,dredging blood vessels,unblocking meridians and collaterals,invigorating spleen and kidney,and strengthening muscles and bones was proposed,hereinafter referred to as Qushi Tongmai method.Under the guidance of Qushi Tongmai method,rheumatoid arthritis can be treated with Chinese medicine based on the modification of empirical formulas such as Kunduan Yimu Formula,Nanxu Yimu Granules and Santeng Shujin Formula,and classical formulas such as Guizhi Shaoyao Zhimu Decoction,Huangqi Guizhi Wuwu Decoction and Banxia Xiexin Decoction according to the deficiency and excess of healthy qi and pathogenic qi as well as the specific symptoms.Moreover,the soft exact,external treatment and functional exercise can be also included.The Chinese medicine therapy combined with the soft exact,external treatment and functional exercise constitutes a unique Chinese medicine system for the prevention and treatment of rheumatoid arthritis.The results of a series of clinical and experimental studies indicated that Qushi Tongmai method exerts efficiency-enhancing and toxin-reducing effect in the treatment of rheumatoid arthritis,and the establishment of Qushi Tongmai method is a theoretical innovation in exerting the advantages of Chinese medicine in the prevention and treatment of rheumatoid arthritis.
6.Study on the correlation between viral load and activation and exhaustion levels of CD8 +T cells in HIV/AIDS patients
Jieqiong ZHAN ; Lili SONG ; Yi LIN ; Yuan DONG ; Yu WANG ; Wei CHU
Chinese Journal of Preventive Medicine 2024;58(11):1690-1696
Objective:To investigate and analyze the correlation between the expression levels of CD38, HLA-DR and programmed cell death-1 (PD-1) on peripheral blood CD8 +T cells and HIV-1 RNA viral load, immune activation and exhaustion in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Methods:A total of 81 HIV/AIDS patients (64 without antiretroviral therapy and 17 with therapy) and 40 healthy donors in the same period were enrolled as the control group. Flow cytometry was used to analyze the CD4 +T lymphocyte count and the expression levels of activation markers CD38 and HLA-DR and apoptosis marker PD-1 on CD8 +T cells. HIV-1 RNA in the plasma of HIV-1 infected patients was quantitatively detected by real-time fluorescence quantitative polymerase chain reaction. Variance analysis was used to compare the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells between HIV/AIDS patients and healthy controls. Spearman correlation analysis was used to analyze the correlation between different T lymphocyte counts and HIV RNA viral load, and the correlation between HIV RNA viral load and peripheral blood CD8 +T cell CD38, HLA-DR and PD-1. Results:Among the 81 HIV/AIDS patients, 69 (85.19%) were males and 12 (14.81%) were females, with an age M ( Q1, Q3) of 58 (36.5, 65.0) years. There were 60 HIV/AIDS patients over 55 years old (74.07%) and 21 HIV/AIDS patients between 18 and 55 years old (25.93%). The results of variance analysis showed that compared with the healthy control group, the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells in HIV/AIDS patients increased, and the differences were statistically significant (all P<0.05). In addition, the expression of CD38, HLA-DR and PD-1 increased significantly in patients with CD4 +T cell count less than 350 cells/μl, and the differences were statistically significant (all P<0.05). Spearman correlation analysis showed that CD4 +and CD4 +/CD8 +were negatively correlated with viral load in HIV/AIDS patients ( r=-0.407 and -0.378, respectively, both P<0.05), and CD8 +was positively correlated with viral load ( r=0.356, P<0.05). When the HIV RNA level was≤10 5 CPs/ml, there was no correlation between the HIV RNA level and the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells (all P>0.05). However, when the level of HIV RNA was>10 5 CPs/ml, the level of HIV RNA was positively correlated with the expression levels of CD38, HLA-DR and PD-1 on CD8 +T cells ( r=0.412, 0.387, 0.395, respectively, all P<0.05). Conclusions:The activation levels of CD38 and HLA-DR and the expression of PD-1 on CD8 +T cells in the peripheral blood of HIV/AIDS patients are increased. When the viral load is high, the HIV RNA viral load is positively correlated with the activation and exhaustion levels of CD8 +T cells.
7.Intramedullary nailing for irreducible spiral subtrochanteric fractures: A comparison of cerclage and non-cerclage wiring
Yan-Hui GUO ; Zhan-Lin SONG ; Hua-Yong ZHENG ; Jie GAO ; Yi-Yun LIN ; Zhi LIU ; Lian-Hua LI
Chinese Journal of Traumatology 2024;27(5):305-310
Purpose::Intramedullary nailing is the preferred internal fixation technique for the treatment of subtrochanteric fractures because of its biomechanical advantages. However, no definitive conclusion has been reached regarding whether combined cable cerclage is required during intramedullary nailing treatment. This study is performed to compare the clinical effects of intramedullary nailing with cerclage and non-cerclage wiring in the treatment of irreducible spiral subtrochanteric fractures.Methods::Patients with subtrochanteric fractures admitted to our center from January 2013 to December 2021 were retrospectively analyzed. The patients were enrolled in the case-control study according to the inclusion and exclusion criteria and divided into the non-cerclage group and the cerclage group. The patients' clinical data, including the operative time, intraoperative blood loss, hospital stay, reoperation rate, fracture union time, and Harris hip score, were compared between these 2 groups. Categorical variables were compared using Chi-square or Fisher's exact test. Continuous variables with normal distribution were presented as mean ± standard deviation and analyzed with Student's t-test. Nonnormally distributed variables were expressed as median (Q 1, Q 3) and assessed using the Mann-Whitney test. A p < 0.05 was considered significant. Results::In total, 69 patients were included in the study (35 patients in the non-cerclage group and 34 patients in the cerclage group). The baseline data of the 2 groups were comparable. There were no significant difference in the length of hospital stay (z = -0.391, p = 0.696), operative time (z = -1.289, p = 0.197), or intraoperative blood loss (z = -1.321, p = 0.186). However, compared with non-cerclage group, the fracture union time was shorter (z = -5.587, p < 0.001), the rate of nonunion was lower (χ 2= 6.030, p = 0.03), the anatomical reduction rate was higher (χ 2= 5.449, p = 0.03), and the Harris hip score was higher (z =-2.99, p = 0.003) in the cerclage group, all with statistically significant differences. Conclusions::Intramedullary nailing combined with cable cerclage wiring is a safe and reliable technique for the treatment of irreducible subtrochanteric fractures. This technique can improve the reduction effect, increase the stability of fracture fixation, shorten the fracture union time, reduce the occurrence of nonunion, and contribute to the recovery of hip joint function.
8.Application and thinking of acupuncture therapy in comprehensive management of hypertension.
Yi-Zhan WANG ; Hong-Wei LIU ; Yan GUO ; Bin LI ; Shao-Song WANG ; Xin WANG ; Lin-Peng WANG ; Yuan-Bo FU
Chinese Acupuncture & Moxibustion 2023;43(2):213-216
The theory of disease prevention with traditional Chinese medicine is introduced into the prevention of chronic diseases such as hypertension. In order to fully implement the advantages of acupuncture, the three-level prevention strategy is strengthened on the whole-process intervention with acupuncture for hypertension, including prevention before disease onset, starting intervention at the early phase, and prevention disease from exacerbating. Moreover, the comprehensive management scheme, multidisciplinary coordination and participation mechanism are investigated in the field of traditional Chinese medicine for preventive treatment of hypertension.
Humans
;
Acupuncture Therapy
;
Medicine, Chinese Traditional
;
Acupuncture
;
Chronic Disease
;
Hypertension
9.Five-year outcomes of biodegradable versus second-generation durable polymer drug-eluting stents used in complex percutaneous coronary intervention.
Na XU ; Lin JIANG ; Yi YAO ; Jingjing XU ; Ru LIU ; Huanhuan WANG ; Ying SONG ; Lijian GAO ; Zhan GAO ; Xueyan ZHAO ; Bo XU ; Yaling HAN ; Jinqing YUAN
Chinese Medical Journal 2023;136(3):322-330
BACKGROUND:
There are few data comparing clinical outcomes of complex percutaneous coronary intervention (CPCI) when using biodegradable polymer drug-eluting stents (BP-DES) or second-generation durable polymer drug-eluting stents (DP-DES). The purpose of this study was to investigate the safety and efficacy of BP-DES and compare that with DP-DES in patients with and without CPCI during a 5-year follow-up.
METHODS:
Patients who exclusively underwent BP-DES or DP-DES implantation in 2013 at Fuwai Hospital were consecutively enrolled and stratified into two categories based on CPCI presence or absence. CPCI included at least one of the following features: unprotected left main lesion, ≥2 lesions treated, ≥2 stents implanted, total stent length >40 mm, moderate-to-severe calcified lesion, chronic total occlusion, or bifurcated target lesion. The primary endpoint was major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction, and total coronary revascularization (target lesion revascularization, target vessel revascularization [TVR], and non-TVR) during the 5-year follow-up. The secondary endpoint was total coronary revascularization.
RESULTS:
Among the 7712 patients included, 4882 (63.3%) underwent CPCI. Compared with non-CPCI patients, CPCI patients had higher 2- and 5-year incidences of MACE and total coronary revascularization. Following multivariable adjustment including stent type, CPCI was an independent predictor of MACE (adjusted hazard ratio [aHR]: 1.151; 95% confidence interval [CI]: 1.017-1.303, P = 0.026) and total coronary revascularization (aHR: 1.199; 95% CI: 1.037-1.388, P = 0.014) at 5 years. The results were consistent at the 2-year endpoints. In patients with CPCI, BP-DES use was associated with significantly higher MACE rates at 5 years (aHR: 1.256; 95% CI: 1.078-1.462, P = 0.003) and total coronary revascularization (aHR: 1.257; 95% CI: 1.052-1.502, P = 0.012) compared with that of DP-DES, but there was a similar risk at 2 years. However, BP-DES had comparable safety and efficacy profiles including MACE and total coronary revascularization compared with DP-DES in patients with non-CPCI at 2 and 5 years.
CONCLUSIONS
Patients underwent CPCI remained at a higher risk of mid- to long-term adverse events regardless of the stent type. The effect of BP-DES compared with DP-DES on outcomes was similar in CPCI and non-CPCI patients at 2 years but had inconsistent effects at the 5-year clinical endpoints.
Humans
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Drug-Eluting Stents/adverse effects*
;
Myocardial Infarction/complications*
;
Polymers/therapeutic use*
;
Treatment Outcome
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Coronary Artery Disease/complications*
;
Percutaneous Coronary Intervention/adverse effects*
;
Absorbable Implants
;
Prosthesis Design
10.Clinical characteristics of 34 adult patients with acute leukemias of ambiguous lineage.
Cai Xia PEI ; Qian ZHAN ; Cen Niao LIU ; Wen PENG ; Li WANG ; Lin LIU ; Yuan Jie LI ; Yi LIAO ; Xiao Hua LUO
Chinese Journal of Hematology 2023;44(11):940-944
Adult
;
Humans
;
Acute Disease
;
Leukemia

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