1.Progress in autophagy effect on the progression of SLE pathogenesis by regulating the immune system.
Tianzhen MA ; Honghui TANG ; Xuan CHEN ; Yuqing GUO ; Liping ZHANG ; Baiqing LI ; Jin XI ; Yuanyuan WANG
Chinese Journal of Cellular and Molecular Immunology 2025;41(7):649-654
Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology*
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Autophagy/immunology*
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Humans
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Animals
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Immunity, Innate
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Adaptive Immunity
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Disease Progression
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Immune System/immunology*
2.Survey on the awareness and clinical application of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians
Yuanyuan KONG ; Yujie GUO ; Yujuan GUAN ; Xuan LIANG ; Zhongjie HU ; Xiaobo LU ; Mingqin LU ; Yongfeng YANG ; Meifang HAN ; Hong YOU ; Zhiyun YANG ; Jidong JIA
Journal of Clinical Hepatology 2025;41(6):1068-1074
ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. MethodsFrom July 19 to December 31, 2024, a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide, including their awareness and practice based on 18 questions regarding testing and referral, diagnosis and treatment, and follow-up. ResultsAmong all respondents, only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B, with an overall awareness rate of 22.0%. Only 20% — 40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy, while 80% — 100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year, 3 years, and 5 years were 67.5% 57.5% and 47.5%,respectively, showing a trend of gradual reduction, which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians, insufficient awareness of the disease among patients, and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection, diagnosis, treatment, and management” for patients with chronic hepatitis B in healthcare institutions, in order to promote the implementation of the guidelines.
3.Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.
Wenzhen DANG ; Xiaomin WANG ; Huaying LI ; Yixuan XU ; Xinyu LI ; Siqi HUANG ; Hongru TAO ; Xiao LI ; Yulin YANG ; Lijiang XUAN ; Weilie XIAO ; Dean GUO ; Hao ZHANG ; Qiong WU ; Jie ZHENG ; Xiaoyan SHEN ; Kaixian CHEN ; Heng XU ; Yuanyuan ZHANG ; Cheng LUO
Acta Pharmaceutica Sinica B 2025;15(8):3997-4013
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.
4.Da Chengqitang Protects Intestinal Barrier in Septic Mice via Endogenous Antimicrobial Peptide mCRAMP
Yuanyuan LI ; Xuan ZHONG ; Lei LIU ; Shuya SUN ; Jiajun LING ; Rongfeng LIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):20-28
ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang (DCQD) on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins [claudin-1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, endogenous antimicrobial peptide mCRAMP, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88)] in sepsis. Fifty C57BL/6 mice were randomized into sham, model, low- and high-dose (4 g∙kg-1 and 8 g∙kg-1) DCQD, and ulinastatin groups (n=10). Before, during, and after the day of modeling surgery, each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue, which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP, TLR4, and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction, on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force, hydrogen bonding, and other conjugated systems. The results of animal experiments showed that compared with the model group, low- or high-dose DCQD lowered the D-lactic acid level in the serum (P<0.01), alleviated damage to the ileal tissue and mucosal edema, protected the small intestine villus integrity, reduced inflammatory cell infiltration, promoted the expression of claudin-1 (P<0.01), lowered the IL-6 level (P<0.01), up-regulated the mRNA and protein levels of mCRAMP (P<0.01), and down-regulated the mRNA and protein levels of TLR4 and MyD88 (P<0.01) in the ileal tissue. In addition, high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue (P<0.01), and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue (P<0.05). ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation, repair intestinal mucosal damage, improve the tight junction protein level, and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.
5.Analysis of potential categories of sexual behaviors among male students who have sex with men and the status of pre exposure prophylaxis use
Chinese Journal of School Health 2024;45(7):974-977
Objective:
To analyze the use of preexposure prophylaxis (PrEP) among male students who had sex with men (MSM) with different sexual behavior patterns using potential categories, so as to provide evidence for determining the use patterns of PrEP consistent with MSM.
Methods:
A questionnaire survey was conducted by proportional sampling method on MSM in 31 provincial administrative regions in mainland China from 20 October to 30 December 2021, a total of 1 040 students were selected for the study. Latent variable analyses were conducted on a total of seven sexual behavioral characteristics, including knowledge of sexual partner HIV infection, frequency of condom use, number of sexual partners, engaging in group sex, provision of commercial sex, use of sex aids, and history of sexually transmitted infections (STIs) in the past year. And demographic characteristics were analyzed by Logistic regression analysis. The rates of PrEP awareness, willingness to use and usage rate in different sexual behavior risk groups were investigated.
Results:
Student MSM could be divided into two potential category groups:a lowrisk behavior group (82.4%) and a highrisk behavior group (17.6%). The PrEP usage rate (15.8%) was higher in the highrisk behavior group, and the difference was statistically significant compared to the lowrisk behavior group (7.2%) (χ2=13.43, P<0.05). Student MSM residing in the northeast, south, and northwest of China, in the pilot city, and with a sex role of "0.5" (possible acceptance and insertion of sexual behavior) were more likely to be in the highrisk behavior group (OR=3.13, 3.07, 3.87, 2.22, 1.66, P<0.05).
Conclusion
Student MSM in highrisk and lowrisk sexual differs in the behavior of PrEP, and targeted interventions should be implemented to promote the use of PrEP and reduce HIV infection in this population.
6.Current status and related factors of antiviral treatment among HIV infected men who have sex with men students
Chinese Journal of School Health 2024;45(12):1798-1801
Objective:
To investigate the current situation and related factors of antiretroviral therapy (ART) among HIV infected male students engaging in men who have sex with men (MSM), so as to provide the reference data for HIV prevention and treatment.
Methods:
In November 2021, 137 MSM students from 31 provincial administrative regions in China were recruited. An online survey was conducted to collect data on demographic characteristics, ART status, CD4 count, and HIV viral load before treatment. Logistic regression was used to analyze the factors related the effectiveness of ART in MSM.
Results:
Among the included research subjects, 14.6% had late detection of HIV,97.1% of participants were currently undergoing ART. Among those whose ART duration was less than 6 months, while 76.9% were undergoing ART. Logistic regression indicated that HIV infected students who received ART for more than 24 months ( OR =5.28, 95% CI =1.38-20.22) had a higher rate of successful HIV suppression. HIV infected students who reported physical sensory side effects ( OR =0.08, 95% CI =0.01-0.71) and cognitive side effects ( OR =0.28, 95% CI =0.09-0.90) were more likely to experience failure of ARI inhibition ( P <0.05).
Conclusions
There is still room for improvement in the efficacy of ART among MSM students. Strategies to improve treatment adherence must consider individual variances among HIV infected patients and the side effects of medications when designing treatment plans.
7.The influence of abnormal thyroid hormone receptor signal of decidua on decidualization in early pregnancy and its association with the occurrence of miscarriage
Muxin ZHAI ; Xuan LI ; Tao YU ; Li ZHAO ; Zhen YU ; Yuanyuan YANG
Acta Universitatis Medicinalis Anhui 2024;59(6):1076-1081
Objective To evaluate the angiogenesis of decidua in spontaneous abortion patients and to investigate the change of thyroid hormone receptor signal expression in decidua in miscarriage patients.Methods The decidua of pregnant women was collected.Patients with miscarriage were taken as the experimental group and healthy preg-nant women who underwent abortion by social factors were taken as the control group.The nuclear translocation of thyroid hormone receptor α(THR-α)and THR-β in decidua tissues was detected by Western blot method,and the distribution of THR-α and TH IR-β in decidua tissues was determined by immunohistochemistry.The expression of Deiodinase 2(DIO2)in decidua tissues was determined by Western blot.The distribution of DIO2 in decidua tissues was determined by immunofluorescence and the fluorescence intensity was measured.The decidual vessel density was determined by immunohistochemistry using CD34 as an endothelial marker.The protein expression of vascular endothelial growth factor receptor(VEGFR-1)was detected by Western blot.Results There was no sig-nificant difference in age,gestation days,TSH,T3,T4 and other basic data between the control group and the a-bortion group.The results of Western blot showed that the expression levels of THR-α and THR-β protein de-creased,and the results of immunohistochemical staining of decidual tissues showed that the nuclear translocation of decidual thyroid hormone receptor in patients with spontaneous abortion decreased(P<0.05).Western blotting results showed that the expression of DIO2 protein in the abortion group was lower than that in the control group,suggesting that thyroid hormone metabolism in decidua of spontaneous abortion pregnant women was affected.The results of immunofluorescence test showed that the fluorescence intensity of DIO2 in the abortion group was weaker than that in the control group(P<0.05).Immunohistochemical CD34 labeling of decidual small blood vessels showed that the number of CD34+blood vessels decreased in the abortion group with statistical difference(P<0.05).Western blot results showed that there was no significant change in VEGFR-1 between the two groups,and the difference between the two groups was not statistically significant.Conclusion The abnormal signal of thyroid hormone receptors in decidua may decrease decidua angiogenesis and participate in spontaneous abortion.
8.Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0
Mingchen SUN ; Shafei WU ; Yumeng CAI ; Yuanyuan LIU ; Kaimi LI ; Dachun ZHAO ; Xuan ZENG
Chinese Journal of Pathology 2024;53(5):464-469
Objective:To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 μltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily.Methods:HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio.Results:The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases ( P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC ( P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC ( P=0.001). Conclusions:Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.
9.Clinicopathological features of breast cancer with HER2 low expression: a real-world retrospective study
Kaimi LI ; Shafei WU ; Mingchen SUN ; Hongxi ZHANG ; Xinyi TENG ; Yuanyuan LIU ; Zhiyong LIANG ; Xuan ZENG
Chinese Journal of Pathology 2024;53(7):691-696
Objective:To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression.Methods:The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected.Results:The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive ( P<0.001), Ki-67 index below 35% ( P<0.001), well or moderate differentiation ( P<0.001) and over the age of 50 ( P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions:The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.
10.Efficacy and safety of acupuncture in the treatment of grand anxiety disorder:a Meta-analysis
Xi YANG ; Jie ZHANG ; Xuan XIAO ; Yuanyuan LIU ; Zengqi MAN ; Tao ZHANG
China Modern Doctor 2024;62(14):37-45
Objective To evaluate the clinical efficacy and safety of acupuncture in the treatment of grand anxiety disorder by applying Meta-analysis.Methods Randomized controlled trials on acupuncture treatment of generalized anxiety disorder in 7 Chinese and English databases from the establishment of the database to May 1,2022 were searched for screening,inclusion and literature risk assessment.Meta-analysis and subgroup analysis of different outcome indicators and/or intervention measures were performed using Stata 16 and Review Manager 5.4 software.Results Finally,20 randomized controlled trials were included,including 1661 cases and 4 intervention measures(acupuncture+electroacupuncture,acupuncture,electroacupuncture and western medicine).The results of meta-analysis indicated that there were statistically significant differences in HAMA and SAS scores between acupuncture group and western medicine group(P<0.05).The results of subgroup analysis showed that there was statistically significant difference in Hamilton anxiety scale(HAMA)score between acupuncture group and alprazolam.There was a statistically significant difference in self-rating anxiety scale(SAS)score between acupuncture group and simple paroxetine,buspirone,chlorhexidine/oryzanol/propranolol.In the evaluation of side effect scale,the difference between acupuncture(including electroacupuncture)group and western medicine group was statistically significant(P<0.01).Conclusion Acupuncture(including electroacupuncture)can effectively improve anxiety and symptoms with efficacy no less than that of Western medicine,and has the advantages of fewer adverse effects and higher safety.However,due to the quantity and quality of the included literature,multi-center,large sample,and high-quality randomized controlled studies are still needed to further corroborate the above conclusions.


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