1.Role of endoplasmic reticulum stress-mediated DEAD-box helicase 3 X-linked in a mouse model of concanavalin A-induced immune-mediated liver injury
Zhenzhen PAN ; Ling XU ; Xianru ZHU ; Zihao FAN ; Yaling CAO ; Yinkang MO ; Sai YAN ; Feng REN
Journal of Clinical Hepatology 2026;42(1):134-142
ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked (DDX3X) in immune-mediated liver injury (ILI), and to clarify its mechanism by regulating endoplasmic reticulum stress (ERS)-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A (ConA) via the caudal vein to establish a model of ILI, PBS (control group) and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice (DDX3XΔHep and DDX3X-flox mice (DDX3Xfl/fl), respectively.. The log-rank survival analysis, measurement of the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and HE staining of liver tissue were performed to assess liver injury, and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid (4-PBA, 100 mg/kg) was performed to inhibit ERS. Serum samples (n=30) and liver tissue samples (n=6) were collected from healthy controls, chronic hepatitis B (CHB) patients, and hepatitis B virus-associated liver failure (HBV-LF) patients; ELISA was used to measure the serum level of DDX3X, and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice, the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury (P<0.05), and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% (compared with 20% in the DDX3Xfl/fl group), with significant reductions in the serum levels of ALT and AST (P<0.000 1) and the expression levels of the ERS markers GRP78 and CHOP (P<0.05). After ERS was inhibited by 4-PBA, there was alleviation of liver injury (with reductions in ALT and AST, P <0.001) and a reduction in DDX3X expression (P<0.01). The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls (all P<0.01), and there was a significant increase in the serum level of DDX3X in HBV-LF patients (P<0.000 1). ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway (GRP78/CHOP), and its expression is associated with the progression of hepatitis B. Therefore, it can be used as a potential therapeutic target.
2.Establishment and evaluation of a CRISPR/Cas13a-based method for HBV DNA detection
Yinkang MO ; Zihao FAN ; Yuan TIAN ; Ling XU ; Yaling CAO ; Feng REN
Chinese Journal of Laboratory Medicine 2025;48(4):478-483
Objective:To construct a method for hepatitis B virus (HBV) DNA detection based on recombinase-mediated isothermal amplification (RAA)-clustered regularly interspaced short palindromic repeats and their associated protein 13a (CRISPR-Cas13a).Methods:Through the alignment and screening of HBV DNA sequences, a positive plasmid was constructed, and recombinase-aided amplification (RAA) primers and CRISPR RNA (crRNA) were designed. A method for detecting HBV DNA based on the RAA-CRISPR-Cas13a system was developed, and the specificity and sensitivity were evaluated. Utilizing the CRISPR-Cas13a system, 70 clinical samples from HBV DNA-positive patients with various viral loads collected at Beijing You′an Hospital from 2019 to 2021 were analyzed. The detection results were further compared with those results using real-time quantitative polymerase chain reaction (qPCR).Results:The optimal RAA amplification primers and crRNA were first screened using the RAA-CRISPR-Cas13a method, with the sensitivities for detecting HBV DNA standards and for clinical samples at 1 IU/ml and<10 IU/ml, respectively, demonstrating specificity for HBV DNA detection. Compared with qPCR (the gold standard), the detection consistency between the two methods was 100% (70/70).Conclusion:This study established a method for detecting HBV DNA by integrating recombinase-aided amplification (RAA) technology with CRISPR/Cas13a technology.
3.Ameliorative effects of Compound Fufangteng Mixture on cyclophosphamide-induced immunosuppression in mice
Li-na LIU ; Yu-fang SHEN ; Qin-qin WANG ; Lin-yu XIAO ; Jing-yu LIU ; Jun-ni MO ; Ren-yi-kun YUAN ; Hong-wei GAO ; Jian XIAO
Chinese Traditional Patent Medicine 2025;47(10):3249-3256
AIM To investigate the ameliorative effects of Compound Fufangteng Mixture(CFM)on cyclophosphamide(CTX)-induced immunosuppression in mice.METHODS Forty-eight male C57BL/6J mice were randomly divided into the blank control group,the model group,the levamisole hydrochloride group(40 mg/kg)and the low-dose,medium-dose and high-dose CFM groups(3.75,7.5,10 g/kg),with 8 mice in each group,and given respective intervention orally once daily for 14 days.On the 5th to 7th day of administration,with the blank control group given normal saline intraperitoneally,the other groups underwent intraperitoneal CTX injections(80 mg/kg).24 hours after the last administration,organ indices of thymus and spleen were calculated;splenic histopathological alterations were assessed by HE staining;serum levels of IL-2,IL-6 and IgG were quantified using ELISA;splenic CD4+,CD8+T lymphocytes,alongside CD86+and CD206+macrophages populations were analyzed by flow cytometry;and splenic expression of CD4,CD8 and F4/80 was evaluated by immunohistochemical staining.RESULTS In CTX-treated mice,CFM administration mitigated body weight loss;enhanced thymus weight and thymic index;ameliorated splenic immune cell populations,elevated serum levels of cytokines IL-2,IL-6 and IgG in serum;and upregulated splenic levels of CD45+CD3+T lymphocytes and F4/80+CD11b+macrophages,alongside increasing the expression of CD4,CD8 and F4/80 surface markers.CONCLUSION CFM alleviates CTX-induced immunosuppression state in mice by modulating immune cells,restoring immune function and enhancing anti-inflammatory and tissue repair capabilities.
4.Development and validation of risk prediction model for carbapenem-resistant Klebsiella pneumoniae infection
Yinzhu MO ; Xianxiong CHENG ; Cangsang SONG ; Shijie LYU ; Baojun REN ; Zhiwei LI ; Jinying BAO ; Huanzhi YANG
China Pharmacy 2025;36(14):1786-1791
OBJECTIVE To investigate the independent risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, develop a nomogram prediction model and validate it. METHODS Clinical data of hospitalized patients infected with CRKP between April 2020 and May 2023 at Kunming First People’s Hospital were retrospectively collected and matched 1∶1 with patients infected with carbapenem-susceptible Klebsiella pneumoniae (CSKP) during the same period as the modeling group. Using the same criteria, data from patients hospitalized and infected with CRKP and matched CSKP between June 2023 and June 2024 were collected as the validation group. Univariate analysis, LASSO regression and multivariate Logistic regression were conducted to identify independent risk factors for CRKP infection and to develop a nomogram prediction model. Internal validation of the model was performed using Bootstrap resampling, and external validation was carried out using the data of validation group. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves and calibration plots. RESULTS A total of 530 patients were enrolled, with 372 in the modeling group and 158 in the validation group. Cerebrovascular disease, indwelling gastric tube, mechanical ventilation, exposure to carbapenem antibiotics, and exposure to β-lactamase inhibitor compound agents were identified as independent risk factors for CRKP infection (P<0.05). The nomogram predicting CRKP infection risk achieved an area under ROC of 0.729 and 0.803 in internal and external validations, respectively. Calibration curves indicated a high degree of consistency between predicted and observed probabilities. CONCLUSIONS Cerebrovascular disease, indwelling gastric tube, mechanical ventilation, exposure to carbapenem antibiotics, and exposure to β-lactamase inhibitor compound agent are independent risk factors for CRKP infection. The developed nomogram model for predicting CRKP infection risk demonstrates good predictive performance and can aid in the early identification of patients at high risk for CRKP infection.
5.Research progress on the role of dopamine system in regulating hippocampal related brain functions.
Jing REN ; Wei-Yi MO ; Ling WANG ; Guang-Jian NI ; Jia-Jia YANG
Acta Physiologica Sinica 2025;77(5):893-904
Dopamine, as a catecholamine neurotransmitter widely distributed in the central nervous system, is involved in physiological functions such as motivation, arousal, reinforcement, and movement through various dopamine signaling pathways. The hippocampus receives dopaminergic neuron projections from regions such as the ventral tegmental area, locus coeruleus, and substantia nigra. Through D1-like and D2-like receptors, dopamine exerts significant regulatory effects such as spatial navigation, episodic memory, fear, anxiety, and reward. This review mainly summarizes the research progress on the functions of dopamine in the hippocampus from aspects including the sources of dopamine, receptor distribution and function, and the association of hippocampal dopamine system dysregulation with neurodegenerative diseases. The aim is to provide insights into the involvement of the dopamine system in hippocampal functions and the diagnosis and treatment of related diseases.
Hippocampus/physiology*
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Dopamine/physiology*
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Humans
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Animals
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Receptors, Dopamine D2/physiology*
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Memory/physiology*
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Signal Transduction/physiology*
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Neurodegenerative Diseases/physiopathology*
6.Effect of lymphatic circulation reconstruction under supermicrosurgery in secondary lymphedema of lower limbs
Linxuan HAN ; Rongyu LAN ; Jian MO ; Weihua ZHANG ; Xiaofei WU ; Jie QIN ; Zhuotan WU ; Xiaoping REN ; Guangmei DENG
Journal of Clinical Surgery 2025;33(9):997-1002
Objective To analyze the efficacy of vascularized lymph node transplantation(VLNT)combined with lymphatic venous anastomosis(LVA)in the treatment of secondary lower extremity lymphedema assisted by super microsurgical techniques.Methods A retrospective analysis was performed for 15 patients with secondary lower limb lymphedema who underwent VLNT+LVA surgery in the Department of Reconstructive and Reconstructive Microsurgery of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2021 to July 2023,and compared the circumference and volume of each segment of the lower limb between the preoperative and postoperative 90 days.LVA according to the results of ICG examination,3-5 parts of the lower limb were selected for"Z"shaped surgery,and the lymphatic vessels and venules were anastomosed under the microscope in the subcutaneous fat layer.VLNT confirmed and labeled the saphenous branch of the descending knee artery and its accompanying veins in the popliteal fossa,and the latissimus dorsi lymph node flap was incised,and the flap vessels were anastomosed with the saphenous branch of the descending knee artery and its accompanying veins.Postoperative observation of flap vascularization.The circumference and volume of the affected limb were measured before surgery and 90 days after surgery.Results A total of 15 patients with lower extremity lymphedema were included without serious complications.Statistical analysis showed that the circumference of all levels of the affected limb and the volume of the affected limb were improved 90 days after operation compared with those before surgery.Among them,the limb circumference and volume at each level from the highest point of the dorsum of the foot to 52 cm above the ankle improved 90 days after the operation compared with those before the operation.Conclusion LNT+LVA treatment for secondary lower extremity lymphedema can effectively control edema and improve the function of the affected limb.
7.Clinical characteristics and prognosis of fetuses with HNF1B gene variants: an analysis of 52 cases
Lanlan MO ; Saisai YANG ; Shumin REN ; Yaqin HOU ; Huirong SHI ; Qinghua WU
Chinese Journal of Perinatal Medicine 2025;28(4):295-300
Objective:To investigate the clinical characteristics and prognosis of fetuses with HNF1B gene variants. Methods:Fifty-two fetuses with HNF1B gene variants diagnosed by chromosomal copy number variation sequencing and/or whole exome sequencing at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2024 were retrospectively enrolled in this study, including 47 cases of 17q12 microdeletion and five cases of HNF1B point mutations. Prenatal ultrasound features, pregnancy outcomes, and postnatal manifestations were summarized and analyzed using descriptive statistics. Results:The prenatal ultrasound features of the 52 fetuses included enhanced renal parenchymal echo in 43 cases (82.7%), renal cysts in 15 cases (28.8%), enlarged kidney volume in 14 cases (26.9%), and pyelectasis in 13 cases (25.0%). Parental verification was completed for 35 cases, with 71.4% (25/35) being de novo mutations and 28.6% (10/35) inherited from either parent. Apart from eight cases with unknown pregnancy outcome (six cases were lost to follow-up, two cases refused to be followed up), the other 44 cases were successfully followed up, among which 68.2% (30/44) terminated the pregnancies and 31.8% (14/44) continued, resulting in live births. Prenatal ultrasound indicated renal abnormalities in all 14 live births, while postnatal follow-up showed seven cases with normal kidneys, one with reduced bilateral renal cysts, one with alleviated bilateral pyelectasis, four with unimproved renal structural abnormalities, and one who did not undergo a re-examination. Conclusion:The rate of renal abnormalities diagnosed by prenatal ultrasound in fetuses with HNF1B gene variants is high, and most of the pregnancies are terminated, although the renal sturctural abnormalities may improve after birth.
8.Clinical and imaging manifestations of posterior tibial tendon dysfunction
Yingli REN ; Jie FAN ; Yunhai MO ; Taoming DU
Journal of Practical Radiology 2025;41(6):1017-1020
Objective To explore the clinical and imaging manifestations of posterior tibial tendon dysfunction(PTTD).Methods A retrospective selection was conducted on 61 patients with clinically diagnosed PTTD.According to the classification criteria of Johnson and Strom,8 patients were classified as stage 1,17 as stage 2,20 as stage 3,and 16 as stage 4.The clinical manifestations and imaging features of patients were summarized at each stage.Results Among the 8 patients with stage 1 PTTD,no abnormalities were found on X-ray examination of the weight-bearing foot,while MRI revealed posterior tibial tendon(PTT)tendinitis in 4 cases(50.0%).For stage 2 patients(n=17),X-ray examination of the weight-bearing foot showed a decrease in the longitudinal arch of the foot in 15 patients(88.2%).MRI mainly revealed PTT degeneration in 12 cases(70.6%),PTT tears in 2 cases(11.8%),and other structural injuries in 5 cases(29.4%).For stages 3-4 patients(n=36),X-ray examination of the weight-bearing foot showed flatfoot in all cases.MRI mainly revealed PTT degeneration in 12 cases(33.3%),PTT tears in 24 cases(66.7%),spring ligament injuries in 33 cases(91.7%),and deltoid ligament injuries in 23 cases(63.9%).Conclusion Patients with stage 1 PTTD often have a normal foot longitudinal arch and may present with PTT tendinitis.Middle-aged females are more commonly affected by advanced PTTD,which is characterized by gradual decrease and collapse of the foot arch,accompanied by varying degrees of PTT degeneration and tears.The spring ligament injuries and deltoid ligament are frequently involved in structural injuries associated with PTTD.
9.Establishment of a Collagen Type Ⅱ-Induced Th17 Cell Proliferation Model in vitro:Exploring the Effects of IL-23 and Collagen Activity on Autoimmune Regulation
Hong MO ; Yong-qiang REN ; Rui SU ; Xiao-ling YANG ; Da-wei XU
Progress in Modern Biomedicine 2025;25(9):1470-1477
Objective:To establish a model of reactive Th17 cells proliferation induced by collagen type Ⅱ(C Ⅱ)in vitro and investigate its influencing factors.Methods:The splenic lymphocytes of normal and CIA mice were isolated and divided into groups.They were given inactivated or non-inactivated C Ⅱ or different concentrations of IL-23(2,10,50 ng/mL),or IL-23p19 antibody.Culturing for 60 hours,the ratio of CD4+RORγt+Th17 cells was detected by flow cytometry.Then,the results obtained are ana lyzed,and the corresponding conclusions are drawn.Results:After 60 hours of culture in vitro,the ratio of Th 17 cells stimulated by inactivated or non-inactivated C Ⅱ in normal mouse spleen lymphocytes was significantly lower than that before culture,and the ratio of Th17 cells not stimulated by C Ⅱ in CIA mouse spleen lymphocytes was also significantly lower than that before culture,while the ratio of Th17 cells stimulated by inactivated C Ⅱ or non-inactivated C Ⅱ in CIA mouse spleen lymphocytes was significantly higher than that before culture,and there was a significant difference compared with the CIA control group(P<0.05).However,there was no statistical difference in the ratio of Th17 cells between the two groups without inactivated C Ⅱ and inactivated C Ⅱ(P=0.44).After the analysis of the data obtained from the study,it was further concluded that different concentrations of IL-23 did not affect the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro,but after adding IL-23p19 antibody neutralization reagent,the Th17 cell ratio of spleen lymphocytes of CIA mice in vitro decreased significantly,with a statistical difference compared with the blank control group(P<0.01).Conclusions:This study established an in vitro Th17 cell proliferation model induced by type Ⅱ collagen,exploring the effects of IL-23 and collagen activity on Th17 cell proliferation.The results showed that CⅡ stimulation significantly promoted Th17 cell proliferation in CIA mice,with both active and inactivated CⅡ inducing proliferation.IL-23 was found to be essential for the maintenance of Th17 cells,although its direct proliferative effect was limited.These findings provide new experimental evidence and theoretical support for the mechanism research of rheumatic diseases and IL-23/IL-17 pathway-targeted therapies,with important implications for immune regulation and drug development.
10.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

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